Genomic characterization of carbapenemase-producing Enterobacterales from Dhaka food markets unveils the spread of high-risk antimicrobial-resistant clones and plasmids co-carrying bla NDM and mcr-1.1.

Background: The transmission of carbapenemase-producing Enterobacterales (CPE) in the external environment, especially through food, presents a significant public health risk. Objectives: To investigate the prevalence and genetic characteristics of CPE in food markets of Dhaka, Bangladesh, using WGS. Methods: CPE isolates were obtained from different food and water samples collected from food markets in the southern part of Dhaka, Bangladesh. The isolates subsequently underwent molecular typing, WGS employing both short- and long-read sequencers, and plasmid analysis. Results: This study unveiled an extensive spread of CPE, with no significant difference in contamination rates observed in samples (N = 136), including meat (n = 8), fish (n = 5), vegetables (n = 36) or various food-washed water (n = 65) from markets near hospitals or residential areas. Thirty-eight Enterobacterales from 33 samples carried carbapenemase genes (bla NDM-1, -4, -7, bla KPC-2, bla OXA-181 or bla IMI-1). Among these, the high-risk Escherichia coli ST410 clone was the most prevalent and distributed across various locations. Furthermore, the identification of IncHI2 plasmids co-harbouring resistance genes like bla NDM-5 and mcr-1.1, without discernible epidemiological connections, is a unique finding, suggesting their widespread dissemination. Conclusions: The analysis unveils a dynamic landscape of CPE dissemination in food markets, underscored by the proliferation of novel IncHI2 hybrid plasmids carrying both colistin- and carbapenem-resistance genes. This illuminates the ever-evolving landscape of antimicrobial resistance in Dhaka, urging us to confront its emergent challenges.

Clinical effects of teriparatide, abaloparatide, and romosozumab in postmenopausal osteoporosis.

In the management of osteoporosis, anti-resorptive agents serve as a primary therapeutic approach. However, in cases where individuals exhibit an increased susceptibility to fractures, such as those characterized by severe low bone mass or a history of vertebral or hip fractures that markedly diminish life expectancy, the immediate reduction of fracture risk through the administration of osteoanabolic agents could be beneficial. Teriparatide, available in daily, once-weekly, or twice-weekly dosages, along with abaloparatide and romosozumab, constitutes a trio of such agents. Each of these medications is defined by unique characteristics, distinct efficacy profiles, and specific adverse effects. There is growing evidence to suggest that these agents have a superior effect on enhancing bone mineral density and reducing fracture incidence when compared to traditional bisphosphonate therapies. Nonetheless, their employment demands thorough consideration of clinical indications, which includes evaluating economic factors, the frequency of injections required, and the potential for adverse effects. The objective of this review is to consolidate the current evidence focusing primarily on the efficacy of these agents, with the goal of enhancing understanding and aiding in making more informed treatment decisions, particularly for those individuals who are at an elevated risk of fractures.

Goal Orientation and Desire for Approval Were Associated With Sports Injuries Among Young Japanese Athletes.

Introduction: This study aimed to clarify the relationship between psychological factors (goal orientation and desire for approval from others) and the severity of sports injuries experienced by young Japanese athletes. Methods: A total of 560 young Japanese athletes (328 males and 232 females) aged 18-24 years completed an online survey in 2022-2023. A web questionnaire was used to investigate participants' task and ego orientations, desire for approval from others (e.g., coaches and friends/families), and history of injury. The samples were then split into 3 groups on the basis of the rest duration due to the injury: noninjury group (0 days), mild-to-moderate injury group (1-27 days), and severe injury group (>28 days). Spearman's test examined a correlation between task and ego orientation scores among all samples. The Mann-Whitney U test was used to compare the scores between the severe injury and noninjury groups. Result: A significant positive correlation was found between task and ego orientation scores from all samples (ρ=0.27, p<0.001). The severe injury group had significantly higher task orientation scores and desire for approval scores than the noninjury group (ρ=0.001, p<0.001). Conclusions: Japanese young athletes with high task orientation and approval desire may be at risk of severe sports injuries requiring >4 weeks to return to sports. The goal orientation profiles should be interpreted with caution. Future research should examine contextual effects such as the perceived motivational climate, in addition to the goal orientation profiles.

Mechanical Evaluation of Bone-Patellar Tendon-Bone Graft Fixation to the Tibia in ACL Reconstruction: Bone Plug Tensioning and Fixation System versus Interference Screw.

This study aimed to evaluate the mechanical properties of bone plug fixation to the tibia with a novel device, the Bone plug Tensioning and Fixation (BTF) system.Forty bone-tendon-bone grafts consisting of the whole patella-patellar tendon-tibial bone plug of 10-mm width and tibiae from the porcine were prepared. After creating a 10-mm tibial tunnel, the tibial bone plug was fixed to the tibia with the BTF system or the interference screw (IFS) to prepare a test specimen of the patella-patellar tendon-tibial bone plug fixed to the tibia. For the graft tension controllability study, a predetermined initial tension of 9.8 or 19.6 N was applied and maintained for 5 minutes. Then the bone plug was fixed to the tibia with the BTF system or IFS in 10 specimens, monitoring the residual tension for an additional 5 minutes. Then, a cyclic loading test and a tension-to-failure test were performed.The mean difference between the residual tension and the predetermined tension was significantly smaller in BTF fixation (9.8 N → 10.6 ± 2.2 N; 19.6 N → 18.9 ± 2.1 N) than in IFS fixation (9.8 N → 23.4 ± 7.4 N; 19.6 N → 28.9 ± 11.5 N). The mean displacement of the bone plug after cyclic loading was significantly less in the BTF group (1.2 ± 0.6 mm) than in the IFS group (2.2 ± 1.0 mm; p < 0.01). Stiffness was significantly greater in the BTF group (504.6 ± 148.8 N/mm) than in the IFS group (294.7 ± 96.7 N/mm; p < 0.01), whereas the maximum failure loads in the two groups did not differ significantly (724.2 ± 180.3 N in the BTF and 634.8 ± 159.4 N in the IFS groups).BTF system better performed in graft tension controllability than IFS did. BTF fixation was superior to IFS fixation in the displacement of the bone plug during the cyclic loading test and in stiffness in the tension-to-failure test.

Cyclic compressive loading induces a mature meniscal cell phenotype in mesenchymal stem cells with an atelocollagen-based scaffold.

Introduction: Biomechanical stimulation is reportedly pivotal in meniscal regeneration, although its effect on mesenchymal stem cell (MSC) meniscal differentiation remains elusive. In this study, we investigated how cyclic compressive loading (CCL) could impact MSCs using three-dimensional cultures in atelocollagen-based meniscal substitute (ACMS). Methods: We extracted MSCs from the meniscus, synovium, and articular cartilage, cultured them in three-dimensional cultures, and exposed them to CCL for 7 days. We then compared the transcriptomes of MSCs treated with and without CCL. Results: Our RNA-seq analysis revealed that CCL induced significant transcriptome changes, significantly affecting chondrocyte-related genes, including SOX9, TGFB1, and PRG4 upregulation. CCL induced transcriptional differentiation of meniscus progenitors toward mature meniscal cells. Conclusion: This study unveils the potential of mechanical stress in promoting MSC meniscal differentiation within ACMS. Our investigations provide new insights for mechanisms underlying meniscal regeneration with ACMS.

Decreased moment of inertia of the lower limb facilitates a rapid hip internal rotation in a simulated foot impact maneuver. A laboratory-controlled biomechanical study for a precursor mechanism of noncontact anterior cruciate ligament injury.

BACKGROUND: Anterior cruciate ligament injury frequently occurs in the deceleration with the knee-extended position. In addition, a rapid hip internal rotation is concomitantly observed. However, how the extended knee position induces the hip internal rotation is unclear. METHODS: Sixteen healthy participants performed the simulated foot impact task on the experimental chair. To vary the knee flexion angle, the following four-foot placement positions relative to the pelvis segment, i.e.: 1) near; 2) middle; 3) far; and 4) far + heel strike, were tested. The reflective marker positions and the ground reaction force (GRF) data were collected. The moment of inertia of the entire lower limb around its long axis as well as the peak hip internal rotation angular velocity were calculated and compared among four conditions (Wilcoxon Signed-Rank Test with Bonferroni correction, P<0.0083). RESULTS: As the knee extended from the near to far + heel strike condition, the moment of inertia of the entire lower limb significantly decreased and hip internal rotation angular velocity significantly increased (P<0.001). CONCLUSIONS: The extended knee position with far foot placement from torso reduces the inertial resistance of the entire lower limb around its long axis and is vulnerable to the hip internal rotation.

Body Part Pain Affects Subjective and Objective Handball Performance in Japanese Male National Athletes-Results of Short-Term Practical Monitoring of Athletes' Conditions.

This short-term survey examined the effect of body part pain on subjective and objective handball performance in Japanese male national handball athletes. Fourteen athletes participated in this study. Assessments of pain in 10 body parts and subjective performance (concentration and satisfaction with body movement) were performed using a visual analog scale from 0 to 10 over four consecutive training days. Monitoring of heart rate and body acceleration during training was also performed to quantify the objective performance. Path analysis and linear mixed modeling were employed to assess the relationship between body pain scores and subjective/objective handball performance. Over the four days of the study period, the body part in which most athletes reported pain was the dominant shoulder (6 of 14 athletes), followed by the dominant knee, the dominant elbow, the dominant ankle joint, and the non-dominant ankle joint (3 of 14 athletes). The path analysis revealed that pain in the dominant elbow negatively correlated with concentration (standardized path coefficient = -0.644, p = 0.00), which was associated with satisfaction with body movement (standardized path coefficient = 0.704, p = 0.00). No significant effect of body pain on objective performance (heart rate and body acceleration) was found among the athletes in this study. The results suggested that the elite athletes were practicing with pain. Even if pain does not physically affect athletes' objective performance, pain in the upper extremities, associated with the primary handball movement of throwing, may reduce the quality of practice by lowering athletes' subjective performance.

Vibration acceleration enhances proliferation, migration, and maturation of C2C12 cells and promotes regeneration of muscle injury in male rats.

Vibration acceleration (VA) using a whole-body vibration device is beneficial for skeletal muscles. However, its effect at the cellular level remains unclear. We aimed to investigate the effects of VA on muscles in vitro and in vivo using the C2C12 mouse myoblast cell line and cardiotoxin-induced injury in male rat soleus muscles. Cell proliferation was evaluated using the WST/CCK-8 assay and proportion of Ki-67 positive cells. Cell migration was assessed using wound-healing assay. Cell differentiation was examined by the maturation index in immunostained cultured myotubes and real-time polymerase chain reaction. Regeneration of soleus muscle in rats was assessed by recruitment of satellite cells, cross-sectional area of regenerated muscle fibers, number of centrally nucleated fibers, and conversion of regenerated muscle from fast- to slow-twitch. VA at 30 Hz with low amplitude for 10 min promoted C2C12 cell proliferation, migration, and myotube maturation, without promoting expression of genes related to differentiation. VA significantly increased Pax7-stained satellite cells and centrally nucleated fibers in injured soleus muscles on Day 7 and promoted conversion of fast- to slow-twitch muscle fibers with an increase in the mean cross-sectional area of regenerated muscle fibers on Day 14. VA enhanced the proliferation, migration, and maturation of C2C12 myoblasts and regeneration of injured rat muscles.

Iguratimod suppresses sclerostin and receptor activator of NF-κB ligand production via the extracellular signal-regulated kinase/early growth response protein 1/tumor necrosis factor alpha pathway in osteocytes and ameliorates disuse osteoporosis in mice.

Disuse osteoporosis is a prevalent complication among patients afflicted with rheumatoid arthritis (RA). Although reports have shown that the antirheumatic drug iguratimod (IGU) ameliorates osteoporosis in RA patients, details regarding its effects on osteocytes remain unclear. The current study examined the effects of IGU on osteocytes using a mouse model of disuse-induced osteoporosis, the pathology of which crucially involves osteocytes. A reduction in distal femur bone mass was achieved after 3 weeks of hindlimb unloading in mice, which was subsequently reversed by intraperitoneal IGU treatment (30 mg/kg; five times per week). Histology revealed that hindlimb-unloaded (HLU) mice had significantly increased osteoclast number and sclerostin-positive osteocyte rates, which were suppressed by IGU treatment. Moreover, HLU mice exhibited a significant decrease in osteocalcin-positive cells, which was attenuated by IGU treatment. In vitro, IGU suppressed the gene expression of receptor activator of NF-κB ligand (RANKL) and sclerostin in MLO-Y4 and Saos-2 cells, which inhibited osteoclast differentiation of mouse bone marrow cells in cocultures. Although IGU did not affect the nuclear translocation or transcriptional activity of NF-κB, RNA sequencing revealed that IGU downregulated the expression of early growth response protein 1 (EGR1) in osteocytes. HLU mice showed significantly increased EGR1- and tumor necrosis factor alpha (TNFα)-positive osteocyte rates, which were decreased by IGU treatment. EGR1 overexpression enhanced the gene expression of TNFα, RANKL, and sclerostin in osteocytes, which was suppressed by IGU. Contrarily, small interfering RNA-mediated suppression of EGR1 downregulated RANKL and sclerostin gene expression. These findings indicate that IGU inhibits the expression of EGR1, which may downregulate TNFα and consequently RANKL and sclerostin in osteocytes. These mechanisms suggest that IGU could potentially be used as a treatment option for disuse osteoporosis by targeting osteocytes.

An investigation of the differential therapeutic effects of romosozumab on postmenopausal osteoporosis patients with or without rheumatoid arthritis complications: a case-control study.

The impact of ROMO on the width of anabolic windows and the increase in BMD was reduced in the RA group compared to the non-RA group, and this reduction was associated with correlations to RA-related factors. PURPOSE: To investigate the effects of romosozumab (ROMO) in postmenopausal osteoporosis, with and without comorbid rheumatoid arthritis (RA). METHODS: In this retrospective, case-controlled, multicenter study, 171 postmenopausal patients who did not receive oral glucocorticoid, comprising 59 in the RA group and 121 in the non-RA group, received uninterrupted ROMO treatment for 12 months. Propensity score matching was employed to ensure comparability in clinical backgrounds, resulting in 41 patients in each group. Baseline characteristics were as follows: overall (mean age, 76.3 years; T-score of lumbar spine (LS), - 3.0; 45.1% were treatment-naive for osteoporosis); RA group (anti-cyclic citrullinated peptide antibody (ACPA) positivity, 80.5%; titer, 206.2 U/ml; clinical disease activity index (CDAI), 13.6; health assessment questionnaire disability index (HAQ-DI), 0.9). Bone mineral density (BMD) and serum bone turnover markers were monitored over a 12-month period. RESULTS: The rate of increase in the bone formation marker, PINP, and the rates of decrease in the bone resorption marker, TRACP-5b, exhibited a trend toward smaller changes in the RA group compared to the non-RA group, implying a smaller anabolic window. After 12 months, the RA group displayed lower BMD increases in the LS (9.1% vs. 12.6%; P = 0.013) and total hip (2.4% vs. 4.8%; P = 0.025) compared to the non-RA group. Multiple regression analysis in the all RA group (n = 59) for the association between RA-specific factors and 12-month BMD changes revealed negative correlations between ACPA titer and LS BMD and between HAQ-DI and femoral neck BMD. CONCLUSIONS: The efficacy of ROMO may be attenuated by RA-related factors.

Absorption function loss due to the history of previous ankle sprain explored by unsupervised machine learning.

BACKGROUND: Ankle sprains are common and cause persistent ankle function reduction. To biomechanically evaluate the ankle function after ankle sprains, the ground reaction force (GRF) measurement during the single-legged landing had been used. However, previous studies focused on discrete features of vertical GRF (vGRF), which largely ignored vGRF waveform features that could better identify the ankle function. PURPOSE: To identify how the history of ankle sprain affect the vGRF waveform during the single-legged landing with unsupervised machine learning considering the time-series information of vGRF. METHODS: Eighty-seven currently healthy basketball athletes (12 athletes without ankle sprain, 49 athletes with bilateral, and 26 athletes with unilateral ankle sprain more than 6 months before the test day) performed single-legged landings from a 20 centimeters (cm) high box onto the force platform. Totally 518 trials vGRF data were collected from 87 athletes of 174 ankles, including 259 ankle sprain trials (from previous sprain ankles) and 259 non-ankle sprain trials (from without sprain ankles). The first 100 milliseconds (ms) vGRF waveforms after landing were extracted. Principal component analysis (PCA) was applied to the vGRF data, selecting 8 principal components (PCs) representing 96% of the information. Based on these 8 PCs, k-means method (k = 3) clustered the 518 trials into three clusters. Chi-square test assessed significant differences (p < 0.01) in the distribution of ankle sprain and non-ankle sprain trials among clusters. FINDINGS: The ankle sprain trials accounted for a significantly larger percentage (63.9%) in Cluster 3, which exhibited rapidly increased impulse vGRF waveforms with larger peaks in a short time. SIGNIFICANCE: PCA and k-means method for vGRF waveforms during single-legged landing identified that the history of previous ankle sprains caused a loss of ankle absorption ability lasting at least 6 months from an ankle sprain.

A distal ileum malignant peripheral nerve sheath tumour after abdominal radiation therapy: case report of a rare tumour.

Malignant peripheral nerve sheath tumours (MPNSTs) are malignant tumours arising from a peripheral nerve or displaying nerve sheath differentiation. Most MPNSTs are found on the head, body trunk and extremities, whereas cases in the gastrointestinal are extremely rare. About half arise in neurofibromatosis type 1 patients and 10% arise post-irradiation. This is probably the first small bowel MPNST post-radiation therapy case reported. A 72-year-old female who received radiotherapy 30 years ago for cervical cancer was admitted with progressive abdominal pain and weight loss. Computed tomography revealed a mass with inhomogeneous enhancement in the lumen of the small intestine. Tumour excision was performed with ileocecal and sigmoid colon resection due to suspicion for peripheral tissue invasion. Histopathological examination revealed spindle-shaped cells with focal cartilage differentiation. Together with immunochemistry stain showing complete loss of H3K27me3, a final diagnosis of MPNST was made. The patient is presently under regular follow-ups, and has remained disease-free for 24 months.

Characteristics of physical activity during beginner-level group tennis lessons and the effect daily activity.

Tennis is a popular leisure sport, and studies have indicated that playing tennis regularly provides many health benefits. We aimed to clarify the characteristics of physical activity during beginner-level group tennis lessons and daily physical activity of the participants. Physical activity was measured using an accelerometer sensor device for four weeks, including the 80-min duration tennis lessons held twice a week. Valid data were categorized for tennis and non-tennis days. The mean physical activity intensity during the tennis lesson was 3.37 METs. The mean ratio of short-bout rest periods to the tennis lesson time in 90 and 120 s was 7% and 4%, respectively. The mean physical activity intensity was significantly higher (p < 0.0001) and the duration of vigorous-intensity physical activity (VPA) was increased in 76% of participants on days with tennis lessons compared to without tennis lessons. Beginner-level tennis lesson has characteristics of less short-bout rest physical activity than previously reported competitive tennis match and increased the duration of VPA in daily activity compared to without tennis lessons, suggesting that beginner-level tennis lessons contribute physical activity of health benefits.

Antimicrobial resistance patterns of WHO priority pathogens isolated in hospitalized patients in Japan: A tertiary center observational study.

BACKGROUND: After issuing the "Global action plan on antimicrobial resistance" in 2015, the World Health Organization (WHO) established a priority pathogens list for supporting research and development of novel antimicrobials. We conducted a comprehensive analysis of the WHO priority organisms in a Japanese tertiary hospital to apprehend the local AMR epidemiology. METHODS: Data were obtained from electrical medical records in Osaka University Hospital between January 2010 and March 2021. The critical, high, and medium "priority pathogens list" categories of the WHO were used to compare results between the early (2010-2015) and late (2016-2021) phases. RESULTS: Out of 52,130 culture-positive specimens, a total of 9,872 (18.9%) contained WHO priority isolates. In comparison to early phases, late phases were likely to have higher rates of carbapenem resistance in Pseudomonas aeruginosa (15.7% vs 25.0%, P<0.001), 3rd generation cephalosporin resistance in Escherichia coli (11.5% vs 17.8%, P<0.001) as well as Klebsiella pneumoniae (1.6% vs 4.4%, P<0.001), and ampicillin resistance in Haemophilus influenzae (2.4% vs 3.9%, P<0.001). After 2015, however, the proportion of methicillin-resistant and vancomycin-intermediate Staphylococcus aureus was low. In this study, in-hospital mortality was comparable among patients with resistance to the three WHO priority pathogen types: critical (5.9%), high (3.9%), and medium (3.8%), and no significant change was observed between two phases in each category. However, significant interactions for in-hospital mortality were observed in subgroup analyses between "critical priority" AMR and the presence of comorbid conditions, such as chronic kidney disease or diabetes mellitus. CONCLUSIONS: To implement better antimicrobial stewardship policies and practices, local priority pathogens and "high-risk" patients for in-hospital death need to be acknowledged and evaluated periodically.

Clinical Significance of Increased Skeletal Muscle Mass During Nab-Paclitaxel Plus Gemcitabine Treatment in Patients With Advanced Pancreatic Cancer.

OBJECTIVES: The clinical significance of increased skeletal muscle mass during nab-paclitaxel plus gemcitabine (AG) treatment in patients with advanced pancreatic cancer (APC) remains unknown. Therefore, we retrospectively investigated the characteristics of patients after AG treatment to evaluate the clinical significance of increased skeletal muscle mass during treatment. METHODS: From January 2015 to August 2021, 67 patients with APC received AG as first-line chemotherapy at Higashiosaka City Medical Center. Of these patients, 39 received second-line (2L) chemotherapy after AG therapy, and 28 received best supportive care. Patients' characteristics at the end of AG treatment were compared retrospectively between these 2 groups, and the relevant factors at the end of first-line treatment for 2L chemotherapy induction were analyzed. RESULTS: A performance status of 0 to 1 and increased skeletal muscle mass during AG therapy were independently associated with 2L chemotherapy induction in multivariate analysis. A high relative dose intensity (≥50%) in the first 8 weeks of AG treatment was more frequently found in patients with increased skeletal muscle mass during treatment ( P = 0.037). CONCLUSIONS: Increased skeletal muscle mass during AG treatment might contribute to the higher prevalence of 2L chemotherapy induction in patients with APC.

Basic life support for non-traumatic out-of-hospital cardiac arrests during school-supervised sports activities in children: A nationwide observational study in Japan.

Objective: To investigate the prognostic impact of bystander-initiated cardiopulmonary resuscitation (CPR) and public-access automated external defibrillator (AED) use on non-traumatic out-of-hospital cardiac arrest (OHCA) occurring during school-supervised sports activities in children. Methods: From a nationwide database of pediatric OHCAs occurring under school supervision in Japan, data between April 2008 and December 2020 were obtained. We analyzed non-traumatic OHCAs that occurred during school-supervised sports activities among schoolchildren from elementary, junior high, high, and technical colleges. A multivariable logistic regression model was used to evaluate the effect of basic life support (BLS) on 1-month survival with favorable neurological outcomes after OHCA. Results: In total, 318 OHCA cases were analyzed. The 1-month survival with favorable neurological outcomes was 64.8% (164/253) in cases receiving both bystander-CPR and AED application, 40.7% (11/27) in cases receiving CPR only, 38.5% (5/13) in patients receiving AED application only, and 28.0% (7/25) in cases receiving no bystander intervention. Compared with cases receiving no BLS, cases receiving both CPR and AED had a significantly higher proportion of 1-month survival with favorable neurological outcomes (adjusted odds ratio [AOR]: 3.97, 95% confidence interval [CI]: 1.32-11.90, p = 0.014). However, compared to cases receiving no BLS, there was no significant difference in the outcome in the cases receiving CPR only (AOR: 1.35, 95% CI: 0.34-5.29, p = 0.671) and the cases receiving AED application only (AOR: 1.26, 95% CI: 0.25-6.38, p = 0.778). Conclusion: The combination of CPR and AED as BLS performed by bystanders for non-traumatic OHCA during school-supervised sports activities improved the outcomes.

Meniscal Circumferential Fiber Augmentation: A Biomechanical Arthroscopic Meniscal Repair Technique.

Radial tears of the human knee meniscus result in the loss of circumferential hoop stress and are highly correlated with knee degeneration. Although a variety of surgical techniques are available to repair radial meniscal tears, including inside-out, outside-in, and all-inside techniques, conventional repair techniques focus only on stabilizing the damaged portion. This Technical Note describes a biomechanical meniscus repair technique of meniscal circumferential fiber augmentation, concomitant with conventional repair, to promote meniscal healing from a biomechanical perspective.

[Providing Opportunities for Close Examination of Lynch Syndrome after Microsatellite Instability Testing in a Hospital Setting].

Microsatellite instability(MSI)testing is performed in cancer patients to determine the indication for chemotherapy with immune checkpoint inhibitors. We report on our scheme to ensure that Lynch syndrome patients are offered the opportunity for genetic counseling and genetic testing. Two hundred and eight cancer patients(107 males and 101 females, 20- 87 years, mean 63.3 years)underwent MSI testing at our hospital between February 2019 and November 2021. From February 2019 to December 2020, the MSI testing was performed with a consent document that included a commentary on Lynch syndrome, and the results were explained only by the attending cancer doctors. Eleven(8.6%)of the 136 cases had MSI-high, but none of them led to a visit to the genetic medicine department. The Genome Center in our hospital, which was operational from April 2020, undertook information sharing by multiple professions and established a system to provide appropriate support to cancer doctors. Consecutively, 72 MSI tests were performed between January and November 2021, and 2 patients(2.8%)with MSI-high(1 with endometrial cancer and 1 with colorectal cancer)were referred to the Department of Clinical Genetics for genetic counseling. Through genetic testing, both were diagnosed with Lynch syndrome, and information on future surveillance and health care for blood relatives was provided.

The deterministic condition for the ground reaction force acting point on the combined knee valgus and tibial internal rotation moments in early phase of cutting maneuvers in female athletes.

BACKGROUND: Combined knee valgus and tibial internal rotation (VL + IR) moments have been shown to stress the anterior cruciate ligament (ACL) in several in vitro cadaveric studies. To utilize this knowledge for non-contact ACL injury prevention in sports, it is necessary to elucidate how the ground reaction force (GRF) acting point (center of pressure (CoP)) in the stance foot produces combined knee VL + IR moments in risky maneuvers, such as cuttings. However, the effects of the GRF acting point on the development of the combined knee VL + IR moment in cutting are still unknown. METHODS: We first established the deterministic mechanical condition that the CoP position relative to the tibial rotational axis differentiates the GRF vector's directional probability for developing the combined knee VL + IR moment, and theoretically predicted that when the CoP is posterior to the tibial rotational axis, the GRF vector is more likely to produce the combined knee VL + IR moment than when the CoP is anterior to the tibial rotational axis. Then, we tested a stochastic aspect of our theory in a lab-controlled in vivo experiment. Fourteen females performed 60° cutting under forefoot/rearfoot strike conditions (10 trials each). The positions of lower limb markers and GRF data were measured, and the knee moment due to GRF vector was calculated. The trials were divided into anterior- and posterior-CoP groups depending on the CoP position relative to the tibial rotational axis at each 10 ms interval from 0 to 100 ms after foot strike, and the occurrence rate of the combined knee VL + IR moment was compared between trial groups. RESULTS: The posterior-CoP group showed significantly higher occurrence rates of the combined knee VL + IR moment (maximum of 82.8%) at every time point than those of the anterior-CoP trials, as theoretically predicted by the deterministic mechanical condition. CONCLUSION: The rearfoot strikes inducing the posterior CoP should be avoided to reduce the risk of non-contact ACL injury associated with the combined knee VL + IR stress.

Anti-NF-κB peptide derived from nuclear acidic protein attenuates ovariectomy-induced osteoporosis in mice.

NF-κB is a transcription factor that is activated with aging. It plays a key role in the development of osteoporosis by promoting osteoclast differentiation and inhibiting osteoblast differentiation. In this study, we developed a small anti-NF-κB peptide called 6A-8R from a nuclear acidic protein (also known as macromolecular translocation inhibitor II, Zn2+-binding protein, or parathymosin) that inhibits transcriptional activity of NF-κB without altering its nuclear translocation and binding to DNA. Intraperitoneal injection of 6A-8R attenuated ovariectomy-induced osteoporosis in mice by inhibiting osteoclast differentiation, promoting osteoblast differentiation, and inhibiting sclerostin production by osteocytes in vivo with no apparent side effects. Conversely, in vitro, 6A-8R inhibited osteoclast differentiation by inhibiting NF-κB transcriptional activity, promoted osteoblast differentiation by promoting Smad1 phosphorylation, and inhibited sclerostin expression in osteocytes by inhibiting myocyte enhancer factors 2C and 2D. These findings suggest that 6A-8R has the potential to be an antiosteoporotic therapeutic agent with uncoupling properties.