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BACKGROUND: Neutrophils are key mediators of inflammation during acute liver injury (ALI). Emerging evidence suggests that they also contribute to injury resolution and tissue repair. However, the different neutrophil subsets involved in these processes and their kinetics are undefined. Herein, we characterized neutrophil kinetics and heterogeneity during ALI. METHODS: We used the carbon tetrachloride model of ALI and employed flow cytometry, tissue imaging, and quantitative RT-PCR to characterize intrahepatic neutrophils during the necroinflammatory early and late repair phases of the wound healing response to ALI. We FACS sorted intrahepatic neutrophils at key time points and examined their transcriptional profiles using RNA-sequencing. Finally, we evaluated neutrophil protein translation, mitochondrial function and metabolism, reactive oxygen species content, and neutrophil extracellular traps generation. RESULTS: We detected 2 temporarily distinct waves of neutrophils during (1) necroinflammation (at 24 hours after injury) and (2) late repair (at 72 hours). Early neutrophils were proinflammatory, characterized by: (1) upregulation of inflammatory cytokines, (2) activation of the noncanonical NF-κB pathway, (3) reduction of protein translation, (4) decreased oxidative phosphorylation, and (5) higher propensity to generate reactive oxygen species and neutrophil extracellular traps. In contrast, late neutrophils were prorepair and enriched in genes and pathways associated with tissue repair and angiogenesis. Finally, early proinflammatory neutrophils were characterized by the expression of a short isoform of C-X-C chemokine receptor 5, while the late prorepair neutrophils were characterized by the expression of C-X-C chemokine receptor 4. CONCLUSIONS: This study underscores the phenotypic and functional heterogeneity of neutrophils and their dual role in inflammation and tissue repair during ALI.
Subject(s)
Neutrophils , Animals , Neutrophils/immunology , Neutrophils/metabolism , Mice , Disease Models, Animal , Mice, Inbred C57BL , Male , Reactive Oxygen Species/metabolism , Liver/pathology , Liver/immunology , Chemical and Drug Induced Liver Injury/immunology , Chemical and Drug Induced Liver Injury/genetics , Cytokines/metabolism , Extracellular Traps/metabolismABSTRACT
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder characterized by excessive hepatic fat accumulation. Intermittent fasting (IF) has emerged as a potential therapeutic strategy with the ability to induce weight loss, improve insulin sensitivity and reduce hepatic steatosis. We aim to compare the efficacy of different IF regimens for MASLD management. A systematic review and network meta-analysis of randomized controlled trials investigating different IF regimens for MASLD. PubMed , EMBASE , WOS , SCOPUS and Cochrane Central Register of Controlled Trials were searched until 10 April 2023. Analysis was performed using R software with the meta and netmeta packages. Mean difference (MD) was used to pool continuous outcomes with 95% confidence intervals (CIs). Our meta-analysis was registered in PROSPERO (CRD42023418467). Our meta-analysis included eight randomized controlled trials with a total of 635 participants. The 5â :â 2 diet significantly improved liver stiffness (MD, -0.32; 95% CI, -0.55 to -0.09; P â <â 0.01). Time-restricted feeding significantly improved liver steatosis (controlled attenuation parameter score) (MD, -39.83; 95% CI, -64.78 to -14.87; P â <â 0.01). No significant changes were observed in asparate aminotransferase, gamma-glutamyl transpeptidase, low-density lipoproteins cholesterol, total cholesterol, triglyceride levels, basal metabolic index, blood pressure, Homeostatic Model Assessment of Insulin Resistance, fasting blood sugar, lean body mass or waist circumference across all IF regimens. However, alternate-day fasting showed positive results in anthropometric measures, including significant improvements in lean body mass, waist circumference, fat mass and weight reduction ( P â <â 0.05). IF regimens showed various positive effects on clinical outcomes in MASLD patients; however, these effects were not consistent. Therefore, a patient-tailored IF regimen should be considered.
Subject(s)
Fatty Liver , Insulin Resistance , Humans , Cholesterol, LDL , Fatty Liver/therapy , Intermittent Fasting , Network Meta-Analysis , Randomized Controlled Trials as Topic , Weight LossABSTRACT
BACKGROUND: Soluble guanylate cyclase (sGC) stimulators have been investigated for heart failure (HF) in several randomized controlled trials (RCTs). However, its place in the management guidelines of either HFrEF or HfpEF is still inconclusive. METHODS: We conducted a network meta-analysis synthesizing RCTs investigating sGC for HF management, which were retrieved by systematically searching five databases until January 24th, 2023. Dichotomous outcomes were pooled using risk ratio (RR) along with confidence interval (CI). RESULTS: Eight RCTs with a total of 7307 patients were included. Vericiguat 10 mg significantly reduced the composite cardiovascular (CVS) mortality and HF hospitalization in HF (RR: 0.88, 95% CI [0.79; 0.98]) and in HFrEF (RR: 0.87, 95% CI [0.78; 0.97]); however, it was not effective in HFpEF (RR: 0.69, 95% CI [0.15; 3.05]). Also, vericiguat 10 mg showed no difference compared to placebo regarding the incidence of all-cause mortality (RR: 0.96, 95% CI [0.84; 1.10]), any adverse events (AEs) (RR: 0.94, 95% CI [0.83; 1.07]), any serious AEs (RR: 0.91, 95% CI [0.81; 1.01]), and any AEs leading to drug discontinuation (RR: 1.14, 95% CI [0.92; 1.40]). CONCLUSION: Vericiguat 10 mg was effective in reducing the composite CVS mortality and HF hospitalization, with an acceptable safety profile. This was only observed in HFrEF patients, but not in HFpEF patients. However, our data regarding other agents (riociguat and praliciguat) and HFpEF can be underpowered, warranting further RCTs to clarify vericiguat 10 mg place in HFrEF management guidelines and to investigate sGC stimulators for HFpEF in large-scale trials.
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STATEMENT OF PROBLEM: The influence of different denture adhesive forms on retention, stability, denture movement, and masticatory efficiency have been studied. However, studies that investigated their effect on patient-based outcomes are scarce. PURPOSE: The purpose of this crossover randomized controlled trial was to investigate the influence of 3 different denture adhesive forms on patient satisfaction and oral health-related quality of life (OHRQoL) in edentulous individuals. MATERIAL AND METHODS: A total of 30 edentulous participants were enrolled. They initially received conventional dentures, which they used for 3 months. They were then instructed to use 3 forms of denture adhesives (cushion, paste, and powder) for 3 months each. Patient satisfaction was assessed by using a visual analog scale (VAS), and OHRQoL was assessed by using the oral health impact profile in the edentulous adults instrument. Assessments were done 3 months after wearing the conventional dentures, then after by using each denture adhesive form for 3 months, with a 1-month washout period. The average retention duration for each form and participant preference were also evaluated. Statistical analysis was conducted by using the repeated measures ANOVA test followed by the Scheffé test for VAS scores and retention duration. The Friedman test followed by the Wilcoxon signed-rank test was used for OHRQoL scores (α=.05). RESULTS: Irrespective of their forms, denture adhesives significantly improved patient satisfaction in most aspects (P<.001) and significantly improved OHRQoL (P<.001). VAS scores for the cushion form were significantly higher than those for the other 2 forms regarding general satisfaction, comfort, and ease of cleaning dentures and tissues. For stability and masticatory ability, the cushion and paste forms were significantly better (P<.05) than the powder form. OHRQoL scores were significantly higher (worse) for the powder form compared with the other 2 forms for the functional limitation, physical pain, and physical disability domains, with insignificant differences between the cushion and paste forms (P>.05). The powder form found the shortest retention duration and the least preference. CONCLUSIONS: Denture adhesives significantly improved OHRQoL and almost all aspects of patient satisfaction. The cushion form provided higher satisfaction levels for most aspects, followed by paste and then powder. OHRQoL outcomes were comparable for all forms, except for the functional limitation, physical pain, and physical disability domains, which were significantly better with the cushion and paste forms. The cushion and paste forms were more retentive and more preferred by the participants than the powder form.
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OBJECTIVE: Colonoscopy is the gold standard method for colorectal cancer screening. Looping occurs in 91% of cases undergoing colonoscopy and can cause patient discomfort, prolonged cecal intubation time (CIT), and colon perforation. This meta-analysis investigates the impact of abdominal compression devices (ACD) on colonoscopy outcomes. METHODS: A systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), retrieved by systematically searching: PubMed, EMBASE, WOS, SCOPUS, and Cochrane through February 2nd, 2023. Continuous and dichotomous outcomes were pooled using mean difference (MD) and risk ratio (RR) along with confidence interval (CI) using Revman. Our review protocol was prospectively published on PROSPERO with ID: CRD42023397344. RESULTS: We included eight RCTs with a total of 1,889 patients. ACD was effective to decrease CIT (MD: -2.15 with a 95% CI [-3.49, -0.80], p = .002), postural change (RR: 0.57 with 95% CI [0.49, 0.66], p = .00001), and VAS pain score (MD: -1.49 with 95% CI [-1.81, -1.17], p = .0001). However, there was no difference between ACD and control groups regarding manual compression (RR: 0.65 with 95% CI [0.42, 1.00], p = .05), complete colonoscopy rate (CCR) (RR: 1.01 with 95% CI [0.99, 1.04], p = .31), and cecal intubation length (CIL) (MD: -2.25 with 95% CI [-7.64, 3.14], p = .41). CONCLUSION: ACD during colonoscopy may enhance patient comfort by reducing CIT, pain, and postural changes. Nevertheless, additional RCTs are necessary to validate these results and determine the most suitable approach to utilize ACD for colonoscopy.
Subject(s)
Colonoscopy , Colorectal Neoplasms , Humans , Randomized Controlled Trials as Topic , Colonoscopy/methods , Colorectal Neoplasms/diagnosis , Pain , Odds RatioABSTRACT
OBJECTIVE: Chronic constipation is a challenging functional gastrointestinal disorder that remains a global burden. Pharmacologic therapy, including laxatives and dietary fibers, are suggested as lines of treatment. Recent trials introduced an orally ingested vibrating capsule (VC) as an eligible option for chronic constipation management. METHODS: We conducted a literature search in English on electronic databases CENTRAL, PubMed, EMBASE, Scopus, and WOS until February 27th, 2023. RevMan was used to perform the meta-analysis. The results were reported as risk ratios (RRs), mean differences (MDs), and 95% confidence intervals (CIs). The study protocol was registered in PROSPERO with ID: (CRD42023409422). RESULTS: Three RCTs with a total of 601 patients were included in our analysis. There was no difference between the VC and placebo in responder rate (RR: 1.37 with 95% CI [0.82, 2.28], p = .22), CSBM change from baseline (MD: 0.21 with 95% CI [-0.26, 0.69], p = .38), SBM change from baseline (MD: 0.14 with 95% CI [-0.22, 0.49], p = .46), and the incidence of any adverse event (RR: 1.45 with a 95% CI of [0.79, 2.63], p = .23). However, VC was associated with increased vibration sensation (RR: 17.23, 95% CI [3.29, 90.20], p = .0008). CONCLUSIONS: VC was not effective to improve bowel movement in patients with functional constipation with no difference in response rate. However, evidence is still uncertain, with only three small RCTs that yielded heterogenous findings, mainly due to the different vibration protocols. Also, our findings suggest that VC is safe and well-tolerated, with no significant harmful effects observed. Therefore, more large-scale RCTs are needed to confirm the efficacy and safety of VC in patients with functional constipation, determining the most effective dose, frequency, and duration of treatment.
Subject(s)
Constipation , Laxatives , Humans , Capsules/therapeutic use , Randomized Controlled Trials as Topic , Constipation/chemically induced , Laxatives/therapeutic use , Dietary Fiber/adverse effectsABSTRACT
BACKGROUND AND OBJECTIVE: Double sequential external defibrillation (DSED) and vector-change defibrillation (VCD) have been suggested to enhance clinical outcomes for patients with ventricular fibrillation (VF) refractory of standard defibrillation (SD). Therefore, this network meta-analysis aims to evaluate the comparative efficacy of DSED, VCD, and SD for refractory VF. METHODS: A systematic review and network meta-analysis synthesizing randomized controlled trials (RCTs) and comparative observational studies retrieved from PubMed, EMBASE, WOS, SCOPUS, and Cochrane through November 15th, 2022. R software netmeta and netrank package (R version 4.2.0) and meta-insight software were used to pool dichotomous outcomes using odds ratio (OR) presented with the corresponding confidence interval (CI). Our protocol was prospectively published in PROSPERO with ID: CRD42022378533. RESULTS: We included seven studies with a total of 1632 participants. DSED was similar to SD in survival to hospital discharge (OR: 1.14 with 95% CI [0.55, 2.83]), favorable neurological outcome (modified Rankin scale ≤2 or cerebral performance category ≤2) (OR: 1.35 with 95% CI [0.46, 3.99]), and return of spontaneous circulation (ROSC) (OR: 0.81 with 95% CI [0.43; 1.5]). In addition, VCD was similar to SD in survival to hospital discharge (OR: 1.12 with 95% CI [0.27, 4.57]), favorable neurological outcome (OR: 1.01 with 95% CI [0.18, 5.75]), and ROSC (OR: 0.88 with 95% CI [0.24; 3.15]). CONCLUSION: Double sequential external defibrillation and VCD were not associated with enhanced outcomes in patients with refractory VF out-of-hospital cardiac arrest, compared to SD. However, the current evidence is still inconclusive, warranting further large-scale RCTs.
Subject(s)
Cardiopulmonary Resuscitation , Out-of-Hospital Cardiac Arrest , Humans , Electric Countershock/methods , Ventricular Fibrillation/complications , Ventricular Fibrillation/therapy , Out-of-Hospital Cardiac Arrest/therapy , Out-of-Hospital Cardiac Arrest/complications , Network Meta-Analysis , Electrocardiography , Cardiopulmonary Resuscitation/methodsABSTRACT
BACKGROUND: Maintaining good oral hygiene is key to preventing dental caries and periodontal disease. Children and adolescents with good oral hygiene behaviours are likely to grow into adults with the same behaviours. This study assessed the frequency of using various oral hygiene methods among children and adolescents from different countries and individual, familial and country-level factors associated with the use of these methods. METHODS: A multi-country online survey collected data from caregivers of children in 2020-21 about children's use of oral hygiene methods including toothbrush, fluoridated toothpaste, mouthwash, dental floss and miswak using self-administered, close-ended questions. Adjusted multilevel logistic regression models were used to assess the relationship between each of the five oral hygiene methods (dependent variables) and the independent factors: sex, age, and history of dental visits (individual factors), mother's education and area of residence (familial factors) as well as country income and region (country-level factors). RESULTS: A total of 4766 parents/caregivers were included from 20 countries (77.4% Eastern Mediterranean-region and 41.6% lower middle income countries). The most frequent oral hygiene methods were using toothbrush and toothpaste (90% and 60.3%). The use of oral hygiene methods differed by age, sex and history of dental visits as well as mother's education and area of residence (P < 0.05). In addition, children from low income countries had significantly lower odds of using mouthwashes and dental floss than those from high income countries (AOR = 0.55, 95% CI 0.31, 0.98 and AOR = 0.34, 95% CI 0.12, 0.97) whereas children from the European region had higher odds of using mouthwash (AOR = 2.82, 95% CI 1.27, 6.26) and those from the region of the Americas had higher odds of using dental floss (AOR = 3.84, 95% CI 1.28, 11.52) than those from the Eastern Mediterranean region. CONCLUSIONS: The use of various oral hygiene methods is associated with individual, familial and country-level factors. Oral health promotion programs should be developed taking into account these influences.
Subject(s)
Dental Caries , Oral Hygiene , Adult , Adolescent , Humans , Child , Dental Caries/prevention & control , Toothpastes , Mouthwashes/therapeutic use , Oral HealthABSTRACT
STUDY OBJECTIVE: The use of race in medicine can contribute to health inequity. Updated equations for estimated glomerular filtration rate (eGFR) without race have been published. Likewise, de-indexation of eGFR to body surface area (BSA) has been recommended by regulatory guidance for drug dosing in renal impairment. Clinical data justifying these recommendations for drug dosing are sparse. We examined the gain or loss of precision in drug dosing with estimated creatinine clearance (eCLcr) and eGFR using serum creatinine (eGFRcr) with and without race and BSA indexation by evaluating the population pharmacokinetics of the aminoglycosides as a classic drug class to probe kidney function. DESIGN: Medical records from adult patients treated with gentamicin or tobramycin over a 13-year period were queried. Population pharmacokinetic analyses were performed using a 1-compartment base structural model. Models compared body size descriptors as covariates of the volume of distribution (V). Estimated creatinine clearance and eGFRcr using multiple contemporary equations with and without BSA indexation were tested as covariates of clearance (CL). MAIN RESULTS: The final data set included 2968 patients treated with either gentamicin (20.2%) or tobramycin (79.8%). Patients self-identified as Caucasian (82%), African-American (10%), or other. The median [5th, 95th percentile] weight and BSA were 80.5 [49.4, 136] kg and 1.94 [1.48, 2.56] m2 , respectively. Models of eCLcr and eGFRcr without indexation to BSA had a better model fit than eGFRcr indexed to BSA for aminoglycoside CL. The 2021 Chronic Kidney Disease Epidemiology collaboration (CKD-EPI) eGFRcr equation (no race, no BSA indexation) provided a comparable model fit to the 2009 CKD-EPI eGFRcr equation (with race, no BSA indexation) for aminoglycoside CL. CONCLUSIONS: Race is not a relevant covariate of aminoglycoside CL. The 2021 CKD-EPI eGFR equation without race and BSA indexation is a better method for gentamicin and tobramycin CL estimation. Confirmation of these results for other drugs can support the harmonization of dosing by kidney function.
Subject(s)
Aminoglycosides , Renal Insufficiency, Chronic , Adult , Humans , Aminoglycosides/therapeutic use , Creatinine , Body Surface Area , Anti-Bacterial Agents , Glomerular Filtration Rate , Tobramycin , Gentamicins/pharmacokinetics , KidneyABSTRACT
Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysis, multiplex-immunofluorescence, 3D-reconstruction, and spatial image analysis to characterize the intrahepatic immune landscape in mice post-CCl4-induced acute liver injury during three distinct phases: necroinflammation, and early and late repair. We observed hepatocellular necrosis and a reduction in liver resident lymphocytes during necroinflammation accompanied by the infiltration of circulating myeloid cells and upregulation of inflammatory cytokines. These parameters returned to baseline levels during the repair phase while pro-repair chemokines were upregulated. We identified resident CLEC4F+ Kupffer cells (KCs) and infiltrating IBA1+CLEC4F- monocyte-derived macrophages (MoMFs) as the main hepatic macrophage populations during this response to injury. While occupying most of the necrotic area, KCs and MoMFs exhibited distinctive kinetics, distribution and morphology at the site of injury. The necroinflammation phase was characterized by low levels of KCs and a remarkable invasion of MoMFs suggesting their potential role in phagoctosing necrotic hepatocytes, while opposite kinetics/distribution were observed during repair. During the early repair phase, yolksac - derived KCs were restored, whereas MoMFs diminished gradually then dissipated during late repair. MoMFs interacted with hepatic stellate cells during the necroinflammatory and early repair phases, potentially modulating their activation state and influencing their fibrogenic and pro-repair functions that are critical for wound healing. Altogether, our study reveals novel and distinct spatial and temporal distribution of KCs and MoMFs and provides insights into their complementary roles during acute liver injury.
Subject(s)
Kupffer Cells , Liver , Animals , Chemokines/metabolism , Cytokines/metabolism , Liver/injuries , Liver/metabolism , Macrophages , MiceABSTRACT
BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is a major health problem with complex pathogenesis. Although sex differences in NAFLD pathogenesis have been reported, the mechanisms underlying such differences remain understudied. Interleukin (IL)22 is a pleiotropic cytokine with both protective and/or pathogenic effects during liver injury. IL22 was shown to be hepatoprotective in NAFLD-related liver injury. However, these studies relied primarily on exogenous administration of IL22 and did not examine the sex-dependent effect of IL22. Here, we sought to characterize the role of endogenous IL22-receptor signaling during NAFLD-induced liver injury in males and females. METHODS: We used immunofluorescence, flow cytometry, histopathologic assessment, and gene expression analysis to examine IL22 production and characterize the intrahepatic immune landscape in human subjects with NAFLD (n = 20; 11 men and 9 women) and in an in vivo Western high-fat diet-induced NAFLD model in IL22RA knock out mice and their wild-type littermates. RESULTS: Examination of publicly available data sets from 2 cohorts with NAFLD showed increased hepatic IL22 gene expression in females compared with males. Furthermore, our immunofluorescence analysis of liver sections from NAFLD subjects (n = 20) showed increased infiltration of IL22-producing cells in females. Similarly, IL22-producing cells were increased in wild-type female mice with NAFLD and the hepatic IL22/IL22 binding protein messenger RNA ratio correlated with expression of anti-apoptosis genes. The lack of endogenous IL22-receptor signaling (IL22RA knockout) led to exacerbated liver damage, inflammation, apoptosis, and liver fibrosis in female, but not male, mice with NAFLD. CONCLUSIONS: Our data suggest a sex-dependent hepatoprotective antiapoptotic effect of IL22-receptor signaling during NAFLD-related liver injury in females.
Subject(s)
Non-alcoholic Fatty Liver Disease , Female , Humans , Male , Mice , Animals , Receptors, Interleukin/genetics , Signal Transduction , Liver Cirrhosis , Mice, KnockoutABSTRACT
OBJECTIVE: To report the flash visual evoked potential (VEP) findings in children with primary congenital glaucoma (PCG) before and after successful surgical control of the intraocular pressure (IOP). METHODS: The study enrolled children presenting with PCG to the Ophthalmology Department of Alexandria Main University Hospital in the period between June and December 2019. All study participants were subjected to a standard protocol of examination, to confirm the diagnosis of PCG. The child was then referred for flash VEP testing. Peaks were designated as negative and positive waves in a numerical sequence (N1, P1, N2, P2, N3 and P3). The child was then scheduled for surgery within 1 week of presentation. Postoperative VEP testing was scheduled as soon as feasible and was conducted in the same way as the preoperative VEP testing. RESULTS: The study was conducted on 11 (four right) eyes of eight (five males) children. The mean ± standard deviation of the age of the study children at presentation and at postoperative VEP testing was 3.5 ± 1.6 and 5.1 ± 3.0 months, respectively. The study eyes mean ± standard deviation IOP at presentation and at postoperative VEP testing was 23.0 ± 6.7 and 8.3 ± 2.4 mmHg, respectively (p < 0.0001). There were a statistically insignificant reduction in P2 implicit time (p = 0.235) and a statistically insignificant increase in each of N1-P1 (p = 0.15) and N2-P2 (p = 0.67) amplitudes postoperatively than preoperatively. CONCLUSIONS: IOP elevation in PCG adversely affects the optic nerve function, but, at least in the short term, has no permanent detrimental effect on the optic nerve function as evidenced by the improvement in the VEP parameters.
Subject(s)
Glaucoma , Optic Nerve Diseases , Child , Evoked Potentials, Visual , Glaucoma/surgery , Humans , Infant , Intraocular Pressure , Male , Pilot ProjectsABSTRACT
STATEMENT OF PROBLEM: Studies on the impact of incorporating attachments in removable prostheses on patient-based outcomes are scarce. PURPOSE: The purpose of this clinical study was to investigate oral health-related quality of life (OHRQoL) and patient satisfaction in partially edentulous participants before and after rehabilitation with mandibular attachment-retained removable prostheses as compared with conventional removable prostheses. MATERIAL AND METHODS: This crossover study included 74 participants (aged 36 to 57). Initially, 56 received conventional clasp-retained removable dental prostheses (RDPs), and 18 received conventional overdentures (ODs) based on their mandibular partially edentulous state. Two months later, of the 56 RDP participants, 24 had received extracoronal attachment-retained RDPs, 17 received telescope-retained RDPs, and 15 received bar-attachment retained RDPs. The 18 OD participants received ball attachment-retained ODs. Assessments included Oral Health Impact Profile-short version-14 for OHRQoL and a visual analog scale (VAS) for patient satisfaction. Assessments were done before treatment and 2 months after wearing each prosthesis with a 1-month washout period. Statistical analysis included the Friedman then the Wilcoxon signed rank test for Oral Health Impact Profile-short version-14 scores and repeated measures ANOVA then the Bonferroni or paired t test for VAS scores (α=.05). RESULTS: There were no dropouts. Rehabilitation, irrespective of prosthesis type, significantly improved OHRQoL in all domains and significantly increased overall patient satisfaction (P<.05). When compared with the conventional prostheses, attachment-retained prostheses significantly improved functional limitation, psychological discomfort, and physical limitation domains in all groups (P<.05), as well as the physical pain domain in the OD group (P=.041). General satisfaction, stability, comfort, ability to speak, and ability to masticate significantly increased (P<.05) with attachment-retained prostheses. Conventional prostheses were significantly easier to clean (P<.05) in all groups, except for the telescope-attachment group. CONCLUSIONS: Both conventional and attachment-retained prostheses significantly increased patient satisfaction and improved OHRQoL in all domains as compared with before treatment. However, incorporation of attachments further improved functional limitation, psychological discomfort, and physical limitation domains in all groups, as well as the physical pain domain in the OD group. Participants were more satisfied with their attachment-retained prostheses in most aspects.
Subject(s)
Dental Implants , Quality of Life , Adult , Cross-Over Studies , Dental Prosthesis, Implant-Supported , Denture, Overlay , Humans , Middle Aged , Patient SatisfactionABSTRACT
The immune landscape of the tumor microenvironment (TME) is a determining factor in cancer progression and response to therapy. Specifically, the density and the location of immune cells in the TME have important diagnostic and prognostic values. Multiomic profiling of the TME has exponentially increased our understanding of the numerous cellular and molecular networks regulating tumor initiation and progression. However, these techniques do not provide information about the spatial organization of cells or cell-cell interactions. Affordable, accessible, and easy to execute multiplexing techniques that allow spatial resolution of immune cells in tissue sections are needed to complement single cell-based high-throughput technologies. Here, we describe a strategy that integrates serial imaging, sequential labeling, and image alignment to generate virtual multiparameter slides of whole tissue sections. Virtual slides are subsequently analyzed in an automated fashion using user-defined protocols that enable identification, quantification, and mapping of cell populations of interest. The image analysis is done, in this case using the analysis modules Tissuealign, Author, and HISTOmap. We present an example where we applied this strategy successfully to one clinical specimen, maximizing the information that can be obtained from limited tissue samples and providing an unbiased view of the TME in the entire tissue section.
Subject(s)
Leukocytes/pathology , Tumor Microenvironment/immunology , Antibodies, Neoplasm/immunology , Antigens, Neoplasm/immunology , Automation , Hot Temperature , Humans , Image Processing, Computer-Assisted , Paraffin Embedding , Staining and Labeling , Stromal Cells/metabolism , Tissue FixationABSTRACT
INTRODUCTION: Computer-aided design (CAD) and computer-aided manufacturing (CAM) monolithic crowns are gaining momentum. Limited evidence exists about the effect of tooth preparation total occlusal convergence (TOC) on marginal and internal gap distances in addition to load to fracture values. AIM: The aim of this study was to evaluate, by microcomputed tomography (µCT), the influence of 12° and 20° TOC on marginal and internal adaptation of zirconia-reinforced lithium silicate (ZLS) crowns. Moreover, values of load to fracture with and without initial cyclic loading (CL) were compared. MATERIAL AND METHODS: Forty ZLS crowns were fabricated on dies with TOC of 12° and 20°, 20 crowns for each group. µCT was used to compare marginal and internal adaptation. Each specimen was measured at 140 points distributed on all tooth preparation surfaces for 2D gap distance assessment. 3D gap volume was also evaluated. Crowns were then cemented and divided into two subgroups; the first was stored in distilled water (no cyclic loading [NCL] subgroup), the second was subjected to CL (CL subgroup). RESULTS: Factorial repeated measures ANOVA followed by Bonferroni post hoc in addition to independent and dependent t-tests were used for statistical analysis. Marginal gap, absolute marginal discrepancy, and occlusal gap measurements showed significant differences between the measurement sites. Static load to fracture values showed significant differences between TOC groups for both NCL (P=0.011) and CL (P=0.025) subgroups. CONCLUSION: An increase of TOC from 12° to 20° did not affect marginal and internal adaptation but resulted in higher values of load to fracture of ZLS crowns. CL simulating 1 year of service did not result in fatigue failure.
ABSTRACT
STATEMENT OF PROBLEM: The effect of the neutral zone (NZ) technique on different functional aspects (masticatory performance, speech, and muscle activity) has been studied objectively. Subjectively, some studies reported that their participants felt that NZ dentures were more stable, retentive, and comfortable than conventionally fabricated dentures. These studies, however, lacked a measurable assessment scale or a specifically designed questionnaire. PURPOSE: The purpose of this within-subject, crossover clinical trial was to investigate patient satisfaction levels in edentulous patients after rehabilitation with dentures fabricated using the NZ concept as compared with conventional dentures using a specific, question-oriented patient satisfaction questionnaire. MATERIAL AND METHODS: The clinical trial included 52 participants. Each received one set of conventional dentures and another fabricated based on the NZ concept with a 1-month wash-out period. Participants randomly chose 1 of 2 closed opaque envelopes with 2 denture sequences, either conventional then NZ or NZ then conventional. Hence, participants were blinded to the dentures they wore. Patient satisfaction with each denture type was assessed 6 weeks after insertion by a blinded staff member using a 5-scale questionnaire developed for the most important functional aspects (esthetics, masticatory ability, retention, stability, speech, and comfort). The Wilcoxon Signed Rank test was used to compare the satisfaction scores of the 2 denture types (α=.05). RESULTS: Patient satisfaction scores were significantly higher with the NZ dentures than with the conventional dentures in all aspects; P=.001 for question 2 (opinion of denture appearance) and P<.001 for all other questions. CONCLUSIONS: NZ dentures offer significantly higher levels of patient satisfaction than conventional dentures in all functional aspects (retention, stability, masticatory ability, and speech) as well as in comfort and appearance.
Subject(s)
Mouth, Edentulous , Patient Satisfaction , Denture Retention , Denture, Complete , Denture, Overlay , Esthetics, Dental , Humans , MasticationABSTRACT
The type 3 cytokines IL-17 and IL-22 play a crucial, well synchronized physiological role in wound healing and repairing tissue damage due to infections or injury at barrier surfaces. These cytokines act on epithelial cells to induce secretion of early immune mediators, recruitment of inflammatory cells to the site of injury, and to trigger tissue repair mechanisms. However, if the damage persists or if these cytokines are dysregulated, then they contribute to a number of inflammatory pathologies, autoimmune conditions and cancer. The liver is a multifunctional organ that plays an essential role in metabolism, detoxification, and immune surveillance. It is also exposed to a variety of pathogens, toxins and injuries. Over the past decade, IL-17 and IL-22 have been implicated in various aspects of liver inflammation. IL-17 is upregulated in chronic liver injury and associated with liver disease progression. In contrast, IL-22 was shown to be hepatoprotective during acute liver injury but exhibited inflammatory effects in other models. Furthermore, IL-22 and IL-17 are both associated with poor prognosis in liver cancer. Finally, the regulatory mechanisms governing the physiological versus the pathological role of these two cytokines during acute and chronic liver injury remain poorly understood. In this review, we will summarize the current state of knowledge about IL-17 and IL-22 in wound healing during acute and chronic liver injury, their contribution to pathogenesis, their regulation, and their role in the transition from advanced liver disease to liver cancer.
Subject(s)
Carcinoma, Hepatocellular/immunology , Chemical and Drug Induced Liver Injury, Chronic/immunology , Chemical and Drug Induced Liver Injury/immunology , Interleukin-17/metabolism , Interleukins/metabolism , Liver Cirrhosis/immunology , Liver Neoplasms/immunology , Animals , Carcinoma, Hepatocellular/pathology , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/microbiology , Chemical and Drug Induced Liver Injury/virology , Chemical and Drug Induced Liver Injury, Chronic/metabolism , Chemical and Drug Induced Liver Injury, Chronic/microbiology , Chemical and Drug Induced Liver Injury, Chronic/virology , Humans , Immunity, Innate , Liver Neoplasms/pathology , Interleukin-22ABSTRACT
STATEMENT OF PROBLEM: The effectiveness of adhesives in enhancing several functional aspects of complete denture performance has been well established. The direct influence of adhesives on occlusal contact simultaneity has not yet been investigated. PURPOSE: The purpose of this crossover clinical trial was to evaluate quantitatively the influence of adhesives on occlusal balance by recording timed occlusal contacts; namely occlusion time (OT) and disocclusion time during right (DT-right) and left (DT-left) excursions by using computerized occlusal analysis. MATERIAL AND METHODS: A crossover clinical trial was adopted. Assessments were carried out while participants (n=49) wore their dentures first without then with adhesives. Computerized occlusal analysis using the T-Scan III system was conducted to perform baseline computer-guided occlusal adjustment for conventionally fabricated dentures. Retention and stability assessment using the modified Kapur index and recording of OT and DT-right and DT-left values using the T-Scan III were subsequently carried out for all dentures, first without adhesives and then after application of adhesive. All T-Scan procedures were carried out by the same clinician. Wilcoxon signed-rank test was used to analyze the Kapur index scores and occlusal parameters (α=.05). RESULTS: Stability and retention of conventional dentures ranged initially from good to very good. However, adhesive application resulted in significant improvement (P<.001) in stability and retention and a significant decrease in duration of all occlusal parameters (OT [P=.003], DT-right [P=.003], and DT-left [P=.008]). CONCLUSIONS: Adhesives significantly decreased OT and DT durations in initially well-fitting complete dentures with fairly well balanced occlusion, and further enhanced denture stability and occlusal contact simultaneity.