Search

Juyoung Khwarg,1 Soyoung Lee,1,2 In-Jin Jang,1 Won-Ho Kang,3 Hye Jung Lee,4 Kyu Yeon Kim,4 Ki-Sun Jeong,4 Chongho Won,4 Youn Woong Choi,5 Dae Chul Ha,5 RaeHoon Jung,5 Min-Gu Han,5 Won Tae Jung,6 Kyu-Yeol Nam,6 YeSeul Kim,6 Kyung-Sang Yu,1 Jaeseong Oh1,7 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea; 2Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, Republic of Korea; 3R&D Center, Korea United Pharm. Inc., Seoul, Republic of Korea; 4Caleb Multilab, Inc., Seoul, Republic of Korea; 5R&D Center, Korea United Pharm.Inc., Sejong, Republic of Korea; 6Global R&D, Korea United Pharm. Inc., Seoul, Republic of Korea; 7Department of Pharmacology, Jeju National University College of Medicine, Jeju, Republic of KoreaCorrespondence: Jaeseong Oh, Department of Pharmacology, Jeju National University College of Medicine, 15, Aran 13-gil, Jeju-si, Jeju-do, 63241, Republic of Korea, Email jaeseong5@jejunu.ac.krPurpose: Statins are widely used in combination with omega-3 fatty acids for the treatment of patients with dyslipidemia. The aim of this study was to compare the pharmacokinetic (PK) profiles of atorvastatin and omega-3-acid ethyl esters between fixed-dose combination (FDC) and loose combination in healthy subjects.Methods: A randomized, open-label, single-dose, 2-sequence, 2-treatment, 4-period replicated crossover study was performed. Subjects were randomly assigned to one of the 2 sequences and alternately received four FDC soft capsules of atorvastatin/omega-3-acid ethyl esters (10/1000 mg) or a loose combination of atorvastatin tablets (10 mg × 4) and omega-3-acid ethyl ester soft capsules (1000 mg× 4) for four periods, each period accompanied by a high-fat meal. Serial blood samples were collected for PK analysis of atorvastatin, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). PK parameters were calculated by a non-compartmental analysis. The geometric mean ratio (GMR) and its 90% confidence interval (CI) of the FDC to the loose combination were calculated to compare PK parameters.Results: A total of 43 subjects completed the study as planned. The GMR (90% CI) of FDC to loose combination for maximum concentration (Cmax) and area under the time-concentration curve from zero to the last measurable point (AUClast) were 1.0931 (1.0054– 1.1883) and 0.9885 (0.9588– 1.0192) for atorvastatin, 0.9607 (0.9068– 1.0178) and 0.9770 (0.9239– 1.0331) for EPA, and 0.9961 (0.9127– 1.0871) and 0.9634 (0.8830– 1.0512) for DHA, respectively. The intra-subject variability for Cmax and AUClast of DHA was 30.8% and 37.5%, respectively, showing high variability. Both the FDC and the loose combination were safe and well tolerated.Conclusion: The FDC of atorvastatin and omega-3-acid ethyl esters showed comparable PK characteristics to the corresponding loose combination, offering a convenient therapeutic option for the treatment of dyslipidemia. Keywords: pharmacokinetics, cardiovascular disease

Objective: To identify the different uses and modalities of digital technologies to diagnose, plan and monitor peri-implant soft tissue conditions and aesthetics., Methods: A comprehensive narrative review of pertinent literature was conducted, critically appraising key digital technologies that may assist peri-implant soft tissue augmentation and assessment. An electronic search on four databases including studies published prior to 1st July 2023 was performed and supplemented by a manual search., Results: Predominantly, tools such as cone beam computed tomography (CBCT), intraoral scanning (iOS), intraoral ultrasonography and digital spectrophotometry were commonly to assess and monitor peri-implant soft tissues. The main clinical and research applications included: (i) initial assessment of mucosal thickness, supra-crestal tissue height and keratinized mucosa width, (ii) evaluation of peri-implant soft tissue health and inflammation, (iii) monitoring profilometric changes and midfacial mucosal margin stability over time and (iv) aesthetic evaluation through colour assessment. While evidence for some digital tools may be limited, the integration of digital technologies into peri-implant soft tissue management holds great promise. These technologies offer improved precision, comfort and speed in assessment, benefiting both patients and clinicians., Conclusion: As digital technologies progress, their full potential in peri-implant soft tissue augmentation and their value will become more evident with ongoing research. Embracing these innovations and their potential benefits is recommended to ensure that during progress in implant dentistry, patient care is not hindered., (© 2024 The Authors. Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

Aim: To assess the influence of the emergence angle on marginal bone loss (MBL) and supracrestal soft tissue around dental implants., Materials and Methods: In six mongrel dogs, the mandibular premolars and molars were extracted. After 3 months of healing, four dental implants were placed in each hemimandible. The implants were randomly allocated to receive one of four customized healing abutments, each with a different value of the restorative emergence angle: 20°, 40°, 60° or 80°. Intra-oral radiographs were taken after placing the healing abutments and at 6, 9, 16 and 24 weeks of follow-up. Then, micro-CT and undecalcified histology and synchrotron were performed. MBL over time was analysed with generalized estimating equations (GEEs) and adjusted for baseline soft-tissue thickness., Results: From implant placement to 24 weeks, GEE modelling showed that the MBL at mesial and distal sites consistently increased over time, indicating MBL in all groups (p < 0.001). The model indicated that MBL varied significantly across the different restorative angles (angle effect, p < 0.001), with 80° showing the greatest bone loss. Micro-CT, histology and synchrotron confirmed the corresponding trends and showed that wide restorative angles (60° and 80°) impaired the integrity of the junctional epithelium of the supracrestal tissue., Conclusions: A wide restorative angle increases MBL and impairs the integrity of the junctional epithelium of the implant supracrestal complex., (© 2024 The Author(s). Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Introduction: Childhood cancer survivors (CCS) are at risk of experiencing lower quality-of-life, fatigue, and depression. Few randomized controlled trials have studied the effect of physical activity (PA) on these in adult long-term CCS. This study investigated the effect of a 1-year individualized PA intervention on health-related quality-of-life (HRQOL), fatigue, and distress symptoms in adult CCS., Methods: The SURfit trial randomized 151 CCS ≥16 years old, <16 at diagnosis and ≥5 years since diagnosis, identified through the Swiss Childhood Cancer Registry. Intervention participants received personalized PA counselling to increase intense PA by ≥2.5 h/week for 1 year. Controls maintained usual PA levels. The authors assessed physical- and mental-HRQOL, fatigue, and distress symptoms at baseline, 3, 6, and 12 months. T-scores were calculated using representative normative populations (mean = 50, standard deviation = 10). Generalized linear mixed-effects models with intention-to-treat (ITT, primary), and three per-protocol allocations were used., Results: At 12 months, ITT (-3.56 larger decrease, 95% confidence interval -5.69 to -1.43, p = .001) and two per-protocol analyses found significantly lower fatigue. Physical-HRQOL improved significantly in two per-protocol analyses at 12 months. No other effects were found., Conclusion: SURfit showed that increased intense PA over 1 year improved fatigue in adult CCS. Survivors should be recommended PA to reduce the burden of late-effects., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Purpose: To investigate the changes in retinal arterial architecture after treatment with voretigene neparvovec in patients with retinal dystrophy caused by bi-allelic mutations in the RPE65 gene., Methods: Sixteen eyes treated with voretigene neparvovec at the University Eye Clinic in Tuebingen, Germany, underwent adaptive optics ophthalmoscopy (AO) imaging at baseline and 2 weeks, 1, 3, 6 and 12 months after treatment. Follow-up was performed in six eyes of four patients. For each eye, five different positions at arterial vessels were selected and the wall-to-lumen ratio (WLR), the lumen diameter (LD) and the wall cross-sectional area (WCSA) were measured by the manufacturer's software over the observational period., Results: Vast retinal atrophy dominated all gained AO images. WLR fluctuated in the observation period without statistically significant change. LD and WCSA changed significantly after 2 weeks from the baseline examination and returned to values similar to baseline thereafter. There were no signs of inflammation such as macrophages or perivascular accumulated fluid visible., Conclusion: AO imaging of the retinal vessels in RPE65-associated retinal dystrophies (IRD) is challenging. There was no change in the retinal arterial vasculature over the observation period of 12 months that would indicate inflammatory changes. Decrease of the LD and WCSA shortly after treatment might be caused by the perioperative prednisolone intake. AO of retinal vessels can be used as a diagnostic module to complement monitoring the disease and effects of genetic treatments if the acquisition is possible in selected cases., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Aim: To investigate whether transmucosal healing is as effective as submerged healing in terms of buccal bone regeneration when guided bone regeneration (GBR) is performed simultaneously with implant placement., Materials and Methods: In six dogs, buccal dehiscence defects were created in the edentulous mandibular ridge, sized 5 × 5 × 3 mm (length × height × depth). In each defect, a bone-level implant was placed, and four experimental groups were randomly assigned as follows: (i) transmucosal healing with GBR (T-GBR), (ii) transmucosal healing without GBR (T-control), (iii) submerged healing with GBR (S-GBR) and (iv) submerged healing without GBR (S-control). Data analyses were based on histological slides 5 months after implant placement., Results: The T-GBR group showed significant differences compared to the control groups regarding defect height resolution, buccal bone thickness and mineralized tissue area (p < .05), but showed no significant differences when compared with the S-GBR group (p > .05)., Conclusions: The mode of healing (transmucosal vs. submerged) does not influence bone regeneration at implant sites. The clinician may therefore choose the approach based on further clinical and patient-specific parameters., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Electrical storm (ES) is a life-threatening condition of recurrent ventricular arrhythmias (VA) in a short period of time. Percutaneous stellate ganglion blockade (SGB) is frequently used - however the efficacy is undefined. The objective of our systematic review was to determine the efficacy of SGB in reducing VA events and mortality among patients with ES. A search of Medline, EMBASE, Scopus, CINAHL and CENTRAL was performed on February 29, 2024 to include studies with adult patients (≥ 18 years) with ES treated with SGB. Our outcomes of interest were VA burden pre- and post-SGB, and in-hospital/30-day mortality. A total of 553 ES episodes in 542 patients from 15 observational studies were included. Treated VAs pre- and post-SGB were pooled from eight studies including 383 patients and demonstrated a decrease from 3.5 (IQR 2.25-7.25) to 0 (IQR 0-0) events (p = 0.008). Complete resolution after SGB occurred in 190 of 294 patients (64.6%). Despite this, in-hospital or 30-day mortality remained high occurring in 140 of 527 patients (random effects prevalence 22%). Repeat SGB for recurrent VAs was performed in 132 of 490 patients (random effects prevalence 21%). In conclusion, observational data suggests SGB may be effective in reducing VAs in ES. Definitive studies for SGB in VA management are needed. Study protocol: PROSPERO - registration number CRD42023430031., (© 2024. The Author(s).)

Objective. To investigate the feasibility of delivering multidimensional feedback using a single channel of peripheral nerve stimulation by complementing intensity percepts with flutter frequency percepts controlled by burst period modulation. Approach. Two dimensions of a distally referred sensation were provided simultaneously: intensity was conveyed by the modulation of the pulse charge rate inside short discrete periods of stimulation referred to as bursts and frequency was conveyed by the modulation of the period between bursts. For this approach to be feasible, intensity percepts must be perceived independently of frequency percepts. Two experiments investigated these interactions. A series of two alternative forced choice tasks (2AFC) were used to investigate burst period modulation's role in intensity discernibility. Magnitude estimation tasks were used to determine any interactions in the gradation between the frequency and intensity percepts. Main results. The 2AFC revealed that burst periods can be individually differentiated as a gradable frequency percept in peripheral nerve stimulation. Participants could correctly rate a perceptual scale of intensity and frequency regardless of the value of the second, but the dependence of frequency differentiability on charge rate indicates that frequency was harder to detect with weaker intensity percepts. The same was not observed in intensity differentiability as the length of burst periods did not significantly alter intensity differentiation. These results suggest multidimensional encoding is a promising approach for increasing information throughput in sensory feedback systems if intensity ranges are selected properly. Significance. This study offers valuable insights into haptic feedback through the peripheral nervous system and demonstrates an encoding approach for neural stimulation that may offer enhanced information transfer in virtual reality applications and sensory-enabled prosthetic systems. This multidimensional encoding strategy for sensory feedback may open new avenues for enriched control capabilities., (Creative Commons Attribution license.)

Objective: The purpose of this study was to evaluate the age-dependency of amplitudes and implicit times in the electroretinograms (ERGs) of healthy individuals and provide clinicians and researchers with a reference for a variety of stimulus paradigms., Design and Methods: Full-field electroretinography was conducted on 73 healthy participants aged 14-73 using an extended ISCEV standard protocol that included an additional 9 Hz flicker stimulus for assessing rod function and special paradigms for isolated On-Off and S-cone responses. Correlation coefficients and best-fit regression models for each parameter's age-dependency were calculated., Results: Dark-adapted ERGs, in particular, displayed notable age-related alterations. The attenuation and delay of the b-wave with higher age were most significant in the dark-adapted, rod-driven 0.001 cd s/m 2 flash ERG. The age-dependent reduction of the a-wave amplitude was strongest in the standard dark-adapted 3 cd s/m 2 flash condition. Cone-driven, light-adapted responses to either flash or flicker stimuli displayed comparatively small alterations at higher age. S-cone function tended to diminish at an early age, but the effect was not significant in the whole population., Conclusion: The results suggest that rod and cone function decline at different rates with age, with rods being generally more affected by aging. Nonetheless, response amplitudes displayed a wide variability across the whole sample., (© 2024. The Author(s).)

Tumor cell heterogeneity defines therapy responsiveness in neuroblastoma (NB), a cancer derived from neural crest cells. NB consists of two primary subtypes: adrenergic and mesenchymal. Adrenergic traits predominate in NB tumors, while mesenchymal features becomes enriched post-chemotherapy or after relapse. The interconversion between these subtypes contributes to NB lineage plasticity, but the underlying mechanisms driving this phenotypic switching remain unclear. Here, we demonstrate that SWI/SNF chromatin remodeling complex ATPases are essential in establishing an mesenchymal gene-permissive chromatin state in adrenergic-type NB, facilitating lineage plasticity. Targeting SWI/SNF ATPases with SMARCA2/4 dual degraders effectively inhibits NB cell proliferation, invasion, and notably, cellular plasticity, thereby preventing chemotherapy resistance. Mechanistically, depletion of SWI/SNF ATPases compacts cis-regulatory elements, diminishes enhancer activity, and displaces core transcription factors (MYCN, HAND2, PHOX2B, and GATA3) from DNA, thereby suppressing transcriptional programs associated with plasticity. These findings underscore the pivotal role of SWI/SNF ATPases in driving intrinsic plasticity and therapy resistance in neuroblastoma, highlighting an epigenetic target for combinational treatments in this cancer., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objectives: Before vaccines and effective treatments were available, quarantine of close contacts was important to limit the spread of SARS-CoV-2. To evaluate potential benefits and harms of quarantine, we aimed to estimate infection rates and describe experiences and mental health among persons in mandated quarantine during the early SARS-CoV-2 pandemic., Methods: We invited adults in mandated quarantine after an exposure to SARS-CoV-2 identified through contact tracing of the Canton of Zurich, Switzerland, between August 2020 and January 2021. Participants completed two questionnaires and received up to two SARS-CoV-2 polymerase chain reaction tests, during and at the end of quarantine., Results: Among 395 participants, quarantine duration ranged from 2 to 20 days. By day 11 since the last contact, 11.1% [95% CI 8.4%-14.7%] were infected with SARS-CoV-2. The proportion of participants with symptoms of depression doubled from 9.3% before quarantine to 18.9% during quarantine, and 12.1% reported quarantine was very or extremely difficult., Conclusion: Although quarantine was only moderately burdensome for most participants, some experienced significant difficulties and burden. Policymakers need to balance infection control with potential harms placed on individuals., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2024 Aschmann, Domenghino, Jung, Ballouz, Menges, Fehr and Puhan.)

Objective: To investigate the efficacy of ribose-crosslinked collagen (RCLC) matrices functionalized by crosslinked hyaluronic acid (xHya) for reconstructive treatment of class I and III (b-c) peri-implantitis lesions in a transmucosal healing mode., Materials and Methods: Thirteen patients presenting with 15 implants were included in this prospective case series. Upon flap reflection, the implants were thoroughly decontaminated employing glycine powder air polishing and adjunctive sodium hypochlorite. For defect augmentation, xHyA was administered to the bony defect walls, exposed implant surfaces, and the RCLC matrix before defect grafting. The full-thickness flap was readapted and sutured around the implant neck for transmucosal healing. Baseline and respective values at the 12 months post-op evaluation were recorded for the clinical parameters peri-implant probing depth (PPD), buccal soft tissue dehiscence (BSTD) and bleeding on probing (BoP). Furthermore, two independent investigators analyzed radiographic changes in the defect area. The mean changes for all variables were analyzed with a paired t-test., Results: The initial mean PPD was 7.2 ± 1.9 mm, and BoP was present in 63% of sites. After 12 months, PPD at the latest visit was 3.2 ± 0.66 mm, which amounted to a respective 3.9 ± 1.85 mm reduction, while the BoP frequency dropped to 10% at all sites. Radiographic bone fill was accomplished for 62.8% of the former defect area, accompanied by a mean MBL gain of 1.02 mm around the treated implants (all p < 0.001)., Conclusions: Within the limits of this case series, we conclude that the proposed treatment sequence substantially improved peri-implant defects and offered a simplified but predictive technique., Clinical Relevance: Reconstructive treatment approaches for peri-implantitis are effective but remain non-superior to open flap debridement. Further research on novel biomaterial combinations that may improve reconstructive treatment outcomes are warranted. Ribose-crosslinked collagen matrices biofunctionalized by hyaluronic acid used in this study yield improved clinical and radiographic peri-implant conditions after 12 months., (© 2024. The Author(s).)

Objective: To digitally evaluate the three-dimensional (3D) remodelling of FGG used to treat RT2 gingival recessions and lack of keratinized tissue on mandibular incisor teeth., Methods: Data from 45 patients included in a previous multicentric RCT were analyzed. Silicone impressions were taken before (baseline) and 3, 6 and 12 months after standardized FGG placement. Casts were scanned and images were superimposed, using digital software, to obtain measurements of estimated soft tissue thickness (eTT; 1, 3, and 5 mm apical to baseline gingival margin). In addition, soft tissue volume (STV) and creeping attachment (CA) were assessed., Results: All patients exhibited postoperative eTT and STV increases, at all time points. The greatest mean thickness gain was observed at eTT3 (1.0 ± 0.4 mm) at 12 months. At 12 months, STV was 52.3 ± 21.1 mm 3 , without relevant changes compared to the 3- and 6-month follow-up. CA, which was observed as early as six months postoperatively, was evident in ∼85 % of teeth at 12 months., Conclusions: Application of FGG was an effective phenotype modification therapy, as shown by the significantly increased tissue thickness postoperatively. Despite the use of FGG technique not aiming for root coverage, digital 3D assessment documented the early and frequent postoperative occurrence of CA, which helped improve recession treatment outcomes., Clinical Significance: The use of 3D assessment methodology allows precise identification of the tissue gain obtained with FGG, which, regardless of technique, results in predictable phenotype modification and frequent occurrence of creeping attachment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: To evaluate clinical, clinician- and patient-reported outcomes (PROs) of two adjacent single posterior implants immediately loaded with definitive single crowns up to 1 year. Ten patients in need of two adjacent posterior single implants were included. All implants were placed applying a fully digital workflow. Definitive screw-retained single zirconia crowns were delivered within 72 h after implant placement. Clinical parameters, patient- and clinician-reported outcomes were assessed up to 1 year of follow-up., Clinical Considerations: Clinical outcomes remained stable, with no implant failures or technical and biological complications throughout the observation period. Patient satisfaction was very high at baseline (crown delivery) and remained consistently high at 6 and 12 months of follow-up. Crown insertion 3 days after implant placement was rated as an easy procedure by clinicians., Conclusions: Two adjacent single implants with immediate definitive restorations (<72 h) in the posterior region appear to be a viable and easy treatment option to shorten the overall treatment time and potentially enhancing patient satisfaction. However, randomized controlled trials are needed to confirm the advantages of this treatment protocol over a delayed loading approach., Clinical Significance: In selected cases, immediate implant loading with definitive restorations in the posterior region appears a valuable and straightforward option to shorten the overall treatment time., (© 2024 The Authors. Journal of Esthetic and Restorative Dentistry published by Wiley Periodicals LLC.)

Over the past several centuries, the integration of contemporary medical techniques and innovative technologies, like genetic sequencing, have played a pivotal role in enhancing our comprehension of congenital vascular and lymphatic disorders. Nonetheless, the uncommon and complex characteristics of these disorders, especially considering their formation during the intrauterine stage, present significant obstacles in diagnosis and treatment. Here, we review the intricacies of these congenital abnormalities, offering an in-depth examination of key diagnostic approaches, genetic factors, and therapeutic methods., Competing Interests: Disclosures None.

Aims: The cytokine interleukin-6 (IL-6) plays a central role in the inflammation cascade as well as cardiovascular disease progression. Since myeloid cells are a primary source of IL-6 formation, we aimed to generate a mouse model to study the role of myeloid cell-derived IL-6 in vascular disease., Methods and Results: Interleukin-6-overexpressing (IL-6 OE ) mice were generated and crossed with LysM-Cre mice, to generate mice (LysM-IL-6 OE mice) overexpressing the cytokine in myeloid cells. Eight- to 12-week-old LysM-IL-6 OE mice spontaneously developed inflammatory colitis and significantly impaired endothelium-dependent aortic relaxation, increased aortic reactive oxygen species (ROS) formation, and vascular dysfunction in resistance vessels. The latter phenotype was associated with decreased survival. Vascular dysfunction was accompanied by a significant accumulation of neutrophils, monocytes, and macrophages in the aorta, increased myeloid cell reactivity (elevated ROS production), and vascular fibrosis associated with phenotypic changes in vascular smooth muscle cells. In addition to elevated Mcp1 and Cxcl1 mRNA levels, aortae from LysM-IL-6 OE mice expressed higher levels of inducible NO synthase and endothelin-1, thus partially accounting for vascular dysfunction, whereas systemic blood pressure alterations were not observed. Bone marrow (BM) transplantation experiments revealed that vascular dysfunction and ROS formation were driven by BM cell-derived IL-6 in a dose-dependent manner., Conclusion: Mice with conditional overexpression of IL-6 in myeloid cells show systemic and vascular inflammation as well as endothelial dysfunction. A decrease in circulating IL-6 levels by replacing IL-6-producing myeloid cells in the BM improved vascular dysfunction in this model, underpinning the relevant role of IL-6 in vascular disease., Competing Interests: Conflict of interest: M.B. received funding and is a consultant for ARCA Biopharma (not related to the presented work). S.K. received funding for consultant lectures from Almiral and Jansson-Cilag (not related to the presented work either)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Bladder cancer (BC) is the 12th most commonly diagnosed cancer worldwide. Although there are several well-established molecular and immunological classifications, prognostic and predictive markers for tumor cells and immune cells are still needed. Using a tissue microarray, we analyzed the expression of the chemokine CC motif ligand 5 (CCL5) by immunohistochemistry (IHC) in 175 muscle-invasive BC samples. The application of a single cutoff for the staining status of tumor cells (TCs; positive vs. negative) and immune cells (ICs; positive vs. negative) revealed 75 patients (42.9%) and 123 patients (70.3%) with CCL5-positive TCs or ICs, respectively. IHC results were associated with prognostic and predictive data. Multivariate Cox regression analysis revealed that positive CCL5 staining in TCs was associated with significantly shorter disease-specific survival (DSS; RR = 1.51; p = 0.047), but CCL5-negative ICs were associated with significantly shorter overall survival (OS; RR = 1.66; p = 0.005), DSS (RR = 2.02; p = 0.001) and recurrence-free survival (RFS; RR = 1.94; p = 0.002). Adjuvant chemotherapy was favorable for patients with CCL5-negative ICs for OS (RR = 0.30; p = 0.006), DSS (RR = 0.36; p = 0.022) and RFS (RR = 0.41; p = 0.046) but not for patients with CCL5-positive ICs, except in the subgroup of N1 + N2 patients, where it was associated with better OS. We suggest that CCL5 expression can be a prognostic and predictive marker for muscle-invasive bladder cancer patients.

Purpose: Investigating influencing factors on the pupillary light response (PLR) as a biomarker for local retinal function by providing epidemiological data of a large normative collective and to establish a normative database for the evaluation of chromatic pupil campimetry (CPC)., Methods: Demographic and ophthalmologic characteristics were captured and PLR parameters of 150 healthy participants (94 women) aged 18 to 79 years (median = 46 years) were measured with L-cone- and rod-favoring CPC protocols. Linear-mixed effects models were performed to determine factors influencing the PLR and optical coherence tomography (OCT) data were correlated with the pupillary function volume., Results: Relative maximal constriction amplitude (relMCA) and latency under L-cone- and rod-favoring stimulation were statistically significantly affected by the stimulus eccentricity (P < 0.0001, respectively). Iris color and gender did not affect relMCA or latency significantly; visual hemifield, season, and daytime showed only minor influence under few stimulus conditions. Age had a statistically significant effect on latency under rod-specific stimulation with a latency prolongation ≥60 years. Under photopic and scotopic conditions, baseline pupil diameter declined significantly with increasing age (P < 0.0001, respectively). Pupillary function volume and OCT data were not correlated relevantly., Conclusions: Stimulus eccentricity had the most relevant impact on relMCA and latency of the PLR during L-cone- and rod-favoring stimulation. Latency is prolonged ≥60 years under scotopic conditions. Considering the large study collective, a representative normative database for relMCA and latency as valid readout parameters for L-cone- and rod-favoring stimulation could be established. This further validates the usability of the PLR in CPC as a biomarker for local retinal function.

Background/objectives: This study investigated the relationship between adherence to the Mediterranean diet among Korean baby boomers and their levels of psychosocial stress., Subjects/methods: The study included 1,656 adults (889 men and 797 women) born between 1955 and 1963 who participated in the 2005-2006 survey of the community-based Korean Genome and Epidemiology Study (KoGES). The Mediterranean-type diet score (MTDS) was calculated from the semi-quantitative food frequency questionnaire (SQFFQ) data. The psychosocial stress levels were calculated using the psychosocial well-being index-short form (PWI-SF). Logistic regression analyses were performed to analyze the association between the MTDS (tertiles) and the prevalence of high psychosocial stress by gender., Results: The ranges of the MTDS tertile groups were T1 (20-33 points), T2 (34-37 points), and T3 (38-39 points) for men, T1 (20-33 points), T2 (34-37 points), and T3 (38-48 points) for women. In both men and women, the consumption of whole grains, potatoes, fruits, vegetables, legumes, and fish increased with higher MTDS, while the consumption of red meat and dairy products decreased ( P for trend < 0.05). As MTDS score increased the intake of energy, fiber, vitamins, and minerals ( P for trend < 0.05). Men in the highest MTDS tertile had a 41% lower odds ratio (OR) of high psychosocial stress compared with those in the lowest tertile (OR, 0.59; 95% confidence interval [CI], 0.38-0.91). Similarly, women in the highest tertile of the MTDS had a 39% lower OR of high psychosocial stress compared with those in the lowest tertile (OR, 0.61; 95% CI, 0.40-0.95)., Conclusion: Promoting adherence to the Mediterranean diet among baby boomers may have a positive impact on reducing their levels of psychosocial stress., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interests., (©2024 The Korean Nutrition Society and the Korean Society of Community Nutrition.)

Objectives: To assess both the radiographic and profilometric outcomes of early implant placement with or without alveolar ridge preservation (ARP) (using two different ARP techniques) after 1 year of loading., Materials and Methods: Seventy-five patients with a failing single tooth in the anterior maxilla were randomly allocated to three groups (1:1:1): (a) ARP using demineralized bovine bone mineral containing 10% collagen (DBBM-C) covered by a collagen matrix (CM), (b) ARP using DBBM-C covered with a palatal graft (PG), and (c) unassisted socket healing (control). Eight weeks after tooth extraction, early implant placement was performed in all patients. Cone-beam computed tomography (CBCT) and impressions were taken 8 weeks after tooth extraction (ARP/unassisted healing) prior to implant placement and 1-year post-loading. Radiographic and profilometric outcomes were evaluated., Results: Out of the 70 patients available for re-examination at 1-year post-loading, 55 datasets could be assessed (ARP-CM 19; ARP-PG 17; Control 19). The need for additional guided bone regeneration (GBR) at implant placement amounted to 31.6% (ARP-CM), 29.4% (ARP-PG), and 68.4% (unassisted healing). Adjusted models revealed that residual buccal bone height and additional GBR at implant placement significantly influenced the magnitude of the alveolar changes at 1 year (p < 0.05). In patients with ARP (group ARP-CM or ARP-PG) without additional GBR, the presence of bone convexity amounted to 36.0% (9/25) at 1-year post-loading. For patients that received ARP and additional GBR at implant placement, the frequency of bone convexity increased to 72.7% (8/11) (p = 0.042). Regarding profilometric measurements, a tendency toward agreement with radiographic outcomes was observed., Conclusions: Early implant placement with ARP can attenuate alveolar ridge changes at 1-year post loading by minimizing both radiographic and profilometric alterations. However, early implant placement with simultaneous GBR consistently yields superior radiographic and profilometric outcomes, regardless of whether ARP is performed., (© 2023 Wiley Periodicals LLC.)

Purpose: To investigate age-dependent wall to lumen ratio (WLR) reference values for healthy individuals in adaptive optics imaging (AO). WLR serves as an objective, dimensionless parameter for the evaluation of structural changes in vessels caused by conditions like arterial hypertension, diabetes or vascular stenosis., Methods: 50 right eyes of healthy individuals were examined by adaptive optics imaging. The central big arterioles and smaller arterial branches at least one disc diameter away from the optic disc, approximately above or below the macula were measured by the manufacturer's software. The wall-lumen-ratio (WLR), the wall cross-sectional area (WCSA) and lumen diameter (LD) were assessed. Subsequent data analysis was performed with a focus on variables including age, gender and blood pressure., Results: Normative values for WLR, WCSA and LD in 5 different age groups could be established. However, no significant differences between the age groups were found. Intra-subject comparisons revealed significantly higher WLRs on peripheral branches when compared to central arterioles. WLR showed in this normotensive cohort no relevant correlation with the systolic, diastolic and mean blood pressure. Gender and intraocular pressure had no influence on the vascular parameters., Conclusion: AO is capable of examining vascular alterations in arterioles at an almost microscopic level. Age did not seem to alter WLR, normotensive blood pressure parameters showed also no significant impact. AO-based vessel analysis may provide clinically useful biomarkers for cardiovascular health and should be tested in future studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kortuem, Merle, Reith, Kuehlewein, Jung, Holocher, Stingl, Stingl and Kempf.)

Novel bioelectronic medical devices that target neural control of visceral organs (e.g., liver, gut, spleen) or inflammatory reflex pathways are innovative class III medical devices like implantable cardiac pacemakers that are lifesaving and life-sustaining medical devices. Bringing innovative neurotechnologies early into the market and the hands of treatment providers would benefit a large population of patients inflicted with autonomic and chronic immune disorders. Medical device manufacturers and software developers widely use the Waterfall methodology to implement design controls through verification and validation. In the Waterfall methodology, after identifying user needs, a functional unit is fabricated following the verification loop (design, build, and verify) and then validated against user needs. Considerable time can lapse in building, verifying, and validating the product because this methodology has limitations for adjusting to unanticipated changes. The time lost in device development can cause significant delays in final production, increase costs, and may even result in the abandonment of the device development. Software developers have successfully implemented an Agile methodology that overcomes these limitations in developing medical software. However, Agile methodology is not routinely used to develop medical devices with implantable hardware because of the increased regulatory burden of the need to conduct animal and human studies. Here, we provide the pros and cons of the Waterfall methodology and make a case for adopting the Agile methodology in developing medical devices with physical components. We utilize a peripheral nerve interface as an example device to illustrate the use of the Agile approach to develop neurotechnologies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Thota and Jung.)

Purpose: Chorioretinal atrophy growth after voretigene neparvovec has been reported recently with its positive correlation with successful treatment. This finding raised the question on long-term effects and the etiology of the chorioretinal atrophy., Methods: Using local retinal functional diagnostics, we tested whether the atrophy growth is connected to the initial local functional improvement after the therapy., Results: The results describe factors predicting the development of atrophy. First, the atrophy emerges after approximately 3 months in an area with local functional rescue before. The areas of the greatest gain in the number of functionally rescued rods are prone to be the initial spots of atrophy growth in almost one-half of the cases and the retinotopy corresponds with the area of a high number of post-treatment functioning rods. Second, the dark-adapted perimetry shows that the atrophy growth is in the area with functioning rescued rods. However, the rods with the greatest sensitivity gain are not the parts of the growing atrophy in the first 2 years after intervention. This preservation of rods with the greatest sensitivity seems to explain the excellent profile of rods rescue over the long term measured by full-field stimulus threshold and reported earlier., Conclusions: A disbalance between the increase of functional rods and their threshold shortly after treatment could be an indicator for a metabolic origin of chorioretinal atrophy after voretigene neparvovec., Translational Relevance: A basic understanding of the photoreceptor rescue aspects after gene therapy can demonstrate a metabolic causal influence of the efficacy on the development of side effects, such as chorioretinal atrophy.

Background: Voretigene neparvovec (Luxturna®) is the first approved gene therapy for RPE65-linked Leber congenital amaurosis (LCA). Though individual effects are highly variable, most recipients report improved vision in everyday life. To describe such effects, visual navigation tests are now frequently used in clinical trials. However, it is still unclear how their results should be interpreted compared to conventional parameters of visual function., Methods: Seven LCA patients underwent a multi-luminance visual navigation test (Ora-VNCTM) before and 3 months after receiving Luxturna gene therapy. Their performance was rated based on the luminance level at which they passed the course. Differences between the first and second test were correlated to changes in visual acuity, full-field stimulus thresholds, chromatic pupil campimetry, and dark-adapted perimetry., Results: A few patients displayed notable improvements in conventional measures of visual function whereas patients with advanced retinal degeneration showed no relevant changes. Independent of these results, almost all participants improved in the visual navigation task by one or more levels. The improvement in the mobility test was best correlated to the change in full-field stimulus thresholds. Other measures of visual functions showed no clear correlation with visual navigation., Discussion: In patients who passed the test's more difficult levels, improved visual navigation can be attributed to the reactivation of rods. However, the performance of patients with low vision seemed to depend much more on confounding factors in the easier levels. In sum, such tests might only be meaningful for patients with better preserved visual functions., (© 2023. The Author(s).)

Purpose: Dental implants are an established treatment option for varying edentulous conditions that has grown in popularity since the 1990s. This increased clinical application has shown a parallel increase in implant-related research. The objective of this paper was to perform a comprehensive bibliometric analysis of five dental implantology journals from 1991 to 2023. Materials and Methods: A search was done in the Web of Science database between 1991 and 2023 in five journals with a focus on dental implantology: Clinical Oral Implant Research, Clinical Implant Dentistry and Related Research, Implant Dentistry, The International Journal of Oral & Maxillofacial Implants, and International Journal of Oral Implantology. Results marked as a correction, retraction notice, retracted article, meeting abstract, or withdrawn publication were removed from the analysis. The time period analyzed was divided into four time periods, organized by decade: 1991 to 2000, 2001 to 2010, 2011 to 2020, and 2021 to 2023. Additionally, the top 100 cited papers were also exported separately. Authors and countries with most publications were tabulated from the Web of Science database. VOSviewer software was used to create network maps of keywords and title word occurrences for each of the time periods. HistCite software was used to analyze the number of publications and citation counts. Results: Network maps of keywords and title word occurrences suggested an early focus on osseointegration and titanium implants between 1991 and 2000. Publications between 2001 and 2010 saw a focus on in vivo studies, implant surface, and peri-implantitis. Publications from 2011 and later saw a focus on bone regeneration, complications, and zygomatic implants. The USA ranked highest in total number of publications in all analyzed time periods. Conclusions: Within the limitations of the present study, a comprehensive bibliometric analysis from 1990 to 2023 was reported. Trends in keywords and titles of implant publications were identified in these journals, which mirrored the trends seen in clinical practice. [ABSTRACT FROM AUTHOR]

Resting-state functional magnetic resonance imaging (rs-fMRI) and brain functional connectome (we use 'brain connectome' hereafter for simplicity) have advanced our understanding of the ageing brain and age-related changes in cognitive function. Previous studies have investigated the association among brain connectome and age, global cognition, and memory function separately. However, very few have predicted age, overall cognitive functioning and memory performance in a single study to better understand their complex relationship. In this cross-sectional study, we applied an exploratory, data-driven method to investigate the brain connectome markers that could predict ageing, overall cognitive functioning assessed as intelligence quotient (IQ, measured by Wechsler Memory Scale) and memory performance assessed as memory quotient (MQ, measured by Wechsler Memory Scale) in a carefully designed, multicentre, normal ageing cohort (n = 313). Our results showed that brain connectome could predict ageing and IQ, but the association with MQ was weak. We found that the connectivity with orbital frontal cortex was associated with both ageing and IQ. Mediation analysis further showed that the brain connectome mediated the relationship between age and overall cognitive functioning, suggesting a protective brain connectomic mechanism for maintaining normal cognitive functions during healthy ageing. This work may shed light on the potential neural correlates of healthy ageing, overall cognitive functioning and memory performance., (© 2024 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Oligodendrocytes (OLs) of the central nervous system require iron for proteolipid biosynthesis during the myelination process. Although most heme is found complexed to hemoglobin in red blood cells, surprisingly, we found that Slc48a1, encoding the heme transporter Hrg1, is expressed at higher levels in OLs than any other cell type in rodent and humans. We confirmed in situ that Hrg1 is expressed in OLs but not their precursors (OPCs) and found that Hrg1 proteins in CNS white matter co-localized within myelin sheaths. In older Hrg1 null mutant mice we observed reduced expression of myelin associated glycoprotein (Mag) and ultrastructural myelin defects reminiscent of Mag-null animals, suggesting myelin adhesion deficiency. Further, we confirmed reduced myelin iron levels in Hrg1 null animals in vivo, and show that OLs in vitro can directly import both the fluorescent heme analogue ZnMP and heme itself, which rescued iron deficiency induced inhibition of OL differentiation in a heme-oxidase-dependent manner. Together these findings indicate OL Hrg1 encodes a functional heme transporter required for myelin integrity., (© 2024 The Author(s). GLIA published by Wiley Periodicals LLC.)

The neuroimaging basis of intelligence remains elusive; however, there is a growing body of research employing connectome-based predictive modeling to estimate individual intelligence scores, aiming to identify the optimal set of neuroimaging features for accurately predicting an individual's cognitive abilities. Compared to adults, the disparities in cognitive performance among children and adolescents are more likely to captivate individuals' interest and attention. Limited research has been dedicated to exploring neuroimaging markers of intelligence specifically in the pediatric population. In this study, we utilized resting-state functional magnetic resonance imaging (fMRI) and intelligence quotient (IQ) scores of 170 healthy children and adolescents obtained from a public database to identify brain functional connectivity markers associated with individual intellectual behavior. Initially, we extracted and summarized relevant resting-state features from whole-brain or functional network connectivity that were most pertinent to IQ scores. Subsequently, these features were employed to establish prediction models for both performance and verbal IQ scores. Within a 10-fold cross-validation framework, our findings revealed that prediction models based on whole-brain functional connectivity effectively predicted performance IQ scores( R = 0.35 , P = 2.2 × 10 - 4 ) but not verbal IQ scores( R = 0.12 , P = 0.20 ). Results of prediction models based on brain functional network connectivity further demonstrated the exceptional predictive ability of the default mode network (DMN) and fronto-parietal task control network (FTPN) for performance IQ scores ( R = 0.71 , P = 2.2 × 10 - 18 ). The above findings have also been validated using an independent dataset. Our findings suggest that the performance IQ of children and adolescents primarily relies on the connectivity of brain regions associated with DMN and FTPN. Moreover, variations in intellectual performance during childhood and adolescences are closely linked to alterations in brain functional network connectivity., (© 2024 International Society for Developmental Neuroscience.)

Purpose of Review: This review delves into recent advancements in understanding generalized and organ-specific lymphatic development. It emphasizes the distinct characteristics and critical anomalies that can impair lymphatic function. By exploring developmental mechanisms, the review seeks to illuminate the profound impact of lymphatic malformations on overall health and disease progression., Recent Findings: The introduction of genome sequencing, single-cell transcriptomic analysis, and advanced imaging technologies has significantly enhanced our ability to identify and characterize developmental defects within the lymphatic system. As a result, a wide range of lymphatic anomalies have been uncovered, spanning from congenital abnormalities present at birth to conditions that can become life-threatening in adulthood. Additionally, recent research highlights the heterogeneity of lymphatics, revealing organ-specific developmental pathways, unique molecular markers, and specialized physiological functions specific to each organ. A deeper understanding of the unique characteristics of lymphatic cell populations in an organ-specific context is essential for guiding future research into lymphatic disease processes. An integrated approach to translational research could revolutionize personalized medicine, where treatments are precisely tailored to individual lymphatic profiles, enhancing effectiveness and minimizing side effects., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To compare early implant placement (EP) to alveolar ridge preservation and delayed implant placement (ARP/DP) in terms of contour changes, along with clinician- and patient-reported outcome measures (PROMs) until the delivery of the implant-supported restoration., Materials and Methods: Patients with a failing single tooth in the maxilla or mandible were recruited in two centres. After tooth extraction, patients were randomly assigned (1:1) to either EP or ARP/DP. At abutment connection and crown delivery, the buccal contour changes at 3 mm below the mucosal margin (primary outcome) along with clinician- (ease of treatment) and patient-reported outcomes were assessed using numeric rating scales and OHIP-14., Results: A total of 46 patients were analysed. The mean buccal contour at abutment connection decreased by -1.2 ± 0.6 mm in group EP and -1.6 ± 0.8 mm in group ARP/DP (estimated mean difference; 0.45 [95%CI, -0.02; 0.94]; p = .061) with no significant differences between the groups. ARP/DP was consistently easier than EP across all stages of the surgery (estimated mean difference; 2.0 [95%CI, 1.3; 2.7] p < .001): during flap elevation (EP: 4.8 vs. ARP/DP: 1.6), implant placement (EP: 5.7 vs. ARP/DP: 2.2) and wound closure (EP: 3.4 vs. ARP/DP: 1.6). Both interventions improved quality of life but patients who underwent ARP/DP were significantly more satisfied at the time of crown delivery (ARP/DP: 9.6 vs. EP: 9.1, p = .02)., Conclusions: EP and ARP/DP show no significant differences in buccal contour changes, aesthetics and patient-reported outcomes. However, ARP/DP is an easier procedure at all stages of the surgery compared to EP and could therefore be the preferred therapy for less experienced clinicians., (© 2024 The Author(s). Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

Objectives: Examine the histomorphometric bone composition, following alveolar ridge preservation techniques and unassisted socket healing., Materials and Methods: Forty-two patients (42) requiring a single rooted tooth extraction were randomly allocated into three groups (n = 14 per group): Group 1: Guided Bone Regeneration (GBR) using deproteinised bovine bone mineral (DBBM) and a porcine collagen membrane; Group 2: Socket Seal (SS) technique using DBBM and a porcine collagen matrix; Group 3: Unassisted socket healing (Control). Trephined bone biopsies were harvested following a 4-month healing period. Forty-two samples underwent Back-Scattered Electrons -Scanning Electron Microscopy (BSE-SEM) imaging, with 15 samples examined using Xray Micro-Tomography (XMT) (n = 6 for each GBR/SS and n = 3 Control). Images were analysed to determine the percentage (%) of connective tissue, new bone formation, residual DBBM particles and direct bone to DBBM particle contact (osseointegration)., Results: BSE-SEM analysis demonstrated that new bone formation was higher in the Control (45.89% ± 11.48) compared to both GBR (22.12% ± 12.7/p < .004) and SS (27.62% ± 17.76/p < .005) groups. The connective tissue percentage in GBR (49.72% ± 9), SS (47.81% ± 12.57) and Control (47.81% ± 12.57) groups was similar. GBR (28.17% ± 16.64) and SS (24.37% ± 18.61) groups had similar levels of residual DBBM particles. XMT volumetric analysis indicated a lower level of bone and DBBM particles in all test groups, when matched to the BSE-SEM area measurements. Osseointegration levels (DBBM graft and bone) were recorded at 35.66% (± 9.8) for GBR and 31.18% (± 19.38) for SS., Conclusion: GBR and SS ARP techniques presented with less bone formation when compared to unassisted healing. GBR had more direct contact/osseointegration between the DBBM particles and newly formed bone., (© 2024 The Author(s). Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

Objective: To assess the clinical, radiographic and patient-reported outcomes (PROMs) of posterior zirconia and titanium implants at 1 year of implant loading., Materials and Methods: Forty-two patients with two adjacent missing teeth were enrolled in a randomized controlled trial with a within-subject controlled design. Each patient received one zirconia (Zr) and one titanium (Ti) implant, with the mesial and distal positions randomized. The implant restoration consisted of multiple layered zirconia, with the buccal aspect veneered. In group Zr, the restoration was intraorally cemented onto the one-piece Zr implant, whereas in group Ti, the restoration was extraorally cemented onto the titanium base abutment and intraorally screw-retained onto the Ti implant. Examinations were performed following restoration delivery at baseline (BL) and at 1 year. Measurements included clinical parameters, radiographic outcomes (MBL) and PROMs., Results: Bleeding on probing showed an increase from BL to 1 year (34 ± 30% for Zr; 25 ± 21% for Ti). MBL remained stable with minimal changes from BL to 1 year, measuring 0.1 ± 0.4 mm (mean ± SD) for Zr and -0.1 ± 0.7 mm for Ti. Veneering fractures were the most frequent technical complication and amounted to 17.5% in group Zr and 5% in group Ti (p = .100). Patients preferred Zr implants for their soft tissue color, with a significant difference in perception between patients and clinicians (p < .017)., Conclusion: The study showed that both Zr and Ti implants had similar clinical outcomes, despite a high prevalence of mucositis and a few technical complications. Both implant types demonstrated stable marginal bone levels and similar patient-reported outcome measures., (© 2024 The Author(s). Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

Objective: To investigate the early impact of plaque accumulation in a buccal dehiscence defect on peri-implant marginal bone resorption., Materials and Methods: In six male Mongrel dogs, four dental implants were placed in the posterior maxilla on both sides (two implants per side). Based on the group allocation, each implant was randomly assigned to one of the following four groups to decide whether buccal dehiscence defect was prepared and whether silk ligation was applied at 8 weeks post-implant placement for peri-implantitis induction: UC (no defect without ligation); UD (defect without ligation); LC (no defect with ligation); and LD (defect with ligation) groups. Eight weeks after disease induction, the outcomes from radiographic and histologic analyses were statistically analyzed (p < .05)., Results: Based on radiographs, the exposed area of implant threads was smallest in group UC (p < .0083). Based on histology, both the distances from the implant platform to the first bone-to-implant contact point and to the bone crest were significantly longer in the LD group (p < .0083). In the UD group, some spontaneous bone fill occurred from the base of the defect at 8 weeks after implant placement. The apical extension of inflammatory cell infiltrate was significantly more prominent in the LD and LC groups compared to the UC group (p < .0083)., Conclusion: Plaque accumulated on the exposed implant surface had a negative impact on maintaining the peri-implant marginal bone level, especially when there was a dehiscence defect around the implant., (© 2024 The Author(s). Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

Objectives: The objective of this long-term retrospective study was to evaluate the fracture rate and the risk factors associated with the fracture of 3.3 mm narrow diameter implants (NDIs)., Materials and Methods: A total of 524 records of patients rehabilitated with 3.3 mm NDIs between 1997 and 2015 were assessed. Data on patients, implants, and prostheses were collected, and descriptive analysis of the variables was performed. NDIs were separated into 2 groups: "fractured" and "non-fractured", and a multilevel logistic regression model was applied to identify the risk factors associated with NDI fracture., Results: Eighty-four patients were removed from the analysis for interrupting follow-up or presenting failures other than fractures. Of the 440 patients included (64.66 ± 13.4 years), 272 were females (61.8%), and 168 males (38.2%), and mean follow-up time was 129 ± 47.1 months. Of the 1428 NDIs, 15 (1.05%) in 9 patients (2.04%) fractured during the studied period. Ten fractures (66.66%) happened in 6 patients (66.66%) showing signs of parafunction. NDI with modified sandblasted, large grit, acid-etched surface was the only implant variable to show a protective statistical significance (p = .0439)., Conclusions: NDI fracture was a rare event in the studied sample. NDIs manufactured with modified sandblasted, large grit, acid-etched surface may provide extra protection against NDI fracture. Patient-specific factors and implant characteristics should be carefully considered to limit the risk of fracture of 3.3 mm NDIs., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The current study presents a quick and simple method for synthesizing Ir nanoclusters decorated on an N-doped carbon (NC) matrix via pulsed laser ablation in liquid, followed by pyrolysis. The resulting Ir-NC material acts as a dual-functional electrocatalyst, efficiently facilitating hydrogen generation through the hydrazine oxidation reaction (HzOR) and the hydrogen evolution reaction (HER) in alkaline seawater. The optimized Ir-NC-2 catalyst exhibits a low operating potential of 23 mV versus the reversible hydrogen electrode for HzOR and a remarkably low overpotential of 24 mV for HER, achieving a current density of 10 mA cm -2 in alkaline seawater, surpassing the performance of the Pt/C catalyst. Notably, the Ir-NC-2 catalyst also demonstrates superior dual-functionality in overall hydrazine-assisted seawater splitting, requiring only 0.1 V at 10 mA cm -2 while maintaining stability. Moreover, density functional theory calculations reveal that the strong electronic interaction between the Ir nanoclusters and the NC matrix enhances mass transfer and electron conductivity, significantly boosting HER activity and accelerating the kinetics of hydrazine dehydrogenation. Consequently, the Ir-NC-2 catalyst performs efficiently in a Zn-hydrazine battery, achieving high energy efficiency of 95.5% and demonstrating excellent stability for 120 h (360 cycles), indicating its potential for practical applications., (© 2024 Wiley‐VCH GmbH.)

Herein, a straightforward approach using pulsed laser technology to synthesize selective hexagonal-close-packed (hcp) Ru nanoparticles attached to Cu nanospheres (Ru/Cu) as bifunctional electrocatalyst for catalyzing the hydrogen evolution reaction (HER) and formaldehyde oxidation reaction (FOR) are reported. Initially, Ru-doped CuO flakes are synthesized using a coprecipitation method followed by transformation into Ru/Cu composites through a strategy involving pulsed laser irradiation in liquid. Specifically, the optimized Ru/Cu-4 composite not only demonstrates a low overpotential of 182 mV at 10 mA·cm -2 for the HER but also an ultralow working potential of 0.078 V (versus reversible hydrogen electrode) for the FOR at the same current density. Remarkably, the FOR∥HER-coupled electrolyzer employing the Ru/Cu-4∥Ru/Cu-4 system achieves H 2 production at both electrodes with a cell voltage of 0.42 V at 10 mA·cm -2 while co-synthesizing formic acid. Furthermore, density functional theory analyses elucidate that the superior activity of the Ru/Cu composite originates from optimized adsorption energies of reactive species on the catalyst surfaces during the HER and FOR, facilitated by the synergistic coupling between Ru and Cu. This study presents an alternative strategy for synthesizing highly effective electrocatalytic materials for use in energy-efficient H 2 production with the cosynthesis of value-added chemicals suitable for practical applications., (© 2024 Wiley‐VCH GmbH.)

Objectives: This controlled preclinical study analyzed the effect of implant surface characteristics on osseointegration and crestal bone formation in a grafted dehiscence defect minipig model., Material and Methods: A standardized 3 mm × 3 mm acute-type buccal dehiscence minipig model grafted with deproteinized bovine bone mineral and covered with a porcine collagen membrane after 2 and 8 weeks of healing was utilized. Crestal bone formation was analyzed histologically and histomorphometrically to compare three implant groups: (1) a novel, commercially available, gradient anodized (NGA) implant, to two custom-made geometric replicas of implant "1," (2) a superhydrophilic micro-rough large-grit sandblasted and acid-etched surface, and (3) a relatively hydrophobic micro-rough large-grit sandblasted and acid-etched surface., Results: At 2 and 8 weeks, there was no difference between the amount and height of newly formed bone (NBH, new bone height; BATA, bone area to total area) for any of the groups (p > 0.05). First bone-to-implant contact (fBIC) and vertical bone creep (VBC) at 2 and 8 weeks were significantly increased for Groups 2 and 3 compared to Group 1 (p < 0.05). At 8 weeks, osseointegration in the dehiscence (dehiscence bone-implant-contact; dBIC) was significantly higher for Groups 2 and 3 compared to Group 1 (p < 0.05)., Conclusions: The amount of newly formed bone (BATA) and NBH was not influenced by surface type. However, moderately rough surfaces demonstrated significantly superior levels of osseointegration (dBIC) and coronal bone apposition (fBIC) in the dehiscence defect compared to the NGA surface at 2 and 8 weeks., Trial Registration: For this type of study, clinical trial registration is not required. This study was conducted at the Biomedical Department of Lund University (Lund, Sweden) and approved by the local Ethics Committee of the University (M-192-14)., (© 2024 The Author(s). Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

Objective: To histomorphometrically determine the effects of hard- and/or soft-tissue augmentation by applying the early implant placement protocol., Materials and Methods: The distal roots of the maxillary second and third premolars were extracted in 10 mongrel dogs. After 1 month, early implant placement was performed in the distal roots, resulting in buccal dehiscence defects. Four treatments were then randomly applied: (1) guided bone regeneration (GBR), (2) connective tissue grafting (CTG), (3) simultaneous GBR and CTG (GBR + CTG) and (4) no further treatment (control). Healing abutments were connected to all implants to allow non-submerged healing. At 4 and 16 weeks, tissue sections were harvested and histomorphometric analyses were performed., Results: Group GBR presented the largest total tissue thickness at 4 weeks, but underwent a greater remodelling compared with the other groups between 4 and 16 weeks. At 16 weeks, the overall tissue thickness was largest in group GBR + CTG. This group was also the most favourable in terms of the level of the margo mucosae and the presence of mineralized tissue at the coronal level. Group CTG demonstrated a stable tissue thickness over time, with a larger thickness at 16 weeks compared with group GBR., Conclusion: Simultaneous CTG and GBR resulted in the most-favourable tissue thickness when applying the early implant placement protocol., (© 2024 The Author(s). Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

The assessment of creativity as an individual difference has historically focused on divergent thinking, which is increasingly viewed as involving the associative processes that are also understood to be a key component of creative potential. Research on associative processes has proliferated in many sub-fields, often using Compound Remote Associates (CRA) tasks with an open response format and relatively small participant samples. In the present work, we introduce a new format that is more amenable to large-scale data collection in survey designs, and present evidence for the reliability and validity of CRA measures in general using multiple large samples. Study 1 uses a large, representative dataset (N = 1,323,480) to demonstrate strong unidimensionality and internal consistency (α = .97; ωt = .87), as well as links to individual differences in temperament, cognitive ability, occupation, and job characteristics. Study 2 uses an undergraduate sample (N = 685) to validate the use of a multiple-choice format relative to the traditional approach. Study 3 uses a crowdsourced sample (N = 357) to demonstrate high test-retest reliability of the items (r =.74). Finally, Study 4 uses a sample that overlaps with Study 1 (N = 1,502,922) to provide item response theory (IRT) parameters for a large set of high-quality CRA items that use a multiple-choice response mode, thus facilitating their use in future research on creativity, insight, and related topics., (© 2024. The Psychonomic Society, Inc.)

Objectives: The objective of this study is to investigate the outcomes of clinically relevant laboratory studies regarding the cementation of implant-supported restorations over ti-bases., Materials and Methods: The present study has been conducted according to PRISMA statement. An electronic search was performed, including publications up to March 2024, to identify studies investigating the parameters affecting the cementation between ti-bases and CAD/CAM prostheses. An assessment of the internal validity was performed, using a custom-made risk of bias tool (QUIN)., Results: From the included studies, 40.1% were reported on luting systems, 25% on ti-base surface treatment, 25% on restoration surface, 21.8% on restoration material, and 18.7% on ti-base height. The majority of the included studies were associated with a medium risk of bias. In the absence of micro-retentive features, air-abrasion of ti-bases with a minimum height of 3.5 mm can be beneficial for restoration's retention. The bonding performance can vary not only between different bonding systems but also for different applications within the same system, based on a restoration's material and surface treatment as well as on ti-base height and surface treatment., Conclusions: The height of the ti-base seems to be the prevailing factor as it constitutes the prerequisite for other modifications of the bonding surfaces to have an advantageous effect. Since the parameters that can affect bonding performance between ti-base and restoration can interact with each other, it is important for the clinician to focus on verified bonding protocols., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: This study aimed to assess hard and soft tissue contour changes following micro crestal flap-alveolar ridge preservation (MCF-ARP) and natural healing (NH) in periodontally compromised molar extraction sites and to analyse the feasibility and need for bone augmentation during implant therapy., Materials and Methods: Fifty-six patients with 70 sites were randomized into two groups at the site level (35 sites from 31 patients in the test group and 35 sites from 29 patients in the control group). Among whom, four patients contributed one tooth to the control group and one tooth to the test group. Hard tissue indicators were measured using cone beam computed tomography performed before tooth extraction and 6 months after surgery. Soft tissue contour changes were assessed using intraoral scanning performed before and immediately after surgery and also 2 weeks and 1, 3 and 6 months after surgery., Results: Six months after surgery, the MCF-ARP group showed less resorption in buccal bone height (p = .032) and greater augmentation in central bone height (p = .001) and ridge width (p = .009). The mean, vertical and horizontal collapse of buccal soft tissue contour in the MCF-ARP group were 0.95 mm (p = .010), 0.61 mm (p = .019) and 0.56 mm (p = .013) less than that in the NH group, respectively. There were significantly (p = .007) fewer sites in the MCF-ARP group than in the NH group (0% vs. 26.7%) for staged bone augmentation and more sites that could be treated with simple implant procedure in the MCF-ARP group than in the NH group (71.9% vs. 56.6%)., Conclusions: Compared with NH, MCF-ARP reduced bone resorption in periodontally compromised molar extraction sites and maintained the buccal soft tissue contour. MCF-ARP reduces the need for complex bone augmentation procedures in implant therapy., Trial Registration: Chinese Clinical Trial Register (ChiCTR) ChiCTR2200056335. Registered on 4 February 2022, Version 1.0., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To determine whether combining cross-linked (CL) collagen-integrated xenogeneic bone blocks stabilized with the fixation of resorbable collagen membranes (CM) can enhance guided bone regeneration (GBR) in the overaugmented calvarial defect model., Materials and Methods: Four circular defects with a diameter of 8 mm were prepared in the calvarium of 13 rabbits. Defects were randomly assigned to receive one of the following treatments: (i) non-cross-linked (NCL) porcine-derived collagen-embedded bone block covered by a CM without fixation (NCL + unfix group); (ii) NCL bone block covered by CM with fixation using bone-tack (NCL + fix group); (iii) cross-linked (CL) porcine-derived collagen-embedded bone block covered by CM without fixation (CL + unfix group); and (iv) CL bone block covered by CM with fixation using bone-tack fixation (CL + fix group). The efficacy of GBR was assessed through histological and molecular analyses after 2 and 8 weeks., Results: At 2 weeks, there were no significant differences in histologically measured areas of newly formed bone among the groups. At 8 weeks, however, the CL + fix group exhibited a larger area of new bone (5.08 ± 1.09 mm 2 , mean ± standard deviation) compared to the NCL + unfix (1.62 ± 0.42 mm 2 ; p < .0083), NCL + fix (3.97 ± 1.39 mm 2 ) and CL + unfix (2.55 ± 1.04 mm 2 ) groups. Additionally, the expression levels of tumour necrosis factor-alpha, fibroblast growth factor-2, vascular endothelial growth factor, osteocalcin and calcitonin receptor were significantly higher in the CL + fix group compared to the other three groups (p < .0083)., Conclusion: Cross-linked bone blocks stabilized with collagen membrane fixation can significantly enhance GBR., (© 2024 The Author(s). Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

Objectives: To evaluate the effect of different cement types on the incidence of failure and loss of retention of zirconia and metal-ceramic single crowns (SCs) cemented on implant abutments., Methods: We placed 567 implant-supported SCs in 358 patients and retrospectively evaluated long-term retention for up to 12.8 years. The frameworks were made from metal alloy (n = 307) or zirconia (n = 260). SCs were cemented with permanent (glass-ionomer cement; n = 376) or semipermanent cement (zinc oxide non-eugenol cement; n = 191) on standardized (n = 446) or customized (n = 121) abutments. Kaplan-Meier curves were used to calculate the incidence of decementation. Differences between survival curves were assessed with log-rank tests. Cox-regression analysis was performed to evaluate multiple risk factors., Results: Of the 567 SCs, 22 failed because of technical complications and four because of implant loss. Loss of retention was observed in 50 SCs. Analysis revealed a 7% probability of loss of retention for zirconia and 16% for metal-ceramic SCs after 10 years (p = .011). After 5 years, loss of retention was higher for standardized abutments than for customized abutments (p = .014). The probability of loss of retention was higher with semipermanent than with permanent cement (p = .001). Cox-regression analysis revealed semipermanent cement as the only significant risk factor for SC failure (p = .026)., Conclusions: In contrast to semipermanent cement, permanent cement provides acceptable long-term retention of cemented implant-supported SCs. These possible positive effects of customized abutments have to be controlled with larger sample sizes., (© 2024 The Author(s). Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

Objectives: The aim of this study was to evaluate esthetic parameters in the anterior maxillary region by comparing single-piece zirconia versus titanium narrow-diameter implants. Additionally, clinical, radiological and patient-reported outcome measures (PROMs) were analyzed., Materials and Methods: Thirty implants (tissue level implant) were placed in 30 patients in the maxillary esthetic sector. Depending on randomization, a zirconia (test) or titanium implant (control) was placed. Esthetic, clinical, and radiological parameters, including the implant crown esthetic index (ICAI), pink esthetic score (PES), probing pocket depth, bleeding on probing, plaque index, and marginal bone levels, were evaluated at 12, 36 and 60 months after loading., Results: Sixty months after crown placement, no significant differences were found between groups. The ICAI values were 5.25 ± 4.21 and 4.50 ± 2.98 for the test and control groups, respectively. The corresponding PES values were 7.44 ± 1.93 and 7.43 ± 1.74 for the test and control groups, respectively. There were no significant intergroup differences for the rest of the parameters evaluated., Conclusion: It can be suggested that monotype zirconia implants may serve as a potential alternative to titanium implants in selected clinical scenarios. While the results demonstrated comparable esthetic, clinical, and radiological aspects for zirconia implants as compared to titanium implants after a 5-year follow-up period, further research with larger sample sizes and longer-term follow-up is recommended., (© 2024 The Author(s). Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

The molecules that constitute myelin are critical for the integrity of axon/myelin-units and thus speed and precision of impulse propagation. In the CNS, the protein composition of oligodendrocyte-derived myelin has evolutionarily diverged and differs from that in the PNS. Here, we hypothesized that the CNS myelin proteome also displays variations within the same species. We thus used quantitative mass spectrometry to compare myelin purified from mouse brains at three developmental timepoints, from brains of male and female mice, and from four CNS regions. We find that most structural myelin proteins are of approximately similar abundance across all tested conditions. However, the abundance of multiple other proteins differs markedly over time, implying that the myelin proteome matures between P18 and P75 and then remains relatively constant until at least 6 months of age. Myelin maturation involves a decrease of cytoskeleton-associated proteins involved in sheath growth and wrapping, along with an increase of all subunits of the septin filament that stabilizes mature myelin, and of multiple other proteins which potentially exert protective functions. Among the latter, quinoid dihydropteridine reductase (QDPR) emerges as a highly specific marker for mature oligodendrocytes and myelin. Conversely, female and male mice display essentially similar myelin proteomes. Across the four CNS regions analyzed, we note that spinal cord myelin exhibits a comparatively high abundance of HCN2-channels, required for particularly long sheaths. These findings show that CNS myelination involves developmental maturation of myelin protein composition, and regional differences, but absence of evidence for sexual dimorphism., (© 2024 The Author(s). GLIA published by Wiley Periodicals LLC.)

Sortase-mediated ligation (SML) is a widely used method for peptide and protein ligation due to ease of substrate preparation and fast enzymatic kinetics. But there are drawbacks that limit broader applications. Sorting motif in substrates may not be exposed to sortase efficiently due to folding or aggregation. In addition, the ligation is reversible under transpeptidation equilibrium that restricts ligation yield. Here we report a simple but robust method to overcome such limitations. By employment of sarkosyl, the detergent alters substrate conformation to raise sorting motif accessibility for sortase catalysis. Moreover, transpeptidation becomes irreversible presumably by formation of micelle to shield ligation products from sortase. In consequence, excellent yields were achieved from sortase variants with different substrate specificity. Notably, this method is compatible with peptides or proteins capable of forming liquid-liquid phase separation (LLPS), presenting a powerful approach for the conjugation of aggregation-prone substrates. Therefore, we believe the sarkosyl-enhanced SML could be widely applied in peptide and protein chemistry and the unique irreversible transpeptidation mechanism offers an insight to detergent-driven equilibrium., (© 2024 Wiley-VCH GmbH.)

Objectives: The aim of this systematic review and meta-analyses was to evaluate the outcomes of alveolar ridge preservation (ARP) following extraction of non-molar teeth in comparison to early implant placement (EIP) in terms of clinical and radiographic changes, need for additional augmentation at the time of implant placement, patient-reported outcomes, and implant failure rate., Methods: Electronic databases were searched to identify randomized and non-randomized studies that compared ARP to EIP. The risk of bias was assessed using the Cochrane Collaboration's Risk of Bias tool. Data were analyzed using a statistical software program., Results: A total of 106 studies were identified, of which five studies with 198 non-molar extraction sockets in 198 participants were included. Overall meta-analysis showed significant differences in changes in midfacial mucosal margin (mean difference (MD) -0.09; 95% confidence interval (CI) -0.17 to -0.01; p = .03) and ridge width (MD -1.70; 95% CI -3.19 to -0.20; p = .03) in favor of ARP. The use of ARP was also associated with less need for additional augmentation at implant placement, but the difference was not statistically significant., Conclusions: Within the limitation of this review, ARP following extraction of non-molar teeth has short-term positive effects on soft tissue contour, mucosal margin and thickness, and alveolar ridge width and height. It can also simplify future implant treatment by minimizing the need for additional augmentation., (© 2024 The Author(s). Clinical Oral Implants Research published by John Wiley & Sons Ltd.)