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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.)

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.)

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).)

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.)

Objective &#xD;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. &#xD; Approach &#xD;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. &#xD; Main Results &#xD;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.&#xD; Significance &#xD;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: 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.)

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.)

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).)

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.)

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.)

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 $$ R=0.35,P=2.2\times {10}^{-4} $$ ) but not verbal IQ scores( R = 0.12 , P = 0.20 $$ R=0.12,P=0.20 $$ ). 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 $$ R=0.71,P=2.2\times {10}^{-18} $$ ). 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.)

Have humans always sold and purchased things? This seemingly trivial question exposes one of the most conspicuous blind spots in our understanding of cultural evolution: the emergence of what we perceive today as 'modern' economic behaviour. Here we test the hypothesis that consumption patterns in prehistoric Europe (around 2300-800 BCE) can be explained by standard economic theory, predicting that everyday expenses are log-normally distributed and correlated to supply, demand and income. On the basis of a large database of metal objects spanning northern and southern Europe (n = 23,711), we identify metal fragments as money, address them as proxies of consumption and observe that, starting around 1500 BCE, their mass values become log-normally distributed. We simulate two alternative scenarios and show that: (1) random behaviour cannot produce the distributions observed in the archaeological data and (2) modern economic behaviour provides the best-fitting model for prehistoric consumption., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

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.)

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 marginal bone levels, biological, and technical outcomes of screw-retained versus cemented all-ceramic implant-supported zirconia-based single crowns after an observation period of 7.5 years., Methods: Forty-four single implants in the esthetic zone in 44 patients (22 females, 22 males) were randomly assigned to two types of restorations: SR (screw-retained); veneered one-piece zirconia abutment and CR (cement-retained); veneered lithium disilicate crown intraorally cemented on a one-piece zirconia abutment. Patients were recalled annually up to 7.5 years and survival rates, biological, and technical parameters assessed., Results: A total of 31 patients attended the 7.5-year follow-up visit (17 SR group, 14 CR group). The survival rate on the restorative level was 77.5% (74.0% CR, 81.0% SR, p = .6399). Median marginal bone loss (MBL) values yielded -0.073 mm (-0.305; 0.238) in the CR and -0.215 mm (-0.500; 0.555) in the SR group (intergroup p = .6194). Mean bleeding on probing (BoP) values were significantly in favor of group SR with 20 ± 17% compared to 40 ± 22% in group CR (p = .011). The overall biological complication rate amounted to 27.5% (42.1% CR, 14.3% SR, p = .0775), whereas the technical complication rate was 32.5% (42.1% CR, 23.8% SR, p = .314). In total, CR restorations showed significantly more complications (84.2% for CR, 38.1% for SR, p = .0041)., Conclusion: One-piece zirconia-based single crowns on two-piece dental implants exhibited a high rate of technical and biological complications at 7.5 years of follow-up. Cemented restorations revealed significant higher rates of bleeding on probing and total complications compared to screw-retained restorations., (© 2024 The Author(s). Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

Objectives: To investigate the effects of alveolar ridge preservation (ARP) on ridge height, sinus pneumatization and the potential need for lateral sinus augmentation following extraction in the posterior maxilla., Materials and Methods: This randomized controlled pilot study included 28 patients requiring extraction in the posterior maxilla with bone height between 6 and 8 mm. The sites were randomly allocated to either unassisted socket healing (Control), ARP with deproteinized bovine bone mineral (DBBM) (Test 1), or collagen-stabilized DBBM (Test 2) groups. Pre- and post-operative CTs at 4 months were taken to determine changes in ridge heights, sinus volume, and the need for sinus floor elevation (SFE) procedures for cases where the residual mid-ridge height was < 5 mm. Site-level analyses for changes in vertical ridge dimensions and sinus volume pre- and post-extraction/ARP were conducted using paired t-tests. Differences in mean changes in vertical ridge dimensions and sinus volume between the groups were determined using one-way ANOVA., Results: Significantly greater mean mid-ridge height reduction occurred in the control group (-2.7 ± 0.9 mm) compared to Test 1 (0.9 ± 3.7 mm) and Test 2 (1.0 ± 2.8 mm) groups (p < .05). No significant changes in mean mid-ridge height were found in either test groups. Volumetric analysis showed a significantly greater increase in sinus volume in the control group (0.7 ± 0.7 cm 3 ) compared to Test 1 (n = 3, -0.7 ± 0.8 cm 3 ) group (p = .03). 89% of patients in the control group would require lateral window SFE  compared to Test 1 (42.8%) and Test 2 (40%) groups., Conclusion: ARP was effective in attenuating height changes in the middle of the ridge and may reduce sinus pneumatization following extraction in the posterior maxilla. This could potentially decrease the need for more invasive sinus augmentation procedures., (© 2024 The Author(s). Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

Objective: This study aimed to assess clinical efficacy of 4-mm-short implants in patients with posterior severe vertical bone atrophy in the medium- and long-term follow-up., Materials and Methods: Patients rehabilitated with 4-mm-short implants in the posterior atrophic jaws, with a minimum follow-up of 3 years post-loading, were included in the study. Data were collected for eligible patients, and marginal bone loss (MBL) for each implant was evaluated. The research outcomes were implant failure, MBL and complications., Results: A total of 212 patients with 496 implants were included, resulting in a mean follow-up of 8.02 ± 2.17 years. The implant survival rate was 95.36% (95% CI: 93.12%-97.04%). More implant failures were observed in the maxilla (p = .02) and fewer failures were observed in patients undergoing more number of hygienic sessions per year (p < .001). The average MBL after 1-year-loading was 0.47 mm, increasing to 0.59 mm after 10 years; after 3 years no statistically significant increase in MBL was observed. Maxillary implants showed greater bone loss than mandibular ones (p < .001). More frequent professional oral hygiene sessions per year resulted being related with reduced MBL (p < .001)., Conclusions: Four-mm-short implants showed high survival rates with an up to 10-year follow-up. Their use can offer a fixed prosthetic solution for patients with posterior vertical bone atrophy, minimizing surgical invasiveness, rehabilitative times and costs., (© 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 compare fully guided flapless implant surgery using a light-cured surgical guide (FG group) with partially guided open flap surgery (PG group) in the posterior maxilla when performing simultaneous sinus floor elevation in terms of the accuracy, time requirements, and patient/clinician-reported outcomes (PROMs and CROMs)., Materials and Methods: In this study, 56 tissue-level implants were placed with crestal sinus floor elevation in 56 patients at single-tooth sites, with 28 implants allocated to the PG group and 28 to the FG group. The deviations of the placed implants from the virtually planned positions were measured at the implant platform and apex and for the angular deviation. The presurgical preparation time and the duration of surgery were measured. PROMs and CROMs were made by administering questionnaires at multiple time points., Results: Horizontal deviations at the platform and apex and the angular deviation were significantly smaller in the FG group than the PG group (p < .05). Presurgical preparation and surgery times were significantly shorter in the FG group (p < .001). Patient satisfaction and willingness to receive repeat treatment were significantly better in the FG group than in the PG group (p < .005 and .025, respectively). Clinicians were more satisfied in the FG group than the PG group (p < .05)., Conclusion: When placing an implant with sinus floor elevation, the flapless approach using a fully guided surgical system can be more accurate, faster, and increase the satisfaction of both the clinician and patient compared to the partially guided surgery., (© 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.)

Assisted reproductive technologies are key to solving the problems of aging and organ defects. Collagen is compatible with living tissues and has many different chemical properties; it has great potential for use in reproductive medicine and the engineering of reproductive tissues. It is a natural substance that has been used a lot in science and medicine. Collagen is a substance that can be obtained from many different animals. It can be made naturally or created using scientific methods. Using pure collagen has some drawbacks regarding its physical and chemical characteristics. Because of this, when collagen is processed in various ways, it can better meet the specific needs as a material for repairing tissues. In simpler terms, collagen can be used to help regenerate bones, cartilage, and skin. It can also be used in cardiovascular repair and other areas. There are different ways to process collagen, such as cross-linking it, making it more structured, adding minerals to it, or using it as a carrier for other substances. All of these methods help advance the field of tissue engineering. This review summarizes and discusses the current progress of collagen-based materials for reproductive medicine., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Restorative material selection has become increasingly challenging due to the speed of new developments in the field of dental material science. The present narrative review gives an overview of the current indications for implant abutments and restoration materials for provisional and definitive implant-supported fixed dental prostheses in partially edentulous patients. For single implant restorations, titanium base abutments for crowns are suggested as an alternative to the conventional stock- and customized abutments made out of metal or zirconia. They combine the mechanical stability of a metallic connection with the esthetic potential of ceramics. For multiple-unit restorations, conical titanium bases especially designed for bridges are recommended, to compensate for deviating implant insertion axes and angulations. Even though titanium base abutments with different geometries and heights are available, certain clinical scenarios still benefit from customized titanium abutments. Indications for the definitive material in fixed implant restorations depend on the region of tooth replacement. In the posterior (not esthetically critical) zone, ceramics such as zirconia (3-5-Ymol%) and lithium-disilicate are recommended to be used in a monolithic fashion. In the anterior sector, ceramic restorations may be buccally micro-veneered for an optimal esthetic appearance. Lithium-disilicate is only recommended for single-crowns, while zirconia (3-5-Ymol%) is also recommended for multiple-unit and cantilever restorations. Attention must be given to the specific mechanical properties of different types of zirconia, as some feature reduced mechanical strengths and are therefore not indicated for all regions and restoration span lengths. Metal-ceramics remain an option, especially for cantilever restorations., (© 2024 The Author(s). Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

Aim: This study investigated the adjunctive effect of polydeoxyribonucleotide (PDRN) on bone formation in alveolar ridge preservation (ARP) sockets., Materials and Methods: Both mandibular second, third and fourth premolars of eight beagle dogs were randomly divided into ARP and ARP/PDRN groups. Following tooth extraction, ARP procedures were conducted using collagenized alloplastic graft material and bilayer collagen membrane soaked with normal saline (ARP group) or PDRN (ARP/PDRN group) for 10 min before application. Both groups were also randomly allocated to 2-, 4- or 12-week healing subgroups. The primary endpoint of this study was to compare histomorphometric differences between ARP and ARP/PDRN. The secondary endpoints of this study were to compare micro-CT analysis and three-dimensional volumetric measurement between the two groups., Results: In the histomorphometric analysis, the ARP/PDRN group exhibited greater new bone formation at coronal, middle and total position compared with the ARP group at 2-week healing. The number of newly formed blood vessels was higher in the ARP/PDRN group than in the ARP group at 2- and 4-week healing. In micro-CT analysis, the mean new bone volume/total bone volume between ARP and ARP/PDRN was statistically significant at 2-week healing. Ridge volume alterations were significantly decreased in the ARP/PDRN group during entire healing time compared with the ARP group, especially on the buccal side., Conclusions: The application of PDRN in ARP might provide additional benefits for early bone regeneration and maintenance of buccal ridge volume., (© 2024 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Objective: This scoping review aimed to (1) critically evaluate the outcomes measures used to assess the accuracy of implant placement with Computer Assisted Implant Surgery (CAIS) and (2) review the evidence supporting the efficient implementation of CAIS in training and education of clinicians., Methods: A scoping literature review was conducted aiming to identify (a) clinical trials assessing accuracy of implant placement with CAIS, and (b) clinical trials or simulation/cadaver studies where CAIS was utilised and assessed for the training/education of clinicians. Studies since 1995 were assessed for suitability and data related to the outcomes measures of accuracy and educational efficacy were extracted and synthesised., Results: Accuracy of CAIS has been mainly assessed through surrogate measures. Individual clinical trials have not shown any difference between static and dynamic CAIS, but recent meta-analyses suggest an advantage of dynamic CAIS in reducing angular deviation. The combination of static and dynamic CAIS might offer higher accuracy than each of the two used alone. Dynamic CAIS is suitable for novice surgeons and might even have added value as an education tool for implant surgery, although mastering the technique requires longer training than static., Conclusion: Meta-analyses of large samples, new and diverse outcomes measures, as well as benchmarking of levels of accuracy with specific clinical outcomes will help to better understand the potential and limitations of CAIS. Dynamic CAIS is suitable for novice operators, but educational interventions distributed over longer periods of time will be required for mastery of the process., (© 2023 The Authors. Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

Purpose: Investigate survival and technical complications of two-unit posterior implant-supported cantilever made of monolithic zirconia on titanium-base abutments (Zr-TiB) vs. porcelain-fused-to-metal on castable gold abutments (PFM-GA) using two different implant connections, internal butt-joint (IBJ) and internal conical (IC)., Materials and Methods: Forty-eight implants (4.3 mm diameter) were divided into four groups (n = 12) to support 2-unit mandibular premolar cantilevers with two different materials (Zr-TiB vs. PFM-GA) and two connection types (IBJ vs. IC). Tested groups were as follows: (1) IBJ/Zr-TiB; (2) IBJ/PFM-GA; (3) IC/Zr-TiB; and (4) IC/PFM-GA. Specimens were thermomechanical aged (1,200,000 cycles, 98 N, 5-55°C) with occlusal axial load on the pontic. Catastrophic and non-catastrophic events were registered, and removal torque values measured before and after aging. Specimens surviving aging were subjected to loading until failure. Survival, total complication rates, torque loss (%), and bending moments were calculated., Results: From 48 specimens, 38 survived aging. Survival rates significantly varied from 16.7% (IC/PFM-GA) to 100% (IBJ/Zr-TiB; IBJ/PFM-GA; IC/Zr-TiB) (p < .01). Internal conical connection revealed significantly higher torque loss (IC/ZrTiB - 67%) compared to internal butt-joint (IBJ/Zr-TiB - 44%; IBJ/PFM-GA - 46%) (p < .01). Bending moments were higher in internal butt-joint connections than in internal conical (p < .05)., Conclusion and Clinical Implications: Two-unit posterior implant-supported cantilever FDPs replacing mandibular premolars composed of monolithic zirconia on titanium-base abutments demonstrated higher mechanical stability compared to porcelain-fused-to-metal on castable gold abutments in this in vitro study. The internal conical connection combined with porcelain-fused-to-metal on gold abutments revealed a high number of failures; therefore, their clinical use may be considered cautiously for this indication., (© 2024 The Authors. Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

Through a multiple-case study of seven German providers, we explore the architecture of commercial offerings of consumer experiences, such as wine-tastings, craft workshops, or wellness activities, which have both digital and physical components. Physical-digital experiences offer participants an opportunity to encounter many different sensations of an experience, as not all (e.g. taste, smell, touch) can be converted to digital form and not all are possible to experience physically (e.g. visual depictions of distant lands). Our empirical study shows that experience providers combine both physical and digital offering architectures by augmenting, substituting, porting, and excluding physical and digital components, a process that changes the value these experiences create for consumers and provides new means by which providers capture value from these offerings. We develop a theoretical model that explains value creation and value capture through the design and provision of physical-digital experiential consumer offerings that leverage physical-digital hybridity at multiple levels to enhance existing or generate new value pathways. [ABSTRACT FROM AUTHOR]

Purpose: To compare the effect of taper, length, angle, and number of vertical axial walls on the retentive strength of a cemented crown on a partially customized hybrid abutment in the esthetic zone. Materials and Methods: A total of 35 metal copings were used and divided into two groups. One group had 30 copings cemented to their corresponding 8-degree tapered abutment with lengths from 3 to 8 mm, increasing in 1-mm increments (5 copings per length). The other group had the remaining 5 copings and consisted of a standardized metal coping that matched a hexagonal abutment with 3-mm vertical axial walls and the sequential removal of 1, 2, and 3 contiguous vertical axial walls. Dislodgment tests were performed for all copings in both groups. Maximum retentive forces were measured in retentive strength (kgF), with a conversion factor of 9.807 N = 1 kgF. Results: At each tapered abutment length, the retentive strength increased proportionally and was significantly different, ranging from 31.67 ± 4.10 kgF to 67.68 ± 11.22 kgF (F [5,24] = 20.46, P < .001). An unmodified hexagonal abutment demonstrated the highest retentive strength (70.15 ± 12.97 kgF). The sequential removal of 1, 2, and 3 contiguous vertical axial walls of the hexagonal abutment resulted in retentive strength values of 59.89 ± 10.06 kgF, 57.01 ± 9.62 kgF, and 55.99 ± 9.35 kgF, respectively, with no significant difference (P > .05) in strength. Conclusions: A partially customized abutment with vertical axial walls on one side and a profile reduction on the opposite side can provide comparable retention to cemented copings at one-third the length and at one-sixth the surface area of an 8-mm abutment with an 8-degree taper. [ABSTRACT FROM AUTHOR]

Purpose: To measure the surface temperature distribution after using a CO2 laser to heat titanium dental implants via different power settings, application intervals, and irradiation times. Materials and Methods: A total of 10 tissue-level titanium implants (Screw-Line Promote Plus, Camlog; 4.3 × 11 mm) were placed (EpoFix, Struers) and irradiated with a CO2 laser (Denta 2, Lutronic) with a wavelength of 10.6 µm at power levels of 4 watts (Group 1), 6 watts (Group 2), 8 watts (Group 3), and 10 watts (Group 4). A continuous beam mode (setting I) and noncontinuous beam modes with 5-second (setting II) and 10-second (setting III) pause intervals were used. For each setting, a total irradiation time of 50 seconds was used and repeated 10 times. The temperature was measured using external thermocouple (Testo) in contact with the implant surface at the implant shoulder, middle, and apex. A linear regression model was used to analyze the data (P = .05). Results: Setting I demonstrated the most rapid increase in implant surface temperature in all three test sites as well as the greatest total temperature at 50 seconds of irradiation time. The greater the pause interval (settings II and III) during the 50 seconds of irradiation, the lower the rate of temperature increase as well as the total temperature in all three test sites and with all power levels. The average temperature difference between the apex and shoulder site was significant for setting III for all groups, but not for any groups in settings I and II. Conclusions: Heating the internal aspect of an implant with a CO2 laser produces different temperature distribution profiles depending on the laser power level and the application interval. Laser-beam irradiation leads to a temperature gradient, which is greatest at the implant apex and smallest at the implant shoulder. [ABSTRACT FROM AUTHOR]

Peripheral giant cell granulomas (PGCGs) are benign oral cavity tumors, reactive in nature, caused by local trauma or irritation. A 51-year-old woman presented with a soft tissue lesion related to an implant at site 36 (FDI numbering system). An excisional biopsy was completed, and the soft tissue mass was diagnosed as a PGCG. The biopsy led to a lack of keratinized tissue and vestibular depth around the implant site. After the initial healing phase, a free gingival graft was completed. Then, following soft tissue maturation, the cement-retained implant-supported prosthesis was converted into a screwretained implant-supported prosthesis that was easily accessible. With a combined periodontal and restorative approach, the KT increased, adequate vestibular depth was achieved, and there was no recurrence of the PGCG. [ABSTRACT FROM AUTHOR]

Purpose: To assess the clinical concept of patient treatment with fixed tooth- and implant-supported restorations in a university-based undergraduate program after 13 to 15 years. Materials and Methods: In total, 30 patients (mean age 56 years) who had received multiple tooth- and implant-supported restorations were recalled after 13 to 15 years. The clinical assessment comprised biologic and technical parameters as well as patient satisfaction. Data were analyzed descriptively, and the 13- to 15-year survival rates for tooth- and implant-supported single crowns and fixed dental prostheses (FDPs) were calculated. Results: The survival rate of tooth-supported restorations amounted to 88.3% (single crowns) and 69.6% (FDPs); in implants, it reached 100% for all types of restorations. Overall, 92.4% of all restorations were free of technical complications. The most common technical complication was chipping of the veneering ceramic (tooth-supported restorations: 5.5%; implant-supported restorations: 13% to 15.9%) regardless of the material used. For tooth-supported restorations, increased probing depth = 5 mm was the most frequent biologic complication (22.8%), followed by endodontic complications of root canal-treated teeth (14%) and loss of vitality at abutment teeth (8.2%). Peri-implantitis was diagnosed in 10.2% of implants. Conclusions: The results of this study indicate that the clinical concept implemented in the undergraduate program and performed by undergraduate students works well. The clinical outcomes are similar to those reported in the literature. In general, the majority of biologic complications occur in reconstructed teeth, whereas implant-supported restorations are more prone to technical complications. [ABSTRACT FROM AUTHOR]

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.)

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.)