Effects of Unrestricted Kinematically Aligned Total Knee Arthroplasty with a Modified Soft-Tissue Respecting Technique on the Deformity of Limb Alignment in Japanese Patients.

Background and Objectives: Unrestricted kinematic alignment total knee arthroplasty (KA-TKA) with a soft-tissue respecting technique (STRT) is a soft-tissue-dependent tibial resection entailing the restoration of the original soft-tissue tension using ligamentotaxis after resurfacing the femur, based on the concept of restoring the native or pre-osteoarthritis alignment in each patient. However, there is no consensus on the indications of unrestricted KA-TKA with the STRT. We modified the STRT, followed by an investigation of the effects of surgery on the postoperative hip-knee-ankle angle (HKAA). Materials and Methods: We retrospectively analyzed the clinical background data, including the preoperative and postoperative HKAA, of 87 patients who underwent unrestricted KA-TKA with the modified STRT. Univariate and multivariate analyses were performed to determine the factors affecting the postoperative HKAA. A receiver operating characteristic (ROC) curve was plotted to investigate the change in the cut-off values of preoperative HKAA with respect to the safe zone of the postoperative HKAA. We generated two regression models, the linear regression model and generalized additive model (GAM) using machine learning, to predict the postoperative HKAA. Results: Univariate and multivariate analyses revealed the preoperative HKAA as the factor most relevant to the postoperative HKAA. ROC analysis revealed that the preoperative HKAA exhibited a high predictive utility, with a cut-off value of -10°, when the safe range of postoperative HKAA was set at ±5°. The GAM was the superior machine learning model, indicating a non-linear association between the preoperative and postoperative HKAA. Patients with preoperative HKAAs ranging from -18° to 4° were more likely to fall within the ±5° safe range of the postoperative HKAA. Conclusions: The preoperative HKAA influences the postoperative HKAA in unrestricted KA-TKA with the modified STRT. Machine learning using the GAM may contribute to the selection of patients eligible for the surgical approach.

Clinical factors affecting pupillary light reflex parameters: a single-centre, cross-sectional study.

PURPOSE: To evaluate the effects of stimulus intensity, aging, sex, smoking and eye symmetry on pupillary light reflex (PLR) parameters. METHODS: We evaluated 2812 eyes from 1406 subjects in a single-centre, cross-sectional study. PLR data were collected using four different stimulus intensities. We prepared two models for each of the eight PLR parameters, and defined the model with the lowest values of Akaike's information criterion (AIC) as being the best-fit. Model A was a linear regression model without adjustment for among-individual variability, while the Model B linear mixed-effects models (LMMs) were adjusted for among-individual variability. The regression coefficients of the two models were compared. RESULTS: Model B showed the lowest AIC values for all parameters and the best fit. For light stimulus intensity, age and eye symmetry, the two models yielded similar results for all PLR parameters. For sex and smoking index, some PLR parameters showed the opposite results, i.e., Model A showed significant effects while Model B did not. CONCLUSION: These results indicate that light stimulus intensity, aging, sex, smoking and eye symmetry are factors that affect PLR parameters. These should be adjusted when evaluating the clinical potential of PLR as a diagnostic tool. In addition, adjusting for among-individual variability due to LMMs can improve the model fit and reduce false positives. This can reveal the association between clinical factors and PLR parameters with increased accuracy.

Caprice/MISP is a novel F-actin bundling protein critical for actin-based cytoskeletal reorganizations.

Caprice [C19orf21 actin-bundling protein in characteristic epithelial cells, also called mitotic interactor and substrate of Plk1 (MISP)] is a novel actin-related protein identified in the highly-insoluble subcellular scaffold proteins. This protein contains multiple actin-binding sites, forms characteristic mesh-like F-actin bundles in vitro, and exhibits capricious localization and expression patterns in vivo. Overexpression or knock-down of Caprice resulted in a dramatic effect on cellular morphology by inducing stress fiber-like thick filaments or filopodial formations, respectively. Caprice is expressed and localized in distinct cells and tissues with specialized actin-based structures, such as growth cones of migrating neurons and stereocilia of inner ear hair cells. However, Caprice gene expression is varied among different cell types; especially enriched in several epithelial cells whereas relatively suppressed in a subset of epithelial cells, fibroblasts, and neuroblastoma cells at the transcriptional level. Thus, this protein is expected to be an effector for cell type-specific actin reorganization with its direct actin-binding properties and provides a novel model of cell morphology regulation by a non-ubiquitous single actin-bundling protein.

Absolute structures and bioactivities of euryspongins and eurydiene obtained from the marine sponge Euryspongia sp. collected at Iriomote Island.

Three unique sesquiterpenes, named euryspongins A-C (1-3), have been isolated from the marine sponge Euryspongia sp. The absolute configuration of 1 was assigned as (4R,6R,9S) by comparing its experimental Electronic Circular Dichroism (ECD) spectrum with the calculated ECD spectra of both enantiomers, and the absolute configurations of 2, 3 and artifact 4 were suggested on the basis of that of 1 by assuming common biogenesis of 1-3. These absolute configurations were opposite to those depicted in the previous communication. Further separation of the remaining fractions lead to the isolation of a new C11-polyketide, named as eurydiene (5), together with a known C11-polyketide, nakitriol (6). The structure of 5 was assigned on the basis of its spectroscopic data as a bicyclic alcohol with a diene side chain. Dehydroeuryspongin A (4) inhibited protein tyrosine phosphatase 1B (PTP1B), an important target enzyme for the treatment of type II diabetes and obesity, with an IC50 value of 3.58µM. Moreover, compound 4 did not inhibit the proliferation of human hepatoma Huh-7 cells at 100µM. One of the locations in which PTP1B has been detected is hepatocytes. Compounds 1-3, 5, and 6 were not active against PTP1B. The growth of human colon (HCT-15) and T-cell lymphoma (Jurkat) cells was not disturbed by compounds 1-6.

Therapeutic potential of a gamma-secretase inhibitor for hearing restoration in a guinea pig model with noise-induced hearing loss.

BACKGROUND: Notch signaling plays a crucial role in the fate determination of cochlear progenitor cells, hair cells, and supporting cells in the developing cochlea. Recent studies have demonstrated the temporal activation of Notch signaling in damaged mature cochleae, and have demonstrated the induction of new hair cells by pharmacologically inhibiting Notch signaling. The present study aimed to illustrate the feasibility of pharmacologically inhibiting Notch signaling by using a gamma-secretase inhibitor for treating sensorineural hearing loss. RESULTS: The effect of the sustained local delivery of MDL28170, a gamma-secretase inhibitor, on hearing and hair cell induction was tested in a guinea pig model with noise-induced hearing loss. MDL28170 was directly delivered into the cochlear fluids via a micro-osmotic pump. Drug application was initiated 7 days after noise exposure. Measurements of auditory brainstem responses revealed better hearing in the MDL28170-treated animals than in the vehicle controls. Histological analysis demonstrated a higher number of outer hair cells in the MDL28170-treated cochleae than the vehicle-treated cochleae. CONCLUSION: These findings strongly suggest that local sustained delivery of a gamma-secretase inhibitor into the cochlea could be a novel strategy for treating acute hearing loss that is refractory to conventional treatment.

Clinical Utility of Machine Learning Methods Using Regression Models for Diagnosing Eosinophilic Chronic Rhinosinusitis.

Objective: Machine learning methods using regression models can predict actual values of histological eosinophil count from blood eosinophil levels. Therefore, these methods might be useful for diagnosing eosinophilic chronic rhinosinusitis, but their utility still remains unclear. We compared 2 statistical approaches, and investigated the utility of machine learning methods for diagnosing eosinophilic chronic rhinosinusitis. Study Design: Retrospective study. Setting: Medical center. Methods: Data, including eosinophilic levels, obtained from blood and sinonasal samples of 264 patients with chronic rhinosinusitis (257 with and 57 without nasal polyps) were analyzed. We determined factors affecting histopathological eosinophil count in regression models. We also investigated optimal cutoff values for blood eosinophil percentages/absolute eosinophil counts (AECs) through receiver operating characteristic curves and machine-learning methods based on regression models. A histopathological eosinophil count ≥10/high-power field was defined as eosinophilic chronic rhinosinusitis. Results: Blood eosinophil levels, nasal polyp presence, and comorbid asthma were factors affecting histopathological eosinophil count. Cutoffs between the 2 statistical approaches differed in the group with nasal polyps, but not in one without nasal polyps. Machine-learning methods identified blood eosinophil percentages ≥1% or AEC ≥100/µL as cut-offs for eosinophilic chronic rhinosinusitis with nasal polyps, while ≥6% or ≥400/µL for one without nasal polyps. Conclusion: Cut-offs of blood eosinophil levels obtained by machine-learning methods might be useful when suspecting eosinophilic chronic rhinosinusitis prior to biopsy because of their ability to adjust covariates, dealing with overfitting, and predicting actual values of histological eosinophil count.

Pharmacokinetics of monoclonal antibodies locally-applied into the middle ear of guinea pigs.

Countless therapeutic antibodies are currently available for the treatment of a broad range of diseases. Some target molecules of therapeutic antibodies are involved in the pathogenesis of sensorineural hearing loss (SNHL), suggesting that SNHL may be a novel target for monoclonal antibody (mAb) therapy. When considering mAb therapy for SNHL, understanding of the pharmacokinetics of mAbs after local application into the middle ear is crucial. To reveal the fundamental characteristics of mAb pharmacokinetics following local application into the middle ear of guinea pigs, we performed pharmacokinetic analyses of mouse monoclonal antibodies to FLAG-tag (FLAG-mAbs), which have no specific binding sites in the middle and inner ear. FLAG-mAbs were rapidly transferred from the middle ear to the cochlear fluid, indicating high permeability of the round window membrane to mAbs. FLAG-mAbs were eliminated from the cochlear fluid 3 h after application, similar to small molecules. Whole-body autoradiography and quantitative assessments of cerebrospinal fluid and serum demonstrated that the biodistribution of FLAG-mAbs was limited to the middle and inner ear. Altogether, the pharmacokinetics of mAbs are similar to those of small molecules when locally applied into the middle ear, suggesting the necessity of drug delivery systems for appropriate mAb delivery to the cochlear fluid after local application into the middle ear.

Angiotensin II produces nociceptive behavior through spinal AT1 receptor-mediated p38 mitogen-activated protein kinase activation in mice.

BACKGROUND: It has been demonstrated that angiotensin II (Ang II) participates in either the inhibition or the facilitation of nociceptive transmission depending on the brain area. Neuronal Ang II is locally synthesized not only in the brain, but also in the spinal cord. Though the spinal cord is an important area for the modulation of nociception, the role of spinal Ang II in nociceptive transmission remains unclear. Therefore, in order to elucidate the role of Ang II in nociceptive transmission in the spinal cord, we examined the effect of intrathecal (i.t.) administration of Ang II into mice. RESULTS: I.t. administration of Ang II produced a behavioral response in mice mainly consisting of biting and/or licking of the hindpaw and the tail along with slight hindlimb scratching directed toward the flank. The behavior induced by Ang II (3 pmol) was dose-dependently inhibited by intraperitoneal injection of morphine (0.1-0.3 mg/kg), suggesting that the behavioral response is related to nociception. The nociceptive behavior was also inhibited dose-dependently by i.t. co-administration of losartan (0.3-3 nmol), an Ang II type 1 (AT1) receptor antagonist, and SB203580 (0.1-1 nmol), a p38 MAPK inhibitor. However, the Ang II type 2 (AT2) receptor antagonist PD123319, the upstream inhibitor of ERK1/2 phosphorylation U0126, and the JNK inhibitor SP600125 had no effect on Ang II-induced nociceptive behavior. Western blot analysis showed that the i.t. injection of Ang II induced phosphorylation of p38 MAPK in the lumbar dorsal spinal cord, which was inhibited by losartan, without affecting ERK1/2 and JNK. Furthermore, we found that AT1 receptor expression was relatively high in the lumbar superficial dorsal horn. CONCLUSIONS: Our data show that i.t. administration of Ang II induces nociceptive behavior accompanied by the activation of p38 MAPK signaling mediated through AT1 receptors. This observation indicates that Ang II may act as a neurotransmitter and/or neuromodulator in the spinal transmission of nociceptive information.

Risk factors with intravenous sedation for patients with disabilities.

The purpose of this study was to identify the risk factors associated with low peripheral oxygen saturation (SpO2) and delayed recovery of dental patients with disabilities after intravenous sedation. A total of 1213 patients with disabilities were retrospectively investigated with respect to demographic parameters and sedation conditions. Multivariate logistic analyses were conducted for patients with an SpO2 <90% and a recovery period of >60 minutes to identify the risk factors for poor sedation conditions. A significant odds ratio related to decreased SpO2 was observed for age, sex, midazolam and propofol levels, concurrent use of nitrous oxide, cerebral palsy, Down syndrome, and mental retardation. The most problematic patients were those diagnosed with Down syndrome (odds ratio, 3.003-7.978; 95% confidence interval; P < .001). Decision tree analysis showed an increased risk of decreased SpO2 in males with Down syndrome or after administration of >0.493 mg/kg propofol in combination with midazolam. An increased risk of delayed awakening was seen in patients aged less than 21 years and in males administered >0.032 mg/kg of midazolam. Intravenous sedation for dental patients with disabilities, particularly those with cerebral palsy, Down syndrome, or mental retardation, increases the risk of decreased SpO2. In addition, delayed recovery is expected after midazolam administration.

Recommendation of using both initial pupil size and constriction latency in pupillary light reflex as objective indicators reflecting subacute pain-related mental fatigue.

A previous study examining clinical subacute pain models under different methodological conditions showed that pain-induced mental fatigue can be associated with decreased initial pupil size (INIT)/shortened constriction latency (LAT) in the pupillary light reflex (PLR). We aimed to investigate the potential of INIT/LAT as objective indicators reflecting mental fatigue under the same methodological conditions. We recruited 118 patients planning to undergo three types of representative otolaryngological head and neck surgery procedures. We used the numerical rating scale (NRS) to assess subjective pain intensity and two mental fatigue-related mood categories of the Profile of Mood States, as well as INIT and LAT measurements (1) in the afternoon one day before surgery (pre1-surgery), (2) in the morning of the day of surgery (pre2-surgery), and (3) in the morning of the day following surgery (post-surgery). We assessed time point-dependent changes using one- or two-way analysis of variance, as well as responses of PLR parameters to mental fatigue using linear mixed-effects models (LMMs). As a result, NRS scores, the two mood categories, as well as LAT and INIT, showed significant time point-dependent changes. In post-hoc analyses, only INIT showed significant changes between the two pre-surgery time points. Thus, INIT values fluctuated even under pain-free conditions due to differences in the time of the day. LMMs demonstrated decreased INIT/shortened LAT related to mental fatigue. All surgical groups showed similar associations between mental fatigue and INIT/LAT findings. As each parameter has advantages and disadvantages, it is recommended to use both INIT and LAT as the indicators.

Psychological states affecting initial pupil size changes after olfactory stimulation in healthy participants.

Odor perception affects physiological and psychological states. Pupillary light reflex (PLR) parameters can be affected by olfactory stimulation and psychological states, although it remains unclear whether the olfactory stimulation-induced psychological changes can associate with PLR parameter changes. This study aimed to investigate effects of olfactory stimulation-induced psychological changes on PLR parameter changes with repeated measurements. We collected data on six mood subscales of the profile of mood states, and on five PLR parameter measurements from 28 healthy participants. Participants underwent a 10-min olfactory stimulation on different days with six odorants available with the T&T olfactometer. As obtained data were clustered, we used linear mixed-effects models for statistical analyses. The olfactory stimulation using the no-odor liquid did not affect mood states and the initial pupil size (INIT). The sweat odorant worsened all mood subscales including fatigue-inertia (Fatigue)/Vigor-Activity (Vigor), and decreased INIT compared to the no-odor liquid. When comparing INIT responses related to changes in mood subscales between the no-odor liquid and the sweat odorant, worsened states of Fatigue/Vigor were associated with decreased INIT in the sweat odorant. Fatigue/Vigor can be used as mental fatigue indicators. Thus, mental fatigue can be associated with decreased INIT in the olfactory stimulation.

Comorbidity of eosinophilic chronic rhinosinusitis in chronic eosinophilic pneumonia.

We aimed to elucidate details of comorbid chronic rhinosinusitis (CRS) in chronic eosinophilic pneumonia (CEP) under the collaboration between otolaryngologists and pulmonologists in a prospective study. The CEP diagnosis was performed by pulmonologists based on clinical symptoms, laboratory findings, and/or eosinophilia detected in bronchoalveolar lavage. All patients were referred to otolaryngologists before undergoing oral corticosteroid treatment for CEP. Ten CEP cases visited to otolaryngologists. All cases showed bilateral sinonasal inflammation in computed tomography (CT), indicating comorbid CRS. Nasal polyps (NPs) were observed in 50% of patients on endoscopy. Eighty percent of patients were diagnosed with eosinophilic CRS. In blood eosinophil levels and the mucosal eosinophil count, there were no significant differences between CRS without and with NPs. In Lund-Mackay CT total scores, among-individual variability was observed in CRS with NPs. The collaboration revealed blood/sinonasal eosinophilia and the variability in Lund-Mackay CT total scores as remarkable findings about the comorbid CRS.

Correlation of right frontal hypoperfusion and urinary dysfunction in iNPH: a SPECT study.

OBJECTIVES: To elucidate the pathophysiology of urinary dysfunction in idiopathic normal-pressure hydrocephalus (iNPH) by single-photon emission computed tomography (SPECT) and statistical brain mapping. METHODS: Urinary symptoms were observed and N-isopropyl-p-[(123)I]-iodoamphetamine (IMP)-SPECT imaging was performed in 97 patients with clinico-radiologically definite iNPH. The patients included 56 men and 41 women; mean age, 74 years. The statistical difference in normalized mean tracer counts was calculated and visualized between patients with urinary dysfunction of severer degrees (>grade 2/4) and milder degrees (

Clinical potential of pupillary light reflex and heart rate variability parameters as objective indicators of tonsillectomy-induced pain.

Objective.Establishing objective indicators of subjective pain intensity is important in pain assessment. Pupillary light reflex (PLR) and heart rate variability (HRV) indicate autonomic nervous system (ANS) activity and may serve as pain indicators because pain can affect ANS activity. In this prospective longitudinal study, we aimed to investigate the potential of PLR/HRV parameters as objective indicators of subjective pain intensity after tonsillectomy.Approach.Sixty-seven patients undergoing tonsillectomy were enrolled. Subjective pain intensity based on a numeric rating scale (NRS) and eight PLR/HRV parameters were assessed at five time points. We investigated the changes in the NRS values over time. We estimated regression coefficients reflecting parameter changes per unit change in the NRS score using linear mixed-effects models.Main Results.The mean NRS score was 0 at two pre-surgery time points, 5 on postoperative days (PODs) 1 and 2, and 0 at postoperative week 3. Two parameters (initial pupil size [INIT] and constriction latency [LAT]) showed significant changes on POD1 and POD2 in comparison to baseline data measured at the pre-surgery time point. Among these parameters, only LAT showed no significant changes between POD1 and POD2. Significant regression coefficients with the narrowest 95% confidence intervals were observed for INIT and LAT. Increased NRS scores were associated with decreased INIT and shortened LAT.Significance.LAT was a robust indicator of subjective pain intensity. Our patients showed decreased INIT with increased NRS scores, indicating the predominance of the parasympathetic, not sympathetic, tone in pupils. Further studies are required to investigate factors causing this predominance.

Decreased initial pupil size and shortened constriction latency due to negative mood states and mental fatigue in clinical subacute pain models.

Previous clinical studies on pupillary light reflex parameters showed shortened constriction latency (LAT) and decreased initial pupil size (INIT) due to increased numeric rating scale (NRS) scores, reflecting subjective pain intensity, in subacute pain models. As noxious stimulation causes pupil dilation, decreased INIT (pupil constriction) was an unexpected finding. Pain-related negative moods and mental fatigue might have caused this finding. We aimed to investigate how psychological states affect LAT/INIT in two subacute pain models. For psychological assessment, we used the Profile of Mood States (POMS) and calculated the total mood disturbance (TMD) score using six mood categories. We collected data on NRS scores, POMS-related scores, LAT, and INIT through a longitudinal study. Using linear mixed-effects models, we evaluated the association of TMD scores with NRS scores, LAT, and INIT. Furthermore, we performed subanalyses targeting two mood categories that represent mental fatigue: Fatigue-Inertia (Fatigue) and Vigor-Activity (Vigor). We investigated whether obtained results can be identical in both models. In total, 141 patients were enrolled. Increased NRS scores were associated with increased TMD/Fatigue scores and decreased Vigor scores, being associated with shortened LAT/decreased INIT in both models. Score changes in NRS, TMD, Fatigue, and Vigor indicated that increased subjective pain intensity can be associated with negative mood states, especially mental fatigue. This study revealed that negative moods and mental fatigue induced by acute pain can be associated with shortened LAT/decreased INIT in both models, indicating clinical potential of LAT/INIT as objective indicators reflecting the psychological states for pain assessment.

Alterations in prefrontal cortical neuregulin-1 levels in post-pubertal rats with neonatal ventral hippocampal lesions.

Genetic studies in humans have implicated the gene encoding neuregulin-1 (NRG-1) as a candidate susceptibility gene for schizophrenia. Furthermore, it has been suggested that NRG-1 is involved in regulating the expression and function of the N-methyl-D-aspartate receptor and the GABAA receptor in several brain areas, including the prefrontal cortex (PFC), the hippocampus, and the cerebellum. Neonatal ventral hippocampal lesioned (NVHL) rats have been considered as a putative model for schizophrenia with characteristic post-pubertal alteration in response to stress and neuroleptics. In this study, we examined NRG-1, erb-b2 receptor tyrosine kinase 4 (erbB4), and phospho-erbB4 (p-erbB4) levels in the PFC and the distribution of NRG-1 in the NVHL rats by using immunoblotting and immunohistochemical analyses. Neonatal lesions were induced by bilateral injection of ibotenic acid in the ventral hippocampus of postnatal day 7 Sprague-Dawley (SD)-rats. NVHL rats showed significantly decreased levels of NRG-1 and p-erbB4 in the PFC compared to sham controls at post-pubertal period, while the level of erbB4 did not differ between sham and NVHL rats. Moreover, microinjection of NRG-1 into the mPFC improved NVHL-induced prepulse inhibition deficits. Our study suggests PFC NRG-1 alteration as a potential mechanism in schizophrenia-like behaviors in the NVHL model.

[Clinical outcomes cochlear reimplantation].

To clarify the clinical features of cochlear reimplantation and surgical changes in auditory performance, we retrospectively reviewed 10 of 252 cochlear implantation surgeries-6 adults and 4 children-among 129 children and 123 adults done between April 1987 and May 2009. Mean duration from initial implantation to reimplantation was 50.3 months in children and 89 months in adults, most commonly due to hard failure and implant exposure/infection (33%) in children and to hard failure (75%) in adults. The initial device implanted was the Nucleus multichannel implant (CI22M, CI24M, or CI24R). The second implant in 7 was the same or an upgrade of the same manufacturer's device, and in 2 children the HiRes 90K (Hifocus 1j) and in 1 adult the Clarion 1.2. Full initial and reinsertion succeeded in 8 cases but reinsertion proved difficult in 2 due to severe intracochlear granulation and osteoneogenseis. Auditory performance analyzed in 7 cases was mostly equal to or better than before reimplantation, although differences were not statistically significant. Reinsertion is rarely difficult, but electrode choice is important in preparing for difficult reinsertion. Post reinsertion auditory performance is satisfactory with some exceptions.

Clinical potential of pupillary light reflex parameters as objective indicators reflecting chronic rhinosinusitis-specific quality of life: a 12-month prospective longitudinal study.

Pupillary light reflex (PLR) and heart rate variability (HRV) parameters can be objective indicators of chronic rhinosinusitis (CRS) status from the viewpoint of autonomic nervous system activity. This study aimed to establish objective indicators for CRS using the 22-item Sino-Nasal Outcome Test (SNOT-22) and PLR/HRV parameters. Sixty-seven patients were prospectively and longitudinally followed up after surgical treatment. We investigated changes in SNOT-22 scores, representing CRS-specific quality of life (QOL). We prepared two models: linear regression model adjusting clinical factors as predictor variables (model 1) and linear mixed-effects model adjusting clinical factors and among-individual variability (model 2). We compared Akaike's information criterion (AIC) values and regression coefficients. The model with lower AIC values was defined as the better-fit model. Model 2 showed lower AIC values in all parameters (better-fit model). Three parameters showed opposite results between the two models. The better-fit models showed significances in the five PLR parameters but not in any HRV parameters. Among these PLR parameters, constriction latency can be the most robust indicator because of the narrowest 95% confidence intervals. Adjusting the among-individual variability while investigating clinical potential of PLR/HRV parameters to reflect CRS-specific QOL can improve the model fit, thereby reaching robust conclusions from obtained data.

Inverted papilloma originating from the lacrimal sac and the nasolacrimal duct with marked FDG accumulation.

Inverted papilloma originating from the lacrimal sac and the nasolacrimal duct is rare, although that in the sinonasal region is a relatively common lesion with local invasion, malignant potential and high recurrence rates after surgery. We report a 52-year-old woman with inverted papilloma of the right lacrimal sac and the nasolacrimal duct, who underwent CT, MR imaging and FDG-PET/CT preoperatively. In addition to CT and MR imaging features similar to those in previous reports, the inverted papilloma exhibited marked FDG accumulation with a maximum standardized uptake value of 7.34 and no other significant FDG accumulation was detected. In summary, our case of inverted papilloma originating from the right lacrimal sac and the nasolacrimal duct noted marked FDG accumulation on PET/CT, which enabled visualization of the localized tumor extension with no metastases.

Functional characterization of 26 CYP2B6 allelic variants (CYP2B6.2-CYP2B6.28, except CYP2B6.22).

Cytochrome P450 2B6 (CYP2B6) is a potentially important enzyme for the metabolism of clinical drugs, and it exhibits genetic polymorphism. Thus far, 29 allelic variants of CYP2B6 (CYP2B6*1-CYP2B6*29) have been identified. This study aimed to investigate whether 26 of the variant alleles of CYP2B6 (CYP2B6*2-CYP2B6*21 and CYP2B6*23-CYP2B6*28) affect its kinetics in the metabolism of 7-ethoxy-4-trifluoromethylcoumarin (7-EFC) and selegiline. Wild-type CYP2B6.1 and the allelic variants were heterologously expressed in COS-7 cells. In-vitro kinetic analysis revealed that when compared with the wild-type protein CYP2B6.1, CYP2B6.10 and CYP2B6.14 exhibited significantly lower V(max)/K(m) values for selegiline N-demethylation. The kinetic parameters of CYP2B6.8, CYP2B6.11, CYP2B6.12, CYP2B6.13, CYP2B6.15, CYP2B6.18, CYP2B6.21, CYP2B6.24, and CYP2B6.28 could not be determined because these enzymes were inactive in the deethylation of 7-EFC and the N-demethylation/N-depropagylation of selegiline. These findings provide useful information for further genotype-phenotype studies on interindividual differences in the metabolism of CYP2B6 substrate drugs.