Clinical performance of monolithic zirconia crowns on titanium-zirconium reduced-diameter implants in the molar area: Interim data at three years of a randomized controlled trial.

AIM: The aim of the present study was (i) to evaluate the clinical performance of reduced-diameter implants placed in the molar area and (ii) to test whether monolithic zirconia implant-supported crowns lead to similar clinical outcomes compared to porcelain-fused-to-metal crowns. MATERIALS AND METHODS: A total of 76 patients needing a single implant crown in the posterior region were recruited. All patients received a titanium-zirconium reduced-diameter implant (Straumann Roxolid, Tissue Level, Standard Plus, diameter 3.3 mm, regular neck) randomly allocated to receive either a (1) monolithic zirconia crown (test) or (2) porcelain-fused-to-metal crown (control). Implant survival, prosthetic outcomes, and patient-reported outcomes were assessed at crown delivery and after 3 years of follow-up. Marginal bone levels (MBL) as well as clinical parameters including probing depth (PD), bleeding on probing (BOP), and plaque levels (PCR) were also recorded. RESULTS: A total of 59 patients were available at the 3-year follow-up; 32 patients with a monolithic zirconia crown (TEST) and 27 patients with a porcelain-fused-to-metal crown (CONTROL). 14 implants (11 implant fractures/3 aseptic losses) were lost leading to an estimated implant survival rate of 80% ± 5.1% (95% CI 70.8%-90.8%). Prosthetic complications were limited to the control group and involved minor chippings. CONCLUSIONS: This type of reduced-diameter implant to support single implant molar crowns in the molar area cannot be recommended. Monolithic zirconia crowns appear to be a viable option in the posterior region showing similar prosthetic outcomes to porcelain-fused-to-metal crowns.

Randomized controlled pilot study comparing small buccal defects around dental implants treated with a subepithelial connective tissue graft or with guided bone regeneration.

AIM: To compare subepithelial connective tissue grafts (SCTG) versus guided bone regeneration (GBR) for the treatment of small peri-implant dehiscence defects in terms of profilometric (primary outcome), clinical, and patient-reported outcome measures (PROMs). METHODS: Sixteen patients who presented with small buccal bone dehiscences (≤3 mm) following single implant placement were recruited. Following implant placement, buccal bone defect sites were randomly treated either with a SCTG or GBR. Six patients who lacked bone dehiscences after implant placement were assigned to a negative control. Transmucosal healing was applied in all patients. Patients were examined prior (T1) and after (T2) implant placement, at suture removal (T3), at implant impression (T5), at crown delivery (T6), and 12 (T7) months after crown delivery. Measurements included profilometric outcomes, marginal bone levels, buccal bone and soft tissue thickness, PROMs, and clinical parameters. All data were analyzed descriptively. RESULTS: The median changes in buccal contour as assessed by profilometric measures between T1 and T5 showed a decrease of 1.84 mm for the SCTG group and 1.06 mm for the GBR group. Between T2 and T7, the median change in the buccal contour amounted to 0.45 mm for SCTG and -0.94 mm (=loss) for GBR. Patients' pain perception tended to be higher in SCTG than in GBR. All peri-implant soft tissue parameters showed healthy oral tissues and no clinically relevant differences between groups. CONCLUSION: Within the limitations of this pilot study, treating small peri-implant dehiscence defects with a SCTG might be a viable alternative to GBR. The use of a SCTG tended to result in more stable profilometric outcomes and comparable clinical outcomes to GBR. However, patient-reported outcome measures tended to favor GBR.

Ten-Year Performance of Posterior 6-mm Implants with Single-Tooth Restorations: A Randomized Controlled Trial.

The aim of the study was to compare the clinical and radiographic outcomes of short dental implants (6-mm test group, TG) to longer implants (10-mm control group, CG) with single crown restorations after 10 y of loading. Patients requiring single-tooth replacement in the posterior jaws were randomly assigned to TG or CG. Implants were loaded with screw-retained single crowns after a healing period of 10 wk. Follow-up appointments were scheduled yearly and comprised patient-adapted oral hygiene reinstructions and polishing of all teeth and implants. After 10 y, clinical and radiographical parameters were assessed again. Out of initially 94 patients (47 in TG and CG, each), 70 (36 TG and 34 CG) could be reassessed. Survival rates accounted for 85.7% (TG) and 97.1% (CG), without significant intergroup difference (P = 0.072). All but 1 lost implant had been located in the lower jaw. These implants were not lost due to peri-implantitis but due to a late loss of osseointegration without signs of inflammation and with actually stable marginal bone levels (MBLs) over the investigation period. In general, MBLs were stable with medians (interquartile ranges) of 0.13 (0.78) mm and 0.08 (1.2) mm, for TG and CG, without significant intergroup differences. Crown-to-implant ratio showed a highly significant intergroup difference of 1.06 ± 0.18 mm and 0.73 ± 0.17 mm (P < 0.001). Few technical complications (i.e., screw loosening or chipping) were registered during the investigation period. In conclusion, given stringent professional maintenance, short dental implants with single-crown restorations show a slightly worse but statistically not different survival rate after 10 y, especially in the lower jaw, but can still be considered a valuable alternative, especially when vertical bone dimensions are limited (German Clinical Trials Registry: DRKS00006290).

Post-coronavirus disease 2019 polyneuropathy with significant response to immunoglobulin therapy: a case report.

BACKGROUND: The symptoms of coronavirus disease 2019, caused by the novel severe acute respiratory syndrome coronavirus 2, were originally assumed to be mainly respiratory. With increasing knowledge, however, it turned out that the spectrum of complaints varies broadly with age and concomitant diseases. While many neurological symptoms were reported in the context of the disease, ranging from permanent fatigue to recurrent headaches and concentration disturbance, treatment approaches are still in development. This case discusses a possible treatment approach with immunoglobulin therapy and its outcomes. CASE PRESENTATION: We present the case of a 56-year-old Caucasian female patient who, following coronavirus disease 2019, developed peripheral sensory and autonomic disturbances that fell within subacute demyelinating neuropathy. Because a significant improvement in symptoms as well as in the results of clinical and electrophysiological examination was reported after immunoglobulin therapy, long-term therapy does not appear to be necessary. CONCLUSION: Given the significant subjective and objective improvement reported, this case provides additional evidence that immunoglobulin therapy can be considered in post-coronavirus disease 2019 syndrome.

Channel-hopping during surface electrical neurostimulation elicits selective, comfortable, distally referred sensations.

Objective.Lack of sensation from a hand or prosthesis can result in substantial functional deficits. Surface electrical stimulation of the peripheral nerves is a promising non-invasive approach to restore lost sensory function. However, the utility of standard surface stimulation methods has been hampered by localized discomfort caused by unintended activation of afferents near the electrodes and limited ability to specifically target underlying neural tissue. The objectives of this work were to develop and evaluate a novel channel-hopping interleaved pulse scheduling (CHIPS) strategy for surface stimulation that is designed to activate deep nerves while reducing activation of fibers near the electrodes.Approach.The median nerve of able-bodied subjects was activated by up to two surface stimulating electrode pairs placed around their right wrist. Subjects received biphasic current pulses either from one electrode pair at a time (single-channel), or interleaved between two electrode pairs (multi-channel). Percept thresholds were characterized for five pulse durations under each approach, and psychophysical questionnaires were used to interrogate the perceived modality, quality and location of evoked sensations.Main results.Stimulation with CHIPS elicited enhanced tactile percepts that were distally referred, while avoiding the distracting sensations and discomfort associated with localized charge densities. These effects were reduced after introduction of large delays between interleaved pulses.Significance.These findings demonstrate that our pulse scheduling strategy can selectively elicit referred sensations that are comfortable, thus overcoming the primary limitations of standard surface stimulation methods. Implementation of this strategy with an array of spatially distributed electrodes may allow for rapid and effective stimulation fitting. The ability to elicit comfortable and referred tactile percepts may enable the use of this neurostimulation strategy to provide meaningful and intuitive feedback from a prosthesis, enhance tactile feedback after sensory loss secondary to nerve damage, and deliver non-invasive stimulation therapies to treat various pain conditions.

Retrospective evaluation of outcomes of bone peg fixation for osteochondral lesion of the talus.

AIMS: The hypothesis of this study was that bone peg fixation in the treatment of osteochondral lesions of the talus would show satisfactory clinical and radiological results, without complications. METHODS: Between September 2014 and July 2017, 25 patients with symptomatic osteochondritis of the talus and an osteochondral fragment, who were treated using bone peg fixation, were analyzed retrospectively. All were available for complete follow-up at a mean 22 of months (12 to 35). There were 15 males and ten females with a mean age of 19.6 years (11 to 34). The clinical results were evaluated using a visual analogue scale (VAS) and the American Orthopaedic Foot and Ankle Society (AOFAS) score preoperatively and at the final follow-up. The radiological results were evaluated using classification described by Hepple et al based on the MRI findings, the location of the lesion, the size of the osteochondral fragment, and the postoperative healing of the lesion. RESULTS: The mean VAS and AOFAS score improved significantly from 6.3 (4 to 8) and 70.6 (44 to 78) preoperatively to 1.6 (0 to 5) and 91.1 (77 to 100) at the final follow-up, respectively (p < 0.001). The classification on MRI was stage 2a in nine patients, stage 3 in 14, and stage 4 in two. The lesion was located on the posteromedial aspect of the dome of the talus in 19 patients, the anterolateral aspect in five, and the centrolateral aspect in one. The mean size of the fragment was 11.2 mm (5 to 20) horizontally, 10.4 mm (7 to 18) vertically, and 5.2 mm (3 to 10) deep, respectively. The postoperative healing state was good in 19 patients and fair in six. CONCLUSION: Bone peg fixation for osteochondral lesions of the talus showed satisfactory clinical and radiographic results, without complications. This technique could be a good form of treatment for patients with this condition who have an osteochondral fragment. Cite this article: Bone Joint J 2020;102-B(10):1349-1353.

Creating a Global Community of Practice for Oncofertility.

Fertility preservation in the cancer setting, known as oncofertility, is a field that requires cross-disciplinary interaction between physicians, basic scientists, clinical researchers, ethicists, lawyers, educators, and religious leaders. Funded by the National Institutes of Health, the Oncofertility Consortium (OC) was formed to be a scientifically grounded, transparent, and altruistic resource, both intellectual and monetary, for building this new field of practice capable of addressing the unique needs of young patients with cancer. The OC has expanded its attention to include other nonmalignant conditions that can threaten fertility, and the work of the OC now extends around the globe, involving partners who together have created a community of shared effort, resources, and practices. The OC creates materials that are translated, disseminated, and amended by all participants in the field, and local programs of excellence have developed worldwide to accelerate the pace and improve the quality of oncofertility research and practice. Here we review the global oncofertility programs and the capacity building activities that strengthen these research and clinical programs, ultimately improving patient care.

Intra-Arterial Verapamil Treatment in Oral Therapy-Refractory Reversible Cerebral Vasoconstriction Syndrome.

Reversible vasoconstriction syndrome is a complex of clinical symptoms and angiographic findings, which, while having a mostly benign clinical course, has clinical and imaging overlap with more serious disorders such as vasculitis and aneurysmal SAH and itself includes a minority of patients with fulminant vasoconstriction resulting in severe intracranial complications. Endovascular options for patients with refractory reversible cerebral vasoconstriction syndrome include intra-arterial vasodilator infusion similar to therapy for patients with vasospasm after SAH. To date, only case reports and 1 small series have discussed the utility of intra-arterial vasodilators for the treatment of reversible cerebral vasoconstriction syndrome. We report an additional series of 11 medically refractory cases of presumed or proved reversible cerebral vasoconstriction syndrome successfully treated with intra-arterial verapamil infusion. Furthermore, we propose that the reversal of vasoconstriction, as seen on angiography, could fulfill a diagnostic criterion.

Adaptive changes in pancreas post Roux-en-Y gastric bypass induced weight loss.

BACKGROUND: Obesity has been shown to trigger adaptive increases in pancreas parenchymal and fat volume. Consecutively, pancreatic steatosis may lead to beta-cell dysfunction. However, it is not known whether the pancreatic tissue components decrease with weight loss and pancreatic steatosis is reversible following Roux-en-Y gastric bypass (RYGB). Therefore, the objective of the study was to investigate the effects of RYGB-induced weight loss on pancreatic volume and glucose homeostasis. METHODS: Eleven patients were recruited in the Obesity Centre of the University Medical Centre Hamburg-Eppendorf. Before and 6 months after RYGB, total GLP-1 levels were measured during oral glucose tolerance test. To assess changes in visceral adipose tissue and pancreatic volume, MRI was performed. Measures of glucose homeostasis and insulin indices were assessed. Fractional beta-cell area was estimated by correlation with the C-peptide-to-glucose ratio; beta-cell mass was calculated by the product of beta-cell area and pancreas parenchymal weight. RESULTS: Pancreas volume decreased from 83.8 (75.7-92.0) to 70.5 (58.8-82.3) cm3 (mean [95% CI], P = .001). The decrease in total volume was associated with a significant decrease in fat volume. Fasting insulin and C-peptide were lower post RYGB. HOMA-IR levels decreased, whereas insulin sensitivity increased (P = .03). This was consistent with a reduction in the estimated beta-cell area and mass. CONCLUSIONS: Following RYGB, pancreatic volume and steatosis adaptively decreased to "normal" levels with accompanying improvement in glucose homeostasis. Moreover, obesity-driven beta-cell expansion seems to be reversible; however, future studies must define a method to more accurately estimate functional beta-cell mass to increase our understanding of glucose homeostasis after RYGB.

Five-Year Survival of Short Single-Tooth Implants (6 mm): A Randomized Controlled Clinical Trial.

The aim of the present study was to evaluate whether 6-mm dental implants in the posterior segments of either jaw perform equally well in terms of clinical and radiographic outcomes when compared with 10-mm implants after 5 y of loading. Patients with single-tooth gaps in the posterior area who were scheduled for implant therapy were randomly assigned to a group receiving either a 6- or 10-mm implant. After a healing period of 10 wk, implants were loaded with a screw-retained single crown and followed up at yearly intervals. Of 96 patients, 86 could be recalled after 5 y. The implant survival rates amounted to 91% (95% confidence interval: 0.836 to 0.998) for the 6-mm group and 100% for the 10-mm group ( P = 0.036). Median crown-to-implant (C/I) ratios were 1.75 (interquartile range [IQR], 1.50 to 1.90) for the 6-mm group and 1.04 (IQR, 0.95 to 1.15) for the 10-mm group, whereas the median marginal bone levels measured -0.29 mm (IQR, -0.92 to 0.23) for the 6-mm group and -0.15 mm (IQR: -0.93 - 0.41) for the 10-mm group after 5 y. The C/I ratio turned out to be statistically significant ( P < 0.001), whereas marginal bone levels showed no significant difference between the groups. The 6-mm implants exhibited significantly lower survival rates than the 10-mm implants over 5 y, whereas there was no difference between upper and lower jaws in terms of survival ( P = 0.58). Lost implants did not show any sign of marginal bone loss or peri-implant infection previous to loss of osseointegration. High C/I ratio and implant length had no significant effect on marginal bone level changes or technical and biological complications (German Clinical Trials Registry: DRKS00006290).

Specificity of late-night salivary cortisol measured by automated electrochemiluminescence immunoassay for Cushing's disease in an obese population.

PURPOSE: Data about the specificity of late-night salivary cortisol (LNSC) in obese subjects are still conflicting. Therefore, with this study, we aimed to evaluate the specificity of LNSC measurement in an obese cohort with or without type 2 diabetes mellitus (T2DM) using an automated electrochemiluminescence immunoassay (ECLIA). METHODS: A total number of 157 patients involving 40 healthy subjects (HS) with BMI < 25 kg/m2, 83 obese subjects (OS) with BMI ≥ 35 kg/m2, and 34 histopathologically proven Cushing's disease (CD) were included. All patients underwent LNSC testing. Salivary cortisol was measured at 11 p.m. for all groups using an ECLIA. Reference range was established using values of LNSCs of HS and ROC curves were used to determine diagnostic cutoffs. RESULTS: In the HS group, mean LNSC was 4.7 nmol/l (SD ± 3.1), while the OS group had a mean value of 10.9 nmol/l (SD ± 7.5) and the CD group of 19.9 nmol/l (SD ± 15.4). All groups differed significantly (p < 0.001). The ROC analysis of CD against HS alone showed a sensitivity of 85.3% and a specificity of 87.5% with a cut-off value of 8.3 nmol/l. The ROC analysis between OS and CD showed a maximum sensitivity of 67.6% and specificity of 78.3% for a cut-off value of 12.3 nmol/l. Taken both (HS and OS) groups together against the CD group, ROC analysis showed a maximum sensitivity of 67.6% and specificity of 85.4% for a cut-off value of 12.3 nmol/l. No correlation was found between BMI, T2DM, and LNSC for all groups. CONCLUSIONS: In our obese cohort, we found that LNSC assayed by ECLIA had a low specificity in the diagnosis of CD.

Mechanical fatigue resistance of an implantable branched lead system for a distributed set of longitudinal intrafascicular electrodes.

OBJECTIVE: A neural interface system has been developed that consists of an implantable stimulator/recorder can with a 15-electrode lead that trifurcates into three bundles of five individual wire longitudinal intrafascicular electrodes. This work evaluated the mechanical fatigue resistance of the branched lead and distributed electrode system under conditions designed to mimic anticipated strain profiles that would be observed after implantation in the human upper arm. APPROACH: Custom test setups and procedures were developed to apply linear or angular strain at four critical stress riser points on the lead and electrode system. Each test was performed to evaluate fatigue under a high repetition/low amplitude paradigm designed to test the effects of arm movement on the leads during activities such as walking, or under a low repetition/high amplitude paradigm designed to test the effects of more strenuous upper arm activities. The tests were performed on representative samples of the implantable lead system for human use. The specimens were fabricated using procedures equivalent to those that will be used during production of human-use implants. Electrical and visual inspections of all test specimens were performed before and after the testing procedures to assess lead integrity. MAIN RESULTS: Measurements obtained before and after applying repetitive strain indicated that all test specimens retained electrical continuity and that electrical impedance remained well below pre-specified thresholds for detection of breakage. Visual inspection under a microscope at 10× magnification did not reveal any signs of damage to the wires or silicone sheathing at the stress riser points. SIGNIFICANCE: These results demonstrate that the branched lead of this implantable neural interface system has sufficient mechanical fatigue resistance to withstand strain profiles anticipated when the system is implanted in an arm. The novel test setups and paradigms may be useful in testing other lead systems.

Multimodal Neuroimaging in Schizophrenia: Description and Dissemination.

In this paper we describe an open-access collection of multimodal neuroimaging data in schizophrenia for release to the community. Data were acquired from approximately 100 patients with schizophrenia and 100 age-matched controls during rest as well as several task activation paradigms targeting a hierarchy of cognitive constructs. Neuroimaging data include structural MRI, functional MRI, diffusion MRI, MR spectroscopic imaging, and magnetoencephalography. For three of the hypothesis-driven projects, task activation paradigms were acquired on subsets of ~200 volunteers which examined a range of sensory and cognitive processes (e.g., auditory sensory gating, auditory/visual multisensory integration, visual transverse patterning). Neuropsychological data were also acquired and genetic material via saliva samples were collected from most of the participants and have been typed for both genome-wide polymorphism data as well as genome-wide methylation data. Some results are also presented from the individual studies as well as from our data-driven multimodal analyses (e.g., multimodal examinations of network structure and network dynamics and multitask fMRI data analysis across projects). All data will be released through the Mind Research Network's collaborative informatics and neuroimaging suite (COINS).

Transverse Coherence Limited Coherent Diffraction Imaging using a Molybdenum Soft X-ray Laser Pumped at Moderate Pump Energies.

Coherent diffraction imaging (CDI) in the extreme ultraviolet has become an important tool for nanoscale investigations. Laser-driven high harmonic generation (HHG) sources allow for lab scale applications such as cancer cell classification and phase-resolved surface studies. HHG sources exhibit excellent coherence but limited photon flux due poor conversion efficiency. In contrast, table-top soft X-ray lasers (SXRL) feature excellent temporal coherence and extraordinary high flux at limited transverse coherence. Here, the performance of a SXRL pumped at moderate pump energies is evaluated for CDI and compared to a HHG source. For CDI, a lower bound for the required mutual coherence factor of |µ 12| ≥ 0.75 is found by comparing a reconstruction with fixed support to a conventional characterization using double slits. A comparison of the captured diffraction signals suggests that SXRLs have the potential for imaging micron scale objects with sub-20 nm resolution in orders of magnitude shorter integration time compared to a conventional HHG source. Here, the low transverse coherence diameter limits the resolution to approximately 180 nm. The extraordinary high photon flux per laser shot, scalability towards higher repetition rate and capability of seeding with a high harmonic source opens a route for higher performance nanoscale imaging systems based on SXRLs.

Application of low-frequency sonophoresis and reduction of antibiotics in the aquatic systems.

A major concern in aquaculture is the use of chemical therapeutics, such as antibiotics, because of their impact on the environment as well as on the fish product. As a potential tool for reducing antibiotic use, we tested the application of low-frequency ultrasound as a method for enhancing antibiotic uptake. Rainbow trout juveniles (Oncorhynchus mykiss) were exposed to two different concentrations of oxytetracycline (OTC), flumequine (FLU) and florfenicol (FLO), administered by bath after the application of ultrasound. After exposure, concentrations of these substances were measured in the liver and blood of treated fish. Results showed that the ultrasound treatment can significantly increase the uptake for all three antibiotics. The uptake of OTC for example, in fish exposed to an OTC concentration of 20 mg L-1 after prior treatment with ultrasound, was similar to the OTC concentrations in their liver and blood to fish exposed to 100 mg L-1 without sonication. For FLU and FLO, the use of ultrasound caused significant differences of uptake in the liver at high antibiotic concentrations. This suggests that the use of ultrasound as a technique to deliver antibiotics to fish can ultimately reduce the amount of antibiotics discharged into the aquatic environment.

The influence of the emergence profile on the amount of undetected cement excess after delivery of cement-retained implant reconstructions.

OBJECTIVE: To test whether or not one of two emergence profile designs (concave or convex) is superior to the other in terms of remaining cement following cementation of reconstructions on individualized abutments and careful cement removal. MATERIALS AND METHODS: A central incisor with a single implant-supported reconstruction was selected as a model. Six types of abutments (n = 10) with two different emergence profile designs (concave (CC) and convex (CV)) and three crown-abutment margin depths (epimucosal, 1.5 mm submucosal, 3 mm submucosal) were fabricated through a CAD/CAM procedure. Lithium disilicate reinforced ceramic crowns were cemented with chemically polymerized resin cement. A blinded investigator attempted to remove all cement excess. Thereafter, the entire reconstruction was unscrewed and analyzed for the overall amount and the depth of cement excess. Kruskal-Wallis and Mann-Whitney tests were used to investigate differences between groups. When more than two groups were compared between each other, a Bonferroni correction of the P value was performed. RESULTS: Concave abutments presented significantly more cement remnants than CV abutments when the entire abutment area of the epimucosal margin groups was evaluated (CC0 mm: mean 2.31 mm2 (SD 0.99) vs. CV0 mm: mean 1.57 mm2 (SD 0.55); P = 0.043). A statistically significant increase in remnants was detected when the crown-abutment margin was located more submucosally for every abutment studied (0 mm vs. 1.5 mm: P < 0.000, 0 mm vs 3 mm: P < 0.000, 1.5 mm vs. 3 mm: P < 0.000). The buccal quadrant demonstrated the least, whereas the oral and interdental quadrants showed the greatest amount of cement excess. CONCLUSIONS: Concave emergence profile abutments and deep crown-abutment margin positions increased the risk of cement excess. Oral and interdental areas are more prone to cement remnants than other surface areas.

Clinical Outcomes of Zirconia Dental Implants: A Systematic Review

To determine the survival rate and marginal bone loss (MBL) of zirconia dental implants restored with single crowns or fixed dental prostheses. An electronic search was conducted up to November 2015 (without any restriction regarding the publication time) through the databases MEDLINE (PubMed), Cochrane Library, and EMBASE to identify randomized controlled clinical trials and prospective clinical trials including >15 patients. Primary outcomes were survival rate and MBL. Furthermore, the influence of several covariates on MBL was evaluated. Qualitative assessment and statistical analyses were performed. This review was conducted according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines for systematic reviews. With the applied search strategy, 4,196 titles could be identified. After a screening procedure, 2 randomized controlled clinical trials and 7 prospective clinical trials remained for analyses. In these trials, a total of 326 patients received 398 implants. The follow-up ranged from 12 to 60 mo. Implant loss was mostly reported within the first year, especially within the healing period. Thereafter, nearly constant survival curves could be observed. Therefore, separate meta-analyses were performed for the first and subsequent years, resulting in an implant survival rate of 95.6% (95% confidence interval: 93.3% to 97.9%) after 12 mo and, thereafter, an expected decrease of 0.05% per year (0.25% after 5 y). Additionally, a meta-analysis was conducted for the mean MBL after 12 mo, resulting in 0.79 mm (95% confidence interval: 0.73 to 0.86 mm). Implant bulk material and design, restoration type, and the application of minor augmentation procedures during surgery, as well as the modes of temporization and loading, had no statistically significant influence on MBL. The short-term cumulative survival rates and the MBL of zirconia implants in the presented systematic review are promising. However, additional data are still needed to confirm the long-term predictability of these implants.

Aldehyde dehydrogenase 1a3 defines a subset of failing pancreatic ß cells in diabetic mice.

Insulin-producing ß cells become dedifferentiated during diabetes progression. An impaired ability to select substrates for oxidative phosphorylation, or metabolic inflexibility, initiates progression from ß-cell dysfunction to ß-cell dedifferentiation. The identification of pathways involved in dedifferentiation may provide clues to its reversal. Here we isolate and functionally characterize failing ß cells from various experimental models of diabetes and report a striking enrichment in the expression of aldehyde dehydrogenase 1 isoform A3 (ALDH(+)) as ß cells become dedifferentiated. Flow-sorted ALDH(+) islet cells demonstrate impaired glucose-induced insulin secretion, are depleted of Foxo1 and MafA, and include a Neurogenin3-positive subset. RNA sequencing analysis demonstrates that ALDH(+) cells are characterized by: (i) impaired oxidative phosphorylation and mitochondrial complex I, IV and V; (ii) activated RICTOR; and (iii) progenitor cell markers. We propose that impaired mitochondrial function marks the progression from metabolic inflexibility to dedifferentiation in the natural history of ß-cell failure.

Creating a Global Community of Practice for Oncofertility.

Fertility preservation in the cancer setting, known as oncofertility, is a field that requires cross-disciplinary interaction between physicians, basic scientists, clinical researchers, ethicists, lawyers, educators, and religious leaders. Funded by the National Institutes of Health, the Oncofertility Consortium (OC) was formed to be a scientifically grounded, transparent, and altruistic resource, both intellectual and monetary, for building this new field of practice capable of addressing the unique needs of young patients with cancer. The OC has expanded its attention to include other nonmalignant conditions that can threaten fertility, and the work of the OC now extends around the globe, involving partners who together have created a community of shared effort, resources, and practices. The OC creates materials that are translated, disseminated, and amended by all participants in the field, and local programs of excellence have developed worldwide to accelerate the pace and improve the quality of oncofertility research and practice. Here we review the global oncofertility programs and the capacity building activities that strengthen these research and clinical programs, ultimately improving patient care.

FoxO1 Deacetylation Decreases Fatty Acid Oxidation in ß-Cells and Sustains Insulin Secretion in Diabetes.

Pancreatic ß-cell dysfunction contributes to onset and progression of type 2 diabetes. In this state ß-cells become metabolically inflexible, losing the ability to select between carbohydrates and lipids as substrates for mitochondrial oxidation. These changes lead to ß-cell dedifferentiation. We have proposed that FoxO proteins are activated through deacetylation-dependent nuclear translocation to forestall the progression of these abnormalities. However, how deacetylated FoxO exert their actions remains unclear. To address this question, we analyzed islet function in mice homozygous for knock-in alleles encoding deacetylated FoxO1 (6KR). Islets expressing 6KR mutant FoxO1 have enhanced insulin secretion in vivo and ex vivo and decreased fatty acid oxidation ex vivo Remarkably, the gene expression signature associated with FoxO1 deacetylation differs from wild type by only ∼2% of the >4000 genes regulated in response to re-feeding. But this narrow swath includes key genes required for ß-cell identity, lipid metabolism, and mitochondrial fatty acid and solute transport. The data support the notion that deacetylated FoxO1 protects ß-cell function by limiting mitochondrial lipid utilization and raise the possibility that inhibition of fatty acid oxidation in ß-cells is beneficial to diabetes treatment.