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International Journal of Molecular... Sep 2023Cocaine abuse is a serious public health problem as this drug exerts a plethora of functional and histopathological changes that potentially lead to death. Cocaine... (Review)
Review
Cocaine abuse is a serious public health problem as this drug exerts a plethora of functional and histopathological changes that potentially lead to death. Cocaine causes complex multiorgan toxicity, including in the heart where the blockade of the sodium channels causes increased catecholamine levels and alteration in calcium homeostasis, thus inducing an increased oxygen demand. Moreover, there is evidence to suggest that mitochondria alterations play a crucial role in the development of cocaine cardiotoxicity. We performed a systematic review according to the Preferred Reporting Items for Systemic Reviews and Meta-Analysis (PRISMA) scheme to evaluate the mitochondrial mechanisms determining cocaine cardiotoxicity. Among the initial 106 articles from the Pubmed database and the 17 articles identified through citation searching, 14 final relevant studies were extensively reviewed. Thirteen articles included animal models and reported the alteration of specific mitochondria-dependent mechanisms such as reduced energy production, imbalance of membrane potential, increased oxidative stress, and promotion of apoptosis. However, only one study evaluated human cocaine overdose samples and observed the role of cocaine in oxidative stress and the induction of apoptosis though mitochondria. Understanding the complex processes mediated by mitochondria through forensic analysis and experimental models is crucial for identifying potential therapeutic targets to mitigate or reverse cocaine cardiotoxicity in humans.
Topics: Animals; Humans; Cardiotoxicity; Cocaine; Cocaine-Related Disorders; Heart; Mitochondria; Oxidative Stress
PubMed: 37833964
DOI: 10.3390/ijms241914517 -
Journal of Psychopharmacology (Oxford,... Nov 2023Major depressive disorder (MDD) is a leading cause of global disability. Several lines of evidence implicate the dopamine system in its pathophysiology. However, the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Major depressive disorder (MDD) is a leading cause of global disability. Several lines of evidence implicate the dopamine system in its pathophysiology. However, the magnitude and consistency of the findings are unknown. We address this by systematically reviewing in vivo imaging evidence for dopamine measures in MDD and meta-analysing these where there are sufficient studies.
METHODS
Studies investigating the dopaminergic system using positron emission tomography or single photon emission computed tomography in MDD and a control group were included. Demographic, clinical and imaging measures were extracted from each study, and meta-analyses and sensitivity analyses were conducted.
RESULTS
We identified 43 studies including 662 patients and 801 controls. Meta-analysis of 38 studies showed no difference in mean or mean variability of striatal D receptor availability ( = 0.06, = 0.620), or combined dopamine synthesis and release capacity ( = 0.19, = 0.309). Dopamine transporter (DAT) availability was lower in the MDD group in studies using DAT selective tracers ( = -0.56, = 0.006), but not when tracers with an affinity for serotonin transporters were included ( = -0.21, = 0.420). Subgroup analysis showed greater dopamine release ( = 0.49, = 0.030), but no difference in dopamine synthesis capacity ( = -0.21, = 0.434) in the MDD group. Striatal D receptor availability was lower in patients with MDD in two studies.
CONCLUSIONS
The meta-analysis indicates striatal DAT availability is lower, but D receptor availability is not altered in people with MDD compared to healthy controls. There may be greater dopamine release and lower striatal D receptors in MDD, although further studies are warranted. We discuss factors associated with these findings, discrepancies with preclinical literature and implications for future research.
Topics: Humans; Dopamine; Depressive Disorder, Major; Tomography, Emission-Computed, Single-Photon; Positron-Emission Tomography; Receptors, Dopamine D2; Dopamine Plasma Membrane Transport Proteins
PubMed: 37811803
DOI: 10.1177/02698811231200881 -
Cureus Aug 2023Acute respiratory distress syndrome (ARDS) is a severe lung disease associated with a high mortality rate. Extracorporeal membrane oxygenation (ECMO) is a life-saving... (Review)
Review
Acute respiratory distress syndrome (ARDS) is a severe lung disease associated with a high mortality rate. Extracorporeal membrane oxygenation (ECMO) is a life-saving therapy for severe ARDS patients who do not respond to conventional treatments. Nevertheless, the optimal management of ARDS patients undergoing ECMO and their mortality rates remain subjects of controversy. Thus, this systematic review aims to assess mortality rates in ARDS patients on ECMO and identify associated factors. The review adhered to the Preferred Reporting Items for Systemic Review and Meta-Analysis (PRISMA) 2020 guidelines. A comprehensive literature search was conducted on PubMed, PubMed Central (PMC), Medline, and Embase. In accordance with our inclusion and exclusion criteria, filters, and key terms, we proceeded to screen the articles. After assessing the relevance of each article to our topic, further screening was carried out. Quality assessment of the articles was conducted, resulting in the inclusion of a total of 12 articles for the review. The primary outcome focused on mortality rates among ARDS patients undergoing ECMO. Secondary outcomes explored potential contributors to mortality, including patient age, underlying cause of ARDS, and Sequential Organ Failure Assessment (SOFA) scores at the initiation of ECMO. Mortality rates exhibited significant variation, ranging from 22% to 62.6%. Several factors emerged as potential predictors of mortality, encompassing patient age, comorbidities, complications during ECMO therapy, and treatment-related variables. This systematic review offers valuable insights into the intricate factors influencing mortality rates among ARDS patients on ECMO. A comprehension of these factors is essential to steer clinical practice and enhance patient outcomes. While ECMO serves as a restorative avenue for ARDS patients, future research is warranted to further elucidate these complex interactions and refine ECMO therapy protocols.
PubMed: 37719572
DOI: 10.7759/cureus.43590 -
Environmental Health Insights 2023Various review papers have been published regarding the occurrence and fate of micropollutants (MPs). MPs in the aquatic environment are still not well reviewed to... (Review)
Review
INTRODUCTION
Various review papers have been published regarding the occurrence and fate of micropollutants (MPs). MPs in the aquatic environment are still not well reviewed to generate comprehensive summaries with a special focus on their removal from wastewater using conventional and advanced treatment processes. Therefore, this review aimed to provide a synopsis of the efficiency of the advanced wastewater treatment plants in the removal of MPs.
MATERIALS AND METHODS
A systematic search of published literature was conducted on the National Library of Medicine (NLM) database, Web of Science, database, Scopus, and Google Scholar, based on studies with evidence of removal of MPs in the wastewater treatment process. Screening of the published articles was made using pre-specified inclusion and exclusion criteria.
RESULTS
Amongst the 1545 studies searched, 21 full-length articles were analyzed that showed 7 treatment options related to the removal of MPs from wastewater. MPs from wastewater effluents were successfully and effectively removed by advanced treatment techniques. Advanced Oxidation Processes (AOPs), membrane processes, and adsorption processes have all been shown to be potential solutions for the removal of MPs in advanced treatment plants (WWTPs). But, there are 2 critical issues associated with the application of the advanced treatment options which are high operational cost and the formation of dangerous by-products and concentrated residues.
CONCLUSION
This study identified that the removal of MPs using WWTPs was commonly incomplete with varying removal efficiency. Therefore, the adaptation and scale-up of the cost-effective and efficient combined wastewater treatment technology are vital to creating an absolute barrier to MPs emissions.
PubMed: 37692976
DOI: 10.1177/11786302231195158 -
Cureus Aug 2023Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer with several risk factors. Exosomes are extracellular vesicles generated by the fusion of... (Review)
Review
Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer with several risk factors. Exosomes are extracellular vesicles generated by the fusion of multivesicular structures with the cell membrane and play an important role as intercellular messengers. MicroRNA (miRNA) is a noncoding RNA and regulates post-transcriptional modification. The present systematic review aims to identify and correlate the possible association and role of circulating exosomes with OSCC. Using the search strategy, articles fulfilling the inclusion criteria, published between January 2012 to March 2022, were retrieved from online databases including PubMed, Scopus, Web of Science, and Cochrane Library. About 904 articles were found using an electronic database and a human search. After reviewing the titles and abstracts, 614 studies were eliminated, and duplicate articles were removed. Five studies were included in this systematic review. Circulating exosomal expression of miRNA27, miRNA 21, and miRNA 155 showed significant upregulation in OSCC patients. Circulating exosomes could be potential biomarkers to be used in the detection of patients with OSCC. More studies are warranted in this area to gain a better understanding of the pathophysiology of OSCC and the function of molecular markers from circulating exosomes. Understanding the role of molecular markers from circulating exosomes in pathogenesis will provide a better understanding of the development of the disease, necessitating more study in this area. According to this review, circulating exosomes might be a potential approach to the identification of OSCC.
PubMed: 37692575
DOI: 10.7759/cureus.43235 -
Frontiers in Endocrinology 2023Autosomal dominant hypocalcemia (ADH1) is a genetic disorder characterized by low serum calcium and low or inappropriately normal levels of parathyroid hormone. The...
Autosomal dominant hypocalcemia (ADH1) is a genetic disorder characterized by low serum calcium and low or inappropriately normal levels of parathyroid hormone. The disease is caused by a heterozygous activating mutation of the calcium-sensing receptor () gene, encoding a G-Protein-coupled cell membrane sensor of extracellular calcium concentration mainly expressed by parathyroid glands, renal tubules, and the brain. ADH1 has been linked to 113 unique germline mutations, of which nearly 96% are missense mutations. There is often a lack of a clear genotype/phenotype correlation in the reported literature. Here, we described a case series of 6 unrelated ADH1 probands, each one bearing a gain-of-function mutation, and two children of one of these cases, matching our identified mutations to the same ones previously reported in the literature, and comparing the clinical and biochemical characteristics, as well as the complication profile. As a result of these genetic and clinical comparisons, we propose that a genotype/phenotype correlation may exist because our cases showed similar presentation, characteristics, and severity, with respect to published cases with the same or similar mutations. We also contend that the severity of the presentation is highly influenced by the specific variant. These findings, however, require further evaluation and assessment with a systematic review.
Topics: Gain of Function Mutation; Receptors, Calcium-Sensing; Calcium; Research; Mutation
PubMed: 37654565
DOI: 10.3389/fendo.2023.1215036 -
International Journal of Molecular... Jul 2023Aquaporins (AQPs) are a family of membrane proteins involved in the transport of water and ions across cell membranes. AQPs have been shown to be implicated in various... (Review)
Review
Aquaporins (AQPs) are a family of membrane proteins involved in the transport of water and ions across cell membranes. AQPs have been shown to be implicated in various physiological and pathological processes in the brain, including water homeostasis, cell migration, and inflammation, among others. Epileptogenesis is a complex and multifactorial process that involves alterations in the structure and function of neuronal networks. Recent evidence suggests that AQPs may also play a role in the pathogenesis of epilepsy. In animal models of epilepsy, AQPs have been shown to be upregulated in regions of the brain that are involved in seizure generation, suggesting that they may contribute to the hyperexcitability of neuronal networks. Moreover, genetic studies have identified mutations in AQP genes associated with an increased risk of developing epilepsy. Our review aims to investigate the role of AQPs in epilepsy and seizure onset from a pathophysiological point of view, pointing out the potential molecular mechanism and their clinical implications.
Topics: Animals; Aquaporins; Water; Homeostasis; Brain; Seizures
PubMed: 37569297
DOI: 10.3390/ijms241511923 -
Evidence-based Dentistry Sep 2023A systematic appraisal and statistical aggregation of primary studies in humans. (Meta-Analysis)
Meta-Analysis
DESIGN
A systematic appraisal and statistical aggregation of primary studies in humans.
DATA SOURCES
The researchers utilized PubMed (Medline) and Scopus databases as the primary data sources for this study. They performed a comprehensive literature search based on free keywords and Medical Subject Heading (MeSH) terms to enhance the search accuracy. The database search was concluded on November 13, 2022. Furthermore, a meticulous examination of the references cited in the selected studies was conducted to identify additional relevant articles that could be incorporated into the analysis.
STUDY SELECTION
The systematic review focused on partially or fully edentulous patients receiving dental implants and aimed to determine if the lack of keratinized mucosa at the implant site increased the risk of peri-implantitis compared to patients with adequate keratinized mucosa. Human studies with a minimum of 100 implants, cross-sectional, cohort, or case-control designs, and a follow-up period of at least one year were included. Studies lacking a clear case definition or information on peri-implantitis and those that did not investigate keratinized mucosa as a risk indicator were excluded.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently utilized a systematic review screening website (Rayyan, Qatar Computing Research Institute, Qatar Foundation) to select potential articles, and conflicts were resolved through discussion or consultation with a third reviewer. The data extraction process involved recording information from the included articles, such as study design, patient and implant numbers, prosthesis type (fixed or removable), follow-up duration, peri-implantitis case definition, prevalence at patient and implant levels, keratinized mucosa cutoff value, odds ratio (OR) of peri-implantitis considering keratinized mucosa, and conclusions on the potential effect of keratinized mucosa from each study. The Newcastle Ottawa scale (NOS) and a modified version of NOS were used, respectively, to assess the quality of cohort and cross-sectional studies. Studies scoring below 6 out of 9 points were classified as low quality. For the meta-analysis, the relationship between peri-implantitis and keratinized mucosa was evaluated using the odds ratio (OR) and standard error (SE). Heterogeneity was assessed through the Chi test and I index, determining whether a random-effects or fixed-effects model should be applied. Subgroup and cluster analyses were conducted based on specific criteria, and forest plots and funnel plots were generated to visualize results and identify potential study bias. Sensitivity analysis was performed to verify the robustness of the meta-analysis, with statistical significance set at p < 0.05. The Review Manager (RevMan) software facilitated data analysis. The GRADE rating system was used to determine the level of evidence, considering factors such as bias risk, imprecision, inconsistency, indirectness, and publication bias. The certainty of the evidence was evaluated based on the overall outcomes of analyzed subgroups.
RESULTS
Twenty-two primary studies were identified, and a meta-analysis was conducted on 16 cross-sectional studies. The prevalence of peri-implantitis ranged from 6.68% to 62.3% at the patient level and from 4.5% to 58.1% at the implant level. The overall analysis revealed a significant association between the lack of keratinized mucosa and a higher prevalence of peri-implantitis (OR = 2.78, 95% CI 2.07-3.74, p < 0.00001). Subgroup analyses with a consistent case definition of peri-implantitis (MBL ≥ 2 mm) showed similar results (OR = 1.96, 95% CI 1.41-2.73, p < 0.0001). Studies focusing on fixed prostheses only demonstrated that the lack of keratinized mucosa was associated with an increased prevalence of peri-implantitis (OR = 2.82, 95% CI 1.85-4.28, p < 0.00001). Among patients under regular implant maintenance, the absence of keratinized mucosa significantly raised the occurrence of peri-implantitis (OR = 2.08, 95% CI 1.41-3.08, p = 0.0002). Studies adjusting for other variables also confirmed a higher risk of peri-implantitis with inadequate keratinized mucosa (OR = 3.68, 95% CI 2.32-5.82, p = 0.007). Although some publication bias was observed, the certainty of evidence based on the GRADE system was judged to be "moderate."
CONCLUSIONS
The lack of keratinized mucosa increased the risk of peri-implantitis, emphasizing the need to consider it during dental implant placement. Inadequate data on patient-specific factors and the predominance of cross-sectional studies influenced the evidence quality (i.e., moderate). Future studies with consistent methodologies shall confirm these findings and identify additional risk indicators to improve implant dentistry practices.
Topics: Humans; Peri-Implantitis; Dental Implants; Cross-Sectional Studies; Mucous Membrane; Risk Factors
PubMed: 37537217
DOI: 10.1038/s41432-023-00913-4 -
Frontiers in Neuroscience 2023Xenon exhibits significant neuroprotection against a wide range of neurological insults in animal models. However, clinical evidence that xenon improves outcomes in...
INTRODUCTION
Xenon exhibits significant neuroprotection against a wide range of neurological insults in animal models. However, clinical evidence that xenon improves outcomes in human studies of neurological injury remains elusive. Previous reviews of xenon's method of action have not been performed in a systematic manner. The aim of this review is to provide a comprehensive summary of the evidence underlying the cellular interactions responsible for two phenomena associated with xenon administration: anesthesia and neuroprotection.
METHODS
A systematic review of the preclinical literature was carried out according to the PRISMA guidelines and a review protocol was registered with PROSPERO. The review included both models of the central nervous system and mammalian studies. The search was performed on 27th May 2022 in the following databases: Ovid Medline, Ovid Embase, Ovid Emcare, APA PsycInfo, and Web of Science. A risk of bias assessment was performed utilizing the Office of Health Assessment and Translation tool. Given the heterogeneity of the outcome data, a narrative synthesis was performed.
RESULTS
The review identified 69 articles describing 638 individual experiments in which a hypothesis was tested regarding the interaction of xenon with cellular targets including: membrane bound proteins, intracellular signaling cascades and transcription factors. Xenon has both common and subtype specific interactions with ionotropic glutamate receptors. Xenon also influences the release of inhibitory neurotransmitters and influences multiple other ligand gated and non-ligand gated membrane bound proteins. The review identified several intracellular signaling pathways and gene transcription factors that are influenced by xenon administration and might contribute to anesthesia and neuroprotection.
DISCUSSION
The nature of xenon NMDA receptor antagonism, and its range of additional cellular targets, distinguishes it from other NMDA antagonists such as ketamine and nitrous oxide. This is reflected in the distinct behavioral and electrophysiological characteristics of xenon. Xenon influences multiple overlapping cellular processes, both at the cell membrane and within the cell, that promote cell survival. It is hoped that identification of the underlying cellular targets of xenon might aid the development of potential therapeutics for neurological injury and improve the clinical utilization of xenon.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier: 336871.
PubMed: 37521706
DOI: 10.3389/fnins.2023.1225191 -
Journal of Personalized Medicine Jul 2023Vernal keratoconjunctivitis (VKC) severely affects the quality of life of affected patients. The development of a shield ulcer is considered one of the most severe... (Review)
Review
BACKGROUND
Vernal keratoconjunctivitis (VKC) severely affects the quality of life of affected patients. The development of a shield ulcer is considered one of the most severe late-stage complications, which when untreated leads to irreversible vision loss. In this systematic review, we outlined the results of surgical treatments of corneal shield ulcers in VKC.
METHODS
We searched 12 literature databases on 3 April 2023 for studies of patients with VKC in which shield ulcers were treated by any surgical treatment. Treatment results were reviewed qualitatively. Assessments of the risk of bias of individual studies were made using the Clinical Appraisal Skills Programme.
RESULTS
Ten studies with 398 patients with VKC were eligible for the qualitative review. Two categories of surgical approaches were described: supratarsal corticosteroid injection and debridement with or without amniotic membrane transplantation. Almost all patients experienced resolution or improvement of their shield ulcers, regardless of treatment modality. Time to healing was faster with surgical debridement. A small proportion experienced recurrence and side effects.
CONCLUSIONS
Surgical treatment for shield ulcers in VKC seems highly effective, but careful post-operative treatment and follow-ups are necessary due to the risk of recurrence and potential side effects.
PubMed: 37511705
DOI: 10.3390/jpm13071092