-
Caries Research 2022Salivary proteins play an important role in repairing mechanisms of damaged tissues and the maintenance of oral health. However, there is a dearth of information in the...
Salivary proteins play an important role in repairing mechanisms of damaged tissues and the maintenance of oral health. However, there is a dearth of information in the literature regarding the concentrations of salivary proteins in caries-free (CF) and caries-active (CA) subjects. Hence, this systematic review was conducted to update our previous systematic review published in 2013 that aimed to assess the association between caries and salivary proteins by comparing CF and CA individuals. Thereby, evaluating the possibility of whether salivary proteins can be regarded as biomarkers for caries. An extensive search of studies was conducted using PubMed, EMBASE, Clarivate Analytics' Web of Science, and Elsevier's Scopus between July 2012 and January 2022, without any language restriction. Manual searching in Google Scholar and evaluation of bibliographies of the included studies were also undertaken. The Newcastle-Ottawa Scale was used to assess the risk of bias (RoB) within the included studies. Of 22 included studies, 1,551 human subjects (range: 30-213 participants) were recruited, of which 848 individuals (54.7%) were CA and 703 (45.3%) were CF. Regarding the utilization of DMFT as the caries index, high variability was observed across different articles. A statistically significant increase in the salivary levels of alpha-amylase, acidic proline-rich protein-1, histatin-5, lactoperoxidase, and mucin-1 was found in CA patients, while the salivary levels of carbonic anhydrase 6, proteinase-3, and statherin were observed to be significantly increased in CF subjects. Conflicting results were found regarding the salivary levels of immunoglobulin A and total proteins among CA and CF subjects. The included studies were categorized as low RoB (n = 15), medium RoB (n = 4), and high RoB (n = 3). Due to significant heterogeneity among the included studies, no meta-analysis could be performed. In conclusion, the salivary levels of protein(s) might be a useful biomarker for caries diagnosis, especially alpha-amylase, acidic proline-rich protein-1, histatin-5, lactoperoxidase, mucin-1, carbonic anhydrase 6, proteinase-3, and statherin. However, their diagnostic value must be verified by large-scale prospective studies.
Topics: Humans; Mucin-1; Dental Caries; Histatins; Lactoperoxidase; Prospective Studies; Salivary Proteins and Peptides; Biomarkers; Proline; alpha-Amylases; Peptide Hydrolases
PubMed: 36116431
DOI: 10.1159/000526942 -
Hypertension (Dallas, Tex. : 1979) Aug 2022Confirmatory tests are recommended for diagnosing primary aldosteronism, but the supporting evidence is unclear. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Confirmatory tests are recommended for diagnosing primary aldosteronism, but the supporting evidence is unclear.
METHODS
We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials. Studies evaluating any guideline-recommended confirmatory test (ie, saline infusion test, salt loading test, fludrocortisone suppression test, and captopril challenge test), compared with a reference standard were included. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess the risk of bias. Meta-analyses were conducted using hierarchical summary receiver operating characteristic models.
RESULTS
Fifty-five studies were included, comprising 26 studies (3654 participants) for the recumbent saline infusion test, 4 studies (633 participants) for the seated saline infusion test, 2 studies (99 participants) for the salt loading test, 7 studies (386 participants) for the fludrocortisone suppression test, and 25 studies (2585 participants) for the captopril challenge test. Risk of bias was high, affecting more than half of studies, and across all domains. Studies with case-control sampling overestimated accuracy by 7-fold (relative diagnostic odds ratio, 7.26 [95% CI, 2.46-21.43]) and partial verification or use of inconsistent reference standards overestimated accuracy by 5-fold (5.12 [95% CI, 1.48-17.77]). There were large variations in how confirmatory tests were conducted, interpreted, and verified. Under most scenarios, confirmatory testing resulted in an excess of missed cases. The certainty of evidence underlying each test (Grading of Recommendations, Assessment, Development, and Evaluations) was very low.
CONCLUSIONS
Recommendations for confirmatory testing in patients with abnormal screening tests and high probability features of primary aldosteronism are based on very low-quality evidence and their routine use should be reconsidered.
Topics: Captopril; Fludrocortisone; Humans; Hyperaldosteronism; ROC Curve; Sensitivity and Specificity
PubMed: 35652330
DOI: 10.1161/HYPERTENSIONAHA.122.19377 -
Cancers Apr 2022Proline has attracted growing interest because of its diverse influence on tumor metabolism and the discovery of the regulatory mechanisms that appear to be involved. In... (Review)
Review
BACKGROUND
Proline has attracted growing interest because of its diverse influence on tumor metabolism and the discovery of the regulatory mechanisms that appear to be involved. In contrast to general oncology, data on proline metabolism in central nervous system malignancies are limited.
MATERIALS AND METHODS
We performed a systematic literature review of the MEDLINE and EMBASE databases according to PRISMA guidelines, searching for articles concerning proline metabolism in malignant glial tumors. From 815 search results, we identified 14 studies pertaining to this topic.
RESULTS
The role of the proline cycle in maintaining redox balance in IDH-mutated gliomas has been convincingly demonstrated. Proline is involved in restoring levels of glutamate, the main glial excitatory neurotransmitter. Proline oxidase influences two major signaling pathways: p53 and NF- κB. In metabolomics studies, the metabolism of proline and its link to the urea cycle was found to be a prognostic factor for survival and a marker of malignancy. Data on the prolidase concentration in the serum of glioblastoma patients are contradictory.
CONCLUSIONS
Despite a paucity of studies in the literature, the available data are interesting enough to encourage further research, especially in terms of extrapolating what we have learned of proline functions from other neoplasms to malignant gliomas.
PubMed: 35454935
DOI: 10.3390/cancers14082030 -
Annals of Medicine Dec 2022Glecaprevir/pibrentasvir (G/P; 300 mg/120 mg) is a new direct-acting antiviral (DAA) that exhibits anti-hepatitis C virus (HCV) pan-genotype (GT) activity for 8,... (Meta-Analysis)
Meta-Analysis
Glecaprevir/pibrentasvir (G/P; 300 mg/120 mg) is a new direct-acting antiviral (DAA) that exhibits anti-hepatitis C virus (HCV) pan-genotype (GT) activity for 8, 12, or 16 weeks. However, the U.S. Food and Drug Administration have received reports that using G/P causes moderate to severe liver impairment. In some cases, isolated hyperbilirubinemia and jaundice have been reported without concomitant evidence of increased transaminase levels or other hepatic decompensation events. This study aimed to analyze the incidence of drug-induced liver injury of G/P for chronic hepatitis C virus. We searched databases from the inception of each database until March 2021. Data were pooled using a random-effects model. The Cochrane Risk of Bias Tool (RoB 2.0) and the OpenMeta [Analyst] software were performed for quality assessment and quantitative studies, respectively. The primary outcome was grade 3 level of drug-induced liver injury (DILI). The nine studies included in the meta-analysis involved a total of 7,650 participants, and the overall sustained virologic response rate was above 95%. The most frequent drug-related laboratory abnormalities in DILI involved total bilirubin, alanine aminotransferase, aspartate aminotransferase, and hemoglobin, but these abnormalities were minimal. The cirrhosis-without cirrhosis incidence risk ratio (IRR) was 2.724 (95% confidence interval: 1.182-6.276) in the grade 3 hyperbilirubinemia subgroup analysis. No significant differences were found within the other subgroups, in HCV GTs, and in treatment duration. DILI was found to occur frequently with G/P treatment. Hyperbilirubinemia occurred most frequently, especially, in patients with cirrhosis. However, G/P is still the primary therapy of choice for CKD and end-stage renal disease (ESRD) patients due to a superior safety rate.
Topics: Aminoisobutyric Acids; Antiviral Agents; Benzimidazoles; Chemical and Drug Induced Liver Injury; Cyclopropanes; Genotype; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Humans; Lactams, Macrocyclic; Leucine; Proline; Pyrrolidines; Quinoxalines; Sulfonamides
PubMed: 34969349
DOI: 10.1080/07853890.2021.2012589 -
Frontiers in Psychiatry 2021The neuropeptide-Y (NPY) is involved in the development of alcoholism through NPY receptors. A T>C mutation causes substitution of leucine to proline at codon 7 (L7P;...
The neuropeptide-Y (NPY) is involved in the development of alcoholism through NPY receptors. A T>C mutation causes substitution of leucine to proline at codon 7 (L7P; rs16139) in the signal peptide of neuropeptide Y is known to cause a 42% increase in plasma NPY levels. Studies that analyzed the association between rs16139 and alcoholism risk did not demonstrate conclusive evidence for this relationship. The present study aims to evaluate the association between gene rs16139 variant and alcohol dependence. An electronic search of databases including PubMed and Google Scholar was performed to retrieve studies investigating the association between rs16139 and alcoholism. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated in allelic and dominant genetic models. Sensitivity analyses and publication bias were assessed in our meta-analysis. The meta-analysis was conducted using the MetaGenyo web tool. Significant heterogeneity was observed across studies ( < 0.001). Our results have shown that there is no significant association between rs16139 variant and the risk of alcoholism in allelic (OR = 0.98, 95% CI 0.70-1.38, = 0.921) and dominant models (OR = 0.98, 95% CI 0.69-1.40, = 0.919). Begg's funnel plot and Egger's test have not shown publication bias ( = 0.332). To the best of our knowledge, this is the first meta-analysis that evaluates the relationship between the rs16139 polymorphism and the risk of alcoholism. Our large-scale meta-analysis suggests that rs16139 polymorphism is not associated with alcoholism. However, further studies are needed to increase our understanding of the relationship between variants in alcoholism.
PubMed: 34777047
DOI: 10.3389/fpsyt.2021.737440 -
Frontiers in Genetics 2021Schizophrenia is a disorder that is characterized by delusions, hallucinations, disorganized speech or behavior, and socio-occupational impairment. The duration of...
Schizophrenia is a disorder that is characterized by delusions, hallucinations, disorganized speech or behavior, and socio-occupational impairment. The duration of observation and variability in symptoms can make the accurate diagnosis difficult. Identification of biomarkers for schizophrenia (SCZ) can help in early diagnosis, ascertaining the diagnosis, and development of effective treatment strategies. Here we review peripheral blood-based gene expression studies for identification of gene expression biomarkers for SCZ. A literature search was carried out in PubMed and Web of Science databases for blood-based gene expression studies in SCZ. A list of differentially expressed genes (DEGs) was compiled and analyzed for overlap with genetic markers, differences based on drug status of the participants, functional enrichment, and for effect of antipsychotics. This literature survey identified 61 gene expression studies. Seventeen out of these studies were based on expression microarrays. A comparative analysis of the DEGs ( = 227) from microarray studies revealed differences between drug-naive and drug-treated SCZ participants. We found that of the 227 DEGs, 11 genes () also showed genetic and epigenetic changes associated with SCZ. Functional enrichment analysis of the DEGs revealed dysregulation of proline and 4-hydroxyproline metabolism. Also, arginine and proline metabolism was the most functionally enriched pathway for SCZ in our analysis. Follow-up studies identified effect of antipsychotic treatment on peripheral blood gene expression. Of the 27 genes compiled from the follow-up studies , and had no effect on their expression status as a result of antipsychotic treatment. Despite the differences in the nature of the study, ethnicity of the population, and the gene expression analysis method used, we identified several coherent observations. An overlap, though limited, of genetic, epigenetic and gene expression changes supports interplay of genetic and environmental factors in SCZ. The studies validate the use of blood as a surrogate tissue for biomarker analysis. We conclude that well-designed cohort studies across diverse populations, use of high-throughput sequencing technology, and use of artificial intelligence (AI) based computational analysis will significantly improve our understanding and diagnostic capabilities for this complex disorder.
PubMed: 34721526
DOI: 10.3389/fgene.2021.736483 -
European Urology Oct 2021Urethral stricture disease (USD) is initially managed with minimally invasive techniques such as urethrotomy and urethral dilatation. Minimally invasive techniques are... (Meta-Analysis)
Meta-Analysis
CONTEXT
Urethral stricture disease (USD) is initially managed with minimally invasive techniques such as urethrotomy and urethral dilatation. Minimally invasive techniques are associated with a high recurrence rate, especially in recurrent USD. Adjunctive measures, such as local drug injection, have been used in an attempt to reduce recurrence rates.
OBJECTIVE
To systematically review evidence for the efficacy and safety of adjuncts used alongside minimally invasive treatment of USD.
EVIDENCE ACQUISITION
A systematic review of the literature published between 1990 and 2020 was conducted in accordance with the PRISMA checklist.
EVIDENCE SYNTHESIS
A total of 26 studies were included in the systematic review, from which 13 different adjuncts were identified, including intralesional injection (triamcinolone, n = 135; prednisolone, n = 58; mitomycin C, n = 142; steroid-mitomycin C-hyaluronidase, n = 103, triamcinolone-mitomycin C-N-acetyl cysteine, n = 50; platelet-rich plasma, n = 44), intraluminal instillation (mitomycin C, n = 20; hyaluronic acid and carboxymethylcellulose, n = 70; captopril, n = 37; 192-iridium brachytherapy, n = 10), application via a lubricated catheter (triamcinolone, n = 124), application via a coated balloon (paclitaxel, n = 106), and enteral application (tamoxifen, n = 30; deflazacort, n = 36). Overall, 13 randomised controlled trials were included in the meta-analysis. Use of any adjunct was associated with a lower rate of USD recurrence (odds ratio [OR] 0.37, 95% confidence interval [CI] 0.27-0.50; p < 0.001) compared to no adjunct use. Of all the adjuncts, mitomycin C was associated with the lowest rate of USD recurrence (intralesional injection: OR 0.23, 95% CI 0.11-0.48; p < 0.001; intraluminal injection: OR 0.11, 95% CI 0.02-0.61; p = 0.01). Urinary tract infection (2.9-14%), bleeding (8.8%), and extravasation (5.8%) were associated with steroid injection; pruritis of the urethra (61%) occurred after instillation of captopril; mild gynaecomastia (6.7%) and gastrointestinal side effects (6.7%) were associated with oral tamoxifen.
CONCLUSIONS
Adjuncts to minimally invasive treatment of USD appear to lower the recurrence rate and are associated with a low adjunct-specific complication rate. However, the studies included were at high risk of bias. Mitomycin C is the adjunct supported by the highest level of evidence.
PATIENT SUMMARY
We reviewed studies on additional therapies (called adjuncts) to minimally invasive treatments for narrowing of the urethra in men. Adjuncts such as mitomycin C injection result in a lower recurrence rate compared to no adjunct use. The use of adjuncts appeared to be safe and complications are uncommon; however, the studies were small and of low quality.
Topics: Captopril; Humans; Injections, Intralesional; Male; Mitomycin; Recurrence; Tamoxifen; Triamcinolone; Urethra; Urethral Stricture
PubMed: 34275660
DOI: 10.1016/j.eururo.2021.06.022 -
Molecules (Basel, Switzerland) Jun 2021The Angiotensin-I-converting enzyme (ACE) is a peptidase with a significant role in the regulation of blood pressure. Within this work, a systematic review on the...
The Angiotensin-I-converting enzyme (ACE) is a peptidase with a significant role in the regulation of blood pressure. Within this work, a systematic review on the enzymatic preparation of Angiotensin-I-Converting Enzyme inhibitory (ACEi) peptides is presented. The systematic review is conducted by following PRISMA guidelines. Soybeans and velvet beans are known to have high protein contents that make them suitable as sources of parent proteins for the production of ACEi peptides. Endopeptidase is commonly used in the preparation of soybean-based ACEi peptides, whereas for velvet bean, a combination of both endo- and exopeptidase is frequently used. Soybean glycinin is the preferred substrate for the preparation of ACEi peptides. It contains proline as one of its major amino acids, which exhibits a potent significance in inhibiting ACE. The best enzymatic treatments for producing ACEi peptides from soybean are as follows: proteolytic activity by Protease P (Amano-P from sp.), a temperature of 37 °C, a reaction time of 18 h, pH 8.2, and an E/S ratio of 2%. On the other hand, the best enzymatic conditions for producing peptide hydrolysates with high ACEi activity are through sequential hydrolytic activity by the combination of pepsin-pancreatic, an E/S ratio for each enzyme is 10%, the temperature and reaction time for each proteolysis are 37 °C and 0.74 h, respectively, pH for pepsin is 2.0, whereas for pancreatin it is 7.0. As an underutilized pulse, the studies on the enzymatic hydrolysis of velvet bean proteins in producing ACEi peptides are limited. Conclusively, the activity of soybean-based ACEi peptides is found to depend on their molecular sizes, the amino acid residues, and positions. Hydrophobic amino acids with nonpolar side chains, positively charged, branched, and cyclic or aromatic residues are generally preferred for ACEi peptides.
Topics: Amino Acids; Angiotensin-Converting Enzyme Inhibitors; Aspergillus; Endopeptidases; Exopeptidases; Globulins; Hydrolysis; Hydrophobic and Hydrophilic Interactions; Mucuna; Pancreatin; Peptide Hydrolases; Peptides; Proline; Soybean Proteins; Glycine max; Temperature
PubMed: 34201554
DOI: 10.3390/molecules26133822 -
Frontiers in Pediatrics 2021Diagnosis of pediatric steatohepatitis is a challenging issue due to a vast number of established and novel causes. Here, we report a child with Multiple Acyl-CoA...
Diagnosis of pediatric steatohepatitis is a challenging issue due to a vast number of established and novel causes. Here, we report a child with Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) presenting with an underrated muscle weakness, exercise intolerance and an atypically severe steatotic liver involvement. A systematic literature review of liver involvement in MADD was performed as well. Our patient is a 11-year-old otherwise healthy, non-obese, male child admitted for some weakness/asthenia, vomiting and recurrent severe hypertransaminasemia (aspartate and alanine aminotransferases up to ×20 times upper limit of normal). Hepatic ultrasound showed a bright liver. MRI detected mild lipid storage of thighs muscles. A liver biopsy showed a micro-macrovacuolar steatohepatitis with minimal fibrosis. Main causes of hypertransaminasemia were ruled out. Serum aminoacids (increased proline), acylcarnitines (increased C4-C18) and a large excretion of urinary glutaric acid, ethylmalonic, butyric, isobutyric, 2-methyl-butyric and isovaleric acids suggested a diagnosis of MADD. Serum acylcarnitines and urinary organic acids fluctuated overtime paralleling serum transaminases during periods of illness/catabolic stress, confirming their recurrent nature. Genetic testing confirmed the diagnosis [homozygous c.1658A > G (p.Tyr553Cys) in exon 12 of the ETFDH gene]. Lipid-restricted diet and riboflavin treatment rapidly ameliorated symptoms, hepatic ultrasonography/enzymes, and metabolic profiles. Literature review (37 retrieved eligible studies, 283 patients) showed that liver is an extramuscular organ rarely involved in late-onset MADD (70 patients), and that amongst 45 patients who had fatty liver only nine had severe presentation. MADD is a disorder with a clinically heterogeneous phenotype. Our study suggests that MADD warrants consideration in the work-up of obesity-unrelated severe steatohepatitis.
PubMed: 34041209
DOI: 10.3389/fped.2021.672004 -
Shoulder & Elbow Apr 2021The EVOLVE implant (Wright Medical Technology, Arlington, TN, USA) is a modular loose-fitting radial head prosthesis. The primary objective was to synthesize all... (Review)
Review
INTRODUCTION
The EVOLVE implant (Wright Medical Technology, Arlington, TN, USA) is a modular loose-fitting radial head prosthesis. The primary objective was to synthesize all available literature investigating the midterm clinical outcomes of the EVOLVE implant.
MATERIALS AND METHODS
An electronic literature search in Pubmed/Medline, Scopus, EMBASE, and Cochrane library was performed querying for studies published in 2000-2017. Articles describing clinical and radiographical outcomes as well as reoperation were included. Outcomes of interest included range of motion, Mayo Elbow Performance Score, Disabilities of the Arm Shoulder and Hand, radiographic outcome, and reason for reoperation.
RESULTS
A total of five articles consisting of 146 patients with EVOLVE implants were included. Mean patient age was 57.4 years (range 22-84), and 43.8% were males (n = 64). Mean follow-up was 4.8 years (range 1-14). Mean Mayo Elbow Performance Score and Disabilities of the Arm Shoulder and Hand score were 87.6 (range 30-100) and 18.9 (range 0-82), respectively. Midterm clinical results were good or excellent (Mayo Elbow Performance Score > 74) in 94 patients. Reoperation was observed in 12 patients, with implant revision required in 2 patients. The primary reason for reoperation was persistent stiffness (n = 9).
CONCLUSION
Midterm outcomes of EVOLVE radial head prosthesis are satisfactory, and associated complication rates are low. Loose-fit implant method appears to be a reliable approach to avoid failure of radial head prosthesis by painful loosening.
PubMed: 33897852
DOI: 10.1177/1758573219850111