Time efficiency and efficacy of a centralized computer-aided-design/computer-aided-manufacturing workflow for implant crown fabrication: A prospective controlled clinical study

OBJECTIVE To assess time efficiency and the efficacy of the prosthetic manufacturing for implant crown fabrication in a centralized workflow applying computer aided design and computer aided manufacturing (CAD-CAM). MATERIAL AND METHODS Fifty-nine patients with one posterior implant each, were randomly allocated to either a centralized digital workflow (c-DW, test) or a laboratory digital workflow (l-DW, control). Patients were excluded from efficiency and efficacy analyses, if any additional restoration than this single implant crown had to be fabricated. A customized titanium abutment and a monolithic zirconia crown were fabricated in the c-DW. In the l-DW, models were digitalized for CAD-CAM fabrication of a monolithic zirconia crown using a standardized titanium base abutment. Time for impression, laboratory operating and delivery time were recorded. The efficacy of the prosthetic manufacturing was evaluated at try-in and at delivery. Data was analyzed descriptively. Statistical analyses using student's unpaired t- and paired Wilcoxon were performed (p < 0.05). RESULTS At impression taking, 12 patients (c-DW) and 19 patients (l-DW) were included. The impression time was 9.4±3.5 min (c-DW) and 15.1 ± 4.6 min (l-DW) (p < 0.05). The laboratory operating time was 130 ± 31 min (c-DW) and 218.0±8 min (l-DW) (p < 0.05). The delivery time was significantly longer in the c-DW (5.9 ± 3.5 1 days) as compared to the l-DW (0.5±0.05 days). At try-in and at delivery, efficacy of prosthetic manufacturing was similar high in both workflows. CLINICAL RELEVANCE The c-DW was more time efficient compared to the lab-DW and rendered a similar efficacy of prosthetic manufacturing

Precision of digital implant models compared to conventional implant models for posterior single implant crowns: A within-subject comparison

OBJECTIVE To calculate the precision of the implant analog position in digital models generated from different computer-assisted design and computer-assisted manufacturing (CAD-CAM) systems compared to gypsum models acquired from conventional implant impressions. MATERIALS AND METHODS In five patients in need of a single implant crown, a within-subject comparison was performed applying four different manufacturing processes for the implant model. Each implant was scanned with three different intraoral scanners: iTero Cadent (ITE), Lava True Definition (LTD), and Trios 3Shape (TRI). All digital implant models were fabricated using the corresponding certified CAD-CAM workflow. In addition, a conventional impression was taken (CON) and a gypsum model fabricated. Three consecutive impressions were acquired with each impression system. Following fabrication, all implant models were scanned. The datasets were aligned by a repeated best-fit algorithm and the precision for the implant analog and the adjacent teeth was measured. The precision served as a measure for reproducibility. RESULTS Mean precision values of the implant analog in the digital models were 57.2 ± 32.6 µm (ITE), 88.6 ± 46.0 µm (TRI), and 176.7 ± 120.4 µm (LTD). Group CON (32.7 ± 11.6 µm) demonstrated a statistically significantly lower mean precision value for the implant position in the implant model as compared to all other groups representing a high reproducibility. The mean precision values for the reference ranged between 31.4 ± 3.5 µm (TRI) and 39.5 ± 16.5 µm (ITE). No statistical significant difference was calculated between the four treatment groups. CONCLUSIONS The conventional implant model represented the greatest reproducibility of the implant position. Digital implant models demonstrated less precision compared to the conventional workflow

Inhibition of nonsense-mediated mRNA decay reduces the tumorigenicity of human fibrosarcoma cells.

Nonsense-mediated mRNA decay (NMD) is a eukaryotic RNA decay pathway with roles in cellular stress responses, differentiation, and viral defense. It functions in both quality control and post-transcriptional regulation of gene expression. NMD has also emerged as a modulator of cancer progression, although available evidence supports both a tumor suppressor and a pro-tumorigenic role, depending on the model. To further investigate the role of NMD in cancer, we knocked out the NMD factor SMG7 in the HT1080 human fibrosarcoma cell line, resulting in suppression of NMD function. We then compared the oncogenic properties of the parental cell line, the SMG7-knockout, and a rescue cell line in which we re-introduced both isoforms of SMG7. We also tested the effect of a drug inhibiting the NMD factor SMG1 to distinguish NMD-dependent effects from putative NMD-independent functions of SMG7. Using cell-based assays and a mouse xenograft tumor model, we showed that suppression of NMD function severely compromises the oncogenic phenotype. Molecular pathway analysis revealed that NMD suppression strongly reduces matrix metalloprotease 9 (MMP9) expression and that MMP9 re-expression partially rescues the oncogenic phenotype. Since MMP9 promotes cancer cell migration and invasion, metastasis and angiogenesis, its downregulation may contribute to the reduced tumorigenicity of NMD-suppressed cells. Collectively, our results highlight the potential value of NMD inhibition as a therapeutic approach

Pontic site development for fixed dental prostheses with and without soft tissue grafting: 1-year results of a cohort study

AIM To describe and compare the pontic site development for fixed-dental prostheses (FDPs) with and without soft tissue grafting up to one-year post insertion of FDPs. MATERIALS AND METHODS A convenience sample of 24 patients participating in an ongoing RCT was provided with three-unit tooth-borne FDPs. Six patients received a subepithelial connective tissue graft (SCTG) at the pontic site, whereas 18 patients were treated without any soft tissue graft (CONTROL). Digital impressions were taken prior to tooth preparation, after tooth preparation, after insertion of the final FDP, and at the 1 year of follow-up. The obtained stereolithography files (STL) were superimposed and profilometric as well as linear changes of the soft tissue profile were assessed at the pontic regions. Profilometric outcomes included changes of the ridge contour, the alveolar ridge width, and the crown height of the pontic. Further outcomes assessed included: the papilla index, the pink esthetic score (PES), probing depth (PD), bleeding on probing (BOP), and plaque control record (PCR). Descriptive and nonparametric statistics were applied for all outcome measures. RESULTS The median profilometric contour between tooth preparation and 1 year after the insertion of the final FDP decreased by - 0.25 mm [Q1, Q3: - 0.36, 0.14] in the CONTROL group and increased by 0.61 mm [Q1, Q3: - 0.18, 1.06] in the SCTG group (intergroup p = 0.038). The alveolar ridge width between prior to tooth preparation and the one-year follow-up amounted to - 0.12 mm [Q1, Q3: - 0.74, 0.70] (= loss) in the CONTROL group and to 2.23 mm [Q1, Q3: 0.62, 3.86] (= gain) in the SCTG group (intergroup p = 0.032). At one year, the median crown height of the pontic tended to decrease by - 1.24 mm [Q1, Q3: - 2.05, - 1.05] in the SCTG group (intragroup p = 0.094) and by - 0.22 mm [Q1, Q3: - 0.58, 0.66] in the CONTROL group (intragroup p = 0.831), with significant differences between the groups (intergroup p = 0.022). The papilla index between prior to tooth preparation and one year of follow-up improved significantly in both groups (p  0.05). CONCLUSION Within the limitations of the present study, soft tissue grafting tends to limit contour changes at pontic sites, thus maintaining the esthetic outcomes over time. The lack of soft tissue grafting results in stable clinical outcomes; however, it may lead to a decrease in aesthetic outcomes over time. CLINICAL RELEVANCE Autogenous soft tissue grafting seems to be a valid therapeutic option for the development of the pontic site to restore ridge defects prior to the delivery of fixed dental prostheses and to limit dimensional changes over time

Vaccination with SARS-CoV-2 variants of concern protects mice from challenge with wild-type virus.

Funder: open philanthropy projectFunder: jpb foundationVaccines against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) have been highly efficient in protecting against Coronavirus Disease 2019 (COVID-19). However, the emergence of viral variants that are more transmissible and, in some cases, escape from neutralizing antibody responses has raised concerns. Here, we evaluated recombinant protein spike antigens derived from wild-type SARS-CoV-2 and from variants B.1.1.7, B.1.351, and P.1 for their immunogenicity and protective effect in vivo against challenge with wild-type SARS-CoV-2 in the mouse model. All proteins induced high neutralizing antibodies against the respective viruses but also induced high cross-neutralizing antibody responses. The decline in neutralizing titers between variants was moderate, with B.1.1.7-vaccinated animals having a maximum fold reduction of 4.8 against B.1.351 virus. P.1 induced the most cross-reactive antibody responses but was also the least immunogenic in terms of homologous neutralization titers. However, all antigens protected from challenge with wild-type SARS-CoV-2 in a mouse model

Is the use of digital technologies for the fabrication of implant-supported reconstructions more efficient and/or more effective than conventional techniques: A systematic Review

OBJECTIVE To identify clinical studies evaluating efficiency and/or effectiveness of digital technologies as compared to conventional manufacturing procedures for the fabrication of implant-supported reconstructions. MATERIALS AND METHODS A systematic search from 1990 through July 2017 was performed using the online databases Medline, Embase, and Cochrane-Central-Register-of-Controlled-Trials. Literature on efficiency and/or effectiveness during the impression session, the manufacturing process, and the delivery session were included. RESULTS In total, 12 clinical studies were included. No meta-analysis was performed due to a large heterogeneity of the study protocols. Nine publications reported on posterior single implant crowns (SIC) and three on full-arch reconstructions. Mean impression time with intraoral scanners ranged between 6.7 and 19.8 min, whereas the range for conventional impressions was 8.8 and 18.4 min. In a fully digital workflow (FD-WF) for posterior SIC, mean fabrication time ranged between 46.8 and 54.5 min (prefabricated abutment) and 68.0 min (customized abutment). In a hybrid workflow (H-WF) including a digitally customized abutment and a manual veneering, mean fabrication time ranged between 132.5 and 158.1 min. For a conventional porcelain-fused-to-metal-crown, a mean time of 189.8 min was reported. The mean time for the delivery of posterior SIC ranged between 7.3 and 7.4 min (FD-WF), 10.5 and 12.5 min (H-WF), and 15.3 min (conventional workflow, C-WF). The FD-WF for posterior SIC was more effective than the H-/C-WF. CONCLUSIONS The implementation of the studied digital technologies increased time efficiency for the laboratory fabrication of implant-supported reconstructions. For posterior SIC, the model-free fabrication, the use of prefabricated abutments, and the monolithic design was most time efficient and most effective

Understanding responses to an organizational takeover: introducing the social identity model of organizational change

This paper presents a Social Identity Model of Organizational Change (SIMOC) and tests this in the context of employees’ responses to a corporate takeover. This model suggests that employees will identify with the newly emerging organization and adjust to organizational change more successfully the more they are able to maintain their pre-existing social identity (an identity maintenance pathway) or to change understanding of their social identity in ways that are perceived as constituting identity gain (an identity gain pathway). We examine this model in the context of an acquisition in the pharmaceutical industry where 225 employees were surveyed before the implementation of the organizational change and then again 18 months later. In line with SIMOC, pre-change identification predicted post-change identification and a variety of beneficial adjustment outcomes for employees (including job satisfaction, organizational citizenship behavior, lower depression, satisfaction with life, and post-traumatic growth) to the extent that either (a) they experienced a sense of identity continuity or (b) their supervisors engaged in identity leadership that helped to build a sense that they were gaining a new positive identity. Results showed a negative impact of pre-change organizational identification on post-change identification and various adjustment outcomes if both pathways were inaccessible, thereby contributing to employees’ experience of social identity loss. Discussion focuses on the ways in which organizations and their leaders can better manage organizational change and associated identity transition

Epidemiology of methicillin-resistant Staphylococcus aureus: results of a nation-wide survey in Switzerland.

To assess the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in Switzerland. One-year national survey of all MRSA cases detected in a large sample of Swiss healthcare institutions (HCI). Analysis of epidemiological and molecular typing data (PFGE) of MRSA strains. During 1997, 385 cases of MRSA were recorded in the 5 university hospitals, in 33 acute care community hospitals, and 14 rehabilitation or long-term care institutions. Half of the cases were found at the University of Geneva Hospitals where MRSA was already known to be endemic (41.1 cases/10,000 admissions). The remaining cases (200) were distributed throughout Switzerland. The highest rates (&gt;100 cases/10,000 admissions) were reported from non-acute care institutions. Rates ranged from 3.3 to 41.1 cases/10,000 admissions for university hospitals (mean 15.5); 0.67 to 90.4 for community hospitals (mean 4.8), and 28.2 to 315 for non-acute care institutions reporting MRSA (mean 85.7). Forty percent of MRSA patients were infected, while 60% were only colonised. The leading infection sites were skin and soft tissue (21%), surgical site (15%), and the urinary tract (26%). Whereas in Eastern Swiss HCI most MRSA cases occurred in acute care hospitals (n = 47, 98%), rehabilitation and long-term care institutions accounted for an important number of the identified cases (n = 107, 38%) in Western Switzerland. Low rates of MRSA were still observed in Swiss HCI, despite one outlying acute care centre with endemic MRSA and some nonacute care institutions with epidemic MRSA. Rehabilitation and long-term care institutions contributed to a substantial proportion of cases in Western Switzerland and may constitute a significant reservoir. Overall, a national approach to surveillance and control of MRSA is mandatory in order to preserve a still favourable situation, and to decrease the risk of epidemic MRSA dissemination

Minor intron splicing is regulated by FUS and affected by ALS-associated FUS mutants

Fused in sarcoma (FUS) is a ubiquitously expressed RNA-binding protein proposed to function in various RNA metabolic pathways, including transcription regulation, pre-mRNA splicing, RNA transport and microRNA processing. Mutations in the FUS gene were identified in patients with amyotrophic lateral sclerosis (ALS), but the pathomechanisms by which these mutations cause ALS are not known. Here, we show that FUS interacts with the minor spliceosome constituent U11 snRNP, binds preferentially to minor introns and directly regulates their removal. Furthermore, a FUS knockout in neuroblastoma cells strongly disturbs the splicing of minor intron-containing mRNAs, among them mRNAs required for action potential transmission and for functional spinal motor units. Moreover, an ALS-associated FUS mutant that forms cytoplasmic aggregates inhibits splicing of minor introns by trapping U11 and U12 snRNAs in these aggregates. Collectively, our findings suggest a possible pathomechanism for ALS in which mutated FUS inhibits correct splicing of minor introns in mRNAs encoding proteins required for motor neuron survival