The effect of nicotine-containing products on peri-implant tissues: A systematic review and network meta-analysis.

INTRODUCTION: Smokers have a higher chance of developing peri-implant diseases and are therefore considered an at-risk population. Our aim was to compare peri-implant characteristics in users of electronic cigarettes (EC), waterpipes (WP), cigarettes (CS), smokeless tobacco (ST), and non-smokers (non-users of any nicotine and tobacco product; NS). METHODS: A systematic search of four electronic databases (PubMed, EMBASE, Web of Science, CENTRAL) was performed until April 2023, restricted to English language. Thirty-nine observational studies were included in the qualitative synthesis, of which 32 studies were included in a Bayesian network meta-analysis. Using a predesigned form, two researchers independently collected data about marginal bone loss (MBL), probing pocket depth (PPD), plaque index (PI), bleeding on probing (BOP), modified plaque index (mPI), probing pocket depth > 4mm (PPD>4), gingival index (GI), peri-implant sulcular fluid (PISF) volume, and TNF-α and IL-1ß levels. QUIPS and CINeMA were used to evaluate the risk of bias and certainty of evidence. RESULTS: NS had the smallest MBL. Most nicotine-containing product users had significantly higher MBL (CS, MD:1.34 CrI: 0.85, 1.79; WP, MD:1.58 CrI: 0.84, 2.35; ST, MD:2.53, CrI: 1.20, 3.87) than NS. EC did not show significant difference compared to NS (MD:0.52 CrI: -0.33, 1.36). In secondary outcomes NS were ranked in first place. Subset analysis based on smoking habit, implant duration, and maintenance control revealed no differences in ranking probability. CONCLUSION: Most nicotine-containing product users presented worse peri-implant parameters compared to non-smokers, while EC users did not show significant differences to NS in many outcomes. IMPLICATION: Alternative nicotine-containing products are gaining popularity and are often considered less harmful by the general public compared to traditional cigarettes. This is the first network meta-analysis comparing users of four nicotine-containing products and non-smokers. This study shows that CS, WP and ST have a detrimental effect on the overall health of peri-implant tissues. EC users also presented inferior parameters compared to NS, however, the difference was not significant in many outcomes. It is essential to educate patients who are using nicotine-containing products, and to provide proper maintenance and appropriate cessation support. Well-designed multi-armed studies are needed for direct comparison of different products, including heated tobacco products. Greater transparency of confounding factors is needed regarding smoking habit and oral hygiene.

Combined Casein Phosphopeptide-Amorphous Calcium Phosphate and Fluoride Is Not Superior to Fluoride Alone in Early Carious Lesions: A Meta-Analysis.

There is a growing need for effective methods in the management of early stage carious lesions. Therefore, the aim of this study was to evaluate the effect of combined casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and fluoride on white spot lesions (WSLs) compared to fluoride-only interventions. This meta-analysis was performed according to PRISMA guidelines and registered in PROSPERO (CRD42021286245). The Medline, Embase, and Cochrane Central databases were searched until October 17, 2022. Eligible studies were randomized controlled trials. Outcome variables included laser fluorescence (LF), quantitative light-induced fluorescence (QLF), and lesion area scores. The random-effects model was used for analysis, and results were given as standardized mean difference (SMD) and mean difference (MD) with a 95% confidence interval. Risk of bias was assessed using the RoB 2 tool, and the level of evidence with GRADE. Our systematic search yielded 973 records after duplicate removal, 21 studies were included for qualitative synthesis, and 15 studies were eligible for quantitative analysis. No significant difference was found between CPP-ACP and fluoride versus fluoride alone in LF at 1, 3, and 6 months of use: SMD -0.30 (-0.64; 0.04); SMD -0.47 (-1.02; 0.07); SMD -0.49 (-1.13; 0.15), respectively. For QLF, the analysis did not demonstrate significant differences between these two kinds of treatment at 1 and 6 months of use: MD 0.21 (-0.30;0.71); MD 0.60 (-1.70;2.90), but at 3 months, higher QLF values were found in the fluoride-only group compared to the CPP-ACP and fluoride combination was shown regarding the WSLs: MD 0.58 (0.25;0.91). On the contrary, data showed a small but statistically significant decrease in the lesion area in favor of the CPP-ACP plus fluoride versus fluoride alone at 6 months MD -0.38 (-0.72; -0.04). None of these observed changes indicated substantial clinical relevance. The combination of CPP-ACP and fluoride did not overcome the effect of fluoride given alone. Our data suggest that fluoride itself is effective in improving WSLs. However, the certainty of evidence was very low. These results indicate that further studies and future development of more effective products than CPP-ACP are needed in addition to fluoride to achieve robust amelioration of WSLs.

Less marginal bone loss around bone-level implants restored with long abutments: A systematic review and meta-analysis.

The aim of this study was to investigate the biological outcomes of bone-level implants restored with long vs. short abutments, with regard to the 'one abutment at one time' protocol. The systematic search was performed in five databases: MEDLINE (PubMed), EMBASE, Web of Science, Scopus, and CENTRAL for randomized controlled trials up to January 14, 2023. Data were collected for marginal bone loss, bleeding on probing, and probing pocket depth by two reviewers. As effect size measure, mean difference (MD), and risk ratio (RR) were used for continuous and categorical outcomes, R-statistics software was used for conducting statistical analyses. For quality and certainty assessment, Risk of Bias Tool 2, ROBINS-I, and GRADE approach were used. The search resulted in 4055 records without any duplicates. After title, abstract, and full-text analysis, eight articles were found eligible for inclusion. Bone-level and platform-switched implants presented less marginal bone loss after 6 months and 1 year as well, when long abutments were used (MD 0.63, 95% CI: [-0.16; 1.42]) and (MD 0.26, 95% CI: [-0.02; 0.53]). However, subgroup analysis revealed no difference in marginal bone loss when applying 'one abutment at one time' protocol (p = 0.973). Bleeding on probing and probing pocket depth presented similarly good results in both groups without almost any differences (RR 0.97, 95% CI: [0.76; 1.23]) and (MD -0.05, 95% CI: [-1.11; 1.01]). Longer abutments on bone-level implants seem to be a favorable choice for decreasing early marginal bone loss, irrespective of connection timing.

Effect of Chitosan on the Number of Streptococcus mutans in Saliva: A Meta-Analysis and Systematic Review.

We conducted a meta-analysis and systematic review to investigate the efficacy of chitosan-containing chewing gums, and to test their inhibitory effects on Streptococcus mutans. The systematic search was performed in three databases (Cochrane Library, EMBASE, and PubMed) and included English-language randomized-controlled trials to compare the efficacy of chitosan in reducing the number of S. mutans. To assess the certainty of evidence, the GRADE tool was used. Mean differences were calculated with a 95% confidence interval for one outcome: bacterial counts in CFU/mL. The protocol of the study was registered on PROSPERO, registration number CRD42022365006. Articles were downloaded (n = 6758) from EMBASE (n = 2255), PubMed (n = 1516), and Cochrane (n = 2987). After the selection process, a total of four articles were included in the qualitative synthesis and three in the quantitative synthesis. Our results show that chitosan reduced the number of bacteria. The difference in mean quantity was -4.68 × 105. The interval of the random-effects model was [-2.15 × 106; 1.21 × 106] and the prediction interval was [1.03 × 107; 9.40 × 106]. The I2 value was 98% (p = 0.35), which indicates a high degree of heterogeneity. Chitosan has some antibacterial effects when used as a component of chewing gum, but further studies are needed. It can be a promising antimicrobial agent for prevention.

Comparative analysis of surgical and prosthetic rehabilitation in maxillectomy: A systematic review and meta-analysis on quality-of-life scores and objective speech and masticatory measurements.

STATEMENT OF PROBLEM: Patients with oro-antral communication, whether from trauma, disease, or congenital anomalies, have options for surgical reconstruction or prosthetic obturation, but guiding interdisciplinary protocols are lacking. PURPOSE: The purpose of this systematic review and meta-analysis was to compare surgical reconstruction and prosthetic obturation, identifying correlations with baseline characteristics to determine the most effective approach for specific patients. MATERIAL AND METHODS: A systematic search was conducted in 4 databases. Searching, screening, data extraction, and risk of bias assessment were performed by 2 reviewers. Eligible studies focused on patients with palatomaxillary defects from cancer-related maxilla surgeries. Traumatic or congenital defects were excluded. The study compared prosthetic restoration (either with surgical or definitive obturators) to surgical reconstruction using flaps or grafts. Patients with surgical restoration after tooth extraction were excluded. Both subjective and objective outcomes were used for comparison. RESULTS: Thirteen articles were included in the qualitative synthesis and 9 in the meta-analysis. Patient scores on quality-of-life questionnaires, objective speech, and masticatory ability evaluations were compared. The number of patients who underwent surgical reconstruction was 206, whereas 260 patients received prosthetic obturators. Results showed no significant differences. In the "activity" domain of the University of Washington QoL questionnaire, however, the 1.92 (0.45, 3.40) score difference was not clinically relevant. However, the heterogeneity of trials, the transient nature of subjective evaluations, the low number of participants, and major confounding biases did not allow a solid conclusion to be drawn. CONCLUSIONS: The growing number of maxillectomy patients demands firm evidence on which rehabilitation to choose and when it should be done. The result suggests that obturator devices and surgical reconstruction have similar effects on quality of life and health outcomes. A multicentric registry in which patient strata could be analyzed separately by age, adjuvant therapies, defect sizes, and remaining dentition is advocated.

Clinical bracket failure rates between different bonding techniques: a systematic review and meta-analysis.

BACKGROUND: Bracket failure increases the treatment time of orthodontic therapy and burdens patients with unnecessary costs, increased chair time, and possible new appointments. OBJECTIVE: To compare the bond failures of different orthodontic materials based on the results of available clinical studies. SEARCH METHODS: A systematic search of clinical trials was performed in the Cochrane, Embase, and Pubmed databases with no limitations. The list of investigated techniques contained conventional acid-etch primer (CM-AEP), self-etch primer (SEP), self-cure resin (SCR), and simple or resin-modified glass ionomer (RM-GIC) materials and procedures. SELECTION CRITERIA: Clinical studies reporting the failure rate of bonded brackets after using direct adhesive techniques on buccal sites of healthy teeth were included. DATA COLLECTION AND ANALYSIS: Bracket failure rates from eligible studies were extracted by two authors independently. Risk ratios (RRs) were pooled using the random-effects model with DerSimonian-Laird estimation. RESULTS: Thirty-four publications, involving 1221 patients, were included. Our meta-analysis revealed no significant difference in the risk of bracket failures between SEP and CM-AEP. After 6, 12, and 18 months of bonding, the values of RR were 1.04 [95% confidence interval (CI), 0.67-1.61], 1.37 (95% CI, 0.98-1.92), and 0.93 (95% CI, 0.72-1.20), respectively. At 18 months, bracket failure was 4.9 and 5.2% for SEP and CM-AEP, respectively. Heterogeneity was good or moderate (I2 < 42.2%). The results of RM-GIC at 12 months indicated a 57% lower risk of bracket failure using SCR as compared with RM-GIC (RR: 0.38; 95% CI, 0.24-0.61). At 18 months, bracket failures for SCR and RM-GIC were 15.8 and 36.6%, respectively (RR: 0.44; 95% CI, 0.37-0.52, I2 = 78.9%), demonstrating three to six times higher failure rate than in the case of etching primer applications. LIMITATIONS: A major limitation of the present work is that the included clinical trials, with no exceptions, showed variable levels of risk of bias. Another possible problem affecting the outcome is the difference between the clustering effects of the split mouth and the parallel group bracket allocation methods. CONCLUSIONS AND IMPLICATIONS: The results revealed no significant difference between SEP and CM-AEP up to 18 months after application. RM-GIC had much worse failure rates than acid-etching methods; additionally, the superiority of SCR over RM-GIC was evident, indicating strong clinical relevance. REGISTRATION: Prospero with CRD42020163362.

The use of autogenous tooth bone graft is an efficient method of alveolar ridge preservation - meta-analysis and systematic review.

BACKGROUND: Ridge resorption following tooth extraction may be reduced by alveolar ridge preservation (ARP). Previous randomized clinical trials and systematic reviews have suggested that autogenous tooth bone graft (ATB) can be an effective alternative material for ARP. However, the results are heterogeneous. Therefore, our research aimed to evaluate the efficacy of ATB in ARP. METHODS: A systematic search was conducted in Cochrane Library, Embase, MEDLINE and Scopus for studies published from inception to 31 November 2021. We searched searched for randomized, non-randomized controlled trials and case series reporting on ATB use for ARP. The primary outcome was the ridge width difference pre- and post-surgery, measured in millimetres (mm) measured on CBCT (cone beam computed tomography). The secondary outcomes were the histological results. We followed the PRISMA2020 recommendations for reporting our systematic review and meta-analysis. RESULTS: The analysis included eight studies for the primary and six for the secondary outcomes. The meta-analysis revealed a positive ridge preservation effect with a pooled mean difference ridge width change of -0.72 mm. The pooled mean residual graft proportion was 11.61%, and the newly formed bone proportion was 40.23%. The pooled mean of newly formed bone proportion was higher in the group where ATB originated from both the root and crown of the tooth. CONCLUSIONS: ATB is an effective particulate graft material in ARP. Complete demineralization of the ATB tends to decrease the proportion of newly formed bone. ATB can be an attractive option for ARP. TRIAL REGISTRATION: The study protocol was registered on PROSPERO (CRD42021287890).

ORGANOLEPTIC AND HALITOMETRIC ASSESSMENTS DO NOT CORRELATE WELL IN INTRA-ORAL HALITOSIS: A SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND: The gold standard method for diagnosing oral halitosis is the subjective organoleptic measurement. Device-supported methods are also widespread worldwide. The challenges and safety concerns around performing organoleptic measurements during pandemics and the diversity of measuring device alternatives raised our clinical question: which halitometer is the most suitable for diagnosing halitosis? METHODS: This systematic review was registered in PROSPERO (ID CRD42022320024). The search was performed on March 23, 2022 in the following electronic databases: MEDLINE, Embase, Scopus, Web of Science, and CENTRAL. Adult populations with or without halitosis were included, and patients with systemic diseases were excluded. Organoleptic (subjective) measurement and the device-supported (objective) methods were compared; the primary outcome was the correlation coefficient, and the secondary was the specificity and sensitivity of the devices. QUADAS-2 and QUADAS-C were used to evaluate the risk of bias in the studies. Random-effects meta analyses were performed on the outcomes, and the secondary outcomes were plotted on a common ROC plot. RESULTS: A total of 1231 records were found in the 5 databases. After the selection process, 76 articles were eligible for the systematic review, and 14,635 patients were involved in the qualitative analysis. The pooled Spearman's correlation coefficient (c.c.) for sulfide monitors was 0.65; 95% CIs: [0.53-0.74]; I2 = 95%, P < .01. The pooled Spearman's c.c. for portable gas chromatographs was 0.69; 95% CIs: [0.63-0.74]; I2 = 12%, P < .01. The pooled Spearman's c.c. for gas chromatographs was 0.76; 95% CIs: [0.67-0.83]; I2 = 0%, P < .01. DISCUSSION: None of the most commonly used halitometers proved to be significantly superior to the others. Halimeter and OralChroma measurements did not correlate well with the organoleptic level of oral halitosis in adults. Therefore, better halitometers need to be developed as an alternative to organoleptic measurements.

Nanoclay-based sensor composites for the facile detection of molecular antioxidants.

The detection and quantification of antioxidant molecules is an important task in food science, the fine chemical industry and healthcare. Antioxidants help in preventing the deterioration of nutrition and healthcare products, while eliminating over-the-limit exogenic reactive species, which may lead to illnesses. In our contribution, an inexpensive and rapid method to determine the concentration of various molecular antioxidants was developed. The principle of the analysis relies on the cupric ion reducing antioxidant capacity (CuPRAC) method, which is based on the color-changing reduction of chelated Cu2+ ions. This complex was successfully immobilized on an alginate-functionalized layered double hydroxide (dLDH) nanosheet via electrostatic interactions. The synthesis conditions of alginate (NaAlg) and the cupric complex were optimized, and the optimized composite was fabricated on cellulose paper to obtain a sensing platform. The paper-based sensor was superior to the ones prepared without the dLDH support, as the limit of detection (LOD) values decreased, and the linearity ranges broadened. The results offer a single-point measurement to evaluate the antioxidant efficiency in a cuvette-based method. The superior ability of the sensor was assigned to the presence of solid dLDH particles, as they offer adsorption sites for the dissolved antioxidant molecules, which contributes significantly to the decrease of the diffusion limitation during the detection process.

Maternal overnutrition elevates offspring's blood pressure-A systematic review and meta-analysis.

BACKGROUND: Maternal overnutrition during pregnancy predisposes the offspring to cardiometabolic diseases. OBJECTIVES: This systematic review and meta-analysis aimed to investigate the association between maternal overnutrition and offspring's blood pressure (BP) and the effect of offspring's obesity on this association. DATA SOURCES: PubMed, EMBASE, Clinicaltrials.gov, CENTRAL. STUDY SELECTION AND DATA EXTRACTION: Human studies published in English before October 2021 were identified that presented quantitative estimates of association between maternal overnutrition just before or during pregnancy and the offspring's BP. SYNTHESIS: Random-effect model with the DerSimonian and Laird weighting method was used to analyse regression coefficients or mean differences. RESULTS: After selection, 17 observational studies (140,517 mother-offspring pairs) were included. Prepregnancy body mass index (ppBMI) showed positive correlation with BP in offspring (regression coefficient for systolic: 0.38 mmHg per kg/m2 , 95% confidence interval (CI) 0.17, 0.58; diastolic: 0.10 mmHg per kg/m2 , 95% CI 0.05, 0.14). These indicate 1.9 mmHg increase in systolic and 0.5 mmHg increase in diastolic BP of offspring with every 5 kg/m2 gain in maternal ppBMI. Results on coefficients adjusted for offspring's BMI also showed association (systolic: 0.08 mmHg per kg/m2 , 95% CI 0.04, 0.11; diastolic: 0.03 mmHg per kg/m2 , 95% CI 0.01, 0.04). Independent from ppBMI, gestational weight gain (GWG) showed positive correlation with systolic BP (systolic BP: 0.05 mmHg per kg, 95% CI 0.01, 0.09), but not after adjustment for offspring's BMI. Mean systolic BP was higher in children of mothers with excessive GWG than in those of mothers with optimal GWG (difference: 0.65 mmHg, 95% CI 0.25, 1.05). CONCLUSIONS: Independent from offspring's BMI, higher prepregnancy BMI may increase the risk for hypertension in offspring. The positive association between GWG and offspring's systolic BP is indirect via offspring's obesity. Reduction in maternal obesity and treatment of obesity in children of obese mothers are needed to prevent hypertension.

Results in Antireflux Surgery, an Analysis of Case-Controlled Cohorts versus Multicenter Studies and Meta-Analyses.

Introduction: With the advent of minimally invasive techniques, laparoscopic Nissen fundoplication and Toupet partial fundoplication have been very successful in the management of GERD. In the past 10 years, a number of very attractive new technologies have entered the market around therapeutic GERD-management such as Transoral Incisionless Gastroplication, other endoscopic plication techniques, and the implantation of the magnetic sphincter augmentation (MSA). These new technologies are excessively promoted by the respective companies, propagating their techniques as causing fewer side effects. The purpose of this paper is an overview on the successrates of these differently used techniques and technologies and, in addition, different study-designs. Methods: A literature review was performed searching for publications on laparoscopic fundoplication (LF), Transoral Incisionless Fundoplication (TIF), and laparoscopic MSA. The reported classified were separated according to their design into (group 1) large case-controlled series or comparative studies (n 100 cases) from high-volume centers and into (group 2) trials between different technologies of antireflux procedures, multicenter-studies, and meta-analyses of GERD-trials. Results: In total, 4030 abstract were screened according to the selected key words. Following the section criteria, 19 publications were selected and analyzed. Regarding group 1 and LF (selected studies 2565 patients), the morbidity ranged from 2.0-4.8 % of cases. With a follow-up time of 36-222 months most of these patients were followed 5 years. In group 2, more than 150 studies and several multicenter-registries were summarized in these 9 selected publications. The overall follow-up periods were substantially shorter with a range of 7-48 months. Conclusions: It can be concluded that special efforts in patient management in high volume centers and a vast experience may substantially contribute to excellent results for several antireflux techniques, which may reach a level of quality above results of registries and meta-analyses.

Aggregation of Halloysite Nanotubes in the Presence of Multivalent Ions and Ionic Liquids.

Colloidal stability was investigated in two types of particle systems, namely, with bare (h-HNT) and polyimidazolium-functionalized (h-HNT-IP-2) alkali-treated halloysite nanotubes in solutions of metal salts and ionic liquids (ILs). The valence of the metal ions and the number of carbon atoms in the hydrocarbon chain of the IL cations (1-methylimidazolium (MIM+), 1-ethyl-3-methylimidazolium (EMIM+), 1-butyl-3-methylimidazolium (BMIM+), and 1-hexyl-3-methylimidazolium (HMIM+)) were altered in the measurements. For the bare h-HNT with a negative surface charge, multivalent counterions destabilized the dispersions at low values of critical coagulation concentration (CCC) in line with the Schulze-Hardy rule. In the presence of ILs, significant adsorption of HMIM+ took place on the h-HNT surface, leading to charge neutralization and overcharging at appropriate concentrations. A weaker affinity was observed for MIM+, EMIM+, and BMIM+, while they adsorbed on the particles to different extents. The order HMIM+ < BMIM+ < EMIM+ < MIM+ was obtained for the CCCs of h-HNT, indicating that HMIM+ was the most effective in the destabilization of the colloids. For h-HNT-IP-2 with a positive surface charge, no specific interaction was observed between the salt and the IL constituent cations and the particles, i.e., the determined charge and aggregation parameters were the same within experimental error, irrespective of the type of co-ions. These results clearly indicate the relevance of ion adsorption in the colloidal stability of the nanotubes and thus provide useful information for further design of processable h-HNT dispersions.

Comparative study of hyperpure chlorine dioxide with two other irrigants regarding the viability of periodontal ligament stem cells.

OBJECTIVES: Periodontal ligament stem cells (PDLSCs) have an underlined significance as their high proliferative capacity and multipotent differentiation provide an important therapeutic potential. The integrity of these cells is frequently disturbed by the routinely used irrigative compounds applied as periodontal or endodontic disinfectants (e.g., hydrogen peroxide (H2O2) and chlorhexidine (CHX)). Our objectives were (i) to monitor the cytotoxic effect of a novel dental irrigative compound, chlorine dioxide (ClO2), compared to two traditional agents (H2O2, CHX) on PDLSCs and (ii) to test whether the aging factor of PDLSC cultures determines cellular responsiveness to the chemicals tested. METHODS: Impedimetry (concentration-response study), WST-1 assays (WST = water soluble tetrazolium salt), and morphology analysis were performed to measure changes in cell viability induced by the 3 disinfectants; immunocytochemistry of stem cell markers (STRO-1, CD90, and CD105) measured the induced mesenchymal characteristics. RESULTS: Cell viability experiments demonstrated that the application of ClO2 does not lead to a significant decrease in viability of PLDSCs in concentrations used to kill microbes. On the contrary, traditional irrigants, H2O2, and CHX are highly toxic on PDLSCs. Aging of PLDSC cultures (passages 3 vs. 7) has characteristic effects on their responsiveness to these agents as the increased expression of mesenchymal stem cell markers turns to decreased. CONCLUSIONS AND CLINICAL RELEVANCE: While the active ingredients of mouthwash (H2O2, CHX) applied in endodontic or periodontitis management have a serious toxic effect on PDLSCs, the novel hyperpure ClO2 is less toxic providing an environment favoring dental structure regenerations during disinfectant interventions.

Hemorheological and Microcirculatory Factors in Liver Ischemia-Reperfusion Injury-An Update on Pathophysiology, Molecular Mechanisms and Protective Strategies.

Hepatic ischemia-reperfusion injury (IRI) is a multifactorial phenomenon which has been associated with adverse clinical outcomes. IRI related tissue damage is characterized by various chronological events depending on the experimental model or clinical setting. Despite the fact that IRI research has been in the spotlight of scientific interest for over three decades with a significant and continuous increase in publication activity over the years and the large number of pharmacological and surgical therapeutic attempts introduced, not many of these strategies have made their way into everyday clinical practice. Furthermore, the pathomechanism of hepatic IRI has not been fully elucidated yet. In the complex process of the IRI, flow properties of blood are not neglectable. Hemorheological factors play an important role in determining tissue perfusion and orchestrating mechanical shear stress-dependent endothelial functions. Antioxidant and anti-inflammatory agents, ischemic conditioning protocols, dynamic organ preservation techniques may improve rheological properties of the post-reperfusion hepatic blood flow and target endothelial cells, exerting a potent protection against hepatic IRI. In this review paper we give a comprehensive overview of microcirculatory, rheological and molecular-pathophysiological aspects of hepatic circulation in the context of IRI and hepatoprotective approaches.

TRPM7-Mediated Calcium Transport in HAT-7 Ameloblasts.

TRPM7 plays an important role in cellular Ca2+, Zn2+ and Mg2+ homeostasis. TRPM7 channels are abundantly expressed in ameloblasts and, in the absence of TRPM7, dental enamel is hypomineralized. The potential role of TRPM7 channels in Ca2+ transport during amelogenesis was investigated in the HAT-7 rat ameloblast cell line. The cells showed strong TRPM7 mRNA and protein expression. Characteristic TRPM7 transmembrane currents were observed, which increased in the absence of intracellular Mg2+ ([Mg2+]i), were reduced by elevated [Mg2+]i, and were inhibited by the TRPM7 inhibitors NS8593 and FTY720. Mibefradil evoked similar currents, which were suppressed by elevated [Mg2+]i, reducing extracellular pH stimulated transmembrane currents, which were inhibited by FTY720. Naltriben and mibefradil both evoked Ca2+ influx, which was further enhanced by the acidic intracellular conditions. The SOCE inhibitor BTP2 blocked Ca2+ entry induced by naltriben but not by mibefradil. Thus, in HAT-7 cells, TRPM7 may serves both as a potential modulator of Orai-dependent Ca2+ uptake and as an independent Ca2+ entry pathway sensitive to pH. Therefore, TRPM7 may contribute directly to transepithelial Ca2+ transport in amelogenesis.

Sol-Gel Synthesis of Ceria-Zirconia-Based High-Entropy Oxides as High-Promotion Catalysts for the Synthesis of 1,2-Diketones from Aldehyde.

Efficient Lewis-acid-catalyzed direct conversion of aldehydes to 1,2-diketones in the liquid phase was enabled by using newly designed and developed ceria-zirconia-based high-entropy oxides (HEOs) as the actual catalysts. The synergistic effect of various cations incorporated in the same oxide structure (framework) was partially responsible for the efficiency of multicationic materials compared to the corresponding single-cation oxide forms. Furthermore, a clear, linear relationship between the Lewis acidity and the catalytic activity of the HEOs was observed. Due to the developed strategy, exclusively diketone-selective, recyclable, versatile heterogeneous catalytic transformation of aldehydes can be realized under mild reaction conditions.

GABA promotes ß-cell proliferation, but does not overcome impaired glucose homeostasis associated with diet-induced obesity.

γ-Aminobutyric acid (GABA) administration has been shown to increase ß-cell mass, leading to a reversal of type 1 diabetes in mice. Whether GABA has any effect on ß cells of healthy and prediabetic/glucose-intolerant obese mice remains unknown. In the present study, we show that oral GABA administration ( ad libitum) to mice indeed increased pancreatic ß-cell mass, which led to a modest enhancement in insulin secretion and glucose tolerance. However, GABA treatment did not further increase insulin-positive islet area in high fat diet-fed mice and was unable to prevent or reverse glucose intolerance and insulin resistance. Mechanistically, whether in vivo or in vitro, GABA treatment increased ß-cell proliferation. In vitro, the effect was shown to be mediated via the GABAA receptor. Single-cell RNA sequencing analysis revealed that GABA preferentially up-regulated pathways linked to ß-cell proliferation and simultaneously down-regulated those networks required for other processes, including insulin biosynthesis and metabolism. Interestingly, single-cell differential expression analysis revealed GABA treatment gave rise to a distinct subpopulation of ß cells with a unique transcriptional signature, including urocortin 3 ( ucn3), wnt4, and hepacam2. Taken together, this study provides new mechanistic insight into the proliferative nature of GABA but suggests that ß-cell compensation associated with prediabetes overlaps with, and negates, its proliferative effects.-Untereiner, A., Abdo, S., Bhattacharjee, A., Gohil, H., Pourasgari, F., Ibeh, N., Lai, M., Batchuluun, B., Wong, A., Khuu, N., Liu, Y., Al Rijjal, D., Winegarden, N., Virtanen, C., Orser, B. A., Cabrera, O., Varga, G., Rocheleau, J., Dai, F. F., Wheeler, M. B. GABA promotes ß-cell proliferation, but does not overcome impaired glucose homeostasis associated with diet-induced obesity.

Clinical Presentation of Gastroesophageal Reflux Disease: A Prospective Study on Symptom Diversity and Modification of Questionnaire Application.

INTRODUCTION: Symptoms occurring in gastroesophageal reflux disease (GERD) such as heartburn, regurgitation, thoracic pain, epigastric pain, respiratory symptoms, and others can show a broad overlap with symptoms from other foregut disorders. The goal of this study is the accurate assessment of symptom presentation in GERD. METHODS: Patients with foregut symptoms were investigated for symptoms as well as endoscopy and gastrointestinal-functional studies for presence of GERD and symptom evaluation by standardized questionnaire. Questionnaire included a graded evaluation of foregut symptoms documenting severity and frequency of each symptom. The three types of questionnaires include study nurse solicitated, self-reported, and free-form self-reported by the patient. RESULTS: For this analysis, 1,031 GERD patients (572 males and 459 females) were enrolled. Heartburn was the most frequently reported chief complaint, seen in 61% of patients. Heartburn and regurgitation are the most common (82.4/58.8%, respectively) in overall symptom prevalence. With regard to modification in questionnaire technique, if patients fill in responses without prompting, there is a trend toward more frequent documentation of respiratory symptoms (up to 54.5% [p < 0.01]), fullness (up to 93.9%), and gas-related symptoms (p < 0.001). Self-reported symptoms are more diverse (e.g., throat-burning [12%], mouth-burning [9%], globus [6%], dyspnea [9%], and fatigue [7%]). CONCLUSIONS: GERD symptoms are commonly heartburn and regurgitation, but overall symptom profile for patients may change depending on the type of questionnaire.

Functional and cell surface characteristics of periodontal ligament cells (PDLCs) on RGD-synthetic polypeptide conjugate coatings.

BACKGROUND AND OBJECTIVE: Periodontal ligament cells (PDLCs) are an important source for periodontal tissue healing and regeneration. Proper cell adhesion is a key for survival of anchorage-dependent cells and also initiates further intracellular signals for essential cellular functions. We aimed to test 3 different synthetic conjugates with integrin-binding RGD sequence (SAK-c[RGDfC], AK-c[RGDfC], and SAK-opn on the adhesion of human PDLCs and subsequent events including proliferation, migration, behavior of cell surface molecules, and osteogenic differentiation. MATERIALS AND METHODS: Synthetic peptides were synthesized by solid-phase technique and attached to branched chain polymeric polypeptides via thioether linkage. Simple adsorption method was used to coat tissue culture plastic or electric arrays. PDLCs were isolated from 24 surgically extracted human third molars. Cell adhesion and proliferation were measured with real-time impedimetric xCELLigence SP system. Cell migration assay was performed with Ibidi® Culture inserts. Cell surface antigens were detected using flow cytometry analysis. Osteogenic differentiation was assessed with alkaline phosphatase (ALP) assay and Alizarin Red S staining, and real-time qPCR was performed to analyze the osteoblast-related gene expression. Osteogenic differentiation and adipogenic differentiation of PDLCs were monitored by real-time Electrical Cell-Substrate Impedance Spectroscopy (ECIS). RESULTS: Primary outcome of this study relies on that all three synthetic RGD peptides improved PDLC adhesion (P < .05). When animal serum is absent in culture medium, SAK-c[RGDfC] and AK-c[RGDfC] elevated cell adhesion (P < .05). Cell migration was enhanced by SAK-c[RGDfC] and AK-c[RGDfC] (P < .05). After 1-week treatment, all synthetic peptides elevated CD105 (1.7- to 2.2-fold) and CD146 (1.3- to 1.5-fold) markers and caused different integrin patterns. ALP activity (1.4-fold) and ARS (1.8- and 2.0-fold) were increased by SAK-c[RGDfC] and AK-c[RGDfC] in absence of osteogenic supplements, and all the peptides supported the mineralization under osteogenic condition (P < .05). RT-qPCR revealed the upregulation of bone sialoprotein (5.0- to 7.8-fold), osteocalcin (2.3- to 2.7-fold), and ALP (1.9- to 2.3-fold) gene expression in osteogenesis-induced PDLCs. ECIS monitoring showed that higher impedance was generated by the osteogenic induction compared with the adipogenic or the non-induced (P < .05). CONCLUSIONS: Our study demonstrates that SAK-c[RGDfC] and AK-c[RGDfC] improved adhesion and migration of PDLCs and supported osteogenic differentiation of PDLCs. These cyclic RGD peptides proved to be applicable biocompatible material in regenerative medicine.

Transanal hybrid colon resection: techniques and outcomes for benign colorectal diseases.

BACKGROUND: Transanal hybrid rectal and colon resection have been introduced in recent years at dedicated surgical centers. The anus is used as a natural orifice for large size access. The use of transanal hybrid colectomy techniques is still in its infancy with outcomes and unique complications being identified. The purpose of this work is the evaluation of outcomes for transanal hybrid colon resections (ta-CR), including intra operative and postoperative complications, results, and advantages. METHODS: A prospectively maintained database was analyzed. Inclusion criteria were any patient who underwent ta-CR for rectal prolapse, slow transit, obstructive defaecation, and chronic sigmoid diverticulitis. Patients were excluded from ta-CR if BMI > 30, major previous abdominal surgery, or presence of a large inflammatory mass in diverticulitis. Transanal access was used for all operative steps requiring access of more than 5 mm, such as staplers, large graspers, and specimen retrieval. Data acquisition and analysis was performed for operative time, complications, and postoperative quality of life. RESULTS: From 2012 to 2017, 82 patients underwent ta-CR [33 males, 49 females, median age 58 (24-80)]. Transanal-subtotal colectomy and ta-CR for constipation was performed in 12 patients; ta-CR and rectopexy in 31, and ta-CR for diverticulitis was performed in 39 patients. Conversion to traditional approach was required in 3 cases (3.6%). Intraoperative complication included 1 rectal tear requiring intervention. Post-op complications included 3 leaks requiring laparoscopic and 1 open revision, the latter developed wound infection and an incisional hernia. Gastrointestinal Quality of Life Index (GIQLI) improved significantly from preoperative 89 to postoperative 119 (p < 0.001). No patients with ta-CR without open revision developed a hernia post-op with median 18 months follow-up. CONCLUSIONS: ta-CR is a safe and effective NOTES Hybrid technique for colorectal procedures in selected patients with benign colon disorders. GIQLI shows improvement and this technique can have the potential in preventing wound and hernia complications.