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Molecular Psychiatry Aug 2023The serotonin hypothesis of depression is still influential. We aimed to synthesise and evaluate evidence on whether depression is associated with lowered serotonin... (Meta-Analysis)
Meta-Analysis
The serotonin hypothesis of depression is still influential. We aimed to synthesise and evaluate evidence on whether depression is associated with lowered serotonin concentration or activity in a systematic umbrella review of the principal relevant areas of research. PubMed, EMBASE and PsycINFO were searched using terms appropriate to each area of research, from their inception until December 2020. Systematic reviews, meta-analyses and large data-set analyses in the following areas were identified: serotonin and serotonin metabolite, 5-HIAA, concentrations in body fluids; serotonin 5-HT receptor binding; serotonin transporter (SERT) levels measured by imaging or at post-mortem; tryptophan depletion studies; SERT gene associations and SERT gene-environment interactions. Studies of depression associated with physical conditions and specific subtypes of depression (e.g. bipolar depression) were excluded. Two independent reviewers extracted the data and assessed the quality of included studies using the AMSTAR-2, an adapted AMSTAR-2, or the STREGA for a large genetic study. The certainty of study results was assessed using a modified version of the GRADE. We did not synthesise results of individual meta-analyses because they included overlapping studies. The review was registered with PROSPERO (CRD42020207203). 17 studies were included: 12 systematic reviews and meta-analyses, 1 collaborative meta-analysis, 1 meta-analysis of large cohort studies, 1 systematic review and narrative synthesis, 1 genetic association study and 1 umbrella review. Quality of reviews was variable with some genetic studies of high quality. Two meta-analyses of overlapping studies examining the serotonin metabolite, 5-HIAA, showed no association with depression (largest n = 1002). One meta-analysis of cohort studies of plasma serotonin showed no relationship with depression, and evidence that lowered serotonin concentration was associated with antidepressant use (n = 1869). Two meta-analyses of overlapping studies examining the 5-HT receptor (largest n = 561), and three meta-analyses of overlapping studies examining SERT binding (largest n = 1845) showed weak and inconsistent evidence of reduced binding in some areas, which would be consistent with increased synaptic availability of serotonin in people with depression, if this was the original, causal abnormaly. However, effects of prior antidepressant use were not reliably excluded. One meta-analysis of tryptophan depletion studies found no effect in most healthy volunteers (n = 566), but weak evidence of an effect in those with a family history of depression (n = 75). Another systematic review (n = 342) and a sample of ten subsequent studies (n = 407) found no effect in volunteers. No systematic review of tryptophan depletion studies has been performed since 2007. The two largest and highest quality studies of the SERT gene, one genetic association study (n = 115,257) and one collaborative meta-analysis (n = 43,165), revealed no evidence of an association with depression, or of an interaction between genotype, stress and depression. The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations. Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration.
Topics: Humans; Depression; Serotonin; Receptor, Serotonin, 5-HT1A; Tryptophan; Hydroxyindoleacetic Acid; Antidepressive Agents; Serotonin Plasma Membrane Transport Proteins
PubMed: 35854107
DOI: 10.1038/s41380-022-01661-0 -
Periodontology 2000 Feb 2024Platelet-rich fibrin (PRF) has been characterized as a regenerative biomaterial that is fully resorbed within a typical 2-3 week period. Very recently, however, a...
Platelet-rich fibrin (PRF) has been characterized as a regenerative biomaterial that is fully resorbed within a typical 2-3 week period. Very recently, however, a novel heating process was shown to extend the working properties of PRP/PRF from a standard 2-3 week period toward a duration of 4-6 months. Numerous clinicians have now utilized this extended-PRF (e-PRF) membrane as a substitute for collagen barrier membranes in various clinical applications, such as guided tissue/bone regeneration. This review article summarizes the scientific work to date on this novel technology, including its current and future applications in periodontology, implant dentistry, orthopedics and facial aesthetics. A systematic review was conducted investigating key terms including "Bio-Heat," "albumin gel," "albumin-PRF," "Alb-PRF," "extended-PRF," "e-PRF," "activated plasma albumin gel," and "APAG" by searching databases such as MEDLINE, EMBASE and PubMed. Findings from preclinical studies demonstrate that following a simple 10-min heating process, the transformation of the liquid plasma albumin layer into a gel-like injectable albumin gel extends the resorption properties to at least 4 months according to ISO standard 10 993 (subcutaneous animal model). Several clinical studies have now demonstrated the use of e-PRF membranes as a replacement for collagen membranes in GTR/GBR procedures, closing lateral windows in sinus grafting procedures, for extraction site management, and as a stable biological membrane during recession coverage procedures. Furthermore, Alb-PRF may also be injected as a regenerative biological filler that lasts extended periods with advantages in joint injections, osteoarthritis and in the field of facial aesthetics. This article highlights the marked improvement in the stability and degradation properties of the novel Alb-PRF/e-PRF technology with its widespread future potential use as a potential replacement for collagen membranes with indications including extraction site management, GBR procedures, lateral sinus window closure, recession coverage among others, and further highlights its use as a biological regenerative filler for joint injections and facial aesthetics. It is hoped that this review will pioneer future opportunities and research development in the field, leading to further progression toward more natural and less costly biomaterials for use in medicine and dentistry.
Topics: Animals; Humans; Biocompatible Materials; Bone Regeneration; Guided Tissue Regeneration, Periodontal; Membranes, Artificial; Platelet-Rich Fibrin
PubMed: 37986559
DOI: 10.1111/prd.12537 -
Phytomedicine : International Journal... Jul 2023Every day the skin is constantly exposed to several harmful factors that induce oxidative stress. When the cells are incapable to maintain the balance between... (Review)
Review
BACKGROUND
Every day the skin is constantly exposed to several harmful factors that induce oxidative stress. When the cells are incapable to maintain the balance between antioxidant defenses and reactive oxygen species, the skin no longer can keep its integrity and homeostasis. Chronic inflammation, premature skin aging, tissue damage, and immunosuppression are possible consequences induced by sustained exposure to environmental and endogenous reactive oxygen species. Skin immune and non-immune cells together with the microbiome are essential to efficiently trigger skin immune responses to stress. For this reason, an ever-increasing demand for novel molecules capable of modulating immune functions in the skin has risen the level of their development, particularly in the field of natural product-derived molecules.
PURPOSE
In this review, we explore different classes of molecules that showed evidence in modulate skin immune responses, as well as their target receptors and signaling pathways. Moreover, we describe the role of polyphenols, polysaccharides, fatty acids, peptides, and probiotics as possible treatments for skin conditions, including wound healing, infection, inflammation, allergies, and premature skin aging.
METHODS
Literature was searched, analyzed, and collected using databases, including PubMed, Science Direct, and Google Scholar. The search terms used included "Skin", "wound healing", "natural products", "skin microbiome", "immunomodulation", "anti-inflammatory", "antioxidant", "infection", "UV radiation", "polyphenols", "polysaccharides", "fatty acids", "plant oils", "peptides", "antimicrobial peptides", "probiotics", "atopic dermatitis", "psoriasis", "auto-immunity", "dry skin", "aging", etc., and several combinations of these keywords.
RESULTS
Natural products offer different solutions as possible treatments for several skin conditions. Significant antioxidant and anti-inflammatory activities were reported, followed by the ability to modulate immune functions in the skin. Several membrane-bound immune receptors in the skin recognize diverse types of natural-derived molecules, promoting different immune responses that can improve skin conditions.
CONCLUSION
Despite the increasing progress in drug discovery, several limiting factors need future clarification. Understanding the safety, biological activities, and precise mechanisms of action is a priority as well as the characterization of the active compounds responsible for that. This review provides directions for future studies in the development of new molecules with important pharmaceutical and cosmeceutical value.
Topics: Humans; Skin Aging; Reactive Oxygen Species; Biological Products; Antioxidants; Inflammation; Anti-Inflammatory Agents; Polyphenols; Peptides; Polysaccharides
PubMed: 37119762
DOI: 10.1016/j.phymed.2023.154824 -
American Journal of Obstetrics &... Jul 2023Various prophylactic antibiotic regimens are used in the management of preterm premature rupture of membranes. We investigated the efficacy and safety of these regimens... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Various prophylactic antibiotic regimens are used in the management of preterm premature rupture of membranes. We investigated the efficacy and safety of these regimens in terms of maternal and neonatal outcomes.
DATA SOURCES
We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to July 20, 2021.
STUDY ELIGIBILITY CRITERIA
We included randomized controlled trials involving pregnant women with preterm premature rupture of membranes before 37 weeks of gestation and a comparison of ≥2 of the following 10 antibiotic regimens: control/placebo, erythromycin, clindamycin, clindamycin plus gentamicin, penicillins, cephalosporins, co-amoxiclav, co-amoxiclav plus erythromycin, aminopenicillins plus macrolides, and cephalosporins plus macrolides.
METHODS
Two investigators independently extracted published data and assessed the risk of bias with a standard procedure following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Network meta-analysis was conducted using the random-effects model.
RESULTS
A total of 23 studies that recruited a total of 7671 pregnant women were included. Only penicillins (odds ratio, 0.46; 95% confidence interval, 0.27-0.77) had significantly superior effectiveness for maternal chorioamnionitis. Clindamycin plus gentamicin reduced the risk of clinical chorioamnionitis, with borderline significance (odds ratio, 0.16; 95% confidence interval, 0.03-1.00). By contrast, clindamycin alone increased the risk of maternal infection. For cesarean delivery, no significant differences were noted among these regimens.
CONCLUSION
Penicillins remain the recommended antibiotic regimen for reducing maternal clinical chorioamnionitis. The alternative regimen includes clindamycin plus gentamicin. Clindamycin should not be used alone.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Clindamycin; Chorioamnionitis; Amoxicillin-Potassium Clavulanate Combination; Network Meta-Analysis; Anti-Bacterial Agents; Premature Birth; Erythromycin; Macrolides; Gentamicins; Cephalosporins
PubMed: 37094635
DOI: 10.1016/j.ajogmf.2023.100978 -
American Journal of Obstetrics &... Jul 2023An emergency (rescue) cervical cerclage can be offered to pregnant women presenting with dilatation and prolapsed membranes in the second trimester of pregnancy because... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
An emergency (rescue) cervical cerclage can be offered to pregnant women presenting with dilatation and prolapsed membranes in the second trimester of pregnancy because of cervical insufficiency. This study aimed to investigate the effectiveness of an emergency cerclage in both singleton and twin pregnancies in the prevention of extreme premature birth.
DATA SOURCES
We performed a systematic literature search in PubMed and Embase from inception to June 2022 for transvaginal cervical emergency cerclages.
STUDY ELIGIBILITY CRITERIA
All studies on transvaginal cervical emergency cerclages with at least 5 patients and reporting survival were included.
METHODS
Included studies were assessed for quality and risk of bias with an adjusted Quality In Prognosis Studies tool. Random-effects meta-analyses and meta-regressions were performed for the primary outcome: survival.
RESULTS
Our search yielded 96 studies, incorporating 3239 women, including 14 studies with an expectant management control group, incorporating 746 women. Overall survival after cervical emergency cerclage was 74%, with a fetal survival of 88% and neonatal survival of 90%. Singleton and twin pregnancies showed similar survival, with a pregnancy prolongation of 52 and 37 days and a gestational age at delivery of 30 and 28 weeks, respectively. Meta-regression analyses indicated a significant inverse association between mean gestational age at diagnosis and pregnancy prolongation and no association between dilatation or gestational age at diagnosis and gestational age at delivery. Compared with expectant management, emergency cerclage significantly increased overall survival by 43%, fetal survival by 17% and neonatal survival by 22%, along with a significant pregnancy prolongation of 37 days and reduction in delivery at <28 weeks of gestation of 55%. These effects were more profound in singleton pregnancies than in twin pregnancies.
CONCLUSION
This systematic review indicates that, in pregnancies threatened by extreme premature birth because of cervical insufficiency, emergency cerclage leads to significantly higher survival, accompanied by significant pregnancy prolongation and reduction in delivery at <28 weeks of gestation, compared with expectant management. The mean gestational age at delivery was 30 weeks, independent of dilatation or gestational age at diagnosis. Survival was similar for singleton and twin pregnancies, implying that emergency cerclage should be considered in both.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Infant; Pregnancy, Twin; Cerclage, Cervical; Premature Birth; Cervix Uteri; Pregnancy Complications
PubMed: 37084870
DOI: 10.1016/j.ajogmf.2023.100971 -
Revista Brasileira de Ginecologia E... Aug 2023To perform a systematic review and meta-analysis of studies on maternal, fetal, and neonatal outcomes of women with singleton pregnancies, after spontaneous... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To perform a systematic review and meta-analysis of studies on maternal, fetal, and neonatal outcomes of women with singleton pregnancies, after spontaneous conception, and with the diagnosis of amniotic sludge before 37 weeks of gestational age.
DATA SOURCES
We conducted a search on the PubMed, Cochrane, Bireme, and Theses databases until June 2022.
SELECTION OF STUDIES
Using the keywords or or , we found 263 articles, 132 of which were duplicates, and 70 were discarded because they did not meet the inclusion criteria.
DATA COLLECTION
The articles retrieved were analyzed by 2 reviewers; 61 were selected for full-text analysis, 18 were included for a qualitative analysis, and 14, for a quantitative analysis.
DATA SYNTHESIS
Among the maternal outcomes analyzed, there was an increased risk of preterm labor (95% confidence interval [95%CI]: 1.45-2.03), premature rupture of ovular membranes (95%CI: 1.99-3.79), and clinical (95%CI: 1.41-6.19) and histological chorioamnionitis (95%CI: 1.75-3.12). Regarding the fetal outcomes, there was a significant increase in the risk of morbidity (95%CI: 1.80-3.17), mortality (95%CI: 1.14-18.57), admission to the Neonatal Intensive Care Unit (NICU; 95%CI: 1.17-1.95), and neonatal sepsis (95%CI: 2.29-7.55).
CONCLUSION
The results of the present study indicate that the presence of amniotic sludge is a risk marker for preterm delivery. Despite the heterogeneity of the studies analyzed, even in patients with other risk factors for prematurity, such as short cervix and previous preterm delivery, the presence of amniotic sludge increases the risk of premature labor. Moreover, antibiotic therapy seems to be a treatment for amniotic sludge, and it may prolong pregnancy.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Premature Birth; Sewage; Gestational Age; Risk Factors; Databases, Factual
PubMed: 37683661
DOI: 10.1055/s-0043-1772189 -
International Journal of Molecular... Oct 2023Recently, advances in molecular biology and bioinformatics have allowed a more thorough understanding of tumorigenesis in aggressive PitNETs (pituitary neuroendocrine... (Review)
Review
Recently, advances in molecular biology and bioinformatics have allowed a more thorough understanding of tumorigenesis in aggressive PitNETs (pituitary neuroendocrine tumors) through the identification of specific essential genes, crucial molecular pathways, regulators, and effects of the tumoral microenvironment. Target therapies have been developed to cure oncology patients refractory to traditional treatments, introducing the concept of precision medicine. Preliminary data on PitNETs are derived from preclinical studies conducted on cell cultures, animal models, and a few case reports or small case series. This study comprehensively reviews the principal pathways involved in aggressive PitNETs, describing the potential target therapies. A search was conducted on Pubmed, Scopus, and Web of Science for English papers published between 1 January 2004, and 15 June 2023. 254 were selected, and the topics related to aggressive PitNETs were recorded and discussed in detail: epigenetic aspects, membrane proteins and receptors, metalloprotease, molecular pathways, PPRK, and the immune microenvironment. A comprehensive comprehension of the molecular mechanisms linked to PitNETs' aggressiveness and invasiveness is crucial. Despite promising preliminary findings, additional research and clinical trials are necessary to confirm the indications and effectiveness of target therapies for PitNETs.
Topics: Animals; Humans; Pituitary Neoplasms; Pituitary Gland; Neuroendocrine Tumors; Aggression; Tumor Microenvironment
PubMed: 37958702
DOI: 10.3390/ijms242115719 -
Cell Proliferation Oct 2023The liver is a common secondary metastasis site of many malignant tumours, such as the colorectum, pancreas, stomach, breast, prostate, and lung cancer. The clinical... (Review)
Review
The liver is a common secondary metastasis site of many malignant tumours, such as the colorectum, pancreas, stomach, breast, prostate, and lung cancer. The clinical management of liver metastases is challenging because of their strong heterogeneity, rapid progression, and poor prognosis. Now, exosomes, small membrane vesicles that are 40-160 nm in size, are released by tumour cells, namely, tumour-derived exosomes (TDEs), and are being increasingly studied because they can retain the original characteristics of tumour cells. Cell-cell communication via TDEs is pivotal for liver pre-metastatic niche (PMN) formation and liver metastasis; thus, TDEs can provide a theoretical basis to intensively study the potential mechanisms of liver metastasis and new insights into the diagnosis and treatment of liver metastasis. Here, we systematically review current research progress about the roles and possible regulatory mechanisms of TDE cargos in liver metastasis, focusing on the functions of TDEs in liver PMN formation. In addition, we discuss the clinical utility of TDEs in liver metastasis, including TDEs as potential biomarkers, and therapeutic approaches for future research reference in this field.
Topics: Humans; Exosomes; Liver Neoplasms; Cell Communication; Pancreas; Biomarkers, Tumor; Tumor Microenvironment; Neoplasm Metastasis
PubMed: 36941028
DOI: 10.1111/cpr.13452 -
Current Pollution Reports Sep 2023There is a growing interest in understanding the health effects of exposure to per- and polyfluoroalkyl substances (PFAS) through the study of the human metabolome. In...
PURPOSE OF REVIEW
There is a growing interest in understanding the health effects of exposure to per- and polyfluoroalkyl substances (PFAS) through the study of the human metabolome. In this systematic review, we aimed to identify consistent findings between PFAS and metabolomic signatures. We conducted a search matching specific keywords that was independently reviewed by two authors on two databases (EMBASE and PubMed) from their inception through July 19, 2022 following PRISMA guidelines.
RECENT FINDINGS
We identified a total of 28 eligible observational studies that evaluated the associations between 31 different PFAS exposures and metabolomics in humans. The most common exposure evaluated was legacy long-chain PFAS. Population sample sizes ranged from 40 to 1,105 participants at different stages across the lifespan. A total of 19 studies used a non-targeted metabolomics approach, 7 used targeted approaches, and 2 included both. The majority of studies were cross-sectional ( = 25), including four with prospective analyses of PFAS measured prior to metabolomics.
SUMMARY
Most frequently reported associations across studies were observed between PFAS and amino acids, fatty acids, glycerophospholipids, glycerolipids, phosphosphingolipids, bile acids, ceramides, purines, and acylcarnitines. Corresponding metabolic pathways were also altered, including lipid, amino acid, carbohydrate, nucleotide, energy metabolism, glycan biosynthesis and metabolism, and metabolism of cofactors and vitamins. We found consistent evidence across studies indicating PFAS-induced alterations in lipid and amino acid metabolites, which may be involved in energy and cell membrane disruption.
PubMed: 37753190
DOI: 10.1007/s40726-023-00269-4 -
BMC Pregnancy and Childbirth Sep 2023Prelabour rupture of membranes at term affects approximately 10% of women during pregnancy, and it is often associated with a higher risk of infection than when the...
INTRODUCTION
Prelabour rupture of membranes at term affects approximately 10% of women during pregnancy, and it is often associated with a higher risk of infection than when the membranes are intact. In an attempt to control the risk of infection, two main approaches have been used most widely in clinical practice: induction of labour (IOL) soon after the rupture of membranes, also called active management (AM), and watchful waiting for the spontaneous onset of labour, also called expectant management (EM). In addition, previous studies have demonstrated that vaginal examinations increase the risk of chorioamnionitis. However, the effect of vaginal examinations in the context of prelabour rupture of membranes have not been researched to the same extent.
METHODS
This systematic review analyses and critiques the latest research on the management of term prelabour rupture of membranes, including the effect of vaginal examinations during labour, with a focus on the outcomes of both normal birth, and chorioamnionitis. Due to its complexity, three research questions were identified using the PICO diagram, and subsequently, the results from these searches were combined. The systematic review aimed to identify randomised controlled trials (RCTs) and observational studies that compared active vs expectant management, included number of vaginal examinations and had chorioamnionitis and/or normal birth as outcomes. The following databases were used: MEDLINE, EMBASE, Maternity and Infant care, LILACS, CINAHL and the Cochrane Central Register of Controlled trials. Quality was assessed using a tool developed especifically for this study that included questions from CASP and the Cochrane risk of bias tool. Due to the high degree of heterogeneity meta-analysis was not deemed appropriate. Therefore, simple narrative analysis was carried out.
RESULTS
Thirty-two studies met the inclusion criteria, of which 27 were RCTs and 5 observational studies. The overall quality of the studies wasn't high, 15 out of the 32 studies were deemed to be low quality and only 17 out of 32 studies were deemed to be of intermediate quality. The systematic review revealed that the management of term prelabour rupture of membranes continues to be controversial. Previous research has compared active management (Induction of labour shortly after the rupture of membrane) against expectant management (watchful waiting for the spontaneous onset of labour). Although previous studies have demonstrated that vaginal examinations increase the risk of chorioamnionitis, no prospective studies have included an intervention to reduce the number of vaginal examinations.
CONCLUSION
A RCT assessing the consequences of active management and expectant management as well as the effect of vaginal examinations during labour for term prelabour rupture of membranes is necessary.
Topics: Female; Pregnancy; Infant; Child; Humans; Chorioamnionitis; Delivery, Obstetric; Labor, Obstetric; Databases, Factual; Infant Care
PubMed: 37684576
DOI: 10.1186/s12884-023-05878-x