Using non-invasive neuroimaging to enhance the care, well-being and experimental outcomes of laboratory non-human primates (monkeys).

Over the past 10-20 years, neuroscience witnessed an explosion in the use of non-invasive imaging methods, particularly magnetic resonance imaging (MRI), to study brain structure and function. Simultaneously, with access to MRI in many research institutions, MRI has become an indispensable tool for researchers and veterinarians to guide improvements in surgical procedures and implants and thus, experimental as well as clinical outcomes, given that access to MRI also allows for improved diagnosis and monitoring for brain disease. As part of the PRIMEatE Data Exchange, we gathered expert scientists, veterinarians, and clinicians who treat humans, to provide an overview of the use of non-invasive imaging tools, primarily MRI, to enhance experimental and welfare outcomes for laboratory non-human primates engaged in neuroscientific experiments. We aimed to provide guidance for other researchers, scientists and veterinarians in the use of this powerful imaging technology as well as to foster a larger conversation and community of scientists and veterinarians with a shared goal of improving the well-being and experimental outcomes for laboratory animals.

International consensus on the assessment of bruxism: Report of a work in progress.

In 2013, consensus was obtained on a definition of bruxism as repetitive masticatory muscle activity characterised by clenching or grinding of the teeth and/or by bracing or thrusting of the mandible and specified as either sleep bruxism or awake bruxism. In addition, a grading system was proposed to determine the likelihood that a certain assessment of bruxism actually yields a valid outcome. This study discusses the need for an updated consensus and has the following aims: (i) to further clarify the 2013 definition and to develop separate definitions for sleep and awake bruxism; (ii) to determine whether bruxism is a disorder rather than a behaviour that can be a risk factor for certain clinical conditions; (iii) to re-examine the 2013 grading system; and (iv) to develop a research agenda. It was concluded that: (i) sleep and awake bruxism are masticatory muscle activities that occur during sleep (characterised as rhythmic or non-rhythmic) and wakefulness (characterised by repetitive or sustained tooth contact and/or by bracing or thrusting of the mandible), respectively; (ii) in otherwise healthy individuals, bruxism should not be considered as a disorder, but rather as a behaviour that can be a risk (and/or protective) factor for certain clinical consequences; (iii) both non-instrumental approaches (notably self-report) and instrumental approaches (notably electromyography) can be employed to assess bruxism; and (iv) standard cut-off points for establishing the presence or absence of bruxism should not be used in otherwise healthy individuals; rather, bruxism-related masticatory muscle activities should be assessed in the behaviour's continuum.

Human tRNA-Derived Small RNAs Modulate Host-Oral Microbial Interactions.

Coevolution of the human host and its associated microbiota has led to sophisticated interactions to maintain a delicate homeostasis. Emerging evidence suggests that in addition to small molecules, peptides, and proteins, small regulatory noncoding RNAs (sRNAs) might play an important role in cross-domain interactions. In this study, we revealed the presence of diverse host transfer RNA-derived small RNAs (tsRNAs) among human salivary sRNAs. We selected 2 tsRNAs (tsRNA-000794 and tsRNA-020498) for further study based on their high sequence similarity to specific tRNAs from a group of Gram-negative oral bacteria, including Fusobacterium nucleatum, a key oral commensal and opportunistic pathogen. We showed that the presence of F. nucleatum triggers exosome-mediated release of tsRNA-000794 and tsRNA-020498 by human normal oral keratinocyte cells. Furthermore, both tsRNA candidates exerted a growth inhibition effect on F. nucleatum, likely through interference with bacterial protein biosynthesis, but did not affect the growth of Streptococcus mitis, a health-associated oral Gram-positive bacterium whose genome does not carry sequences bearing high similarity to either tsRNA. Our data provide the first line of evidence for the modulatory role of host-derived tsRNAs in the microbial-host interaction.

Peripheral nerve crushing to relieve chronic pain in diabetic and ischaemic foot ulcers.

OBJECTIVE: We retrospectively assessed the effectiveness of peripheral nerve crushing (Smithwick operation) in relieving intractable chronic pain associated with foot ulcers caused by diabetes mellitus (DM) or atherosclerosis. METHOD: From April 2009 to April 2012, patients underwent peripheral nerve crushing in the leg affected by foot ulceration. The cause of ulceration was either DM alone, atherosclerosis alone, or both DM and atherosclerosis. Because sensation in the foot is associated with five nerves: the tibial, deep peroneal, superficial peroneal, sural, and saphenous, one or more of these nerves were crushed over a length of 1.5cm by using a 'pean' in the distal third of leg the where there are no major motor nerves. RESULTS: There were 36 patients recruited with ulcers grade 3-5 according to the Wagner ulcer classification system that affected the toes, dorsum pedis, or any part of the plantar surface or the heel. The mean duration of foot ulcerations before the nerve crushing was 22.3±9.7 weeks. In all 36 patients, the nerve crushing was performed successfully without any perioperative surgical complication. Of the 36 patients, 34 (94.4%) had substantial pain relief immediately after nerve crushing. While the mean pain level before the procedure was 86.6±0.51mm on visual analogue scale (VAS), pain level dropped significantly after the operation to 18.6 ± 5.4mm at one week, 14.8±4.8mm at one month, 13.7±4.1mm at two months, 9.8±4.1mm at three months, 11.8±5.7mm at four months, 10.1±4.7mm at five months and 8.8±3.3mm at six months. The time to regeneration of the sensory nerves was 121±6.5 days (range: 80-181 days). The surgical complications were wound infection (6 patients) and temporary toe paralysis (three patients). The foot ulcers in 20 of the 36 patients (55.6%) were resolved by debridement or minor amputation. In seven patients (19.4%), a major amputation (five below and two above the knee) was required because of ischemia or infection. No patient died within 30 days of the operation, while nine patients died during the observation period because of comorbid conditions. CONCLUSION: Peripheral nerve crushing could be the alternative procedure for achieving analgesia in patients with intractable chronic pain from foot ulcers caused by DM or atherosclerosis.

Objective assessment of mastication predominance in healthy dentate subjects and patients with unilateral posterior missing teeth.

We aimed to investigate mastication predominance in healthy dentate individuals and patients with unilateral posterior missing teeth using objective and subjective methods. The sample comprised 50 healthy dentate individuals (healthy dentate group) and 30 patients with unilateral posterior missing teeth (partially edentulous group). Subjects were asked to freely chew three kinds of test foods (peanuts, beef jerky and chewing gum). Electromyographic activity of the bilateral masseter muscles was recorded. The chewing side (right side or left side) was judged by the level of root mean square electromyographic amplitude. Mastication predominance was then objectively assessed using the mastication predominant score and the mastication predominant index. Self-awareness of mastication predominance was evaluated using a modified visual analogue scale. Mastication predominance scores of the healthy dentate and partially edentulous groups for each test food were analysed. There was a significant difference in the distribution of the mastication predominant index between the two groups (P < 0·05). The mastication predominant score was weakly correlated with self-awareness of mastication predominance in the healthy dentate group, whereas strong correlation was observed in the partially edentulous group (P < 0·05). The results suggest that the individuals with missing unilateral posterior teeth exhibited greater mastication predominance and were more aware of mastication predominance than healthy dentate individuals. Our findings suggest that an objective evaluation of mastication predominance is more precise than a subjective method.

Effect of prosthetic restoration on masticatory function in patients with shortened dental arches: a multicentre study.

The aim of this multicentre study was to investigate the effect of prosthetic restoration for missing posterior teeth on mastication in patients with shortened dental arches (SDAs). Partially dentate patients who had an intact teeth in anterior region and missed distal molar(s) (2-12 missing occlusal units) classified as Kennedy Class I or Class II were recruited from seven university-based dental hospitals in Japan. Of the 125 subjects who underwent baseline (pre-treatment) and follow-up/post-treatment evaluation, 53 chose no replacement of missing teeth and 72 chose treatment with removable partial dentures (n = 53) or implant-supported fixed partial dentures (n = 19). Objective masticatory performance (MP) was evaluated using a gummy jelly test. Perception of chewing ability (CA) was rated using a food intake questionnaire. In the no-treatment group, mean MP and CA scores at baseline were similar to those at follow-up evaluation (P > 0·05). In the treatment group, mean MP after treatment was significantly greater than the pre-treatment mean MP (P < 0·05). However, the mean perceived CA in the treatment groups was similar at pre- and post-treatment (P > 0·05). In a subgroup analysis of subjects in the treatment group, subjects with lower pre-treatment CA showed a significant CA increase after treatment (P = 0·004), but those with higher pre-treatment CA showed a significant decrease in CA (P = 0·001). These results suggest that prosthetic restoration for SDAs may benefit objective masticatory performance in patients needing replacement of missing posterior teeth, but the benefit in subjective chewing ability seems to be limited in subjects with perceived impairment in chewing ability before treatment.

Effect of prosthetic restoration on oral health-related quality of life in patients with shortened dental arches: a multicentre study.

The aim of this multicentre prospective study was to investigate the effect of prosthetic restoration for missing posterior teeth in patients with shortened dental arches (SDAs). SDA patients with 2-12 missing occlusal units (a pair of occluding premolars corresponds to one unit, and a pair of occluding molars corresponds to two units) were consecutively recruited from seven university-based dental hospitals in Japan. Patients chose no replacement of missing teeth or prosthetic treatment with removable partial dentures (RPDs) or implant-supported fixed partial dentures (IFPDs). Oral health-related quality of life (OHRQoL) was measured using the oral health impact profile (Japanese version - OHIP-J) at baseline and follow-up/post-treatment evaluation. Of the 169 subjects who completed baseline evaluation, 125 subjects (mean age; 63.0 years) received follow-up/post-treatment evaluation. No-treatment was chosen by 42% (53/125) of the subjects, and 58% (72/125) chose treatment with a RPD (n = 53) or an IFPD (n = 19). In the no-treatment (NT) group, the mean OHIP summary score at baseline was similar to that at follow-up evaluation (P = 0.69). In the treatment (TRT) group, the mean OHIP summary score decreased significantly after the RPD treatment (P = 0.002), and it tended to decrease, though not statistically significant (P = 0.18), after the IFPD treatment. The restoration of one occlusal unit was associated with a 1.2-point decrease in OHIP summary score (P = 0.034). These results suggest that the replacement of missing posterior teeth with RPDs or IFPDs improved OHRQoL. Prosthetic restoration for SDAs may benefit OHRQoL in patients needing replacement of missing posterior teeth.

Occlusion on oral implants: current clinical guidelines.

Proper implant occlusion is essential for adequate oral function and the prevention of adverse consequences, such as implant overloading. Dental implants are thought to be more prone to occlusal overloading than natural teeth because of the loss of the periodontal ligament, which provides shock absorption and periodontal mechanoreceptors, which provide tactile sensitivity and proprioceptive motion feedback. Although many guidelines and theories on implant occlusion have been proposed, few have provided strong supportive evidence. Thus, we performed a narrative literature review to ascertain the influence of implant occlusion on the occurrence of complications of implant treatment and discuss the clinical considerations focused on the overloading factors at present. The search terms were 'dental implant', 'dental implantation', 'dental occlusion' and 'dental prosthesis'. The inclusion criteria were literature published in English up to September 2013. Randomised controlled trials (RCTs), prospective cohort studies and case-control studies with at least 20 cases and 12 months follow-up interval were included. Based on the selected literature, this review explores factors related to the implant prosthesis (cantilever, crown/implant ratio, premature contact, occlusal scheme, implant-abutment connection, splinting implants and tooth-implant connection) and other considerations, such as the number, diameter, length and angulation of implants. Over 700 abstracts were reviewed, from which more than 30 manuscripts were included. We found insufficient evidence to establish firm clinical guidelines for implant occlusion. To discuss the ideal occlusion for implants, further well-designed RCTs are required in the future.

The effect of intermittent use of occlusal splint devices on sleep bruxism: a 4-week observation with a portable electromyographic recording device.

This randomised controlled study investigated the effect of intermittent use of occlusal splints on sleep bruxism compared with that of continuous use by measuring masseter muscle electromyographic activity using a portable electromyographic recording system. Twenty bruxers were randomly allocated to the continuous group and intermittent group. Subjects in the continuous group wore stabilisation splints during sleep for 29 nights continuously, whereas those in the intermittent group wore splints during sleep every other week, that is they used splints on the 1st-7th, 15th-21st and 29th nights. Electromyographic activity of the masseter muscle during sleep was recorded for the following six time points: before (baseline), immediately after, and 1, 2, 3 and 4 weeks after the insertion of a stabilisation splint. The number of nocturnal masseter electromyographic events, duration and the total activity of sleep bruxism were analysed. In the continuous group, nocturnal masseter electromyographic events were significantly reduced immediately and 1 week after the insertion of the stabilisation splint, and duration was reduced immediately after the insertion (P < 0·05, Dunnett's test), but no reduction was observed at 2, 3 and 4 weeks after insertion. In the intermittent group, nocturnal masseter electromyographic events and duration were significantly reduced immediately after and also 4 weeks after insertion of the stabilisation splint (P < 0·05, Dunnett's test). The obtained results of the present exploratory trial indicate that the intermittent use of stabilisation splints may reduce sleep bruxism activity for a longer period compared with that of continuous use.

HDlive imaging of intra-amniotic umbilical vein varix with thrombosis.

We present a case of intra-amniotic umbilical vein varix with thrombosis using conventional two-dimensional (2D) sonography, power Doppler, three-dimensional (3D) HD-flow, and HDlive at 35 weeks of gestation. 2D sonography showed a large banana-like umbilical cord enlargement (100 × 43.3 × 45.9 mm) including umbilical vein varix (maximum vein diameter = 25.5 mm) with massive thrombosis. Power Doppler and 3D HD-flow revealed bidirectional turbulent blood flow inside the varix. The HDlive clearly demonstrated fragile massive thrombosis inside the varix. Elective cesarean section was performed on the same day in order to avoid additional risks of umbilical cord complications and umbilical venous embolism. A male infant weighing 2501 g was delivered with an umbilical artery pH of 7.334, and Apgar score of 8/9 at 1 and 5 min, respectively. The macroscopic and microscopic findings revealed umbilical cord vein varix with thrombosis. On the basis of the laboratory date of the neonate, the diagnosis of consumptive coagulopathy was made. However, the neonate followed a favorable course after delivery.

Bruxism defined and graded: an international consensus.

To date, there is no consensus about the definition and diagnostic grading of bruxism. A written consensus discussion was held among an international group of bruxism experts as to formulate a definition of bruxism and to suggest a grading system for its operationalisation. The expert group defined bruxism as a repetitive jaw-muscle activity characterised by clenching or grinding of the teeth and/or by bracing or thrusting of the mandible. Bruxism has two distinct circadian manifestations: it can occur during sleep (indicated as sleep bruxism) or during wakefulness (indicated as awake bruxism). For the operationalisation of this definition, the expert group proposes a diagnostic grading system of 'possible', 'probable' and 'definite' sleep or awake bruxism. The proposed definition and grading system are suggested for clinical and research purposes in all relevant dental and medical domains.

Bio-psycho-social assessment of occlusal dysaesthesia patients.

Dentists occasionally experience occlusal dysaesthesia (OD) patients, who complain of bite discomfort without evident occlusal abnormalities. It is suggested that this condition is related to somatosensory abnormalities of the trigeminal system and/or psychological problems such as somatoform disorders. The aim of this study was to investigate the characteristics of OD with a bio-psycho-social approach. Twelve OD patients (10 women, two men; mean age 54.7 years) and twelve healthy volunteers (10 women, two men; mean age 54.8 years) were selected. They were assessed using (i) interdental thickness discrimination ability test using 2-, 5- and 10-mm-thick standard blocks and 12 test blocks that were thinner or thicker than the corresponding standard block and (ii) psychological tests: General Health Questionnaire (GHQ60) and Profile of Mood States (POMS) brief-form. There was no significant difference in the interdental thickness discrimination ability between OD patients and controls (mixed-model anova, P=1.000). Regarding psychological tests, there were no significant differences between OD patients and controls in the total scores for either GHQ60 (P=0.143) or POMS brief-form (P=0.319) (Wilcoxon's test). However, OD patients showed significant differences from controls in several subscales, that is, 'somatic symptoms' (P=0.039) and 'severe depression' (P=0.039) for GHQ60 and 'depression-dejection' (P=0.014) and 'vigour' (P=0.008) for POMS brief-form (Wilcoxon's test). These results suggest there is no difference in interdental thickness discrimination ability between OD patients and normal controls, but OD patients tend to score higher on psychosomatic distress.

Rehabilitation of occlusion - science or art?

The primary objective of rehabilitating occlusion is to improve stomatognathic function in patients experiencing dysfunction in mastication, speech, and swallowing as a consequence of tooth loss. The procedure of occlusal treatment involves improving the morphology and the stomatognathic function. Several practical methods and morphological endpoints have been described in occlusal rehabilitation. We made a selection of these (mandibular position, occlusal plane, occlusal guidance, occlusal contact, face-bow transfer, use of an adjustable articulator and occlusal support) and performed a literature review to verify the existence of compelling scientific evidence for each of these. A literature search was conducted using Medline/PubMed in March 2011. Over 400 abstracts were reviewed, and more than 50 manuscripts selected. An additional hand search was also conducted. Of the many studies investigating stomatognathic function in relation to specific occlusal schemes, most studies were poorly designed and of low quality, thus yielding ambiguous results. Overall, there is no scientific evidence that supports any specific occlusal scheme being superior to others in terms of improving stomatognathic function, nor that sophisticated methods are superior to simpler ones in terms of clinical outcomes. However, it is obvious that the art of occlusal rehabilitation requires accurate, reproducible, easy and quick procedures to reduce unnecessary technical failures and/or the requirement for compensatory adjustments. Therefore, despite the lack of scientific evidence for specific treatments, the acquisition of these general skills by dentists and attaining profound knowledge and skills in postgraduate training will be necessary for specialists in charge of complicated cases.

Factors related to prosthetic restoration in patients with shortened dental arches: a multicentre study.

The aim of this study was to identify the factors related to prosthetic restoration in patients with shortened dental arches (SDA). SDA patients with 2-12 missing occlusal units were consecutively enrolled from seven university-based dental hospitals in Japan. Of the 145 subjects (mean age; 63·4 years), 41% chose no treatment and 59% sought to replace their edentulous spaces with removable partial dentures or implant-supported fixed partial dentures. Restoration decisions were related to tooth loss patterns. Only 3% of subjects missing just second molar(s) sought to receive prosthetic treatment, while the percentage increased to 58% in subjects who were missing first and second molars and 93% in subjects missing premolar(s). Logistic regression analyses found that young age, increased number of missing occlusal units, asymmetric arch and presence of chewing complaint were significant predictors for prosthetic restoration (P<0·05). Increased number of missing occlusal units and asymmetric arch were significant predictors for the presence of chewing complaint (P<0·05). These results suggest that perceived impairment of chewing ability owing to missing occlusal units is a critical factor for prosthetic restoration in SDA patients.

Simvastatin enhances bone formation around titanium implants in rat tibiae.

Statins are cholesterol-lowering drugs that have been reported to promote bone formation. The purpose of this study was to investigate the effect of simvastatin on the enhancement of bone formation around titanium implants. Thirty-week-old female rats received pure titanium implants in both tibiae. The animals were intra-peritoneally administered 0, 0.125, 1, 5 or 10 mg kg(-1) of simvastatin daily. After 30 days, the animals were sacrificed, and specimens were prepared. The bone contact ratio of the implant, bone density in the medullary canal and percentage of cortical bone were obtained. Markers for bone turnover were also measured using sera collected at the time of euthanasia. In the medullary canal, a scanty amount of bone was observed in the 0, 0.125 and 1 mg kg(-1) groups. In contrast, in both the 5 and 10 mg kg(-1) groups, thicker bone trabeculae were abundant. Histometric observations showed that the bone contact ratio and the bone density of both groups were significantly greater than those of the other groups (anova, P < 0.01). However, no significant difference in the percentage of cortical bone was found between groups. Serum chemistry showed that statin increased bone formation markers and decreased bone resorption markers. In conclusion, although the dose equivalent to that used in human patients with hypercholesterolemia was not effective, a simvastatin dose of 5 mg kg(-1) or higher increased medullary bone formation around the titanium. In contrast, no effect of simvastatin on pre-existing cortical bone was indicated.

Platelet-rich plasma suppresses osteoclastogenesis by promoting the secretion of osteoprotegerin.

BACKGROUND AND OBJECTIVE: Platelet-rich plasma is characterized by containing fundamental protein growth factors. Although many in vitro studies have documented the capability of platelet-rich plasma to induce the growth of osteoblasts or osteoblast-like cells, the effect of platelet-rich plasma on osteoclastogenesis has not yet been studied. The aim of the present study was to evaluate the effects of platelet-rich plasma and platelet-poor plasma on osteoclastogenesis with rat bone marrow cell culture. MATERIAL AND METHODS: Platelet-rich plasma and platelet-poor plasma were produced from the whole blood of rat. For cell culture, rat bone marrow cells were isolated from rat tibiae and then treated with 1,25alpha dihydroxy vitamin D(3) and with different concentrations of platelet-rich plasma or platelet-poor plasma. After 4 d of culture, rat bone marrow cells were stained with tartrate-resistant acid phosphatase (TRAP), and TRAP-positive cells that had more than three nuclei (TRAP-positive multinucleated cells) were counted as osteoclast-like cells. Osteoprotegerin, known as an osteoclastogenesis-related factor, cells was quantified using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Although platelet-poor plasma had no effect on the formation of TRAP-positive multinucleated cells, platelet-rich plasma decreased the number of TRAP-positive multinucleated cells in a dose-dependent manner. The amount of osteoprotegerin produced from rat bone marrow cells and from MC3T3-E1 cells was enhanced in platelet-rich plasma-treated groups. CONCLUSION: Under our experimental conditions, platelet-rich plasma decreased the formation of TRAP-positive multinucleated cells and increased the secretion of osteoprotegerin. This study suggests that platelet-rich plasma suppresses osteoclastogenesis, therefore inhibiting bone resorption. In addition we also demonstrated that platelet-rich plasma increased the secretion of osteoprotegerin, an inhibitor for osteoclast formation, thus suggesting that the enhancement of osteoprotegerin secretion induces this inhibitory effect.

Assessment of bruxism in the clinic.

Bruxism is a much-discussed clinical issue in dentistry. Although bruxism is not a life-threatening disorder, it can influence the quality of human life, especially through dental problems, such as tooth wear, frequent fractures of dental restorations and pain in the oro-facial region. Therefore, various clinical methods have been devised to assess bruxism over the last 70 years. This paper reviews the assessment of bruxism, provides information on various assessment methods which are available in clinical situations and discusses their effectiveness and usefulness. Currently, there is no definitive method for assessing bruxism clinically that has reasonable diagnostic and technical validity, affects therapeutic decisions and is cost effective. One future direction is to refine questionnaire items and clinical examination because they are the easiest to apply in everyday practice. Another possible direction is to establish a method that can measure actual bruxism activity directly using a device that can be applied to patients routinely. More clinical studies should examine the clinical impact of bruxism on oral structures, treatment success and the factors influencing the decision-making process in dental treatment.

The effect of oral splint devices on sleep bruxism: a 6-week observation with an ambulatory electromyographic recording device.

This study investigated the effect of stabilization splint (SS) and palatal splint (PS), which had the same design as SS except for the elimination of the occlusal coverage, on sleep bruxism (SB) using a portable electromyographic (EMG) recording system. Sixteen bruxers participated in this study. The EMG activities of the right masseter muscle during sleep were recorded for three nights each in the following five recording periods: before, immediately after, and 2, 4 and 6 weeks after the insertion of the splint. The crossover design, in which each splint was applied to each subject for 6 weeks with an interval of 2 months for a washout period, was employed in this randomized-controlled study. The number of SB events, duration and total activities of SB were analysed. The number of SB events before the insertion of splints (baseline) was 2.98 +/- 1.61 times h(-1). Both splints significantly reduced SB immediately after the insertion of devices (P < 0.05, one-way repeated-measures anova followed by Dunnett); however, no reduction was observed in 2, 4 or 6 weeks (P > 0.05). There was no statistical difference in the effect on SB between the SS and PS (P > 0.05, two-way repeated-measures anova). Both splints reduced the masseter EMG activities associated with SB; however, the effect was transient.

Analysis of sagittal condylar path inclination in consideration of Fischer's angle.

This study investigated the sagittal condylar path during protrusive and lateral excursions by analysing the actually measured jaw movement data and re-evaluated the setting of the sagittal condylar path inclination in consideration of Fischer's angle. Protrusive and lateral excursions of 10 healthy subjects were measured using a three-dimensional mandibular movement analysing system. Condylar path inclinations at the hinge-axis point and the corresponding external point laterally extending from the condyle were evaluated in the sagittal plane. Fischer's angle was defined as the difference between the sagittal condylar inclinations during protrusive and lateral excursions on the non-working side, by keeping the corresponding horizontal distance from the intercuspal position (ICP) equivalent at the incisal point. Analysis was performed at three different magnitudes of excursions, where the incisal point was located at 1, 3 and 5 mm away from the ICP. There was no significant difference in the sagittal condylar path inclination or the Fischer's angle between two condylar reference points. However, they were significantly different across the three different magnitudes of excursions for both condylar reference points, i.e. sagittal condylar path inclination (P = 0.003 for protrusive excursion, and P < 0.001 for lateral excursion respectively; two-way repeated-measures anova), and Fischer's angle (P = 0.013, two-way repeated-measures anova) became smaller as the incisal point became distant from the ICP. Moreover, 3- and 5-mm eccentric positions were included in the 95% CI where Fischer's angle equals zero and were considered to be clinically acceptable to adjust the sagittal condylar inclination on the semiadjustable articulators.

Deeply located granule cells and mitral cells undergo apoptosis after transection of the central connections of the main olfactory bulb in the adult rat.

The main olfactory bulb (MOB) is the first relay station of the olfactory system: it receives afferents from sensory neurons and sends efferents to the primary olfactory cortex. The MOB also receives many centrifugal afferents from various regions. Transection of peripheral afferents to the MOB has been reported to induce cell death in granule cells. However, little is known about the effect of transection of these central connections of the MOB in adult rats. Here, we used a unilateral olfactory peduncle transection model in the adult rat to examine neuronal degeneration in the MOB. In the MOB ipsilateral to the surgery, the granule cell layer (GCL) was smaller, and the number of mitral cells was decreased compared with the contralateral MOB at 7 days after surgery. Many degenerating cells were present in both the mitral cell layer (MCL) and GCL in the ipsilateral MOB at 3 days after surgery, although there were no obvious changes in the gross morphology. We also found terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labeling (TUNEL)-positive cells in the MCL and GCL in the ipsilateral MOB at 3 days after surgery. The majority of the degenerating and TUNEL-positive cells were located in the deep, rather than the superficial, GCL. Immunohistochemistry for activated caspase-9 further supported the occurrence of apoptotic cell death in the mitral and deeply located granule cells. These results indicate that not only axotomized mitral cells, but also deeply located granule cells that were not directly injured, underwent apoptosis after transection of the central connections, and suggest that sensitivities to transection of the central connections differ among granule cells according to their depth in the GCL.