Synovial Tissue Heterogeneity in Japanese Patients With Rheumatoid Arthritis Elucidated Using a Cell-Type Deconvolution Approach.

OBJECTIVE: Recent advances in single-cell RNA sequencing technology have improved our understanding of the immunological landscape of rheumatoid arthritis (RA). We aimed to stratify the synovium from East Asian patients with RA by immune cell compositions and gain insight into the inflammatory drivers of each synovial phenotype. METHODS: Synovial tissues were obtained from East Asian patients in Japan with RA (n = 41) undergoing articular surgery. The cellular composition was quantified by a deconvolution approach using a public single-cell-based reference. Inflammatory pathway activity was calculated by gene set variation analysis, and chromatin accessibility was evaluated using assay of transposase accessible chromatin-sequencing. RESULTS: We stratified RA synovium into three distinct subtypes based on the hierarchical clustering of cellular composition data. One subtype was characterized by abundant HLA-DRAhigh synovial fibroblasts, autoimmune-associated B cells, GZMK+ GZMB+ CD8+ T cells, interleukin (IL)1-ß+ monocytes, and plasmablasts. In addition, tumor necrosis factor (TNF)-α, interferons (IFNs), and IL-6 signaling were highly activated in this subtype, and the expression of various chemokines was significantly enhanced. Moreover, we found an open chromatin region overlapping with RA risk locus rs9405192 near the IRF4 gene, suggesting the genetic background influences the development of this inflammatory synovial state. The other two subtypes were characterized by increased IFNs and IL-6 signaling, and expression of molecules associated with degeneration, respectively. CONCLUSION: This study adds insights into the synovial heterogeneity in East Asian patients and shows a promising link with predominant inflammatory signals. Evaluating the site of inflammation has the potential to lead to appropriate drug selection that matches the individual pathology.

Evolution of genetic architecture and gene regulation in biphenyl/PCB-degrading bacteria.

A variety of bacteria in the environment can utilize xenobiotic compounds as a source of carbon and energy. The bacterial strains degrading xenobiotics are suitable models to investigate the adaptation and evolutionary processes of bacteria because they appear to have emerged relatively soon after the release of these compounds into the natural environment. Analyses of bacterial genome sequences indicate that horizontal gene transfer (HGT) is the most important contributor to the bacterial evolution of genetic architecture. Further, host bacteria that can use energy effectively by controlling the expression of organized gene clusters involved in xenobiotic degradation will have a survival advantage in harsh xenobiotic-rich environments. In this review, we summarize the current understanding of evolutionary mechanisms operative in bacteria, with a focus on biphenyl/PCB-degrading bacteria. We then discuss metagenomic approaches that are useful for such investigation.

A-910823, a squalene-based emulsion adjuvant, induces T follicular helper cells and humoral immune responses via α-tocopherol component.

Background: Adjuvants are chemical or biological materials that enhance the efficacy of vaccines. A-910823 is a squalene-based emulsion adjuvant used for S-268019-b, a novel vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is currently in clinical development. Published evidence has demonstrated that A-910823 can enhance the induction of neutralizing antibodies against SARS-CoV-2 in humans and animal models. However, the characteristics and mechanisms of the immune responses induced by A-910823 are not yet known. Methods and Results: To characterize A-910823, we compared the adaptive immune response profile enhanced by A-910823 with that of other adjuvants (AddaVax, QS21, aluminum salt-based adjuvants, and empty lipid nanoparticle [eLNP]) in a murine model. Compared with other adjuvants, A-910823 enhanced humoral immune responses to an equal or greater extent following potent T follicular helper (Tfh) and germinal center B (GCB) cell induction, without inducing a strong systemic inflammatory cytokine response. Furthermore, S-268019-b containing A-910823 adjuvant produced similar results even when given as a booster dose following primary administration of a lipid nanoparticle-encapsulated messenger RNA (mRNA-LNP) vaccine. Preparation of modified A-910823 adjuvants to identify which components of A-910823 play a role in driving the adjuvant effect and detailed evaluation of the immunological characteristics induced by each adjuvant showed that the induction of humoral immunity and Tfh and GCB cell induction in A-910823 were dependent on α-tocopherol. Finally, we revealed that the recruitment of inflammatory cells to the draining lymph nodes and induction of serum cytokines and chemokines by A-910823 were also dependent on the α-tocopherol component. Conclusions: This study demonstrates that the novel adjuvant A-910823 is capable of robust Tfh cell induction and humoral immune responses, even when given as a booster dose. The findings also emphasize that α-tocopherol drives the potent Tfh-inducing adjuvant function of A-910823. Overall, our data provide key information that may inform the future production of improved adjuvants.

Diversity and Evolution of Integrative and Conjugative Elements Involved in Bacterial Aromatic Compound Degradation and Their Utility in Environmental Remediation.

Integrative and conjugative elements (ICEs) are mobile DNA molecules that can be transferred through excision, conjugation, and integration into chromosomes. They contribute to the horizontal transfer of genomic islands across bacterial species. ICEs carrying genes encoding aromatic compound degradation pathways are of interest because of their contribution to environmental remediation. Recent advances in DNA sequencing technology have increased the number of newly discovered ICEs in bacterial genomes and have enabled comparative analysis of their evolution. The two different families of ICEs carry various aromatic compound degradation pathway genes. ICEclc and its related ICEs contain a number of members with diverse catabolic capabilities. In addition, the Tn4371 family, which includes ICEs that carry the chlorinated biphenyl catabolic pathway, has been identified. It is apparent that they underwent evolution through the acquisition, deletion, or exchange of modules to adapt to an environmental niche. ICEs have the property of both stability and mobility in the chromosome. Perspectives on the use of ICEs in environmental remediation are also discussed.

Extension contracture stiff knee in haemophilia: Surgical timing and procedure for total knee arthroplasty.

INTRODUCTION: Total knee arthroplasty (TKA) for a stiff knee of patients with haemophilia (PWH) represents a challenge for orthopaedic surgeons for the difficulties of exposing the knee and high complication rate compared to a flexible knee. AIM: To optimize the surgical exposure in primary TKA for PWH and to propose a threshold angle of extension contracture in treating haemophilic knee joints, retrospectively. METHODS: Sixty-seven primary TKAs for PWH (mean age, 48 years) were performed, and incisional approaches to joint were standard (58 cases) and V-Y quadricepsplasty (V-Y) (9 cases). The decision of surgical approach was decided intraoperatively by two surgeons. Pre- and post-knee angles were evaluated in each group. Variables in the V-Y group were evaluated using univariate logistic regression analysis and receiver operating characteristic curve analysis. RESULTS: Univariate logistic regression analysis demonstrated that the preoperative range of motion (ROM) and flexion were significantly associated with V-Y. Threshold values of preoperative flexion and ROM resulting in V-Y using receiver operating characteristic analysis were 45° and 35°, respectively. CONCLUSIONS: Primary TKA for PWH using a standard approach may be performed before the stage preoperative flexion <45° and ROM <35°.

Accuracy of an Artificial Intelligence-Based Model for Estimating Leftover Liquid Food in Hospitals: Validation Study.

BACKGROUND: An accurate evaluation of the nutritional status of malnourished hospitalized patients at a higher risk of complications, such as frailty or disability, is crucial. Visual methods of estimating food intake are popular for evaluating the nutritional status in clinical environments. However, from the perspective of accurate measurement, such methods are unreliable. OBJECTIVE: The accuracy of estimating leftover liquid food in hospitals using an artificial intelligence (AI)-based model was compared to that of visual estimation. METHODS: The accuracy of the AI-based model (AI estimation) was compared to that of the visual estimation method for thin rice gruel as staple food and fermented milk and peach juice as side dishes. A total of 576 images of liquid food (432 images of thin rice gruel, 72 of fermented milk, and 72 of peach juice) were used. The mean absolute error, root mean squared error, and coefficient of determination (R2) were used as metrics for determining the accuracy of the evaluation process. Welch t test and the confusion matrix were used to examine the difference of mean absolute error between AI and visual estimation. RESULTS: The mean absolute errors obtained through the AI estimation approach were 0.63 for fermented milk, 0.25 for peach juice, and 0.85 for the total. These were significantly smaller than those obtained using the visual estimation approach, which were 1.40 (P<.001) for fermented milk, 0.90 (P<.001) for peach juice, and 1.03 (P=.009) for the total. By contrast, the mean absolute error for thin rice gruel obtained using the AI estimation method (0.99) did not differ significantly from that obtained using visual estimation (0.99). The confusion matrix for thin rice gruel showed variation in the distribution of errors, indicating that the errors in the AI estimation were biased toward the case of many leftovers. The mean squared error for all liquid foods tended to be smaller for the AI estimation than for the visual estimation. Additionally, the coefficient of determination (R2) for fermented milk and peach juice tended to be larger for the AI estimation than for the visual estimation, and the R2 value for the total was equal in terms of accuracy between the AI and visual estimations. CONCLUSIONS: The AI estimation approach achieved a smaller mean absolute error and root mean squared error and a larger coefficient of determination (R2) than the visual estimation approach for the side dishes. Additionally, the AI estimation approach achieved a smaller mean absolute error and root mean squared error compared to the visual estimation method, and the coefficient of determination (R2) was similar to that of the visual estimation method for the total. AI estimation measures liquid food intake in hospitals more precisely than visual estimation, but its accuracy in estimating staple food leftovers requires improvement.

Transcription Factor Hematopoietically Expressed Homeobox Protein (Hhex) Negatively Regulates Osteoclast Differentiation by Controlling Cyclin-Dependent Kinase Inhibitors.

We investigated the role of hematopoietically expressed homeobox protein (Hhex) in osteoclast development. Trimethylation of lysine 27 of histone H3 at the cis-regulatory element of Hhex was maintained and that of lysine 4 was reduced during receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis, which was associated with a reduction of Hhex expression. Overexpression of Hhex in bone marrow-derived macrophages inhibited, whereas Hhex suppression promoted, RANKL-induced osteoclastogenesis in vitro. Conditional deletion of Hhex in osteoclast-lineage cells promoted osteoclastogenesis and reduced cancellous bone volume in mice, confirming the negative regulatory role of Hhex in osteoclast differentiation. Expression of cyclin-dependent kinase inhibitors such as Cdkn2a and Cdkn1b in osteoclast precursors was negatively regulated by Hhex, and Hhex deletion increased the ratio of cells at the G1 phase of the cell cycle. In conclusion, Hhex is an inhibitor of osteoclast differentiation that is regulated in an epigenetic manner and regulates the cell cycle of osteoclast precursors and the skeletal homeostasis. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Clinical Outcomes After First Metatarsophalangeal Joint Arthrodesis by Flat Cut Joint Preparation With Individual Adjustment for Sagittal Alignment.

Sagittal misalignment is a major cause of patient dissatisfaction and re-operation after first metatarsophalangeal (MTP) joint arthrodesis. The stereotypical application of the fixed angle would be undesirable, especially in cases of flat or cavus foot. We retrospectively reviewed 31 cases (27 patients) in which first MTP joint arthrodesis was performed using the flat cut joint preparation technique with reference to the plantar clearance beneath the pulp of the toe while simulating weightbearing by pushing a board against the sole. The most common underlying cause of surgery was rheumatoid arthritis (22 cases [71%]). Clinical outcomes were evaluated by the Japanese of Surgery of the Foot (JSSF) hallux scale and the self-administered foot evaluation questionnaire (SAFE-Q). Twenty-three cases were also examined by pedobarography to evaluate postoperative walking plantar pressure. At the most recent follow-up of a mean 19.6 months, the toe-to-floor distance of the hallux in static standing posture was a mean of 2.5 mm (range, 0-10 mm). All but 1 foot (97%) achieved bone union. There were no complications or revisions due to misalignment of the fused MTP joint. JSSF hallux scales improved significantly from 47 preoperatively to 82 postoperatively. All subscale scores except general health and well-being in the SAFE-Q improved significantly at final follow-up versus preoperative period. Plantar pressure under the hallux was correlated with the toe-to-floor distance but not radiographic parameter. In conclusion, first MTP joint arthrodesis achieved good clinical outcomes when using toe-to-floor distance and Kirschner wire template for flat cut joint preparation.

A New ICEclc Subfamily Integrative and Conjugative Element Responsible for Horizontal Transfer of Biphenyl and Salicylic Acid Catabolic Pathway in the PCB-Degrading Strain Pseudomonas stutzeri KF716.

Integrative and conjugative elements (ICEs) are chromosomally integrated self-transmissible mobile genetic elements. Although some ICEs are known to carry genes for the degradation of aromatic compounds, information on their genetic features is limited. We identified a new member of the ICEclc family carrying biphenyl catabolic bph genes and salicylic acid catabolic sal genes from the PCB-degrading strain Pseudomonas stutzeri KF716. The 117-kb ICEbph-salKF716 contains common core regions exhibiting homology with those of degradative ICEclc from P. knackmussii B13 and ICEXTD from Azoarcus sp. CIB. A comparison of the gene loci collected from the public database revealed that several putative ICEs from P. putida B6-2, P, alcaliphila JAB1, P. stutzeri AN10, and P. stutzeri 2A20 had highly conserved core regions with those of ICEbph-salKF716, along with the variable region that encodes the catabolic genes for biphenyl, naphthalene, toluene, or phenol. These data indicate that this type of ICE subfamily is ubiquitously distributed within aromatic compound-degrading bacteria. ICEbph-salKF716 was transferred from P. stutzeri KF716 to P. aeruginosa PAO1 via a circular extrachromosomal intermediate form. In this study, we describe the structure and genetic features of ICEbph-salKF716 compared to other catabolic ICEs.

Outcomes of Scarf and Akin Osteotomy with Intra-Articular Stepwise Lateral Soft Tissue Release for Correcting Hallux Valgus Deformity in Rheumatoid Arthritis.

BACKGROUND: The effectiveness of scarf and Akin osteotomy with intra-articular lateral soft tissue release for the correction of hallux valgus (HV) in patients with rheumatoid arthritis (RA) has not been elucidated. METHODS: A total of 36 feet in 28 patients with RA who had scarf and Akin osteotomy with intra-articular stepwise lateral soft tissue release between 2015 and 2020 at a single institute were investigated retrospectively, with a mean follow-up period of 32.0 ± 16.9 months. Radiographic evaluations including the HV angle, intermetatarsal angle, and sesamoid position were performed preoperatively and postoperatively. Clinical outcomes were assessed using the Japanese Society of Surgery of the Foot (JSSF) hallux scale and self-administered foot evaluation questionnaire (SAFE-Q). RESULTS: The procedure resulted in significant HV correction, with a recurrence rate of 13.9%. The JSSF scale and all five SAFE-Q subscale scores significantly improved (p < 0.05), with no major complications. More than 90% of cases achieved adequate lateral soft tissue release without sacrificing the adductor tendon of the hallux. CONCLUSIONS: Intra-articular stepwise lateral soft tissue release in combination with scarf and Akin osteotomy provided satisfactory radiographic and patient-reported outcomes for the correction of HV in patients with RA with minimum lateral soft tissue release.

Lateral Heel Pain Caused by Impingement of Hypertrophic Peroneal Tubercle and Os Peroneum.

Hypertrophic peroneal tubercle (HPT) is an overgrowth of the peroneal tubercle located on the lateral aspect of the hindfoot, which could cause tenosynovitis of the peroneus longus tendon. Os peroneum (OP) is an accessory ossicle that exists in the peroneus longus tendon at the lateral aspect of the calcaneocuboid joint. Both HPT and OP can cause lateral foot pain and occasionally require surgical treatment. We encountered a case of lateral foot pain of HPT coexisting with OP. Careful preoperative magnetic resonance imaging, dynamic ultrasonographic image, and block injection suggested an impingement of HPT and OP as a cause of lateral foot pain. Surgical resection of HPT, while retaining OP, successfully achieved pain relief in the patient. To the best of our knowledge, this is the first report presenting a case of HPT coexisting with OP successfully treated without OP resection.

An Electrical Stimulation Culture System for Daily Maintenance-Free Muscle Tissue Production.

Low-labor production of tissue-engineered muscles (TEMs) is one of the key technologies to realize the practical use of muscle-actuated devices. This study developed and then demonstrated the daily maintenance-free culture system equipped with both electrical stimulation and medium replacement functions. To avoid ethical issues, immortal myoblast cells C2C12 were used. The system consisting of gel culture molds, a medium replacement unit, and an electrical stimulation unit could produce 12 TEMs at one time. The contractile forces of the TEMs were measured with a newly developed microforce measurement system. Even the TEMs cultured without electrical stimulation generated forces of almost 2 mN and were shortened by 10% in tetanic contractions. Regarding the contractile forces, electrical stimulation by a single pulse at 1 Hz was most effective, and the contractile forces in tetanus were over 2.5 mN. On the other hand, continuous pulses decreased the contractile forces of TEMs. HE-stained cross-sections showed that myoblast cells proliferated and fused into myotubes mainly in the peripheral regions, and fewer cells existed in the internal region. This must be due to insufficient supplies of oxygen and nutrients inside the TEMs. By increasing the supplies, one TEM might be able to generate a force up to around 10 mN. The tetanic forces of the TEMs produced by the system were strong enough to actuate microstructures like previously reported crawling robots. This daily maintenance-free culture system which could stably produce TEMs strong enough to be utilized for microrobots should contribute to the advancement of biohybrid devices.

Association between fall history and performance-based physical function and postural sway in patients with rheumatoid arthritis.

OBJECTIVES: Patients with rheumatoid arthritis (RA) are at increased risk of falling; therefore, fall prevision and prevention are critical. The present study aimed to evaluate the ability of physical performance assessments to discriminate between RA patients with and without a history of falling. METHODS: Fifty patients with RA were divided into two groups according to the presence or absence of a history of falls within the previous 1 year. Physical performance was assessed using the short physical performance battery (SPPB), which consists of the timed standing balance, gait speed, and chair stand tests. Standing balance was also assessed as postural sway using a force platform in several positions including standing with both feet together, semitandem, and tandem. Backgrounds, SPPB, and postural sway were compared between the two groups. RESULTS: Fourteen patients (28%) reported one or more falls within the previous year. There were no significant intergroup differences in baseline characteristics or SPPB score. The group with a history of falls had significantly longer measured time for the 5-repetition chair stand test and significantly longer postural sway in the semitandem position. The discriminate analysis revealed that 5-repetition chair stand test or its combination with postural sway in the semitandem position significantly discriminated between fallers and non-fallers. CONCLUSION: Numerical evaluation of the chair stand test and postural sway in the semitandem position seems more appropriate than SPPB for assessing the fall risk of patients with RA.

Parsing multiomics landscape of activated synovial fibroblasts highlights drug targets linked to genetic risk of rheumatoid arthritis.

OBJECTIVES: Synovial fibroblasts (SFs) are one of the major components of the inflamed synovium in rheumatoid arthritis (RA). We aimed to gain insight into the pathogenic mechanisms of SFs through elucidating the genetic contribution to molecular regulatory networks under inflammatory condition. METHODS: SFs from RA and osteoarthritis (OA) patients (n=30 each) were stimulated with eight different cytokines (interferon (IFN)-α, IFN-γ, tumour necrosis factor-α, interleukin (IL)-1ß, IL-6/sIL-6R, IL-17, transforming growth factor-ß1, IL-18) or a combination of all 8 (8-mix). Peripheral blood mononuclear cells were fractioned into five immune cell subsets (CD4+ T cells, CD8+ T cells, B cells, natural killer (NK) cells, monocytes). Integrative analyses including mRNA expression, histone modifications (H3K27ac, H3K4me1, H3K4me3), three-dimensional (3D) genome architecture and genetic variations of single nucleotide polymorphisms (SNPs) were performed. RESULTS: Unstimulated RASFs differed markedly from OASFs in the transcriptome and epigenome. Meanwhile, most of the responses to stimulations were shared between the diseases. Activated SFs expressed pathogenic genes, including CD40 whose induction by IFN-γ was significantly affected by an RA risk SNP (rs6074022). On chromatin remodelling in activated SFs, RA risk loci were enriched in clusters of enhancers (super-enhancers; SEs) induced by synergistic proinflammatory cytokines. An RA risk SNP (rs28411362), located in an SE under synergistically acting cytokines, formed 3D contact with the promoter of metal-regulatory transcription factor-1 (MTF1) gene, whose binding motif showed significant enrichment in stimulation specific-SEs. Consistently, inhibition of MTF1 suppressed cytokine and chemokine production from SFs and ameliorated mice model of arthritis. CONCLUSIONS: Our findings established the dynamic landscape of activated SFs and yielded potential therapeutic targets associated with genetic risk of RA.

Identification of the Gene Responsible for Lignin-Derived Low-Molecular-Weight Compound Catabolism in Pseudomonas sp. Strain LLC-1.

Pseudomonas sp. strain LLC-1 (NBRC 111237) is capable of degrading lignin-derived low-molecular-weight compounds (LLCs). The genes responsible for the catabolism of LLCs were characterized in this study using whole-genome sequencing. Despite the close phylogenetic relationship with Pseudomonas putida, strain LLC-1 lacked the genes usually found in the P. putida genome, which included fer, encoding an enzyme for ferulic acid catabolism, and vdh encoding an NAD+-dependent aldehyde dehydrogenase specific for its catabolic intermediate, vanillin. Cloning and expression of the 8.5 kb locus adjacent to the van operon involved in vanillic acid catabolism revealed the bzf gene cluster, which is involved in benzoylformic acid catabolism. One of the structural genes identified, bzfC, expresses the enzyme (BzfC) having the ability to transform vanillin and syringaldehyde to corresponding acids, indicating that BzfC is a multifunctional enzyme that initiates oxidization of LLCs in strain LLC-1. Benzoylformic acid is a catabolic intermediate of (R,S)-mandelic acid in P. putida. Strain LLC-1 did not possess the genes for mandelic acid racemization and oxidation, suggesting that the function of benzoylformic acid catabolic enzymes is different from that in P. putida. Genome-wide characterization identified the bzf gene responsible for benzoylformate and vanillin catabolism in strain LLC-1, exhibiting a unique mode of dissimilation for biomass-derived aromatic compounds by this strain.

Predictability of postoperative recurrence on hepatocellular carcinoma through data mining method.

Hepatocellular carcinoma (HCC) is a highly lethal tumor and the majority of postoperative patients experience recurrence. In the present study, we focus on the predictability of postoperative recurrence on HCC through the data mining method. In total, 323 patients with HCC who underwent hepatic resection were included in the present study, 156 of whom suffered from cancer recurrence. Clinicopathological data including prognosis were analyzed using the data mining method for the predictability of postoperative recurrence on HCC. The resulting alternating decision tree (ADT) was described using data mining method. This tree was validated using a 10-fold cross validation process. The average and standard deviation of the accuracy, sensitivity, and specificity were 69.0±8.2, 59.7±14.5 and 77.7±10.2%, respectively. The identified postoperative recurrence factors were age, viral hepatitis, stage, GOT and T-cholesterol. Data mining method could identify the factors associated at different levels of significance with postoperative recurrence of HCC. These factors could help to predict the postoperative recurrence of HCC.

Joint-Preserving Surgery for Hyperextension Deformity of the Hallux Interphalangeal Joint in a Patient with Rheumatoid Arthritis.

Interphalangeal hyperextension is one of the major hallux deformities in patients with rheumatoid arthritis; however, there is yet no established surgical method for this deformity. We here present the case of a 69-year-old female patient with rheumatoid arthritis who developed hallux interphalangeal hyperextension and painful callosity on the plantar hallux accompanied by limited dorsiflexion at the metatarsophalangeal joint. Lateral weight-bearing radiograph of the foot revealed misalignment of the medial column and hallux, including a collapsed medial arch, elevated first metatarsal, plantar flexion and deviation of the proximal phalanx, and hyperextension of the distal phalanx. The foot was successfully treated and became symptom-free with opening wedge osteotomy of the medial cuneiform, plantar and proximal translation of the metatarsal head, and tenotomy of the extensor hallucis longus. This case suggests that reconstruction of the sagittal alignment of the medial column and hallux through a combination of osteotomy and soft tissue intervention could be an optional treatment for interphalangeal hyperextension.

Sustained anti-osteoporotic action of risedronate compared to anti-RANKL antibody following discontinuation in ovariectomized mice.

Bisphosphonates and the anti-receptor activator of nuclear factor-kappa B ligand (RANKL) antibody denosumab are effective anti-resorptive drugs commonly prescribed for osteoporosis. Both drugs may, however, have intolerable side effects; so, it is critical to examine their residual efficacy such as maintenance of bone mass following cessation. Therefore, we compared the changes in bone histology following discontinuation of the aminobisphosphonate risedronate and anti-RANKL antibody in ovariectomized (OVX) mice. Twelve-week-old female C57BL/6 N mice were OVX or sham operated. Four weeks after surgery, mice were treated with vehicle, a single injection of anti-RANKL antibody (5 mg/kg), or risedronate (5 µg/kg/day, s.c.) for 4 weeks (the treatment period), followed by vehicle treatment for an additional 4 weeks (discontinuation period). The lumbar spine and proximal tibia were evaluated by micro-computed tomography. In addition, the lumbar spine, proximal tibia, and the femoral shaft were examined by bone histomorphometry. After 4 weeks of discontinuation, OVX mice initially treated with the anti-RANKL antibody exhibited a trend of bone loss associated with increased turnover in both trabecular and cortical bones, although the difference was not significant. By contrast, OVX mice treated with risedronate exhibited maintained or even increased bone mass and suppressed bone turnover. Patients discontinuing denosumab should be carefully monitored for recurrent osteoporosis symptoms, and a replacement drug should be considered.

The role of medical informatics in the management of medical information.

With progress in information and communication technology, medical information has been converted to digital formats and stored and managed using computer systems. The construction, management, and operation of medical information systems and regional medical liaison systems are the main components of the clinical tasks of medical informatics departments. Research using medical information accumulated in these systems is also a task for medical informatics department. Recently, medical real-world data (RWD) accumulated in medical information systems has become a focus not only for primary use but also for secondary uses of medical information. However, there are many problems, such as standardization, collection, cleaning, and analysis of them. The internet of things and artificial intelligence are also being applied in the collection and analysis of RWD and in resolving the above problems. Using these new technologies, progress in medical care and clinical research is about to enter a new era. J. Med. Invest. 67 : 27-29, February, 2020.