Bone dimensions in the posterior mandible: a retrospective radiographic study using cone beam computed tomography. Part 2- analysis of edentulous sites.

A precise radiographic evaluation of the local bone dimensions and morphology is important for preoperative planning of implant placement. The purpose of this retrospective study was to analyze dimensions and morphology of edentulous sites in the posterior mandible using cone beam computed tomography (CBCT) images. This retrospective radiographic study measured the bone width (BW) of the mandible at three locations on CBCT scans for premolars (PM1, PM2) and molars (M1, M2): at 1 mm and 4 mm below the most cranial point of the alveolar crest (BW1, BW2) and at the superior border of the mandibular canal (BW3). Furthermore, the height (H) of the alveolar process (distance between the measuring points BW1 and BW3), as well as the presence of lingual undercuts, were analyzed. A total of 56 CBCTs met the inclusion criteria, resulting in a sample size of 127 cross sections. There was a statistically significant increase from PM1 to M2 for the BW2 (P < .001), which was not present for BW1 and BW3 values. For the height of the alveolar process, the values exhibited a decrease from PM1 to M2 sites. Sex was a statistically significant parameter for H (P = .001) and for BW1 (P = .03). Age was not a statistically significant parameter for bone width (BW1: P = .37; BW2: P = .31; BW3: P = .51) or for the height of the alveolar process (P = .41) in the posterior mandible. Overall, 73 (57.5%) edentulous sites were evaluated to be without visible lingual undercuts; 13 (10.2%) sites exhibited lingual undercuts classified as influential for implant placement. Precise evaluation of the alveolar crest by cross-sectional imaging is of great value to analyze vertical and buccolingual bone dimensions in different locations in the posterior mandible. In addition, CBCTs are valuable to diagnosing the presence of and potential problems caused by lingual undercuts prior to implant placement.

Horizontal ridge augmentation in conjunction with or prior to implant placement in the anterior maxilla: a systematic review.

PURPOSE To systematically review clinical studies examining the survival and success rates of implants in horizontal ridge augmentation, either prior to or in conjunction with implant placement in the anterior maxilla. MATERIALS AND METHODS A literature search was undertaken up to September 2012 including clinical studies in English with ≥ 10 consecutively treated patients and a mean follow-up of at least 12 months. Two reviewers screened the pertinent articles and extracted the data. Key words focused on the outcome parameters (implant success, implant survival, horizontal bone gain, and intra- and postoperative complications) in studies utilizing either a simultaneous approach (ridge augmentation performed at the time of implant placement) or a staged approach (ridge augmentation performed prior to implant placement) were analyzed. RESULTS A total of 13 studies met the inclusion criteria, with 2 studies in the simultaneous group and 11 studies in the staged group. In the simultaneous group, survival rates of implants were 100% in both studies, with one study also reporting a 100% implant success rate. No data on horizontal bone gain were available. In the staged group, success rates of implants placed in horizontally augmented ridges ranged from 96.8% to 100% (two studies), and survival rates ranged from 93.5% to 100% (five studies). However, follow-up periods differed widely (up to 4.1 years). Mean horizontal bone gain determined at reentry (implant placement) ranged from 3.4 to 5.0 mm with large overall variations (0 to 9.8 mm, five studies). Intraoperative complications were not reported. Postsurgical complications included mainly mucosal dehiscences (five studies), and, occasionally, complete failures of block grafts were described in one study. CONCLUSIONS Staged and simultaneous augmentation procedures in the anterior maxilla are both associated with high implant success and survival rates. The level of evidence, however, is better for the staged approach than for the simultaneous one.

Immunologic response to the survivin-derived multi-epitope vaccine EMD640744 in patients with advanced solid tumors

PURPOSE Survivin is a member of the inhibitor-of-apoptosis family. Essential for tumor cell survival and overexpressed in most cancers, survivin is a promising target for anti-cancer immunotherapy. Immunogenicity has been demonstrated in multiple cancers. Nonetheless, few clinical trials have demonstrated survivin-vaccine-induced immune responses. EXPERIMENTAL DESIGN This phase I trial was conducted to test whether vaccine EMD640744, a cocktail of five HLA class I-binding survivin peptides in Montanide(®) ISA 51 VG, promotes anti-survivin T-cell responses in patients with solid cancers. The primary objective was to compare immunologic efficacy of EMD640744 at doses of 30, 100, and 300 μg. Secondary objectives included safety, tolerability, and clinical efficacy. RESULTS In total, 49 patients who received ≥2 EMD640744 injections with available baseline- and ≥1 post-vaccination samples [immunologic-diagnostic (ID)-intention-to-treat] were analyzed by ELISpot- and peptide/MHC-multimer staining, revealing vaccine-activated peptide-specific T-cell responses in 31 patients (63 %). This cohort included the per study protocol relevant ID population for the primary objective, i.e., T-cell responses by ELISpot in 17 weeks following first vaccination, as well as subjects who discontinued the study before week 17 but showed responses to the treatment. No dose-dependent effects were observed. In the majority of patients (61 %), anti-survivin responses were detected only after vaccination, providing evidence for de novo induction. Best overall tumor response was stable disease (28 %). EMD640744 was well tolerated; local injection-site reactions constituted the most frequent adverse event. CONCLUSIONS Vaccination with EMD640744 elicited T-cell responses against survivin peptides in the majority of patients, demonstrating the immunologic efficacy of EMD640744.

Exercise capacity, physical activity patterns and outcomes six years after cardiac rehabilitation in patients with heart failure.

OBJECTIVE To determine the short- and long-term effects of an intensive, concentrated rehabilitation programme in patients with chronic heart failure. DESIGN Randomized controlled trial, with one-month and six-year evaluations. SETTING Residential rehabilitation centre in Switzerland. SUBJECTS Fifty patients with chronic heart failure, randomized to exercise or control groups. INTERVENTIONS A rehabilitation programme lasting one month, including educational sessions, a low-fat diet, and 2 hours of individually prescribed exercise daily. MAIN MEASURES Exercise test responses, health outcomes and physical activity patterns. RESULTS Peak Vo(2) increased 21.4% in the exercise group during the rehabilitation programme (P<0.05), whereas peak Vo(2) did not change among controls. After the six-year follow-up period, peak Vo(2) was only slightly higher than that at baseline in the trained group (7%, NS), while peak Vo(2) among controls was unchanged. During long-term follow-up, 9 and 12 patients died in the exercise and control groups, respectively (P = 0.63). At six years, physical activity patterns tended to be higher in the exercise group; the mean energy expenditure values over the last year were 2,704 +/- 1,970 and 2,085 +/- 1,522 kcal/week during recreational activities for the exercise and control groups, respectively. However, both groups were more active compared to energy expenditure prior to their cardiac event (P<0.001). CONCLUSIONS Six years after participation in a residential rehabilitation programme, patients with chronic heart failure had slightly better outcomes than control subjects, maintained exercise capacity and engaged in activities that exceed the minimal amount recommended by guidelines for cardiovascular health.

"Sounds Funny? – Humor Effects of Phonological and Prosodic Figures of Speech"

Whereas semantic, logical, and narrative features of verbal humor are well-researched, phonological and prosodic dimensions of verbal funniness are hardly explored. In a 2 × 2 design we varied rhyme and meter in humorous couplets. Rhyme and meter enhanced funniness ratings and supported faster processing. Rhyming couplets also elicited more intense and more positive affective responses, increased subjective comprehensibility and more accurate memory. The humor effect is attributed to special rhyme and meter features distinctive of humoristic poetry in several languages. Verses that employ these formal features make an artful use of typical poetic vices of amateurish poems written for birthday parties or other occasions. Their metrical patterning sounds “mechanical” rather than genuinely “poetic”; they also disregard rules for “good” rhymes. The processing of such verses is discussed in terms of a metacognitive integration of their poetically deviant features into an overall effect of processing ease. The study highlights the importance of nonsemantic rhetorical features in language processing.

Is preoperative chemotherapy followed by surgery the appropriate treatment for signet ring cell containing adenocarcinomas of the esophagogastric junction and stomach?

BACKGROUND Recent data suggest primary resection as the preferable approach in patients with signet ring cell gastric cancer (SRC). The aim of our retrospective exploratory study was to evaluate the influence of SRC on prognosis and response in esophagogastric adenocarcinoma treated with neoadjuvant chemotherapy. METHODS A total of 723 locally advanced esophagogastric adenocarcinomas (cT3/4 N any) documented in a prospective database from two academic centers were classified according to the WHO definition for SRC (more than 50 % SRC) and analyzed for their association with response and prognosis after neoadjuvant treatment. RESULTS A total of 235 tumors (32.5 %) contained SRC. Median survival of SRC was 26.3 compared with 46.6 months (p < 0.001) for non-SRC. SRC were significantly associated with female gender, gastric localization, advanced ypT and R1/2 categories, and lower risk of surgical complications and anastomotic leakage (each p < 0.001). Clinical (21.1 vs. 33.7 %, p = 0.001) and histopathological response (less than 10 % residual tumor: 16.3 vs. 28.9 %, p < 0.001) were significantly less frequent in SRC. Clinical response (p = 0.003) and complete histopathological response (pCR) (3.4 %) (p = 0.003) were associated with improved prognosis in SRC. Clinical response, surgical complications, ypTN categories, but not SRC were independent prognostic factors in forward Cox regression analysis in R0 resected patients. Risk of peritoneal carcinomatosis was increased (p < 0.001), while local (p = 0.015) and distant metastases (p = 0.02) were less frequent than in non-SRC. CONCLUSIONS Prognosis of SRC is unfavorable. Although response to neoadjuvant chemotherapy is rare in SRC, it is associated with improved outcome. Thus, chemotherapy might not generally be abandoned in SRC. A stratification based on SRC should be included in clinical trials.

De novo loss- or gain-of-function mutations in KCNA2 cause epileptic encephalopathy.

Epileptic encephalopathies are a phenotypically and genetically heterogeneous group of severe epilepsies accompanied by intellectual disability and other neurodevelopmental features. Using next-generation sequencing, we identified four different de novo mutations in KCNA2, encoding the potassium channel KV1.2, in six isolated patients with epileptic encephalopathy (one mutation recurred three times independently). Four individuals presented with febrile and multiple afebrile, often focal seizure types, multifocal epileptiform discharges strongly activated by sleep, mild to moderate intellectual disability, delayed speech development and sometimes ataxia. Functional studies of the two mutations associated with this phenotype showed almost complete loss of function with a dominant-negative effect. Two further individuals presented with a different and more severe epileptic encephalopathy phenotype. They carried mutations inducing a drastic gain-of-function effect leading to permanently open channels. These results establish KCNA2 as a new gene involved in human neurodevelopmental disorders through two different mechanisms, predicting either hyperexcitability or electrical silencing of KV1.2-expressing neurons.

Screening for complex healing processes and psychological intervention in injured individuals

Introduction Injured individuals face a high risk for the development of psychological symptoms such as depression or anxiety, which influences early return to work after an accident. So far, it is unclear to which extent early psychological interventions can improve the ability to return to work. Purpose of the study The aim of the study was to investigate whether an improvement of the treatment-triage (by the screening questionnaire work and health [FAB]) influences early return to work and well being in injured individuals. Methods The study sample consists of injured individuals with different mental health-related or work-related disabilities after an accident. Participants are included eight weeks after an accident. Participants are randomly assigned to the intervention or to the control group. The intervention is an individualized psychotherapy consisting of cognitive-behavioral therapy and work related topics in an individual setting. Well being and work related actors are assessed at baseline and after six months. Results The recruitment is still ongoing. The preliminary results of this randomized controlled study will be presented at the conference. Conclusion An individualized psychotherapy might have the potential to improve the rehabilitation process in injured individuals and improve the ability to return to work.

Psychological intervention in injured individuals

Aim: Injured individuals face a high risk for the development of psychological symptoms such as depression or anxiety, which influences early return to work after an accident. So far, it is unclear to which extent early psychological interventions can improve the ability to return to work. The aim of the study was to investigate whether an improvement of the treatment‐triage influences early return to work and well being in injured individuals. Method: The study sample consists of injured individuals with different mental health-related or work-related disabilities after an accident. Participants are included eight weeks after an accident. Participants are randomly assigned to the intervention or to the control group. The intervention is an individualized psychotherapy consisting of cognitive‐behavioral therapy and work related topics in an individual setting. Wellbeing and work related factors are assessed at baseline and after six months. Result: The recruitment is still ongoing. The preliminary results of this randomized controlled study will be presented at the conference. Discussion: An individualized psychotherapy might have the potential to improve the rehabilitation process in injured individuals and improve the ability to return to work.

Controlled assembly and single electron charging of monolayer protected Au 144 clusters: an electrochemistry and scanning tunneling spectroscopy study

Single gold particles may serve as room temperature single electron memory units because of their size dependent electronic level spacing. Here, we present a proof-of-concept study by electrochemically controlled scanning probe experiments performed on tailor-made Au particles of narrow dispersity. In particular, the charge transport characteristics through chemically synthesized hexane-1-thiol and 4-pyridylbenzene-1-thiol mixed monolayer protected Au144 clusters (MPCs) by differential pulse voltammetry (DPV) and electrochemical scanning tunneling spectroscopy (EC-STS) are reported. The pyridyl groups exposed by the Au-MPCs enable their immobilization on Pt(111) substrates. By varying the humidity during their deposition, samples coated by stacks of compact monolayers of Au-MPCs or decorated with individual, laterally separated Au-MPCs are obtained. DPV experiments with stacked monolayers of Au144-MPCs and EC-STS experiments with laterally separated individual Au144-MPCs are performed both in aqueous and ionic liquid electrolytes. Lower capacitance values were observed for individual clusters compared to ensemble clusters. This trend remains the same irrespective of the composition of the electrolyte surrounding the Au144-MPC. However, the resolution of the energy level spacing of the single clusters is strongly affected by the proximity of neighboring particles.

Distinct characteristics of e13a2 versus e14a2 BCR-ABL1 driven chronic myeloid leukemia under first-line therapy with imatinib

The vast majority of chronic myeloid leukemia patients express a BCR-ABL1 fusion gene mRNA encoding a 210 kDa tyrosine kinase which promotes leukemic transformation. A possible differential impact of the corresponding BCR-ABL1 transcript variants e13a2 ("b2a2") and e14a2 ("b3a2") on disease phenotype and outcome is still a subject of debate. A total of 1105 newly diagnosed imatinib-treated patients were analyzed according to transcript type at diagnosis (e13a2, n=451; e14a2, n=496; e13a2+e14a2, n=158). No differences regarding age, sex, or Euro risk score were observed. A significant difference was found between e13a2 and e14a2 when comparing white blood cells (88 vs. 65 × 10(9)/L, respectively; P<0.001) and platelets (296 vs. 430 × 10(9)/L, respectively; P<0.001) at diagnosis, indicating a distinct disease phenotype. No significant difference was observed regarding other hematologic features, including spleen size and hematologic adverse events, during imatinib-based therapies. Cumulative molecular response was inferior in e13a2 patients (P=0.002 for major molecular response; P<0.001 for MR4). No difference was observed with regard to cytogenetic response and overall survival. In conclusion, e13a2 and e14a2 chronic myeloid leukemia seem to represent distinct biological entities. However, clinical outcome under imatinib treatment was comparable and no risk prediction can be made according to e13a2 versus e14a2 BCR-ABL1 transcript type at diagnosis. (clinicaltrials.gov identifier:00055874).

Older patients with chronic myeloid leukemia (≥65 years) profit more from higher imatinib doses than younger patients: a subanalysis of the randomized CML-Study IV

The impact of imatinib dose on response rates and survival in older patients with chronic myeloid leukemia in chronic phase has not been studied well. We analyzed data from the German CML-Study IV, a randomized five-arm treatment optimization study in newly diagnosed BCR-ABL-positive chronic myeloid leukemia in chronic phase. Patients randomized to imatinib 400 mg/day (IM400) or imatinib 800 mg/day (IM800) and stratified according to age (≥65 years vs. <65 years) were compared regarding dose, response, adverse events, rates of progression, and survival. The full 800 mg dose was given after a 6-week run-in period with imatinib 400 mg/day. The dose could then be reduced according to tolerability. A total of 828 patients were randomized to IM400 or IM800. Seven hundred eighty-four patients were evaluable (IM400, 382; IM800, 402). One hundred ten patients (29 %) on IM400 and 83 (21 %) on IM800 were ≥65 years. The median dose per day was lower for patients ≥65 years on IM800, with the highest median dose in the first year (466 mg/day for patients ≥65 years vs. 630 mg/day for patients <65 years). Older patients on IM800 achieved major molecular remission and deep molecular remission as fast as younger patients, in contrast to standard dose imatinib with which older patients achieved remissions much later than younger patients. Grades 3 and 4 adverse events were similar in both age groups. Five-year relative survival for older patients was comparable to that of younger patients. We suggest that the optimal dose for older patients is higher than 400 mg/day. ClinicalTrials.gov identifier: NCT00055874