Uncovering the "riddle of femininity" in osteoarthritis: a systematic review and meta-analysis of menopausal animal models and mathematical modeling of estrogen treatment.

OBJECTIVE: Post-menopausal women are disproportionately affected by osteoarthritis (OA). As such, the purpose of this study was to (1) summarize the state-of-the-science aimed at understanding the effects of menopause on OA in animal models and (2) investigate how dosage and timing of initiation of estrogen treatment affect cartilage degeneration. DESIGN: A systematic review identified articles studying menopausal effects on cartilage in preclinical models. A meta-analysis was performed using overlapping cartilage outcomes in conjunction with a rigor and reproducibility analysis. Ordinary differential equation models were used to determine if a relationship exists between cartilage degeneration and the timing of initiation or dosage of estrogen treatment. RESULTS: Thirty-eight manuscripts were eligible for inclusion. The most common menopause model used was ovariectomy (92%), and most animals were young at the time of menopause induction (86%). Most studies did not report inclusion criteria, animal monitoring, protocol registration, or data accessibility. Cartilage outcomes were worse in post-menopausal animals compared to age-matched, non-menopausal animals, as evidenced by cartilage histological scoring [0.75, 1.72], cartilage thickness [-4.96, -0.96], type II collagen [-4.87, -0.56], and c-terminal cross-linked telopeptide of type II collagen (CTX-II) [2.43, 5.79] (95% CI of Effect Size (+greater in menopause, -greater in non-menopause)). Moreover, modeling suggests that cartilage health may be improved with early initiation and higher doses of estrogen treatment. CONCLUSIONS: To improve translatability, animal models that consider aging and natural menopause should be utilized, and more attention to rigor and reproducibility is needed. Timing of initiation and dosage may be important factors modulating therapeutic effects of estrogen on cartilage.

Impact of technically qualified surgeons on laparoscopic colorectal resection outcomes: results of a propensity score-matching analysis.

BACKGROUND: The Endoscopic Surgical Skill Qualification System (ESSQS) was introduced in Japan to improve the quality of laparoscopic surgery. This cohort study investigated the short- and long-term postoperative outcomes of colorectal cancer laparoscopic procedures performed by or with qualified surgeons compared with outcomes for unqualified surgeons. METHODS: All laparoscopic colorectal resections performed from 2010 to 2013 in 11 Japanese hospitals were reviewed retrospectively. The procedures were categorized as performed by surgeons with or without the ESSQS qualification and patients' clinical, pathological and surgical features were used to match subgroups using propensity scoring. Outcome measures included postoperative and long-term results. RESULTS: Overall, 1428 procedures were analysed; 586 procedures were performed with ESSQS-qualified surgeons and 842 were done by ESSQS-unqualified surgeons. Upon matching, two cohorts of 426 patients were selected for comparison of short-term results. A prevalence of rectal resection (50·3 versus 40·5 per cent; P < 0·001) and shorter duration of surgery (230 versus 238 min; P = 0·045) was reported for the ESSQS group. Intraoperative and postoperative complication and reoperation rates were significantly lower in the ESSQS group than in the non-ESSQS group (1·2 versus 3·6 per cent, P = 0·014; 4·6 versus 7·5 per cent, P = 0·025; 1·9 versus 3·9 per cent, P = 0·023, respectively). These findings were confirmed after propensity score matching. Cox regression analysis found that non-attendance of ESSQS-qualified surgeons (hazard ratio 12·30, 95 per cent c.i. 1·28 to 119·10; P = 0·038) was independently associated with local recurrence in patients with stage II disease. CONCLUSION: Laparoscopic colorectal procedures performed with ESSQS-qualified surgeons showed improved postoperative results. Further studies are needed to investigate the impact of the qualification on long-term oncological outcomes.

ANTECEDENTES: El Sistema de Certificación de Habilidades Quirúrgicas Endoscópicas (Endoscopic Surgical Skill Qualification System, ESSQS) fue introducido en Japón para mejorar la calidad de la cirugía laparoscópica. En este estudio de cohortes se investigaron los resultados postoperatorios a corto y a largo plazo de las intervenciones laparoscópicas de cáncer colorrectal realizadas por o con la asistencia de cirujanos con certificación en comparación con cirujanos no certificados. MÉTODOS: Todas las resecciones colorrectales laparoscópicas realizadas entre 2010 y 2013 en 11 hospitales japoneses fueron revisadas retrospectivamente. Los procedimientos se clasificaron en función de si habían sido realizados por cirujanos con o sin certificación del ESSQS, y las características clínicas, patológicas y quirúrgicas de los pacientes se utilizaron para emparejar los subgrupos mediante puntuaciones de propensión. Las variables de resultado incluyeron los resultados postoperatorios y a largo plazo RESULTADOS: En total se analizaron 1.428 procedimientos, incluyendo 586 y 842 procedimientos realizados con y sin cirujanos certificados por ESSQS, respectivamente. Tras el emparejamiento, se seleccionaron dos cohortes de 426 pacientes para la comparación de resultados a corto plazo. Se observó una mayor prevalencia de resecciones rectales (50,3% versus 40,1%, P = 0,0001) y un tiempo quirúrgico más corto (230 versus 238 min, P = 0,04) en el grupo ESSQS. Las tasas de complicaciones intra- y postoperatorias y de reoperaciones fueron significativamente más bajas en el grupo ESSQS que en el grupo no ESSQS (1,2%, 4,6% y 1,9% versus 3,6%, 7,5% y 3,9%, P = 0,01; 0,03, y 0,02, respectivamente). Estos hallazgos se confirmaron tras el análisis de emparejamiento por puntaje de propensión. El análisis de regresión de Cox mostró que la no participación de cirujanos certificados con ESSQS (razón de oportunidades, odds ratio, OR 12,3; i.c. del 95%, 1,28-119,1; P = 0,03) se asoció independientemente con la recidiva local en los casos en estadio II. CONCLUSIÓN: Los procedimientos colorrectales laparoscópicos realizados por cirujanos certificados por ESSQS presentaron mejores resultados postoperatorios. Son necesarios más estudios para determinar el impacto de la certificación en los resultados oncológicos a largo plazo.

Weak influence of near-surface layer on solar deep convection zone revealed by comprehensive simulation from base to surface.

The solar convection zone is filled with turbulent convection in highly stratified plasma. Several theoretical and observational studies suggest that the numerical calculations overestimate the convection velocity. Since all deep convection zone calculations exclude the solar surface due to substantial temporal and spatial scale separations, the solar surface, which drives the thermal convection with efficient radiative cooling, has been thought to be the key to solve this discrepancy. Thanks to the recent development in massive supercomputers, we are successful in performing the comprehensive calculation covering the whole solar convection zone. We compare the results with and without the solar surface in the local domain and without the surface in the full sphere. The calculations do not include the rotation and the magnetic field. The surface region has an unexpectedly weak influence on the deep convection zone. We find that just including the solar surface cannot solve the problem.

Trunk movement asymmetry associated with pain, disability, and quadriceps strength asymmetry in individuals with knee osteoarthritis: a cross-sectional study.

OBJECTIVE: This study examined 1) the clinical relevance of trunk movement asymmetry, which was evaluated using a trunk-mounted inertial measurement unit (IMU), and 2) the relationship between trunk movement asymmetry and lower limb muscle strength asymmetry in individuals with knee osteoarthritis (OA). DESIGN: One-hundred-thirty-one participants (mean age, 74.2 years; 71.8% female; Kellgren and Lawrence [K&L] grade ≥1) underwent gait analysis at their preferred pace for IMU-based measurement of trunk movement asymmetry (harmonic ratio [HR] and improved HR). The isometric strength of quadriceps and hip abductors was evaluated using a hand-held dynamometer. Pain and disability level were evaluated using a validated self-reported questionnaire. Multiple regression analyses with covariate adjustment were performed to examine the relationship between trunk movement asymmetry (independent variable) and pain, disability level, or muscle strength asymmetry (dependent variables). RESULTS: Individuals with severe knee OA (K&L grade ≥3) had increased trunk movement asymmetry in the medio-lateral axis compared to those with a K&L grade of 1. Increased trunk movement asymmetry was associated with a greater knee pain and disability. The increased trunk movement asymmetry was significantly associated with an increase in the asymmetry of quadriceps strength, but not with asymmetry in the strength of hip abductor. CONCLUSION: Our findings indicate that increased medio-lateral trunk movement asymmetry may be an indicator of impairment, rather than adaptation, in individuals with knee OA. This preliminary finding warrants validation by future study. Paying close attention to medio-lateral trunk movement asymmetry may be key to our understanding of OA-related pain and disability.

A review of urban wildlife management from the animal personality perspective: The case of urban deer.

Wildlife living around urbanized areas is often a cause of crucial issues such as zoonosis and wildlife-vehicle collisions. Despite this, residents hold positive views on the presence of urban wildlife primarily due to aesthetic reasons. This accepting attitude towards our coexistence with urban wildlife has made it difficult for wildlife managers to come to a consensus concerning the importance of human-urban wildlife conflicts. Although countermeasures such as lethal force and/or fencing are commonly used to control human-wildlife conflicts, these approaches are rarely applied in the case of urban wildlife. It is essential to recognize the gap between the current state of urban wildlife management and advanced scientific knowledge of urban wildlife behavior in order to mitigate urban deer conflicts. Fortunately, behavioral ecologists have been attempting to apply the perspective of individual differences, such as animal personality, to wildlife management. Studies have shown how the personalities of wildlife contribute to their adaptation to urban habitats. In order to prevent human-urban wildlife conflicts, recognizing the personalities of wildlife and selective culling of bold individuals should be conducted for deliberate selection for shyness when developing wildlife management plans. Making wildlife shy away from humans is essential to urban wildlife management. The aim of this study is to review observed measures against human-urban wildlife conflicts in Japan and to propose a new direction for innovative and effective approaches that takes animals personality into account to mitigate urban-wildlife conflicts. For this review we will target deer as a model species because deer are among the most serious of problem-causing urban wildlife.

Interaction between low back pain and knee pain contributes to disability level in individuals with knee osteoarthritis: a cross-sectional study.

OBJECTIVE: To test the hypothesis that the interaction between low back pain (LBP) and knee pain intensity contributes to the disability level of individuals with knee osteoarthritis (OA). DESIGN: Community-dwelling participants with knee OA (Kellgren/Lawrence [K/L] grade ≥1) were enrolled. LBP and its severity were identified using questionnaires. Knee pain severity and disability level were evaluated using the Japanese Knee Osteoarthritis Measure (JKOM) subscale. Multiple linear regression analyses were performed to examine the effect of the LBP-knee pain interaction, an independent variable, on disability, a dependent variable. RESULTS: A total of 260 participants (age, 48-88 years; 77.7% women) were included. Of them, 151 (58.1%) had LBP. The LBP-knee pain interaction was significantly associated with disability after the adjustment for covariates. A post-hoc subgroup analysis revealed that the relationship between knee pain intensity and disability level was higher in individuals with LBP (beta: 0.621 points; 95% confidence interval [CI]: 0.511 to 0.731 points) than in those without LBP (beta: 0.402 points; 95% CI: 0.316 to 0.487 points). CONCLUSIONS: LBP interacts with knee pain intensity and contributes to disability level in individuals with knee OA. Coexisting LBP and knee pain had a stronger impact on disability level than LBP or knee pain alone. These findings highlight the potential deteriorative effects of the LBP-knee interaction on disability. Maximal treatment effects for disability might be achieved when LBP and knee pain are targeted simultaneously, rather than separately.

Coexisting lateral tibiofemoral osteoarthritis is associated with worse knee pain in patients with mild medial osteoarthritis.

OBJECTIVE: To examine the clinical impact of coexisting lateral osteoarthritis (OA) in knees with mild medial OA. DESIGN: In patients with Kellgren/Lawrence (K/L) grade 2 OA in the medial compartment (n = 100; age: 56-89 years; 80.0% female), anteroposterior knee radiography was used to assess the presence of lateral OA, using grading systems from the Osteoarthritis Research Society International (OARSI) atlas and the K/L classification. The Japanese Knee Osteoarthritis Measure (JKOM), knee range of motion (ROM), and performance-based functional measures (10 m walk, timed up and go and five repetition chair stand maneuvers) were evaluated. The outcomes were compared between patients with and without lateral OA using an analysis of covariance (ANCOVA) or nonparametric rank ANCOVA. Furthermore, ordinal logistic regression analysis was performed, with responses on individual JKOM pain questionnaires as the outcomes and lateral OA as the predictor. RESULTS: Knees with coexisting lateral OA had a significantly worse score of JKOM pain question compared with those without, after adjusting for covariates. The presence of lateral OA was significantly associated with knee pain while ascending/descending stairs and standing. These results were consistent between different definitions of the K/L and OARSI grading systems. The knee ROM and performance-based functional measures were not significantly different between patients with and without lateral OA. CONCLUSION: Knees with concomitant lateral and mild medial OA may be more symptomatic compared to those without lateral OA. These findings might help to define a clinically distinct subgroup based on a simple radiographic finding in mild knee OA.

Physiological exercise loading suppresses post-traumatic osteoarthritis progression via an increase in bone morphogenetic proteins expression in an experimental rat knee model.

OBJECTIVE: To evaluate the dose-response relationship of exercise loading in the cartilage-subchondral bone (SB) unit in surgically-induced post-traumatic osteoarthritis (PTOA) of the knee. DESIGN: Destabilized medial meniscus (DMM) surgery was performed on the right knee of 12-week-old male Wistar rats, and sham surgery was performed on the contralateral knee. Four weeks after the surgery, the animals were subjected to moderate (12 m/min) or intense (21 m/min) treadmill exercises for 30 min/day, 5 days/week for 4 weeks. PTOA development in articular cartilage and SB was examined using histological and immunohistochemical analyses, micro-computed tomography (micro-CT) analysis, and biomechanical testing at 8 weeks after surgery. Gremlin-1 was injected to determine the role of bone morphogenetic protein (BMP) signaling on PTOA development following moderate exercise. RESULTS: Moderate exercise increased BMP-2, BMP-4, BMP-6, BMP receptor 2, pSmad-5, and inhibitor of DNA binding protein-1 expression in the superficial zone chondrocytes and suppressed cartilage degeneration, osteophyte growth, SB damage, and osteoclast-mediated SB resorption. However, intense exercise had little effect on BMP expression and even caused progression of these osteoarthritis (OA) changes. Gremlin-1 injection following moderate exercise caused progression of the PTOA development down to the level of the non-exercise DMM-operated knee. CONCLUSIONS: Exercise regulated cartilage-SB PTOA development in DMM-operated knees in a dose-dependent manner. Our findings shed light on the important role of BMP expression in superficial zone chondrocytes in attenuation of PTOA development following physiological exercise loading. Further studies to support a mechanism by which BMPs would be beneficial in preventing PTOA progression are warranted.

Serum Wisteria floribunda agglutinin-positive Mac-2-binding protein for patients with chronic hepatitis B and C: a comparative study.

We compared Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+ -M2BP) levels between patients with chronic hepatitis B (n=249) and chronic hepatitis C (n=386) based on the degree of liver fibrosis. We examined WFA+ -M2BP levels in patients with F4 (cirrhosis), F3 or more (advanced fibrosis) and F2 or more (significant fibrosis) in the two groups. We further examined the relationship between five fibrosis markers and the degree of fibrosis. The WFA+ -M2BP values ranged from 0.25 cut-off index (COI) to 12.9 COI in patients with hepatitis B and 0.34-20.0 COI in patients with hepatitis C (P<.0001). The median WFA+ -M2BP values in F4 in the two groups were 2.83 COI in patients with hepatitis B and 5.03 COI in patients with hepatitis C (P=.0046). The median WFA+ -M2BP values in F3 or more in the two groups were 1.79 COI in patients with hepatitis B and 3.79 COI in patients with hepatitis C (P<.0001). The median WFA+ -M2BP values in F2 or more in the two groups were 1.49 COI in the hepatitis B cohort and 3.19 COI in the hepatitis C group (P<.0001). Among five liver fibrosis markers, WFA+ -M2BP had the highest correlation coefficient (rs =.629) in terms of correlation with the degree of fibrosis in the patients with hepatitis C and had the second highest rs value (.415) in the hepatitis B group. Although WFA+ -M2BP could be a useful indicator of liver fibrosis, WFA+ -M2BP levels in the two groups significantly differed even in the same degree of fibrosis. Individual cut-off values in each aetiology for the degree of fibrosis should be determined.

Three-day regimen of oseltamivir for postexposure prophylaxis of influenza in wards.

Inpatients who had been in close contact with patients with influenza were given oseltamivir [75mg capsules once daily for adults or 2mg/kg (maximum of 75mg) once daily for children] for three days as postexposure prophylaxis (PEP). The index patients with influenza were prescribed a neuraminidase inhibitor and were discharged immediately or transferred to isolation rooms. The protective efficacy of oseltamivir for three days was 93% overall [95% confidence interval (CI) 53-99%; P=0.023] and 94% for influenza A (95% CI 61-99%; P=0.017), which is comparable to that of seven- to 10-day regimens of oseltamivir as PEP.

Exercise intervention increases expression of bone morphogenetic proteins and prevents the progression of cartilage-subchondral bone lesions in a post-traumatic rat knee model.

OBJECTIVE: This study aimed to determine whether treadmill walking (TW) prevents the progression of post-traumatic osteoarthritic changes in cartilage-subchondral bone unit, and whether the exercise timing changes the exercise efficacy in destabilized medial meniscus (DMM) rat knees. DESIGN: Twelve-week-old male Wistar rats underwent DMM surgery on their right knees and sham surgery on their left knees and were assigned to either the sedentary (n = 10) or walking (n = 24) groups. The rats in the walking group were subjected to TW from day 2 through 4 weeks, from 4 through 8 weeks, or from day 2 through 8 weeks (n = 8 per group). Osteoarthritic changes of cartilage and subchondral bone were assessed with micro-computed tomography, histology, and immunohistochemistry 8 weeks after surgery. RESULTS: TW prevented the progression of cartilage and subchondral bone lesions induced by the DMM, and increased bone morphogenetic protein (BMP)-2 and -6 expressions in superficial zone chondrocytes and bone-lining cells including osteoblasts. Furthermore, the TW-induced increase in BMPs varied with the exercise timing. Beginning TW 4 weeks after DMM surgery was the best option for increasing BMPs, coinciding with the most robust prevention of osteoarthritic changes. CONCLUSIONS: TW increased the expression of BMPs and prevented the progression of cartilage-subchondral bone lesions in rat knees with a DMM. Selective exercise timing may be a key factor in the development of an exercise regimen for preventing the progression of post-traumatic osteoarthritis (PTOA). Furthermore, exercise may have favorable effects even after the PTOA has been developed.

Subchondral plate porosity colocalizes with the point of mechanical load during ambulation in a rat knee model of post-traumatic osteoarthritis.

OBJECTIVE: This study investigated the association between spatiotemporal cartilage-subchondral bone plate alterations and mechanical load during ambulation in an experimental rat model of destabilized medial meniscus (DMM). DESIGN: Twelve-week-old Wistar rats (n = 38) underwent DMM surgery on the right knee and sham surgery on the left knee. At 2 and 4 weeks after surgery, subchondral bone changes were evaluated via micro-computed tomography with various knee flexion angles to simulate weight-bearing during rat ambulation under a 3-dimensional motion capture apparatus. Additionally, the biomechanical properties, histology, and ultrastructure of the medial tibia and femoral condyle were evaluated. RESULTS: Focal subchondral bone plate perforations were confirmed in the medial tibia within 2 weeks after surgery and were aggravated rapidly 2 weeks later. This subchondral plate porosity colocalized with articular cartilage lesions as confirmed by histology and scanning electron microscopy, and coincided with the likely point of contact between the posterior femoral condyle and tibial plateau during ambulation. Biomechanical properties were confirmed at the medial tibia, at which stiffness was reduced to approximately half that of the sham-operated knee at 4 weeks after surgery. CONCLUSIONS: Cartilage-subchondral bone plate alterations localized in the region of the point of mechanical load during ambulation in DMM-operated knees, at which the mechanical integrity of cartilage was impaired. These results indicate that DMM-induced increases in mechanical load play an important role in the pathogenesis of early post-traumatic osteoarthritis (OA), and it might accelerate the development of the disease via cartilage-subchondral bone plate crosstalk through increased subchondral plate perforations.

Effects of short-term gentle treadmill walking on subchondral bone in a rat model of instability-induced osteoarthritis.

OBJECTIVE: Subchondral bone cyst (SBC) growth, caused by osteoclast activity during early knee osteoarthritis (OA) pathogenesis, should be treated to prevent further progressions of OA. In the present study, we evaluated the effects of gentle treadmill walking on subchondral bone and cartilage changes in an experimental rat model of destabilized medial meniscus (DMM). METHOD: Twelve-week-old Wistar rats underwent DMM surgery in their right knee and sham surgery in their left knee and were assigned to either the sedentary group or walking group (n = 42/group). Animals in the walking group were subjected to treadmill exercise 2 days after surgery, which included walking for 12 m/min, 30 min/day, 5 days/week for 1, 2, and 4 week(s). Subchondral bone and cartilage changes were evaluated by micro-CT analysis, histological analysis, and biomechanical analysis. RESULTS: Treadmill walking had a tendency to suppress SBC growth, which was confirmed by micro-CT (P = 0.06) and positive staining for tartrate-resistant acid phosphatase (TRAP) activity for the osteoclast number per bone surface (P = 0.09) 4 weeks after surgery. These changes coincide with the prevention of cartilage degeneration as evaluated by the Osteoarthritis Research Society International (OARSI) score (P < 0.05) and biomechanically softening (P < 0.05). Furthermore, treadmill walking could suppressed increasing osteocyte deaths (P < 0.01), which was positively correlated with the OARSI score (r = 0.77; P < 0.01). CONCLUSION: These results indicate biomechanical and biological links exist between cartilage and subchondral bone; preventive effects of treadmill walking on subchondral bone deterioration might be partly explained by the chondroprotective effects.

Genomewide association study identifies HAS2 as a novel susceptibility gene for adult asthma in a Japanese population.

BACKGROUND: It is increasingly clear that asthma is not a single disease, but a disorder with vast heterogeneity in pathogenesis, severity, and treatment response. To date, 30 genomewide association studies (GWASs) of asthma have been performed, including by our group. However, most gene variants identified so far confer relatively small increments in risk and explain only a small proportion of familial clustering. OBJECTIVE: To identify additional genetic determinants of susceptibility to asthma using a selected Japanese population with reduced tobacco smoking exposure. METHODS: We performed a GWAS by genotyping a total of 480 098 single-nucleotide polymorphisms (SNPs) for a Japanese cohort consisting of 734 healthy controls and 240 patients with asthma who had smoked for no more than 10 pack-years. The SNP with the strongest association was genotyped in two other independent Japanese cohorts consisting of a total of 531 healthy controls and 418 patients with asthma who had smoked for no more than 10 pack-years. For the hyaluronan synthase 2 (HAS2) gene, we investigated SNP-gene associations using an expression quantitative trait loci (eQTL) database and also analysed its gene expression profiles in 13 different normal tissues. RESULTS: In the discovery GWAS, a SNP located upstream of HAS2, rs7846389, showed the strongest statistical significance (P = 1.43 × 10(-7) ). In the two independent replication cohorts, rs7846389 was consistently associated with asthma (nominal P = 0.0152 and 0.0478 in the first and second replication cohorts, respectively). In the meta-analysis, association of rs7846389 with susceptibility to asthma reached the level of genomewide significance (P = 7.92 × 10(-9) ). This variant was strongly correlated with HAS2 mRNA expression. The strongest expression of the gene was detected in the lung. CONCLUSIONS: Our study identified HAS2 as a novel candidate gene for susceptibility to adult asthma.

Destabilization of the medial meniscus leads to subchondral bone defects and site-specific cartilage degeneration in an experimental rat model.

OBJECTIVE: This study aimed to investigate subchondral bone changes using micro-computed tomography (micro-CT) and regional differences in articular cartilage degeneration, focusing on changes of cartilage covered by menisci, in the early phase using a destabilization of the medial meniscus (DMM) model. METHOD: The DMM model was created as an experimental rat osteoarthritis (OA) model (12 weeks old; n = 24). At 1, 2, and 4 weeks after surgery, the rats were sacrificed, and knee joints were scanned using a Micro-CT system. Histological sections of the medial tibial plateau, which was divided into inner, middle, and outer regions, were prepared and scored using the modified OARSI scoring system. The cartilage thickness was also calculated, and matrix metalloproteinase 13 (MMP13), Col2-3/4c, and vascular endothelial growth factor (VEGF) expression was assessed immunohistochemically. RESULTS: Subchondral bone defects were observed in the middle region, in which the cartilage thickness decreased over time after surgery, and these defects were filled with MMP13- and VEGF-expressing fibrous tissue. The OARSI score increased over time in the middle region, and the score was significantly higher in the middle region than in the inner and outer regions at 1, 2, and 4 weeks after surgery. Col2-3/4c and MMP13 expression was observed primarily in the meniscus-covered outer region, in which the cartilage thickness increased over time. CONCLUSION: Loss of meniscal function caused cartilage degeneration and subchondral bone defects in the early phase site-specifically in the middle region. Furthermore, our results might indicate cartilage covered by menisci is easily degraded resulting in osmotic swelling of the cartilage in early OA.

Orbital masses: the usefulness of diffusion-weighted imaging in lesion categorization.

INTRODUCTION: Diffusion-weighted imaging (DWI) produces contrast among different kinds of tissues according to their diffusibility characteristics. The purpose of our study was to evaluate the role of DWI including measurement of apparent diffusion coefficient (ADC) values in recognizing benignancy or malignancy of orbital masses. METHODS: A total of 39 orbital masses were evaluated visually for signal characteristics on DWI and ADC maps. ADC values were calculated for each lesion. Visual signal characteristics were compared using the Fisher exact test. Receiver operating characteristic (ROC) analysis was carried out to determine sensitivity and specificity for distinguishing malignant from benign lesions using ADC values. The Mann-Whitney U test was applied to compare the ADC values between orbital lymphomas and idiopathic orbital inflammatory (IOI) lesions, and between optic nerve sheath meningiomas and gliomas. RESULTS: Visual assessment revealed no significant difference between benign and malignant lesions on DWI (p-value = 0.66). However, visual assessment of ADC maps revealed a statistically significant (p-value ≤ 0.0001) between benign and malignant lesions. ROC analysis showed a sensitivity of 83.33 % and a specificity of 85.71 % when using an optimal cut off ADC value of 0.84 × 10(-3) mm(2)/s for differentiating malignant from benign lesions. Significant differences in mean ADC values were observed between lymphomas and IOI lesions (p-value = 0.05), and between optic nerve sheath meningiomas and gliomas (p-value = 0.03). CONCLUSION: DWI is useful for differentiating malignant and benign orbital tumors if accompanied by visual assessment of ADC maps and ADC value calculations.

Association study of genetic variants on chromosome 7q31 with susceptibility to normal tension glaucoma in a Japanese population.

The caveolin 1 to caveolin 2 (CAV1-CAV2) gene region on chromosome 7q31 has been reported to be associated with susceptibility to primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) in previous studies. We investigated whether genetic variants in the CAV1-CAV2 region are associated with NTG in Japanese patients. Two hundred and ninety-two Japanese patients with NTG and 352 Japanese healthy controls were recruited. We genotyped three single-nucleotide polymorphisms; that is, rs1052990, rs4236601, and rs7795356, in the CAV1-CAV2 gene region and assessed the allelic diversity among cases and controls. The frequency of the minor allele (G) of rs1052990 was significantly decreased in NTG cases compared with controls (P=0.014, OR=0.71), whereas NTG or POAG cases had a significantly higher frequency of the allele than controls in previous studies. Conversely, rs7795356 did not show any significant association with NTG cases, and rs4236601 was monomorphic in the Japanese study population. Our findings did not correspond with previous positive results, suggesting that CAV1-CAV2 variants studied in the present study are not important risk factors for NTG susceptibility in all populations. Further studies are needed to elucidate the possible contribution of the CAV1-CAV2 region to the development of glaucoma.