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.

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.

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.

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.

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.

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.

Sensor-controlled scalp cooling to prevent chemotherapy-induced alopecia in female cancer patients.

BACKGROUND: Scalp cooling has been used since the 1970s to prevent chemotherapy-induced alopecia, one of the most common and psychologically troubling side effects of chemotherapy. Currently available scalp cooling systems demonstrate varying results in terms of effectiveness and tolerability. METHODS: For the present prospective study, 55 women receiving neoadjuvant, adjuvant, or palliative chemotherapy were enrolled. The aim was to assess the effectiveness of a sensor-controlled scalp cooling system (DigniCap: Sysmex Europe GmbH, Norderstedt, Germany) to prevent chemotherapy-induced alopecia in breast or gynecologic cancer patients receiving 1 of 7 regimens. Clinical assessments, satisfaction questionnaires, and alopecia evaluations [World Health Organization (who) grading for toxicity] were completed at baseline, at each cycle, and at completion of chemotherapy. RESULTS: Of the 55 patients, 78% underwent scalp cooling until completion of chemotherapy. In multivariate analysis, younger women and those receiving paclitaxel weekly or paclitaxel-carboplatin experienced less alopecia. The compound successful outcome ("no head covering" plus "who grade 0/1") was observed in all patients 50 years of age and younger receiving 4 cycles of docetaxel-cyclophosphamide or 6 cycles of paclitaxel-carboplatin. Conversely, alopecia was experienced by all women receiving triplet polychemotherapy (6 cycles of docetaxel-doxorubicin-cyclophosphamide). For women receiving sequential polychemotherapy regimens (3 cycles of fluorouracil-epirubicin-cyclophosphamide followed by 3 cycles of docetaxel or 4 cycles of doxorubicin-cyclophosphamide followed by 4 cycles of docetaxel), the subgroup 50 years of age and younger experienced a 43% success rate compared with a 10% rate for the subgroup pf older women receiving the same regimens. CONCLUSIONS: The ability of scalp cooling to prevent chemotherapy-induced alopecia varies with the chemotherapy regimen and the age of the patient. Use of a compound endpoint with subjective and objective measures provides insightful and practical information when counselling patients.

Activation patterns of different brain areas during incremental exercise measured by near-infrared spectroscopy.

Recent studies postulated that increased oxygenation of the prefrontal cortex (PFC) during elevating exercise intensities reflects a specific activation of this region. Furthermore, the drop in PFC oxygenation often measured shortly before exhaustion is interpreted as a main factor limiting exercise. Nevertheless, a limitation of these studies is that they often measured NIRS only in the PFC. Within this study, we hypothesized that these findings are not region specific but rather result from systemic blood redistribution to the working skeletal muscle. NIRS was measured in three different brain regions and the working skeletal muscle during incremental cycling till exhaustion in nine healthy men. Oxygenated hemoglobin of the PFC increased from low to submaximal intensities and leveled off at maximal intensities. There was no drop in PFC oxygenation before exercise abortion. Interestingly, the occipital cortex was unaffected during exercise, while the motor cortex showed an increasing deoxygenation with elevating exercise intensities, just as observed in the skeletal muscle. In conclusion, this study does not support the notion that PFC deoxygenation is involved in the limitation of maximum exercise capacity. Against the hypothesis, the NIRS signals of the other cortices differed clearly, indicating that the previously reported findings indeed represent region-specific activations.

Bone augmentation using a synthetic hydroxyapatite/silica oxide-based and a xenogenic hydroxyapatite-based bone substitute materials with and without recombinant human bone morphogenetic protein-2.

AIM: To test whether or not bone regeneration using deproteinized bovine bone mineral (DBBM) is comparable to hydroxyapatite/silica oxide (HA/SiO) and to test the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) as an adjunct to DBBM for localized bone regeneration. MATERIALS AND METHODS: In each of the 10 rabbits, 4 titanium cylinders were placed on the external cortical plates of their calvaria. Four treatment modalities were randomly allocated: (i) empty, (ii) HA/SiO, (iii) DBBM, and (iv) DBBM plus rhBMP-2 (DBBM/BMP). The animals were sacrificed at week 8. Descriptive histology and histomorphometric assessment using a superimposed test grid of points and cycloids were performed. RESULTS: The mean number of points of the test grid coinciding with bone within the cylinder reached 124 ± 35 bone points for empty controls, 92 ± 40 bone points for DBBM, 98 ± 44 bone points for synthetic HA/SiO, and 146 ± 34 bone points DBBM/BMP. The P-value for DBBM with and without BMP reached a borderline statistical significance of 0.051. However, the area of bone regeneration within the cylinders peaked for DBBM/BMP and was statistically significantly higher compared with empty cylinders (P < 0.05). The bone-to-bone substitute contact ranged between 32.9% ± 21.7 for DBBM, 39.6 ± 18.4% for HA/SiO, and 57.8% ± 10.2 for DBBM/BMP. The differences between DBBM/BMP and controls (DBBM, HA/SiO) were statistically significant (P < 0.05). CONCLUSIONS: DBBM and HA/SiO rendered comparable amounts of bone regeneration. The addition of rhBMP-2 to DBBM resulted in more favorable outcomes with respect to the area of bone regeneration and to bone-to-implant contact, thereby indicating the potential of this growth factor to enhance bone regeneration within this animal model.

EAO Supplement Working Group 4 - EAO CC 2015 Short implants versus sinus lifting with longer implants to restore the posterior maxilla: a systematic review.

OBJECTIVE: To compare short implants in the posterior maxilla to longer implants placed after or simultaneously with sinus floor elevation procedures. The focused question was as follows: Are short implants superior to longer implants in the augmented sinus in terms of survival and complication rates of implants and reconstructions, patient-reported outcome measures (PROMs) and costs? METHODS: A MEDLINE search (1990-2014) was performed for randomized controlled clinical studies comparing short implants (≤8 mm) to longer implants (>8 mm) in augmented sinus. The search was complimented by an additional hand search of the selected papers and reviews published between 2011 and 2014. Eligible studies were selected based on the inclusion criteria, and quality assessments were conducted. Descriptive statistics were applied for a number of outcome measures. Survival rates of dental implants were pooled simply in case of comparable studies. RESULTS: Eight randomized controlled clinical trials (RCTs) comparing short implants versus longer implants in the augmented sinus derived from an initial search count of 851 titles were selected and data extracted. In general, all studies were well conducted with a low risk of bias for the majority of the analyzed parameters. Based on the pooled analyses of longer follow-ups (5 studies, 16-18 months), the survival rate of longer implants amounted to 99.5% (95% CI: 97.6-99.98%) and for shorter implants to 99.0% (95% CI: 96.4-99.8%). For shorter follow-ups (3 studies, 8-9 months), the survival rates of longer implants are 100% (95% CI: 97.1-100%) and for shorter implants 98.2% (95% CI: 93.9-99.7%). Complications were predominantly of biological origin, mainly occurred intraoperatively as membrane perforations, and were almost three times as higher for longer implant in the augmented sinus compared to shorter implants. PROMs, morbidity, surgical time and costs were generally in favor of shorter dental implants. All studies were performed by surgeons in specialized clinical settings. CONCLUSIONS: The outcomes of the survey analyses demonstrated predictably high implant survival rates for short implants and longer implants placed in augmented sinus and their respective reconstructions. Given the higher number of biological complications, increased morbidity, costs and surgical time of longer dental implants in the augmented sinus, shorter dental implants may represent the preferred treatment alternative.

Long-term imatinib treatment does not cause testicular toxicity in male adolescents with chronic myeloid leukemia and in a juvenile rat model.

BACKGROUND: The impact of exposure to the tyrosine kinase inhibitor (TKI) imatinib (IMA) on the male reproductive endocrine system is still discussed controversially. We therefore investigated testosterone (Testo) and inhibin B (InB) in blood serum from male adolescents with chronic myeloid leukemia (CML) under long-term TKI treatment. Also long-term exposure to TKIs was studied in a juvenile rat model. METHODS: Serum was collected at 3 months intervals from 13 boys (age: 7.8-18.9 years, median: 12.8 years) with CML receiving TKI treatment over 3-58 months (median: 18 months). 4 weeks (w) old male rats were exposed, either chronically or intermittently, via the drinking water to a standard (SD) and a high dose (=2-fold SD) of IMA, dasatinib (DASA), or bosutinib (BOSU) over a 10 w period. Controls received water only. Animals were sacrificed after 2 w (prepubertal), 4 w (pubertal), and 10 w (postpubertal) of exposure. Testo and InB serum levels were measured by ELISA. RESULTS: Boys exhibited Testo and InB levels within normal age-related reference ranges and no pattern of rising or falling levels during TKI treatment could be observed. In rats, Testo levels under IMA exposure tended to be non-significantly lowered at postpubertal age compared to controls while no significant differences were found under DASA and BOSU exposure. Animals' InB levels did not significantly differ from controls for all TKIs, at all doses, and by all application schemes tested. CONCLUSION: With the limitation that the number of individuals tested was rather small, testicular toxicity due to TKI seems unlikely as no alterations of Testo and InB blood levels neither in male adolescent patients nor in rats under long-term TKI exposure was observed.

Using joint ICA to link function and structure using MEG and DTI in schizophrenia.

In this study we employed joint independent component analysis (jICA) to perform a novel multivariate integration of magnetoencephalography (MEG) and diffusion tensor imaging (DTI) data to investigate the link between function and structure. This model-free approach allows one to identify covariation across modalities with different temporal and spatial scales [temporal variation in MEG and spatial variation in fractional anisotropy (FA) maps]. Healthy controls (HC) and patients with schizophrenia (SP) participated in an auditory/visual multisensory integration paradigm to probe cortical connectivity in schizophrenia. To allow direct comparisons across participants and groups, the MEG data were registered to an average head position and regional waveforms were obtained by calculating the local field power of the planar gradiometers. Diffusion tensor images obtained in the same individuals were preprocessed to provide FA maps for each participant. The MEG/FA data were then integrated using the jICA software (http://mialab.mrn.org/software/fit). We identified MEG/FA components that demonstrated significantly different (p<0.05) covariation in MEG/FA data between diagnostic groups (SP vs. HC) and three components that captured the predominant sensory responses in the MEG data. Lower FA values in bilateral posterior parietal regions, which include anterior/posterior association tracts, were associated with reduced MEG amplitude (120-170 ms) of the visual response in occipital sensors in SP relative to HC. Additionally, increased FA in a right medial frontal region was linked with larger amplitude late MEG activity (300-400 ms) in bilateral central channels for SP relative to HC. Step-wise linear regression provided evidence that right temporal, occipital and late central components were significant predictors of reaction time and cognitive performance based on the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) cognitive assessment battery. These results point to dysfunction in a posterior visual processing network in schizophrenia, with reduced MEG amplitude, reduced FA and poorer overall performance on the MATRICS. Interestingly, the spatial location of the MEG activity and the associated FA regions are spatially consistent with white matter regions that subserve these brain areas. This novel approach provides evidence for significant pairing between function (neurophysiology) and structure (white matter integrity) and demonstrates that this multivariate, multimodal integration technique is sensitive to group differences in function and structure.

Postictal psychosis in temporal lobe epilepsy: a case-control study.

BACKGROUND AND PURPOSE: To investigate the prevalence of postictal psychosis (PP) in patients with temporal lobe epilepsy (TLE) and to estimate the predictive value of various variables for the development of PP. METHODS: By retrospectively reviewing the charts of all patients evaluated with video-electroencephalogram (EEG)-monitoring at our unit between January 1995 and February 2012, we identified 684 patients with TLE, of which 48 patients had a history of PP. Patients with TLE and PP were compared with 200 controls (patients with TLE without a psychotic history) on demographic, clinical, EEG and magnetic resonance imaging (MRI) variables. RESULTS: The prevalence of PP in our TLE sample was 7.0%. Aggressive behaviour during PP was present in 22.9% of the sample. Univariate analysis revealed that PP was significantly associated with early age at epilepsy onset (P = 0.007), longer duration of epilepsy (P = 0.002), presence of ictal fear (P = 0.005), impaired intellectual function (P = 0.045), and bilateral ictal and interictal epileptiform activity (both P < 0.0001). Using logistic regression analysis, ictal fear [odds ratio (OR) 2.88; P = 0.015] and bilateral interictal EEG activity (OR 6.40; P < 0.0001) were predictive of PP development. No association of PP with MRI pathology or epilepsy-relevant aetiological factors was found. CONCLUSIONS: PP is a frequent and potentially dangerous complication within the course of TLE. Bilateral or widespread functional central nervous system disturbances rather than distinct structural brain alterations or certain predisposing aetiologies of epilepsy appear to be a risk factor for the development of PP. Ictal fear may be a predictive clinical variable of PP in TLE.

The effect of early prednisolone treatment on the generalization rate in ocular myasthenia gravis.

BACKGROUND AND PURPOSE: Several small retrospective studies have observed that patients with a purely ocular manifestation of myasthenia gravis (MG) are significantly less likely to convert to a generalized disease when treated early on with corticosteroids. However, given the limited number of reported patients in the literature these findings still remain controversial. METHODS: In order to increase the number of published cases, we performed a retrospective analysis on 44 patients with newly diagnosed ocular MG who were subsequently either treated with corticosteroids or received no immunosuppressive therapy at all. The generalization rate was assessed at the end of a 2-year follow-up period. RESULTS: Whereas none of 17 treated patients generalized, 11 of 27 (41%) untreated patients developed generalized symptoms. The difference between the groups was significant (P=0.003). CONCLUSIONS: Our results agree well with previous studies on this issue. Taken together, published data indicate risk ratios for generalization of below 0.32 under corticosteroid treatment in comparison to untreated patients.

TK inhibitor treatment disrupts growth hormone axis: clinical observations in children with CML and experimental data from a juvenile animal model.

BACKGROUND: Long-term treatment of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors (TKIs) exerts off-target effects on bone growth by either impaired growth hormone (GH) action or osseous modelling impairment. METHODS: Body height and the GH-related parameters insulin-like growth factor 1 (IGF-1) and insulin-like growth factor-binding protein 3(IGFBP-3) were determined repetitively 3-monthly over 2 years in 21 pediatric CML-patients on standardized imatinib treatment. In an animal model 4-week-old male Wistar rats were exposed over 10 weeks to imatinib, dasatinib, or bosutinib at varying concentrations via the drinking water. Blood was collected at prepubertal age, pubertal age, and at adult age, respectively, and animals' serum levels of IGFBP-3 were measured. RESULTS: Independent from treatment duration patients exhibited IGF-1 and IGFBP-3 levels almost exclusively in the very low range when compared to age-matched references. No clear pattern of rising or falling IGF-1 and IGFBP-3 levels was observed. In rats, compared to controls, serum IGFBP-3 was significantly lowered for all TKIs tested, at all concentrations applied, and at all ages under investigation. CONCLUSION: Besides direct off-target effects on the growing skeleton, TKI treatment also results in lowered blood levels of IGF-1 and IGFBP-3.A juvenile rat model predicts this side effect for dasatinib and bosutinib. Thus, growth and GH- related parameters should be monitored regularly in pediatric patients with CML on TKIs.

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).

Dynamics of self-generated, large amplitude magnetic fields following high-intensity laser matter interaction.

The dynamics of magnetic fields with an amplitude of several tens of megagauss, generated at both sides of a solid target irradiated with a high-intensity (~10(19) W/cm(2)) picosecond laser pulse, has been spatially and temporally resolved using a proton imaging technique. The amplitude of the magnetic fields is sufficiently large to have a constraining effect on the radial expansion of the plasma sheath at the target surfaces. These results, supported by numerical simulations and simple analytical modeling, may have implications for ion acceleration driven by the plasma sheath at the rear side of the target as well as for the laboratory study of self-collimated high-energy plasma jets.

Spatially resolved measurements of laser filamentation in long scale length underdense plasmas with and without beam smoothing.

The onset of filamentation, following the interaction of a relatively long (τ(L)≃1 ns) and intense (I(L)≃5×10(14) W/cm(2)) laser pulse with a neopentane filled gas bag target, has been experimentally studied via the proton radiography technique, in conditions of direct relevance to the indirect drive inertial confinement fusion scheme. The density gradients associated with filamentation onset have been spatially resolved yielding direct and unambiguous evidence of filament formation and quantitative information about the filamentation mechanism in agreement with previous theoretical modelings. Experimental data confirm that, once spatially smoothed laser beams are used, filamentation is not a relevant phenomenon during the heating laser beams propagation through typical hohlraum gas fills.

1H-MRS at 4 tesla in minimally treated early schizophrenia.

We investigated glutamate-related neuronal dysfunction in the anterior cingulate (AC) early in schizophrenia before and after antipsychotic treatment. A total of 14 minimally treated schizophrenia patients and 10 healthy subjects were studied with single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) of the AC, frontal white matter and thalamus at 4 T. Concentrations of N-acetylaspartate (NAA), glutamate (Glu), glutamine (Gln) and Gln/Glu ratios were determined and corrected for the partial tissue volume. Patients were treated with antipsychotic medication following a specific algorithm and (1)H-MRS was repeated after 1, 6 and 12 months. There were group x region interactions for baseline NAA (P=0.074) and Gln/Glu (P=0.028): schizophrenia subjects had lower NAA (P=0.045) and higher Gln/Glu (P=0.006) in the AC before treatment. In addition, AC Gln/Glu was inversely related to AC NAA in the schizophrenia (P=0.0009) but not in the control group (P=0.92). Following antipsychotic treatment, there were no further changes in NAA, Gln/Glu or any of the other metabolites in any of the regions studied. We conclude that early in the illness, schizophrenia patients already show abnormalities in glutamatergic metabolism and reductions in NAA consistent with glutamate-related excitotoxicity.