Percentage of residual B cells after 2 weeks of rituximab treatment predicts the improvement of systemic sclerosis-associated interstitial lung disease

The benefit of rituximab (RTX) for systemic sclerosis-associated interstitial lung disease (SSc-ILD) has been shown in previous clinical trials. However, predictors of RTX efficacy have not been clarified. We investigated whether B-cell responsiveness to RTX is related to therapeutic effect. Ten SSc-ILD patients treated with RTX in an independent clinical trial (Japan Registry of Clinical Trials, jRCTs031180373) were included in this analysis. Peripheral B-cell counts were examined retrospectively before RTX administration (baseline) and at 2, 4, 12, and 24 weeks after the first RTX administration, along with percent-predicted forced vital capacity (%FVC) before and 24 weeks after RTX treatment. Relative to baseline, the percentage of residual peripheral blood B cells at 2 weeks after RTX was negatively correlated with the %FVC improvement at the 24-week assessment (r = ?0.41, p = 0.04). In the subgroup with less than 5% B-cell persistence at week 2, %FVC at the 24-week assessment was significantly improved compared to baseline (p = 0.02). In another subgroup with more than 5% residual B cells, %FVC was not significantly different after 24 weeks compared to baseline (p = 0.41). In conclusion, the removal rate of B cells after 2 weeks of RTX treatment may be a useful surrogate marker of subsequent SSc-ILD improvement.     

Locomotive syndrome: Prevalence,surgical outcomes,and physical performance of patients treated to correct adult spinal deformity

BackgroundLocomotive syndrome (LS) was proposed by the Japanese Orthopedic Association and refers to a scenario in which imminent future nursing care services will be required by elderly adults to manage the functional deterioration of their locomotive organs. It is a social imperative to clarify the risk factors and treatment strategy for LS. However, the relationship between LS and adult spinal deformity (ASD) in those who are treated with spinal corrective surgery remains largely unknown.MethodsForty consecutive patients who had ASD and underwent spinal surgery for their disorder were included in this study. Locomotive dysfunction was evaluated using the 25-item Geriatric Locomotive Function Scale-25 (GLFS-25) questionnaire and physical performance tests including the one-legged standing test, the two-step test, the stand-up test, the handgrip strength, and gait speed test which were measured preoperatively, 6 months after surgery, and 1 year after surgery.ResultsOf the patients with ASD treated surgically, 95% of them had LS preoperatively and LS prevalence decreased significantly 1 year after surgery by 67.5% compared with the preoperative rate. Among physical performance tests, the walking stride and one-legged standing test improved significantly after spinal corrective surgery. The GLFS-25 items for the domains of pain, mobility, and domestic life improved overall postoperatively, whereas items in the self-care domain did not and the item for difficulty in putting on and taking off trousers and pants worsened.ConclusionsSpinal corrective surgery significantly improved physical performance tests as well as the frequency and severity of LS in patients with ASD. However, some GLFS-25 items can worsen after surgery and require attention.     

Potential application of high-resolution microfocus X-ray techniques for observation of bone structure and bone-implant interface

PURPOSE: The aim of the present study was to evaluate the potential application of 2 types of microfocus x-ray units to study the bone structure around dental implants and at the bone-implant interface. MATERIALS AND METHODS: IMZ titanium implants were placed in the maxilla and mandible of a beagle dog. After implantation periods of 1, 2, and 3 months, the bone-implant interface was evaluated with microfocus x-ray computed tomography (CT) and microfocus x-ray fluoroscopy. RESULTS: Microfocus x-ray CT images of the bone-implant specimen at 3 months after implant placement revealed a clear distinction between the implant and the bone. The implant surface was partially covered with bone, and direct contact between the implant and bone could be clearly seen. Differences in degrees of calcification were identified by the differences in relative black and white intensity. Microfocus x-ray fluoroscopy also showed clear features of the bone and titanium implant The original drill hole and new bone formation could be recognized. These findings corresponded with traditional histologic observations by light microscopy. DISCUSSION AND CONCLUSION: Microfocus x-ray techniques are non-destructive and require a very short examination time. They are considered useful to observe details of the bone structure and bone-implant interface. Microfocus x-ray fluoroscope and microfocus x-ray CT techniques can provide a clear and distinguishable image of the bone-implant interface because of their high spatial resolution.     

Comparison of stability of mandibular segments following the sagittal split ramus osteotomy with poly-l-lactic acid (PLLA) screws and titanium screws fixation

The purpose of this study was to retrospectively compare the stability of the mandible following the surgical orthodontic treatment by sagittal split ramus osteotomy (SSRO) and orthodontic multi-bracket treatment using fixation methods with poly-l-lactic acid (PLLA) or titanium screws. The sample examined was 23 subjects with PLLA screws (PLLA group) and 22 subjects with titanium screws (Titan group). Lateral cephalometric radiographs were reviewed before surgery (T0), 2–3 days after surgery (T1), 1 month after surgery (T2), and after postoperative orthodontic treatment (T3) and changes in the position of bony segments were examined by cephalometric linear and angular measurements. A similar movement of the mandible following setback surgery was indicated, and statistical analysis showed no significant differences in skeletal changes between the two groups during whole postoperative periods. However, a relapse following surgical counterclockwise rotation of the distal segment in PLLA group tended to be slightly greater during T1–T2 compared with Titan group. These results suggest that a use of the PLLA screw fixation may not influence on the stability of bony segments after mandibular setback surgery by SSRO during the postoperative period, although a slight tendency for clockwise rotation of the distal segment was indicated in patients with PLLA screws. It is suggested that fixation of bony segments with PLLA screws after SSRO may be effective in properly selected cases.     

Significance of occlusal force for dietary fibre and vitamin intakes in independently living 70-year-old Japanese: from SONIC Study

Objectives

The number of teeth has frequently been used as an indicator of oral health in investigations of food intake; however, this measure does not represent the efficacy of the masticatory performance. Masticatory performance may be more important for food selection and avoidance than number of remaining teeth. The aim of this study was to investigate the association of occlusal force with habitual dietary intakes in independently living older Japanese.

Methods

The study population was 757 community-dwelling people aged 69–71 years old. Bilateral maximal occlusal force in the intercuspal position was measured with pressure-sensitive sheets. Removable denture wearers kept their dentures in place during the measurements. Dietary habits during the preceding month were assessed using a brief-type self-administered diet history questionnaire that measures consumption frequencies of selected food commonly consumed and calculates energy-adjusted dietary intakes. Linear trends of food and nutrient intakes with decreasing occlusal force were tested after adjusting for gender and socioeconomic factors.

Results

After adjusting for socioeconomic status and the number of remaining teeth, decline of occlusal force was significantly associated with lower intakes of vegetables, vitamins A, C, B₆, folate, and dietary fibre (P for trend < 0.05). In contrast, number of teeth was significantly associated only with calcium and zinc, controlling for occlusal force.

Conclusions

It is concluded that occlusal force was significantly associated with intakes of vitamins and dietary fibre rather than number of remaining teeth in independently living older Japanese.     

Multiple system atrophy variant with severe hippocampal pathology

The striatonigral and olivopontocerebellar systems are known to be vulnerable in multiple system atrophy (MSA), showing neuronal loss, astrogliosis, and alpha-synuclein-immunoreactive inclusions. MSA patients who displayed abundant neuronal cytoplasmic inclusions (NCIs) in the regions other than the striatonigral or olivopontocerebellar system have occasionally been diagnosed with variants of MSA. In this study, we report clinical and pathologic findings of MSA patients characterized by prominent pathologic involvement of the hippocampus. We assessed 146 consecutively autopsied MSA patients. Semi-quantitative analysis of anti-alpha-synuclein immunohistochemistry revealed that 12 of 146 patients (8.2%) had severe NCIs in two or more of the following areas: the hippocampal granule cells, cornu ammonis areas, parahippocampal gyrus, and amygdala. In contrast, the remaining 134 patients did not show severe NCIs in any of these regions. Patients with severe hippocampal involvement showed a higher representation of women (nine women/three men; Fisher's exact test, p = 0.0324), longer disease duration (13.1 ± 5.9 years; Mann–Whitney U-test, p = 0.000157), higher prevalence of cognitive impairment (four patients; Fisher's exact test, p = 0.0222), and lower brain weight (1070.3 ± 168.6 g; Mann–Whitney U-test, p = 0.00911) than other patients. The hippocampal granule cells and cornu ammonis area 1/subiculum almost always showed severe NCIs. The NCIs appeared to be ring-shaped or neurofibrillary tangle-like, fibrous configurations. Three of 12 patients also had dense, round-shaped NCIs that were morphologically similar to pick bodies. The patients with Pick body-like inclusions showed more severe atrophy of the medial temporal lobes and broader spreading of NCIs than those without. Immunohistochemistry for hyperphosphorylated tau and phosphorylated TDP-43 revealed minimal aggregations in the hippocampus of the hippocampal MSA patients. Our observations suggest a pathological variant of MSA that is characterized by severe involvement of hippocampal neurons. This phenotype may reinforce the importance of neuronal alpha-synucleinopathy in the pathogenesis of MSA.     

An essential role of cytosolic phospholipase A2alpha in prostaglandin E2-mediated bone resorption associated with inflammation

Prostaglandin E (PGE)2 produced by osteoblasts acts as a potent stimulator of bone resorption. Inflammatory bone loss is accompanied by osteoclast formation induced by bone-resorbing cytokines, but the mechanism of PGE2 production and bone resorption in vivo is not fully understood. Using cytosolic phospholipase A2alpha (cPLA2alpha)-null mice, we examined the role of cPLA2alpha in PGE2 synthesis and bone resorption. In bone marrow cultures, interleukin (IL)-1 markedly stimulated PGE2 production and osteoclast formation in wild-type mice, but not in cPLA2alpha-null mice. Osteoblastic bone marrow stromal cells induced the expression of cyclooxygenase (COX)-2 and membrane-bound PGE2 synthase (mPGES) in response to IL-1 and lipopolysaccharide (LPS) to produce PGE2. Osteoblastic stromal cells collected from cPLA2alpha-null mice also induced the expression of COX-2 and mPGES by IL-1 and LPS, but could not produce PGE2 due to the lack of arachidonic acid release. LPS administration to wild-type mice reduced femoral bone mineral density by increased bone resorption. In cPLA2alpha-null mice, however, LPS-induced bone loss could not be observed at all. Here, we show that cPLA2alpha plays a key role in PGE production by osteoblasts and in osteoclastic bone resorption, and suggest a new approach to inflammatory bone disease by inhibiting cPLA2alpha.     

Physical exercise on the rat ventral prostate: Steroid hormone receptors,apoptosis and cell proliferation

Studies have investigated the effect of exercise on prostate cancer risk. However, there are still doubts regarding the correlation between physical activity and the steroid hormones with respect to the reduction of the risk for prostatic lesions. We evaluated the levels of corticosterone, dihydrotestosterone (DHT), testosterone, estradiol, and steroid hormone receptors, and investigated the relationship between apoptosis and cell proliferation in the rat ventral prostate after training. Two groups were included in this study: control and trained. The trained group was submitted to training for 13 weeks (1 week of adaptation). Two days after the last training session, all animals were euthanized, and the intermediate and distal regions of the ventral prostate were collected and processed for immunohistochemistry, Western blotting and hormonal analyses. Physical exercise increased the corticosterone plasma, DHT and testosterone. In addition, androgen receptor expression was lower and estrogen receptor (ER) α and ER β expression were higher in the trained group. However, the trained group showed disruption of the ratio of apoptotic to proliferating cells, indicating a predominance of apoptosis. We conclude that physical exercise alters the sex hormones and their receptors and is associated with the disruption of the balance between apoptosis and cell proliferation in the rat ventral prostate.