Influence of the number of implants in the edentulous mandible on chewing efficacy and oral health-related quality of life-A within-subject design study.

OBJECTIVES: To investigate the chewing efficiency and oral health-related quality of life of edentulous patients wearing complete dentures, successively supported by one, two, and three implants in the mandible. METHODS: Thirteen (13) edentulous patients of at least 50 years of age received three implants in the mandible. After a conventional submerged healing period, the central implant was uncovered and connected to the denture base using a stud attachment. Two months later, chewing efficacy was evaluated, and the two lateral implants were uncovered and connected to the denture base. The central retention element was replaced by a short healing abutment with no connection to the denture base. Chewing efficiency was evaluated two months later. Afterward, the healing abutment of the central implant was replaced by a stud attachment and again connected to the denture base. Two months later, chewing efficacy was evaluated again. Oral health-related quality of life (OHRQoL) was measured at each recall visit using the summary score of the oral health impact profile. For statistical analysis of chewing efficacy, the changes from baseline (with no implants) to one, two, and three implants were used and tested by analysis of variance with repeated mesurements. RESULTS: Chewing efficacy clearly increased after implant loading, with a significant increase when two implants were loaded (p ≤ .05), compared to the chewing efficacy with no implants. OHRQoL also significantly improved after implant loading. CONCLUSIONS: Within the limitations of the present clinical trial regarding the number of patients, chewing efficacy as well OHRQoL of edentulous patients improve after implant placement in the mandible, irrespective of the number of implants. The best chewing efficacy was achieved with two implants.

Lysyl oxidase like-4 monoclonal antibody demonstrates therapeutic effect against head and neck squamous cell carcinoma cells and xenografts.

A new member of the lysyl oxidase (LOX) family, lysyl oxidase-like 4 (LOXL4), is overexpressed in head and neck squamous cell carcinoma (HNSCC) compared to normal squamous epithelium. A monoclonal antibody (mAb) derived from fusion of Balb/c mouse splenocytes immunized with LOXL4 specific peptide was used to evaluate its therapeutic efficacy in 15 HNSCC cell lines associated with LOXL4 overexpression. For xenograft experiments 41 severe combined immunodeficient (SCID) mice were used to analyze LOXL4-mAb mediated tumor regression. Cell viability was analyzed using cytotoxicity-, and clonogenic-assays. Significant suppression of tumor cell growth was observed in 12 out of 15 (80%) tumor cell lines after 48 hr exposure to the mAb (LD50 of 15 µg/ml to 45 µg/ml). The effect induced by the antibody could be blocked by pre-incubation of the antibody with the peptide used for immunization of the mice and antibody generation, indicating that the effect of the antibody is specific. In mice inoculated with HNSCC cells, i.v. injections of the LOXL4-mAb resulted within 70 days in extensive tumor destruction in all treated animals whereas no tumor regression occurred in control animals. In mice pre-immunized i.v. with LOXL4-mAb and subsequently injected with HNSCC cells, tumor development was considerably delayed in contrast to non LOXL4-mAb pre-immunized animals. These results demonstrate that the LOXL4-mAb has potent antitumor activity and suggest its suitability as a therapeutic immune agent applicable to HNSCC exhibiting tumor specific upregulation of LOXL4.

Psychophysics of human echolocation.

The skills of some blind humans orienting in their environment through the auditory analysis of reflections from self-generated sounds have received only little scientific attention to date. Here we present data from a series of formal psychophysical experiments with sighted subjects trained to evaluate features of a virtual echo-acoustic space, allowing for rigid and fine-grain control of the stimulus parameters. The data show how subjects shape both their vocalisations and auditory analysis of the echoes to serve specific echo-acoustic tasks. First, we show that humans can echo-acoustically discriminate target distances with a resolution of less than 1 m for reference distances above 3.4 m. For a reference distance of 1.7 m, corresponding to an echo delay of only 10 ms, distance JNDs were typically around 0.5 m. Second, we explore the interplay between the precedence effect and echolocation. We show that the strong perceptual asymmetry between lead and lag is weakened during echolocation. Finally, we show that through the auditory analysis of self-generated sounds, subjects discriminate room-size changes as small as 10%.In summary, the current data confirm the practical efficacy of human echolocation, and they provide a rigid psychophysical basis for addressing its neural foundations.

Development of generic Asian pelvic bone models using CT-based 3D statistical modelling.

BACKGROUND/OBJECTIVE: Artificial bone models (ABMs) are used in orthopaedics for research of biomechanics, development of implants and educational purposes. Most of the commercially available ABMs approximate the morphology of Europeans, but they may not depict the Asian anatomy. Therefore, our aim was to develop the first Asian ABM of the pelvis and compare it with the existing pelvic ABM (Synbone®; Caucasian male). METHODS: One hundred clinical computed tomography (CTs) of adult pelvises (male n â€‹= â€‹50, female n â€‹= â€‹50) of Malay, Chinese and Indian descent were acquired. CTs were segmented and defined landmarks were placed. Three 3D statistical pelvic model and mean models (overall, male, female) were generated. Anatomical variations were analysed using principal component analysis. To measure gender-related differences and differences to the existing ABM, distances between the anterior superior iliac spines (ASIS), the anterior inferior iliac spines (AIIS), the promontory and the symphysis (conjugate vera, CV) as well as the ischial spines (diameter transversa, DT) were quantified. RESULTS: Principal component analysis displayed large variability regarding the pelvic shape and size. Female and male statistical models were similar in ASIS (225 â€‹± â€‹20; 227 â€‹± â€‹13 â€‹mm; P â€‹= â€‹0.4153) and AIIS (185 â€‹± â€‹11; 187 â€‹± â€‹10 â€‹mm; P â€‹= â€‹0.3982) and differed in CV (116 â€‹± â€‹10; 105 â€‹± â€‹10 â€‹mm; P â€‹< â€‹0.0001) and DT (105 â€‹± â€‹7; 88 â€‹± â€‹8 â€‹mm; P â€‹< â€‹0.0001). Comparing the unisex mean model with the pre-existing ABM, the ASIS (226; 275 â€‹mm; P â€‹< â€‹0.0001), the AIIS (186; 209 â€‹mm; P â€‹< â€‹0.0001) and the CV (111; 105 â€‹mm; P â€‹< â€‹0.0001) differed significantly. Both models were similar regarding DT (97; 95 â€‹mm; P â€‹= â€‹0.6927). The analysis revealed notable gender- and size-dependent anatomical variations within the Asian population. Chinese, Malay and Indian descents did not differ notably. The overall Asian model was smaller than the existing ABM. THE TRANSLATION POTENTIAL OF THIS ARTICLE: Owing to the large differences between the Asian ABM and the pre-existing ABM, as well as differences between genders, the use of an Asian- and gender-specific ABM is important to consider in research, biomechanics and implant development for this population.

Discovering your inner bat: echo-acoustic target ranging in humans.

Echolocation is typically associated with bats and toothed whales. To date, only few studies have investigated echolocation in humans. Moreover, these experiments were conducted with real objects in real rooms; a configuration in which features of both vocal emissions and perceptual cues are difficult to analyse and control. We investigated human sonar target-ranging in virtual echo-acoustic space, using a short-latency, real-time convolution engine. Subjects produced tongue clicks, which were picked up by a headset microphone, digitally delayed, convolved with individual head-related transfer functions and played back through earphones, thus simulating a reflecting surface at a specific range in front of the subject. In an adaptive 2-AFC paradigm, we measured the perceptual sensitivity to changes of the range for reference ranges of 1.7, 3.4 or 6.8 m. In a follow-up experiment, a second simulated surface at a lateral position and a fixed range was added, expected to act either as an interfering masker or a useful reference. The psychophysical data show that the subjects were well capable to discriminate differences in the range of a frontal reflector. The range-discrimination thresholds were typically below 1 m and, for a reference range of 1.7 m, they were typically below 0.5 m. Performance improved when a second reflector was introduced at a lateral angle of 45°. A detailed analysis of the tongue clicks showed that the subjects typically produced short, broadband palatal clicks with durations between 3 and 15 ms, and sound levels between 60 and 108 dB. Typically, the tongue clicks had relatively high peak frequencies around 6 to 8 kHz. Through the combination of highly controlled psychophysical experiments in virtual space and a detailed analysis of both the subjects' performance and their emitted tongue clicks, the current experiments provide insights into both vocal motor and sensory processes recruited by humans that aim to explore their environment by echolocation.

Cerebrospinal fluid pleocytosis: pitfalls and benefits of combined analysis using cytomorphology and flow cytometry.

BACKGROUND: Cerebrospinal fluid samples with doubtful morphologic interpretation are a common problem in the workup of patients with clinical signs for leptomeningeal disease. The authors report on the combination of morphology and flow cytometry in the diagnosis of leptomeningeal disease in patients with radiological, clinical, or cytological findings suspicious for leukemia or lymphoma with spread into the cerebrospinal fluid. METHODS: The authors defined a set of antibodies for flow cytometric analysis, which is capable of distinguishing between malignant and nonmalignant hematopoietic cells. One hundred twenty-seven cases were analyzed with both methods. RESULTS: The additional application of flow cytometry resulted in an improvement of diagnostic reliability in 29 of 127 cases. Diagnostic sensitivity was raised from 73% (cytology) to 96% (flow cytometry), specificity from 94% to 97%, the positive predictive value from 88% to 96%, and the negative predictive value from 76% to 97%. CONCLUSIONS: Because the appropriate selection of markers is crucial to successful analysis, the authors suggested a highly selected panel of antibodies for flow cytometry analysis of cerebrospinal fluid samples. The authors were able to demonstrate that leptomeningeal disease caused by leukemia or lymphoma can be diagnosed by flow cytometry and discriminated from reactive pleocytosis in most cases of doubtful morphology.

Stress doses of hydrocortisone reduce severe systemic inflammatory response syndrome and improve early outcome in a risk group of patients after cardiac surgery.

OBJECTIVE: Severe systemic inflammation with a vasodilatory syndrome occurs in about one third of all patients after cardiac surgery with cardiopulmonary bypass. Hydrocortisone has been used successfully to reverse vasodilation in septic patients. We evaluated if stress doses of hydrocortisone attenuate severe systemic inflammatory response syndrome in a predefined risk group of patients after cardiac surgery with cardiopulmonary bypass. DESIGN: Randomized, nonblinded, controlled trial. SETTING: Anesthesiologic intensive care unit for cardiac surgical patients of an university hospital. PATIENTS: After a risk analysis, we enrolled 91 patients into a prospective randomized trial. Patients were included according to the evaluated criteria (preoperative ejection fraction, duration of cardiopulmonary bypass, type of surgery). INTERVENTIONS: The treatment group received stress doses of hydrocortisone perioperatively: 100 mg before induction of anesthesia, then 10 mg/hr for 24 hrs, 5 mg/hr for 24 hrs, 3 x 20 mg/day, and 3 x 10 mg/day. MEASUREMENTS AND MAIN RESULTS: We measured various laboratory (e.g., lactate) and clinical variables (e.g., duration of ventilation and length of stay in the intensive care unit), characterizing the patients' outcome. The two study groups did not differ regarding age, preoperative medication, duration of the cardiopulmonary bypass, and type of surgery. The patients in the treatment group had significantly lower concentrations of IL-6 and lactate, higher antithrombin III concentration, lower need for circulatory and ventilatory support and for transfusions, lower Therapeutic Intervention Scoring System values, and shorter length of stay in the intensive care unit and in the hospital. The mortality rate did not differ significantly between the groups. CONCLUSIONS: Although we acknowledge the limitations of a nonblinded interventional trial, stress doses of hydrocortisone seem to attenuate systemic inflammation in a predefined risk group of patients after cardiac surgery with cardiopulmonary bypass and improve early outcome.

Essential role of brain-derived neurotrophic factor in adult hippocampal function.

Brain-derived neurotrophic factor (BDNF) regulates neuronal development and function. However, it has been difficult to discern its role in the adult brain in influencing complex behavior. Here, we use a recently developed inducible knockout system to show that deleting BDNF in broad forebrain regions of adult mice impairs hippocampal-dependent learning and long-term potentiation. We use the inducible nature of this system to show that the loss of BDNF during earlier stages of development causes hyperactivity and more pronounced hippocampal-dependent learning deficits. We also demonstrate that the loss of forebrain BDNF attenuates the actions of desipramine, an antidepressant, in the forced swim test, suggesting the involvement of BDNF in antidepressant efficacy. These results establish roles for BDNF in the adult, and demonstrate the strength of this inducible knockout system in studying gene function in the adult brain.