High-Performance Bioinspired Microspheres for Boosting Dental Adhesion.

Dental adhesives are widely used in daily practice for minimally invasive restorative dentistry but suffer from bond degradation and biofilm attack. Bio-inspired by marine mussels having excellent surface-adhesion capability and high chemical affinity of polydopamine (PDA) to metal ions, herein, experimental zinc (Zn)-containing polydopamine-based adhesive formulation, further being referred to as "Zn-PDA@SiO2"-incorporated adhesive is proposed as a novel dental adhesive. Different Zn contents (5 and 10 mm) of Zn-PDA@SiO2 are prepared. Considering the synergistic effect of Zn and PDA, Zn-PDA@SiO2 not only presents excellent antibacterial potential and notably inhibits enzymatic activity (soluble and matrix-bound proteases), but also exhibits superior biocompatibility and biosafety in vitro/vivo. The long-term bond stability is substantially improved by adding 5 wt% 5 mm Zn-PDA@SiO2 to the primer. The aged bond strength of the experimentally formulated dental adhesives applied in self-etch (SE) bonding mode is 1.9 times higher than that of the SE gold-standard adhesive. Molecular dynamics calculations indicate the stable formation of covalent bonds, Zn-assisted coordinative bonds, and hydrogen bonds between PDA and collagen. Overall, this bioinspired dental adhesive provides an avenue technology for innovative biomedical applications and has already revealed promising perspectives for dental restorative dentistry.

Unveiling the enigma of the blood-brain barrier in glioblastoma: current advances from preclinical and clinical studies.

PURPOSE OF REVIEW: Glioblastoma (GBM), the most prevalent primary brain malignancy in adults, poses significant challenges in terms of treatment. Current therapeutic strategies for GBM patients involve maximal safe resection, followed by radiotherapy with concurrent and adjuvant temozolomide. However, despite this multimodal approach for GBM, the prognosis of GBM patients remains dismal because of their inherent primary and secondary resistances to treatments. RECENT FINDINGS: Several molecular and cellular mechanisms, including the presence of the blood-brain barrier (BBB), contribute to these resistances. The BBB, comprising multiple layers surrounding brain vessels, acts as a barrier limiting effective drug delivery to the brain. Invasive and noninvasive tools to deliver drugs and pharmaceutical formulations locally or systemically are continuously evolving to overcome the BBB in GBM toward improving drug bioavailability in the brain and reducing systemic toxicities. SUMMARY: Preliminary studies utilizing these approaches have demonstrated promising results in terms of safety and signals of efficacy during early-phase clinical trials. However, further work through additional clinical trials is necessary to evaluate the potential clinical benefits for GBM patients.

Comparative analysis of deeply phenotyped GBM cohorts of 'short-term' and 'long-term' survivors.

BACKGROUND: Glioblastoma (GBM) is an aggressive brain cancer that typically results in death in the first 15 months after diagnosis. There have been limited advances in finding new treatments for GBM. In this study, we investigated molecular differences between patients with extremely short (≤ 9 months, Short term survivors, STS) and long survival (≥ 36 months, Long term survivors, LTS). METHODS: Patients were selected from an in-house cohort (GLIOTRAIN-cohort), using defined inclusion criteria (Karnofsky score > 70; age < 70 years old; Stupp protocol as first line treatment, IDH wild type), and a multi-omic analysis of LTS and STS GBM samples was performed. RESULTS: Transcriptomic analysis of tumour samples identified cilium gene signatures as enriched in LTS. Moreover, Immunohistochemical analysis confirmed the presence of cilia in the tumours of LTS. Notably, reverse phase protein array analysis (RPPA) demonstrated increased phosphorylated GAB1 (Y627), SRC (Y527), BCL2 (S70) and RAF (S338) protein expression in STS compared to LTS. Next, we identified 25 unique master regulators (MR) and 13 transcription factors (TFs) belonging to ontologies of integrin signalling and cell cycle to be upregulated in STS. CONCLUSION: Overall, comparison of STS and LTS GBM patients, identifies novel biomarkers and potential actionable therapeutic targets for the management of GBM.

Expression and Prognostic Value of CD80 and CD86 in the Tumor Microenvironment of Newly Diagnosed Glioblastoma.

BACKGROUND: Strategies to modulate the tumor microenvironment (TME) have opened new therapeutic avenues with dramatic yet heterogeneous intertumoral efficacy in multiple cancers, including glioblastomas (GBMs). Therefore, investigating molecular actors of TME may help understand the interactions between tumor cells and TME. Immune checkpoint proteins such as a Cluster of Differentiation 80 (CD80) and CD86 are expressed on the surface of tumor cells and infiltrative tumor lymphocytes. However, their expression and prognostic value in GBM microenvironment are still unclear. METHODS: In this study, we investigated, in a retrospective local discovery cohort and a validation TCGA dataset, expression of CD80 and CD86 at mRNA level and their prognostic significance in response to standard of care. Furthermore, CD80 and CD86 at the protein level were investigated in the discovery cohort. RESULTS: Both CD80 and CD86 are expressed heterogeneously in the TME at mRNA and protein levels. In a univariate analysis, the mRNA expression of CD80 and CD86 was not significantly correlated with OS in both local OncoNeuroTek dataset and TCGA datasets. CD80 and CD86 mRNA high expression was significantly associated with shorter progression free survival (PFS) (p < 0.05). These findings were validated using the TCGA cohort; higher CD80 and CD86 expressions were correlated with shorter PFS (p < 0.05). In multivariate analysis, CD86 mRNA expression was an independent prognostic factor for PFS in the TCGA dataset only (p < 0.05). CONCLUSION: CD86 could be used as a potential biomarker for the prognosis of GBM patients treated with immunotherapy; however, additional studies are needed to validate these findings.

Adhesive sonic agitation improves bonding durability to class-II cavity preparation.

The purpose of this study was to evaluate the effect of adhesive sonic agitation on resin-dentin micro-tensile bond strength (µTBS) and interfacial morphology at the gingival wall of class-II cavity preparation. Seventy-two molars with prepared class-II cavities were divided into six groups (n = 12) according to the bonding mode; etch-and-rinse (E&R) or self-etch (SE) and application protocol of the universal adhesive (UA) employed (Clearfil Universal Bond Quick, Kuraray Noritake); following the manufacturer instructions (MI), manual agitation for 20 s (20s), or sonic agitation for 20 s using a modified sonic micro-brush mounted on EndoActivator device, Dentsply Sirona, (sonic). Restored teeth were sectioned into resin-dentin beams and slaps and µTBS was evaluated at 1 week (1w) and after thermocycling (10k). µTBS data were analyzed using the linear mixed-effects modeling with specific contrast (p < 0.05). The resin-dentin interfacial morphology was evaluated using a scanning electron microscope. Adhesive sonic agitation resulted in significantly higher µTBS means in both E&R and SE modes, compared to MI group. The µTBS of MI group showed significant reduction upon aging when applied in SE mode. Sonic agitation was associated with enhanced adhesive infiltration into dentin specially in E&R mode. Sonic agitation of UA using modified sonic micro-brush attached to EndoActivator device significantly improved the resin-dentin µTBS and interfacial morphology at the gingival wall of class-II cavity preparation.

Quick bonding using a universal adhesive.

OBJECTIVES: This study aimed to measure the microtensile bond strength (µTBS) of a new universal adhesive (UA) bonded to dentin following a quick bonding mode. MATERIALS AND METHODS: The experimental UA 'SKB-100,' now commercialized as Clearfil Universal Bond Quick ('C-UBq'; Kuraray Noritake), was investigated, with Scotchbond Universal ('SBU'; 3M Oral Care) and the two-step self-etch (SE) adhesive Clearfil SE Bond 2 ('C-SE2'; Kuraray Noritake) serving as references. The adhesives were employed separately in etch&rinse (E&R) and SE modes on each tooth half following a split-tooth design and following their respective instructions for use, except for C-UBq that besides the manufacturer's instructed quick bonding mode was also applied and left untouched for 20 s prior to light curing ('C-UBq_20s') and for C-SE2 that was also applied in the E&R mode. µTBS of half of the specimens was measured upon 1 week (1w), with the other half tested after 6-month (6m) storage in distilled water at 37 °C. Data were statistically analyzed using linear mixed-effects modeling and three-way ANOVA (p < 0.05). The adhesive-dentin interfaces were ultrastructurally characterized by TEM. RESULTS: C-UBq revealed a significantly lower µTBS than C-SE2. The highest µTBS was recorded for C-UBq_20s_1w and C-SE2_1w, both when applied in E&R mode. However, µTBS of C-UBq_20s significantly decreased upon aging in both modes. C-SE2 presented the significantly highest 'aged' µTBS. CONCLUSION: C-UBq applied in the quick bonding mode did not underperform to the UAs applied for 20 s. Superior bonding effectiveness was achieved by C-SE2 in SE and E&R bonding modes. CLINICAL RELEVANCE: Extended application time of C-UBq improved solely its immediate but not aged bonding effectiveness.

Low immediate scientific yield of the PhD among medical doctors.

BACKGROUND: We studied the scientific yield of the medical PhD program at all Danish Universities. METHODS: We undertook a retrospective observational study. Three PhD schools in Denmark were included in order to evaluate the postdoctoral research production over more than 18 years through individual publications accessed by PubMed. RESULTS: A total of 2686 PhD-graduates (1995-2013) with a medical background were included according to registries from all PhD schools in Denmark. They had a median age of 35 years (interquartile range (IQR), 32-38) and 53 % were women at the time of graduation. Scientific activity over time was assessed independently of author-rank and inactivity was measured relative to the date of graduation. Factors associated with inactivity were identified using multivariable logistic regression. 88.6 % of the PhD theses were conducted in internal medicine vs. 11.4 % in surgery. During follow-up (median 6.9 years, IQR 3.0-11.7), PubMed data searches identified that 87 (3.4 %) of the PhD graduates had no publication after they graduated from the PhD program, 40 % had 5 or less, and 90 % had 30 or less. The median number of publications per year after PhD graduation was 1.12 (IQR 0.61-1.99) papers per year. About 2/3 of the graduates became inactive after 1 year and approximately 21 % of the graduates remained active during the whole follow-up. Female gender was associated with inactivity: adjusted odds ratio 1.59 (95 % confidence interval 1.24-2.05). CONCLUSIONS: The scientific production of Danish medic PhD-graduates was mainly produced around the time of PhD-graduation. After obtaining the PhD-degree the scientific production declines suggesting that scientific advance fails and resources are not harnessed.

Multi-Parameter Characterization of HEMA/BPA-free 1- and 2-step Universal Adhesives Bonded to Dentin.

PURPOSE: This study aimed to investigate the bonding effectiveness of two HEMA/BPA-free universal adhesives (UAs) to flat dentin, to characterize their adhesive-dentin interfacial ultrastructure, and to measure their water sorption (Wsp), water solubility (Wsl), and hydrophobicity. MATERIALS AND METHODS: The immediate and aged (50,000 thermocycles) microtensile bond strength (µTBS) to flat dentin of the HEMA/BPA-free UAs Healbond Max (HbMax; Elsodent) and Healbond MP (HbMP; Elsodent) as well as the reference adhesives OptiBond FL (Opti-FL; Kerr), Clearfil SE Bond 2 (C-SE2; Kuraray Noritake), and Scotchbond Universal (SBU; 3M Oral Care) was measured. The adhesive-dentin interfaces of HbMax and HbMP were characterized by TEM. Wsp and Wsl of all adhesive resins and of the primer/adhesive resin mixtures of HbMax, Opti-FL, and C-SE2 were measured. Hydrophobicity was determined by measuring the contact angle of water dropped on adhesive-treated dentin. RESULTS: In terms of µTBS, HbMax and HbMP performed statistically similarly to Opti-FL and C-SE2, but outperformed SBU. Aging only significantly reduced the µTBS of SBU when applied in E&R bonding mode. TEM revealed typical E&R and SE hybrid-layer ultrastructures at dentin, while electron-lucent globules of unknown origin, differing in size and shape, were observed within the adhesive resin of HbMP and even more frequently in that of HbMax. Higher Wsp was measured for the primer/adhesive resin mixtures than for the adhesive resins. Opti-FL was more hydrophobic than all other adhesives tested. CONCLUSION: The HEMA/BPA-free UAs bonded durably to flat dentin with bond strengths comparable to those of the gold-standard E&R/SE adhesives and superior to that of the HEMA/BPA-containing 1-step UA.

Bonding of Composite Cements Containing 10-MDP to Zirconia Ceramics Without Dedicated Ceramic Primer.

PURPOSE: To measure zirconia-to-zirconia microtensile bond strength (µTBS) using composite cements with and without primer. MATERIALS AND METHODS: Two Initial Zirconia UHT (GC) sticks (1.8x1.8x5.0 mm) were bonded using four cements with and without their respective manufacturer's primer/adhesive (G-CEM ONE [GOne] and G-Multi Primer, GC; Panavia V5 [Pv5]), and Panavia SA Cement Universal [PSAu], and Clearfil Ceramic Plus, Kuraray Noritake; RelyX Universal (RXu) and Scotchbond Universal Plus [SBUp], 3M Oral Care). Specimens were trimmed to an hour-glass shaped specimen whose isthmus is circular in cross-section. After 1-week water storage, the specimens were either tested immediately (1-week µTBS) or first subjected to 50,000 thermocycles (50kTC-aged µTBS). The fracture mode was categorized as either adhesive interfacial failure, cohesive failure in composite cement, or mixed failure, followed by SEM fracture analysis of selected specimens. Data were analyzed using linear mixed-effects statistics (α = 0.05; variables: composite cement, primer/adhesive application, aging). RESULTS: The statistical analysis revealed no significant differences with aging (p = 0.3662). No significant difference in µTBS with/without primer and aging was recorded for GOne and PSAu. A significantly higher µTBS was recorded for Pv5 and RXu when applied with their respective primer/adhesive. Comparing the four composite cements when they were applied in the manner that resulted in their best performance, a significant difference in 50kTC-aged µTBS was found for PSAu compared to Pv5 and RXu. A significant decrease in µTBS upon 50kTC aging was only recorded for RXu in combination with SBUp. CONCLUSION: Adequate bonding to zirconia requires the functional monomer 10-MDP either contained in the composite cement, in which case a separate 10-MDP primer is no longer needed, or in the separately applied primer/adhesive.

Antibacterial Dental Adhesive Containing Cetylpyridinium Chloride Montmorillonite.

Oral bacteria cause tooth caries and periodontal disease. Much research is being conducted to prevent both major oral diseases by rendering dental materials' antimicrobial potential. However, such antimicrobial materials are regarded as 'combination' products and face high hurdles for regulatory approval. We loaded inorganic montmorillonite with the antimicrobial agent cetylpyridinium chloride, referred to below as 'CPC-Mont'. CPC-Mont particles in a 1, 3 and 5 wt% concentration were added to the considered gold-standard self-etch adhesive Clearfil SE Bond 2 ('CSE2'; Kuraray Noritake) to render its antibacterial potential (CSE2 without CPC-Mont served as control). Besides measuring (immediate) bonding effectiveness and (aged) bond durability to dentin, the antibacterial activity against S. mutans and the polymerization-conversion rate was assessed. Immediate and aged bond strength was not affected by 1 and 3 wt% CPC-Mont addition, while 5 wt% CPC-Mont significantly lowered bond strength and bond durability. The higher the concentration of the antimicrobial material added, the stronger the antimicrobial activity. Polymerization conversion was not affected by the CPC-Mont addition in any of the three concentrations. Hence, adding 3 wt% CPC-Mont to the two-step self-etch adhesive rendered additional antimicrobial potential on top of its primary bonding function.

A Review of Artificial Intelligence in Breast Imaging.

With the increasing dominance of artificial intelligence (AI) techniques, the important prospects for their application have extended to various medical fields, including domains such as in vitro diagnosis, intelligent rehabilitation, medical imaging, and prognosis. Breast cancer is a common malignancy that critically affects women's physical and mental health. Early breast cancer screening-through mammography, ultrasound, or magnetic resonance imaging (MRI)-can substantially improve the prognosis for breast cancer patients. AI applications have shown excellent performance in various image recognition tasks, and their use in breast cancer screening has been explored in numerous studies. This paper introduces relevant AI techniques and their applications in the field of medical imaging of the breast (mammography and ultrasound), specifically in terms of identifying, segmenting, and classifying lesions; assessing breast cancer risk; and improving image quality. Focusing on medical imaging for breast cancer, this paper also reviews related challenges and prospects for AI.

Experimental two-step universal adhesives bond durably in a challenging high C-factor cavity model.

OBJECTIVES: To determine the bonding effectiveness of experimental 2-step universal adhesives (UAs) to high C-factor class-I cavity-bottom dentin and to assess the potential bond-strength contribution of an additional flowable composite layer. METHODS: Three experimental 2-step UA formulations, involving the application of a 10-MDP-based primer followed by a hydrophobic adhesive resin with a 15-to-20-µm film thickness and differing only for filler, referred to as BZF-21 (silica and bioglass filler), BZF-29 (silica filler) and BZF-29_hv (higher silica-filler loading resulting in a higher viscosity), all prepared by GC, along with three representative commercial adhesives, Clearfil SE Bond 2 (C-SE2, Kuraray Noritake), G-Premio Bond (G-PrB, GC) and OptiBond FL (Opti-FL, Kerr), were comparatively investigated for their 'immediate' and 'aged' (50,000 thermocycles) micro-tensile bond strength (µTBS), when applied either in etch-and-rinse (E&R) or self-etch (SE) mode, to high C-factor class-I cavity-bottom dentin (n = 10; 10 experimental groups). Four additional experimental groups involved the extra application of the flowable composite G-ænial Universal Flo (GC), employed as an intermediate liner in combination with the adhesives BZF-29 and G-PrB and again applied both in E&R or SE mode. Statistical analysis was performed using linear mixed-effects (LME) modelling and linear regression analysis (p < 0.05). RESULTS: All 2-step UAs performed similarly when compared to the gold-standard E&R Opti-FL and SE C-SE2 adhesives, except for the aged µTBS of BZF-29_hv applied in E&R mode, and significantly outperformed the 1-step UA G-PrB. Significant reduction in µTBS upon aging was only recorded for 2-step UAs applied in E&R mode. The extra flowable composite layer significantly improved G-PrB's µTBS. SIGNIFICANCE: The experimental 2-step UAs revealed favorable bonding performance in the challenging high C-factor class-I cavity model, comparable to that of the multi-step gold-standard E&R and SE adhesives and superior to that of the 1-step UA investigated. An additionally applied flowable composite layer compensated for the lower bonding effectiveness of the 1-step UA in the high C-factor cavity model.

Adhesive Performance Assessment of Universal Adhesives and Universal Adhesive/Composite Cement Combinations.

PURPOSE: To investigate the bonding performance of three universal adhesives (UAs) to dentin and the effect of different curing modes and hydrofluoric-acid (HF) etching of lithium-disilicate glass-ceramic on the adhesive performance of two UA/composite cement (CC) combinations. MATERIALS AND METHODS: In the first project part, the immediate and aged (25k and 50k thermocycles) microtensile bond strength (µTBS) of the two light-curing UAs G2-Bond Universal (G2B; GC) and Scotchbond Universal Plus (SBUp; 3M Oral Care), and the self-curing UA Tokuyama Universal Bond II (TUBII; Tokuyama) to flat dentin was measured, when applied in both E&R and SE bonding mode using a split-tooth design (n = 10). The resultant adhesive-dentin interfaces were characterized using TEM. In the second project part, CAD/CAM composite blocks were luted to flat dentin with either Scotchbond Universal Plus/RelyX Universal (SBUp/RxU; 3M Oral Care) or Tokuyama Universal Bond II/Estecem II Plus (TUBII/ECIIp; Tokuyama Dental) using different curing modes (AA mode: auto-curing of both adhesive and cement; AL mode: auto-curing of adhesive and light-curing of cement), upon which their immediate and aged (25k and 50k thermocycles) µTBS was measured. In the third project part, the same UA/CC combinations were luted to CAD/CAM glass-ceramic to measure their immediate and aged (6-month water storage) shear bond strength (SBS). RESULTS: In E&R bonding mode, the performance of G2B, SBUp and TUBII was not significantly different in terms of µTBS, while G2B and SBUp significantly outperformed TUBII in SE bonding mode. No significant difference in µTBS was found between the SBUp/RxU and TUBII/ECIIp UA/CC combinations, regardless of bonding mode, aging time, or curing mode. The cement-curing mode did not significantly influence µTBS, while a significantly higher µTBS was recorded for the UA/CC combinations applied in E&R bonding mode. HF significantly improved the SBS of the UA/CC combinations to glass-ceramic. CONCLUSION: The self-curing adhesive performed better when applied in E&R than in SE bonding mode. The curing mode did not influence the adhesive performance of the composite cements, while an E&R bonding mode rendered more favorable adhesion in a self-curing luting protocol. When bonding to glass-ceramic, the adhesive performance of the universal adhesive/composite cement combinations benefited from HF etching.

Low-Intensity Pulsed Ultrasound-Mediated Blood-Brain Barrier Opening Increases Anti-Programmed Death-Ligand 1 Delivery and Efficacy in Gl261 Mouse Model.

Therapeutic antibodies targeting immune checkpoints have shown limited efficacy in clinical trials in glioblastoma (GBM) patients. Ultrasound-mediated blood-brain barrier opening (UMBO) using low-intensity pulsed ultrasound improved drug delivery to the brain. We explored the safety and the efficacy of UMBO plus immune checkpoint inhibitors in preclinical models of GBM. A blood-brain barrier (BBB) opening was performed using a 1 MHz preclinical ultrasound system in combination with 10 µL/g microbubbles. Brain penetration of immune checkpoint inhibitors was determined, and immune cell populations were evaluated using flow cytometry. The impact of repeated treatments on survival was determined. In syngeneic GL261-bearing immunocompetent mice, we showed that UMBO safely and repeatedly opened the BBB. BBB opening was confirmed visually and microscopically using Evans blue dye and magnetic resonance imaging. UMBO plus anti-PDL-1 was associated with a significant improvement of overall survival compared to anti-PD-L1 alone. Using mass spectroscopy, we showed that the penetration of therapeutic antibodies can be increased when delivered intravenously compared to non-sonicated brains. Furthermore, we observed an enhancement of activated microglia percentage when combined with anti-PD-L1. Here, we report that the combination of UMBO and anti-PD-L1 dramatically increases GL261-bearing mice's survival compared to their counterparts treated with anti-PD-L1 alone. Our study highlights the BBB as a limitation to overcome in order to increase the efficacy of anti-PD-L1 in GBM and supports clinical trials combining UMBO and in GBM patients.

Tissue-Mimetic Supramolecular Polymer Networks for Bioelectronics.

Addressing the mechanical mismatch between biological tissue and traditional electronic materials remains a major challenge in bioelectronics. While rigidity of such materials limits biocompatibility, supramolecular polymer networks can harmoniously interface with biological tissues as they are soft, wet, and stretchable. Here, an electrically conductive supramolecular polymer network that simultaneously exhibits both electronic and ionic conductivity while maintaining tissue-mimetic mechanical properties, providing an ideal electronic interface with the human body, is introduced. Rational design of an ultrahigh affinity host-guest ternary complex led to binding affinities (>1013  M-2 ) of over an order of magnitude greater than previous reports. Embedding these complexes as dynamic cross-links, coupled with in situ synthesis of a conducting polymer, resulted in electrically conductive supramolecular polymer networks with tissue-mimetic Young's moduli (<5 kPa), high stretchability (>500%), rapid self-recovery and high water content (>84%). Achieving such properties enabled fabrication of intrinsically-stretchable stand-alone bioelectrodes, capable of accurately monitoring electromyography signals, free from any rigid materials.

Prognostic significance of complement factors in severely ill patients with COVID-19.

Coagulopathy, cytokine release, platelet hyperactivity and endothelial activation are regarded as potential major contributors to COVID-19 morbidity. Complement activation might provide a bridge linking these factors in severe COVID-19 illness. In this study, we investigated the prognostic significance of selected complement factors in hospitalized patients with severe COVID-19 infection. The study included 300 hospitalized adults with severe COVID-19 infection. Complement factors (C3, C3a, C4, sC5b-9) were assessed by commercial ELISA kits. Outcome parameters included mortality, intensive care unit admission and duration of hospital stay. It was found that survivors had significantly higher serum C3 (median (IQR): 128.5 (116.3-141.0) mg/dL vs 98.0 (70.0-112.8) mg/dL, p<0.001) and C4 (median (IQR): 36.0 (30.0-42.0) mg/dL vs 31.0 (26.0-35.0) mg/dL, p<0.001) levels when compared with non-survivors. On the other hand, it was shown that survivors had significantly lower C3a (median (IQR): 203.0 (170.3-244.0) ng/mL vs 385.0 (293.0-424.8) ng/mL, p<0.001) and sC5b-9 (median (IQR): 294.0 (242.0-318.8) ng/mL vs 393.0 (342.0-436.5) ng/mL, p<0.001) levels when compared with non-survivors. Multivariate logistic regression analysis identified C3a (OR: 0.97 (95% CI 0.96 to 0.99), p<0.001) and C4 (OR: 0.92 (95% CI 0.86 to 0.98), p=0.011) levels as significant predictors of mortality. In conclusion, serum levels of complement factors are related to mortality in severely ill patients with COVID-19.

Laparoscopy-Assisted Endoscopic Retrograde Cholangiopancreatography: New Insight in Management of Iatrogenic Bile Duct Injury.

Bile duct injury (BDI) is a severe and sometimes life-threatening complication of cholecystectomy. Several series have described a 0.5% to 0.6% incidence of BDI during laparoscopic cholecystectomy. We received an emergency call from the operating theater by the surgery team to assess an iatrogenic BDI in a 58-year-old man with cirrhosis who presented for laparoscopic cholecystectomy. After many trials by endoscopic retrograde cholangiopancreatography (ERCP) the guide wire passed to the peritoneal cavity and failed to pass proximally. Laparoscopy resumed, and the surgeon tried to pass the flexible guide wire proximally unsuccessfully. Then, a decision to hold the sphincterotome by laparoscopy and passing it proximally in harmony with ERCP was taken, which was successful. A regular ERCP with 10F plastic stent insertion was carried out, and the perforation was secured by the inserted stent without any further surgical intervention. Laparoscopy-assisted ERCP may give new insights into the immediate repair of iatrogenic bile duct injuries.

10-Methacryloyloxydecyl Dihydrogen Phosphate (10-MDP)-Containing Cleaner Improves Bond Strength to Contaminated Monolithic Zirconia: An In-Vitro Study.

Contamination of zirconia restorations before cementation can impair the resin-zirconia bonding durability. The objective of this study was to evaluate the effect of human saliva or blood decontamination with 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP)-containing cleaner on the resin-zirconia shear bond strength (SBS). METHODS: A total of 220 zirconia specimens were prepared and air-abraded and randomly distributed into 11 groups (n = 20 per group). Except for the control group (no contamination), zirconia specimens were contaminated with either human saliva (five groups) or blood (five groups), and then subjected to one of five cleaning methods: water rinsing, 38% phosphoric acid etchant (Pulpdent Corp., Watertown, MA, USA), 70% isopropanol alcohol (Avalon Pharma, Riyadh, Saudi Arabia), Ivoclean (Ivoclar Vivadent, Schaan, Lichtenstein) and Katana Cleaner (Kuraray Noritake, Tokyo, Japan). The resin-zirconia SBS was tested at 24 h and after thermocycling (10 k cycles). Three-way ANOVA followed by Tukey's multiple comparisons test were utilized to analyze the SBS data. Failure modes were evaluated using a scanning electron microscope. RESULTS: Both blood and saliva significantly affected resin-zirconia SBS as contaminants. After thermocycling, there was no statistically significant difference between SBS obtained after decontamination with the Katana Cleaner (blood, 6.026 ± 2.805 MPa; saliva, 5.206 ± 2.212 MPa) or Ivoclean (blood, 7.08 ± 3.309 MPa; saliva, 6.297 ± 3.083 MPa), and the control group (no contamination, 7.479 ± 3.64 MPa). Adhesive and mixed failures were the most frequent among the tested groups. CONCLUSION: Both 10-MDP-containing cleaner (Katana Cleaner) and zirconium oxide-containing cleaner (Ivoclean) could eliminate the negative effect of saliva and blood contamination on resin-zirconia SBS.

Optimizing glass-ceramic bonding incorporating new silane technology in an experimental universal adhesive formulation.

OBJECTIVE: Incorporating silane-coupling agent into universal adhesives (UAs) to simplify adhesive luting of glass-ceramic restorations appeared ineffective due to silane's instability in an acidic aqueous solution. This study aimed to evaluate new silane technology added to an experimental UA to be bonded to glass ceramics without separate prior silanization. METHODS: Combined silane technology, consisting of 3-(aminopropyl)triethoxysilane (APTES) and γ-methacryloxypropyltriethoxysilane (γMPTES), was incorporated into an experimental UA formulation, being referred to as ADH-XTE (3M Oral Care). Immediate and aged shear bond strength (SBS) of ADH-XTE onto as-milled ('AM'), tribochemical silica-coated ('TSC'), HF-etched ('HF'), and mirror-polished ('MP') glass-ceramic CAD/CAM blocks (IPS e.max CAD) with/without separate silanization was measured (n = 10/group). The control adhesives included Scotchbond Universal ('SBU') and Scotchbond 1 XT ('SB1-XT'). The glass-ceramic surface topography and the fractography of the SBS-debonded specimens were observed by SEM. RESULTS: Without separate prior silanization, the experimental UA ADH-XTE, containing combined APTES/γMPTES silane technology, significantly outperformed the glass-ceramic bonding efficiency of its silane-containing SBU precursor, while it performed equally effective as SBU applied with prior silanization. Upon aging, significant reduction in SBS was recorded when ADH-XTE was bonded to TSC glass-ceramic surfaces (p < 0.05), while not to HF ones. Notably, the lowest SBS was obtained when the UAs were bonded to AM and MP glass-ceramic surfaces, in particular when applied without separate prior silanization (p < 0.05). SIGNIFICANCE: The glass-ceramic bonding capacity of the new combined APTES/γMPTES silane-containing UA ADH-XTE surpassed that of its SBU precursor. HF etching remains needed to durably bond to glass-ceramics.

Extra Bonding Layer Compensates Universal Adhesive's Thin Film Thickness.

PURPOSE: Universal adhesives (UAs) are applied in 2-step etch-and-rinse (2-E&R) or 1-step self-etch (1-SE) mode. This study investigated whether three UAs could benefit from a highly filled extra bonding layer (EBL), turning them into 3-E&R and 2-SE UAs, respectively, thus also compensating for the commonly thin film thickness of UAs. MATERIALS AND METHODS: Microtensile bond strength (µTBS) to bur-cut dentin of Clearfil Universal Bond Quick (C-UBq, Kuraray Noritake), G-Premio Bond (G-PrB, GC) and Prime&Bond Active (P&Ba, Dentsply Sirona), applied in E&R and SE mode without/with the adhesive resin (EBL) of OptiBond FL (Opti-FL_ar, Kerr), was compared to that of the 3-E&Ra OptiBond FL (Opti-FL; Kerr), which was also employed in 2-SE mode. As a cross reference, the SE primer of Clearfil SE Bond 2 (Kuraray Noritake) was combined with Opti-FL_ar (C-SE2/Opti-FL) and again applied in 2-SE and 3-E&R mode. µTBS was measured after 1 month of water storage (37°C) and additional 25,000 and 50,000 thermocycles (TC). All µTBS were statistically analyzed using three different linear mixed-effects models with specific contrasts (p < 0.05). RESULTS: Overall, the four parameters (adhesive, bonding mode, aging, EBL) significantly influenced µTBS. G-PrB and P&Ba benefited from EBL when applied in both E&R and SE bonding modes. In E&R mode, P&Ba generally revealed the highest µTBS; C-UBq presented an intermediate and G-PrB the lowest µTBS. No significant differences were found between different bonding modes. C-SE2/Opti-FL outperformed Opti-FL in 3-E&R and 2-SE_1 month/25k. CONCLUSION: The overall benefit of EBL on the 1-month and TC-aged bonding efficacy differed for the different UAs tested.