Effect of anti-claudin 18.2 monoclonal antibody zolbetuximab alone or combined with chemotherapy or programmed cell death-1 blockade in syngeneic and xenograft gastric cancer models.

The development of targeted cancer therapies based on monoclonal antibodies against tumor-associated antigens has progressed markedly over recent decades. This approach is dependent on the identification of tumor-specific, normal tissue-sparing antigenic targets. The transmembrane protein claudin-18 splice variant 2 (CLDN18.2) is frequently and preferentially displayed on the surface of primary gastric adenocarcinomas, making it a promising monoclonal antibody target. Phase 3 studies of zolbetuximab, a chimeric immunoglobulin G1 monoclonal antibody targeting CLDN18.2, combined with 5-fluorouracil/leucovorin plus oxaliplatin (modified FOLFOX6) or capecitabine plus oxaliplatin (CAPOX) in advanced or metastatic first-line gastric or gastroesophageal junction (G/GEJ) adenocarcinoma have demonstrated favorable clinical results with zolbetuximab. In studies using xenograft or syngeneic models with gastric cancer cell lines, zolbetuximab mediated death of CLDN18.2-positive human cancer cell lines via antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity in vitro and demonstrated anti-tumor efficacy as monotherapy and combined with chemotherapy in vivo. Mice treated with zolbetuximab plus chemotherapy displayed a significantly higher frequency of tumor-infiltrating CD8+ T cells versus vehicle/isotype control-treated mice. Furthermore, zolbetuximab combined with an anti-mouse programmed cell death-1 antibody more potently inhibited tumor growth compared with either agent alone. These results support the potential of zolbetuximab as a novel treatment option for G/GEJ adenocarcinoma.

Relationship between increased knee joint line obliquity after medial open-wedge high tibial osteotomy and patient-reported outcome measures.

INTRODUCTION: This study evaluated the correlation between postoperative knee joint line obliquity after medial open-wedge high tibial osteotomy and patient-reported outcome measures excluding excessively overcorrected knees. This study further identified preoperative radiological factors related to the increased postoperative knee joint line obliquity. MATERIALS AND METHODS: We retrospectively evaluated patients who underwent medial open-wedge high tibial osteotomy between March 2013 and March 2021. Postoperative excessively overcorrected knees with hip-knee-ankle angle > 7° were excluded. We investigated radiological parameters and patient-reported outcome measures preoperatively and at the last follow-up. The following radiologic parameters were measured: hip-knee-ankle angle, weight-bearing line ratio, mechanical medial proximal tibial angle, mechanical lateral distal femoral angle, lateral distal tibial angle, joint line convergent angle, knee joint line obliquity, ankle joint line obliquity, hip abduction angle, tibial posterior slope, Carton-Deschamps index, and patella tilting angle. Clinical outcomes were evaluated using Japanese knee outcome measures. This assessment criterion is based on the Western Ontario McMaster Universities Arthritis Index and MOS Short Form 36. Multiple regression analysis was performed to evaluate the association between postoperative knee joint line obliquity and patient-reported outcome measures or preoperative radiological factors (P < .05). RESULTS: A total of 52 knees were included. The mean age at the time of the surgery was 61.6 ± 9.0 years and the mean follow-up period was 30.6 ± 10.1 months. Increased postoperative knee joint line obliquity was associated with lower Japanese knee outcome measures. The preoperative hip-knee-ankle angle was significantly associated with postoperative knee joint line obliquity. CONCLUSIONS: Increased knee joint line obliquity after medial open-wedge high tibial osteotomy is associated with inferior clinical outcomes. Care should be given to the center of the rotational angulation in around-knee osteotomy to avoid postoperative increased knee joint line obliquity. LEVEL OF EVIDENCE: Retrospective comparative study, Level III.

Efficacy, durability, and safety of faricimab in patients from Asian countries with neovascular age-related macular degeneration: 1-Year subgroup analysis of the TENAYA and LUCERNE trials.

PURPOSE: To evaluate 1-year efficacy, durability, and safety of faricimab among patients from Asian countries in the TENAYA/LUCERNE trials of neovascular age-related macular degeneration (nAMD). METHODS: Treatment-naïve patients with nAMD were randomly assigned (1:1) to faricimab 6.0 mg up to every 16 weeks (Q16W), based on disease activity at weeks 20 and 24, or aflibercept 2.0 mg Q8W. The primary endpoint was change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48. RESULTS: In the pooled TENAYA/LUCERNE trials, there were 120 (9.0%) and 1209 (91.0%) patients in the Asian (faricimab n = 61; aflibercept n = 59) and non-Asian country (faricimab n = 604; aflibercept n = 605) subgroups, respectively. In the Asian country subgroup, mean BCVA change from baseline at the primary endpoint visits was 7.1 (95% CI, 4.3-9.8) letters with faricimab and 7.2 (4.4-10.0) letters with aflibercept. In non-Asian country patients, mean vision gains were 6.1 (5.2-7.1) and 5.7 (4.8-6.7) letters with faricimab and aflibercept, respectively. At week 48, 59.6% of Asian country patients in the faricimab group achieved Q16W dosing (vs. 43.9% non-Asian) and 91.2% achieved ≥ Q12W dosing (vs. 77.5% non-Asian). Central subfield thickness reductions were similar between the subgroups, with meaningful and similar reductions from baseline observed at the primary endpoint visits and over time. Faricimab was well tolerated in both subgroups, with an acceptable safety profile. CONCLUSION: Consistent with the global TENAYA/LUCERNE findings, faricimab up to Q16W showed sustained visual and anatomical benefits in patients with nAMD from Asian and non-Asian countries. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03823287 (TENAYA); NCT03823300 (LUCERNE). Date of registration: January 30, 2019.

Satisfactory outcomes after one-stage revision anterior cruciate ligament reconstruction using rectangular tunnel technique.

PURPOSE: One-stage revision anterior cruciate ligament reconstruction (ACLR) with the anatomic rectangular tunnel (RT) technique using bone-patellar tendon-bone (BTB) grafts results in anatomically precise tunnel placement and secure graft fixation. This study evaluated knee joint laxity and clinical outcomes in terms of femoral tunnel overlap. It was hypothesised that there would be no significant differences in knee joint laxity or clinical outcomes regardless of femoral tunnel overlap. METHODS: Between 2012 and 2021, a single surgeon conducted 196 one-stage revision ACLRs with the RT technique using BTB grafts. Patients were divided based on the presence of femoral tunnel overlap. Knee joint laxity was evaluated using the Lachman test, pivot shift test, and side-to-side difference measured with a KT-1000 arthrometer. Clinical outcomes were assessed using the Lysholm score, Knee Injury and Osteoarthritis Outcome Score (KOOS), and International Knee Documentation Committee (IKDC) Knee Examination Form 2000. Knee joint laxity and clinical outcomes were compared between groups after a median follow-up of 2.5 years (range 2.0-8.0). RESULTS: The study included 30 and 73 patients in the overlap and non-overlap groups, respectively. No significant differences were observed in the results of the Lachman test, pivot shift test, or KT-1000 arthrometer as well as in the Lysholm, KOOS, or IKDC scores between the two groups. Based on the IKDC scores, all patients were graded as normal or nearly normal. CONCLUSION: One-stage revision ACLR with the RT technique using BTB grafts improved knee joint laxity and had favourable clinical outcomes regardless of femoral tunnel overlap. To achieve optimal results in one-stage revision ACLR, it is crucial to create a tunnel within the anatomical attachment area and ensure proper graft fixation and tensioning. LEVEL OF EVIDENCE: III.

Less tunnel enlargement in triple-bundle versus double-bundle anterior cruciate ligament reconstruction: A randomized clinical trial.

BACKGROUND: No study thus far has compared tunnel enlargement between double-bundle and triple-bundle anterior cruciate ligament reconstruction. We compared tibial tunnel enlargement and rate of tibial tunnel coalition between these two reconstructions, hypothesizing that tibial tunnel enlargement in triple-bundle reconstruction is less than that in double-bundle reconstruction, and that the tunnel coalition rate is equal between the two procedures. METHODS: This prospective randomized clinical trial included 25 patients who underwent computed tomography 2 weeks and 1 year postoperatively. Eleven patients underwent double-bundle anterior cruciate ligament reconstruction and 14 underwent triple-bundle anterior cruciate ligament reconstruction. Tunnel positions and tunnel coalition at the tibial tunnel aperture were assessed using three-dimensional computed tomography. Tunnel enlargement rate was calculated by measuring the sagittal and axial widths of the tibial bone tunnel 10 mm from the tibial tunnel aperture. These parameters were then compared between the groups. RESULTS: The changes in tunnel positions and tunnel coalitions between groups were not significantly different. On both sagittal and axial views, the tunnel enlargement rates of the medial and lateral sections of the anteromedial bundle in the triple-bundle group were significantly smaller than those in the double-bundle group (sagittal view, p = 0.02 and < 0.01, respectively; axial view, p = 0.02 and ≤ 0.05, respectively). The groups did not differ significantly in terms of posterolateral tunnel enlargement. CONCLUSION: Tunnel widening in the medial and lateral sections of the anteromedial bundle-associated tibial tunnel in triple-bundle anterior cruciate ligament reconstruction was smaller than that of double-bundle reconstruction. The tunnel coalition rates between the two reconstructions were not significantly different.

Patient-reported outcome measures after mobile-bearing unicompartmental knee arthroplasty were better than medial opening-wedge high tibial osteotomy in early elderly patients with severe osteoarthritis.

BACKGROUND: Many countries are faced with aging populations. However, few studies have directly compared the clinical outcomes of medial opening-wedge high tibial osteotomy (OWHTO) and mobile-bearing unicompartmental knee arthroplasty (MB-UKA) in early elderly patients. Thus, we aimed to investigate the clinical outcomes after OWHTO and MB-UKA in early elderly patients with similar demographics and osteoarthritis (OA) severity. METHODS: Three hundred and fifteen OWHTO and 142 MB-UKA were performed for medial compartment OA by a single surgeon between August 2009 and April 2020. Among them, patients aged 65-74 years with more than two years of follow-up were enrolled. The patient-reported outcome measures (PROMs), including visual analog scale (VAS) score and Japanese Knee Osteoarthritis Measure (JKOM) score, were compared between both procedures preoperatively and at the last follow-up. The PROMs were compared between the groups by Kellgren-Lawrence (K-L) OA grades. RESULTS: Seventy-three OWHTO and 37 MB-UKA patients were enrolled. No significant differences were found in the distribution of age, gender, follow-up period, body mass index, and Tegner activity scale between the two procedures. The postoperative PROMs in patients with K-L grade 4 were better after MB-UKA than OWHTO at the mean follow-up of 5 years. No significant difference was found in PROMs in patients with K-L grades 2 and 3. CONCLUSION: ThePROMs after MB-UKA were superior to that after OWHTO in early elderly patients with severe OA. In particular, pain relief was better after MB-UKA than OWHTO with severe OA. Meanwhile, no significant difference in PROMs was found with moderate OA patients. LEVEL OF EVIDENCE: Level IVprospective cohort study.

Mutagenesis and homology modeling reveal a predicted pocket of lysophosphatidylcholine acyltransferase 2 to catch Acyl-CoA.

Platelet-activating factor (PAF) is a potent proinflammatory phospholipid mediator that elicits various cellular functions and promotes several pathological events, including anaphylaxis and neuropathic pain. PAF is biosynthesized by two types of lyso-PAF acetyltransferases: lysophosphatidylcholine acyltransferase 1 (LPCAT1) and LPCAT2, which are constitutive and inducible forms of lyso-PAF acetyltransferase, respectively. Because LPCAT2 mainly produces PAF under inflammatory stimuli, understanding the structure of LPCAT2 is important for developing specific drugs against PAF-related inflammatory diseases. Although the structure of LPCAT2 has not been determined, the crystal structure was reported for Thermotoga maritima PlsC, an enzyme in the same gene family as LPCAT2. Here, we identified residues in mouse LPCAT2 essential for its enzymatic activity and a potential acyl-coenzyme A (CoA)-binding pocket, based on homology modeling of mouse LPCAT2 with PlsC. We also found that Ala115 of mouse LPCAT2 was important for acyl-CoA selectivity. In conclusion, these results predict the three-dimensional (3D) structure of mouse LPCAT2. Our findings have implications for the future development of new drugs against PAF-related diseases.

Efficient Transformer-Based Compressed Video Modeling via Informative Patch Selection.

Recently, Transformer-based video recognition models have achieved state-of-the-art results on major video recognition benchmarks. However, their high inference cost significantly limits research speed and practical use. In video compression, methods considering small motions and residuals that are less informative and assigning short code lengths to them (e.g., MPEG4) have successfully reduced the redundancy of videos. Inspired by this idea, we propose Informative Patch Selection (IPS), which efficiently reduces the inference cost by excluding redundant patches from the input of the Transformer-based video model. The redundancy of each patch is calculated from motions and residuals obtained while decoding a compressed video. The proposed method is simple and effective in that it can dynamically reduce the inference cost depending on the input without any policy model or additional loss term. Extensive experiments on action recognition demonstrated that our method could significantly improve the trade-off between the accuracy and inference cost of the Transformer-based video model. Although the method does not require any policy model or additional loss term, its performance approaches that of existing methods that do require them.

Aortic Insufficiency Causes Symptomatic Heart Failure during Left Ventricular Assist Device Support.

De novo aortic insufficiency is often documented during long-term left ventricular assist device (LVAD) support, despite the absence of aortic insufficiency at the time of LVAD implantation. However, whether aortic insufficiency affects long-term mortality and symptomatic heart failure in LVAD-supported patients remains controversial. We aimed to examine whether aortic insufficiency development influenced mortality and symptomatic heart failure following LVAD implantation. Fifty-three patients who underwent durable LVAD implantation between January 1, 2008 and April 31, 2017 were retrospectively examined in a single center institute. After discharge, we performed the echocardiographic examination in accordance with the Japanese registry for the mechanically assisted circulatory support protocol. Aortic insufficiency was graded on an interval scale (severe = 4, moderate = 3, mild = 2, trivial or none = 1). Kaplan-Meier estimates for long-term mortality at the follow-up were generated. We used a logistic regression model to identify risk factors for symptomatic heart failure. The overall median duration of LVAD support was 856.3 ± 430.8 days (range, 12-1,744 days). We did not observe a significant difference in long-term mortality in patients with aortic insufficiency ≥ 3 grade compared with patients with aortic insufficiency < 3 grade (P = 0.767; log-rank). Aortic insufficiency was associated with an increased risk for heart failure event after discharge (odds ratio, 4.12; confidence interval, 1.48-16.93; P = 0.005). Aortic insufficiency was an independent risk factor for symptomatic heart failure and was not associated with long-term mortality. Aortic insufficiency progression was associated with symptomatic heart failure.

Comparison of tendon-bone healing between a newly developed ultrasound device and the conventional metallic drill in a rabbit MCL reconstruction model.

BACKGROUND: Ligament reconstructive surgeries demand tunnel creation using an over-drilling technique, though this technique has some problems such as metallic particle liberation or difficulties in tunnel creation other than circular cross-section. Recently, a new ultrasound (US) device for bone excavation to overcome these problems was developed. This study aimed to compare the tendon-bone healing in tunnels created using the new US device to that created using the conventional drill in a rabbit model. METHODS: A total of 72 rabbits underwent a reconstruction for the anterior half of the medial collateral ligament (MCL) using a half of the patellar tendon. For the femoral tunnel creation, a new US device was used in 36 rabbits (US group), while a conventional metallic drill was used for the remaining 36 rabbits (DR group). At 4, 8, and 12 weeks postoperatively, biomechanical (n = 10) and histological (n = 2) evaluations were performed. RESULTS: The ultimate failure load was almost equivalent between the US and DR groups at each period (US/DR; 4 weeks, 50.0 ± 12.8 N/43.4 ± 18.9 N, p = 0.62; 8 weeks, 78.6 ± 11.5 N/77.3 ± 29.9 N, p = 0.92; and 12 weeks: 98.9 ± 33.5 N/102.2 ± 38.3 N, p = 0.80). Pull-out failure from the femoral tunnel was only observed in two rabbits in the US group and one rabbit in the DR group at 4 weeks postoperatively. At 8 and 12 weeks, all specimens had a mid-substance tear. The collagen fiber continuity between tendon and bone occurred 8 weeks postoperatively in both groups and no histological difference was recognized throughout the evaluation period. CONCLUSIONS: The tunnels created using the new US device and the conventional drill had equivalent biomechanical and histological features in tendon-bone healing. The bone excavation technology by the new US device may be applicable in ligament reconstructive surgeries.

Environmental impacts of a rice-beef-biogas integrated system in the Mekong Delta, Vietnam evaluated by life cycle assessment.

It is essential to increase the production of foods to meet the increasing future food demand, but this should be done in an environmentally sustainable manner. Integrated crop-livestock systems have been suggested to balance the reduction of environmental impacts and the increase in food production. Here we assessed and compared the environmental impacts of specialized (SPC) and integrated (ITG) rice and beef production systems in the Mekong Delta, Vietnam, using a life-cycle assessment (LCA). The productions of rice and beef are separated in the SPC, whereas they are integrated in the ITG: cattle manure is treated by a biodigester for biogas production, its digestate is applied to rice paddy fields as fertilizer, and part of the rice straw is used as cattle feed. We developed an LCA model based on data collected by site investigations of rice and beef farms and the relevant literature and LCA databases. Our evaluation of the ITG and SPC rice-beef production systems using the LCA revealed that among the four environmental impact categories investigated herein, the ITG had less environmental impacts on climate change (22%), energy consumption (22%), and eutrophication (14%) compared to the SPC. With the ITG, the reduction of methane emissions from paddy fields, the avoided energy consumption by the biogas produced, and the lower ammonia, nitrate, and phosphorous emissions from cattle manure and no eutrophying pollutant emissions from grassland were the main contributors to the lower greenhouse gas emissions, energy consumption, and eutrophication potential of this system, respectively. A sensitivity analysis showed that the use of cover for digestate storage resulted in lower environmental impacts of the ITG system compared to SPC system in all of the impact categories investigated here. These results provide helpful information to develop a circular and resource-efficient rice and beef production system that balances increasing productivity with environmental sustainability in rice-producing countries, particularly in Asia.

[Anomalous Origin of the Right Coronary Artery from the Pulmonary Artery Treated with Fistula Closure and Coronary Artery Bypass Grafting:Report of a Case].

An anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA) is a rare congenital disease, and it sometimes remains unnoticed until cardiac symptoms appear in adulthood. We report an adult case of surgically treated ARCAPA. A 72-year-old male was diagnosed with ARCAPA by examination for heart failure. The origin of the right coronary artery (RCA) was dilated, and ischemic change was found in the RCA area by myocardial scintigraphy. Therefore, coronary artery bypass grafting to distal RCA was performed at first, then the fistula was closed using an autologous pericardial patch, and the dilated origin of RCA was resected. Postoperative scintigraphy showed disappearance of the ischemic pattern, and the patient was discharged without any symptom of heart failure.

Structure-based drug design of 1,3,5-triazine and pyrimidine derivatives as novel FGFR3 inhibitors with high selectivity over VEGFR2.

Fibroblast growth factor receptor 3 (FGFR3) is an attractive therapeutic target for the treatment of bladder cancer. We identified 1,3,5-triazine derivative 18b and pyrimidine derivative 40a as novel structures with potent and highly selective FGFR3 inhibitory activity over vascular endothelial growth factor receptor 2 (VEGFR2) using a structure-based drug design (SBDD) approach. X-ray crystal structure analysis suggests that interactions between 18b and amino acid residues located in the solvent region (Lys476 and Met488), and between 40a and Met529 located in the back pocket of FGFR3 may underlie the potent FGFR3 inhibitory activity and high kinase selectivity over VEGFR2.

Functional Adaptation of the Fibrocartilage and Bony Trabeculae at the Attachment Sites of the Anterior Cruciate Ligament.

The direct insertion of an enthesis is composed of uncalcified fibrocartilage (FC) and calcified FC, believed to function as buffers for multidirectional forces applied to the ligament. This study was performed to investigate the relationship between the FC thickness and bony trabecular orientation of the anterior cruciate ligament (ACL) on both the femoral and tibial sides. Six cadavers were examined (age at death: 73-92 years). Both femoral and tibial insertions of the ACL were harvested and used to make 0.5 mm interval semi-serial sections. Microdigital images were taken and used to measure the maximum thickness of both the uncalcified FC and Calcified FC. Two-dimensional discrete Fourier analysis was also performed to determine the orientation angle and orientation intensity of bony trabeculae directly under the FC. The mean thicknesses of the uncalcified FC at the femoral and tibial insertions were 0.98 mm and 0.49 mm, respectively. The mean thicknesses of the calcified FC were 0.47 mm and 0.38 mm, respectively. There was a significant difference in the uncalcified FC thickness, but not in the calcified FC thickness. The bony trabeculae showed a prominent orientation parallel to the ACL fiber on both sides, but it was more intense on the tibial side than on the femoral side. The trabecular orientation was prominent in the proximal-posterior part of the femoral side and in the anteromedial part of the tibial side, suggesting that mechanical stress is greater in these parts. The dominant bony trabecular angle was 69.0° on the femoral side and 59.8° on the tibial side when the tidemark was set at 0°. These findings suggest that the femoral side receives multidirectional stresses, while relatively unidirectional stress is loaded on the tibial side. Furthermore, stress is considered to be greater in the proximal-posterior part of the femoral insertion and in the anteromedial part of the tibial insertion. At the time of ACL reconstruction, attention should be paid to assign a robust portion of the graft to the posterior part of the femoral insertion and anteromedial part of the tibial insertion. Clin. Anat., 33:988-996, 2020. © 2019 Wiley Periodicals, Inc.

[Cystic Myxoma which Obstructed the Mitral Valve Orifice;Report of a Case].

A 44-year-old male presented to our hospital with exertional dyspnea. Transthoracic echocardiography revealed a large cystic mass in the left atrium obstructing the mitral valve orifice. Transesophageal echocardiography during emergency operation showed a large cystic mass along with a solid part near the stalk. The mass was resected en bloc including the margin of the left atrium around the stalk. His hemodynamics improved immediately after the operation and the patient was discharged shortly with uneventful postoperative course. While intra cardiac cystic mass has some possible pathologies including malignancy, pathological examination of this tumor revealed a myxoma with large hematoma which had probably grown up rapidly. This tumor was successfully eradicated under the guide of both transthoracic and transesophageal echocardiography.

A Biomechanical Comparison of Single-, Double-, and Triple-Bundle Anterior Cruciate Ligament Reconstructions Using a Hamstring Tendon Graft.

PURPOSE: The first objective of our cadaveric study was to perform a biomechanical comparison of single-bundle (SB), double-bundle (DB), and triple-bundle (TB) anterior cruciate ligament (ACL) reconstructions using a hamstring tendon graft to determine the laxity match pre-tension (LMP) value, which is the tension within the graft required to re-create the same anterior laxity as the ACL-intact knee. The second objective was to determine the anterior laxity and force distribution during the application of both an anterior force and a simulated pivot-shift test. METHODS: Eleven fresh-frozen cadaveric knees were tested using a robotic/universal force-moment sensor system in the intact state, TB-reconstructed knee, DB-reconstructed knee, and SB-reconstructed knee. The LMP in each reconstruction was recorded. Each reconstructed knee was tested with an external load of 100-N anterior drawer and combined rotatory loads of 10-Nm valgus moment and 5-Nm internal rotation. The anterior tibial translation and tensile forces of each graft bundle were measured. RESULTS: The LMP values for the TB reconstruction were 1.7 N for the anteromedial-medial graft, 1.7 N for the anteromedial-lateral graft, and 3.4 N for the posterolateral graft (PLG). The LMP value was 5.6 N for the anteromedial graft and PLG in the DB reconstruction. The LMP value was 26.3 N for the whole graft in the SB reconstruction. No statistically significant difference in stability was found between TB and DB reconstructions during the anterior load and the combined rotatory load test. For force distribution, the PLG tension in the TB reconstruction was statistically lower than that in the DB reconstruction. CONCLUSIONS: Anatomic TB ACL reconstruction with the lowest initial tension on the graft stabilized the knee equally to DB or SB reconstruction, which required greater initial tension. CLINICAL RELEVANCE: Although SB, DB, and TB ACL reconstructions through the anatomic tunnel position could equally restore stability, the initial tension on the graft required to restore stability was less in the latter 2 multi-tunnel reconstructions.

Enteric methane emissions, energy partitioning, and energetic efficiency of zebu beef cattle fed total mixed ration silage.

OBJECTIVE: The main objective of this study was to evaluate the effect of different feeding levels of a total mixed ration silage-based diet on feed intake, total tract digestion, enteric methane emissions, and energy partitioning in two beef cattle genotypes. METHODS: Six mature bulls (three Thai natives, and three Thai natives - Charolais crossbreeds) were assigned in a replicated 3×3 Latin square design, with cattle breed genotype in separate squares, three periods of 21 days, and three energy feeding above maintenance levels (1.1, 1.5, and 2.0 MEm, where MEm is metabolizable energy requirement for maintenance). Bulls were placed in a metabolic cage equipped with a ventilated head box respiration system to evaluate digestibility, record respiration gases, and determine energy balance. RESULTS: Increasing the feeding level had no significant effect on digestibility but drastically reduced the enteric methane emission rate (p<0.05). Increasing the feeding level also significantly increased the energy retention and utilization efficiency (p<0.01). The Thai native cattle had greater enteric methane emission rate, digestibility, and energy utilization efficiency than the Charolais crossbred cattle (p<0.05). The daily metabolizable energy requirement for maintenance in Thai native cattle (388 kJ/kg BW0.75, where BW0.75 is metabolic body weight) was 15% less than that in Charolais crossbred cattle (444 kJ/kg BW0.75). CONCLUSION: Our results suggested that the greater feeding level in zebu beef cattle fed above maintenance levels resulted in improved energy retention and utilization efficiency because of the reduction in enteric methane energy loss. The results also indicated higher efficiency of metabolisable energy utilization for growth and a lower energy requirement for maintenance in Bos indicus than in Bos taurus.

[Factors related to life expectancy in prefectures: An ecological study using the National Database].

Objective　In recent years, studies have reported a prefectural-level disparity in life expectancy. Therefore, we analyzed the related factors using the National Database (NDB), which includes data pertaining to the specific health checkup conducted for 20 million individuals. By doing so, we aimed to obtain basic data for developing future health promotion measures.Methods　We used specific health checkup items from NDB Open Data for 2014, and life expectancy data from Prefecture Life Table for 2015. The specific health checkup items were adjusted by age using Japanese population data for 2015. A multiple linear regression analysis was conducted using specific health checkup items that were significantly related to average life expectancy as explanatory variables.Results　In men, excessive drinking, smoking, antihypertensive drug use, systolic blood pressure, and hyperglycemia were independently and inversely related to life expectancy. In women, smoking and antihypertensive drug use emerged as significant factors.Conclusions　Analysis using NDB Open Data showed that lifestyle factors such as smoking and drinking, and cardiovascular risk factors such as high blood pressure and hyperglycemia, were strongly related to life expectancy. These result suggest that it is necessary to focus on the above factors when prefectural authorities implement health promotion measures.

Effectiveness of clarithromycin in patients with yellow nail syndrome.

BACKGROUND: Yellow nail syndrome (YNS) is a rare disease characterized by the triad of thickened, slow-growing yellow nails, lymphedema, and chronic respiratory manifestations. The cause of YNS is not known; however, it is suggested to be due to a congenital lymph abnormality. Since YNS is accompanied by chronic bronchial infection in more than half of patients, we hypothesized that treatment with clarithromycin (CAM) could be effective. We therefore evaluated the effectiveness of CAM against nail discoloration and respiratory manifestation in patients with YNS. METHODS: We conducted an observational study involving 5 patients with YNS who were treated at our institution between January 2005 and January 2016. CAM was prescribed for every patient. Patient demographic information, comorbidities, medications, chest radiographs, and clinical data such as nail color were extracted to evaluate clinical outcome. RESULTS: Mean patient age was 71.6 years, and 2 patients (40%) were male. Four patients had sinusitis, and 2 had rheumatoid arthritis. Regarding respiratory manifestations, 4 patients had sinobronchial syndrome and 2 had pleural effusion. Nail discoloration improved in every patient after CAM treatment. Four patients also experienced improvement in their respiratory manifestations. CONCLUSIONS: In patients with YNS, the anti-inflammatory activity of macrolides might improve their systemic inflammation. This improvement could help to reduce lymphedema and promote nail growth. TRIAL REGISTRATION: Ethical approval was provided by the institutional review board of the National Center of Global Health and Medicine (NCGM-G-002143-00), in January 2017. This study is retrospectively registered for UMIN Clinical Trial Registry ( UMIN000028514 ) in August 4th, 2017.

Application of actuator-driven pulsed water jet for coronary artery bypass grafting: assessment in a swine model.

Actuator-driven pulsed water-jet (ADPJ) dissection is an emerging surgical method for dissecting tissue without heat and mechanical injury to vessels. We elucidated the mechanical properties of the piezo ADPJ and evaluated its usefulness and safety in coronary artery bypass grafting procedures. The relationship between the input voltage (10-100 V) and peak pressure of the pulsed water jet was evaluated. The tissue strengths of swine internal thoracic and coronary arteries and the surrounding tissues were measured to assure tissue-selective dissection. Internal thoracic arteries were harvested by conventional electric cautery and the water jet in four swine, and eight coronary arteries surrounded by myocardium were attempted to be exposed with the water jet. The dissected specimens were histologically evaluated. The peak pressure of the pulsed water jet was positively correlated with the input voltage (R 2 = 0.9984, P < 0.001). The breaking strengths of the target vessels (internal thoracic and coronary arteries) and the surrounding tissues were significantly different (P = 0.002 and P < 0.001, respectively). Histologic examination revealed that internal thoracic arteries were isolated with less heat damage using the pulsed water jet (P = 0.002) compared with electric cautery, and coronary arteries also were dissected without apparent histologic damage. ADPJ has the possibility of assuring tissue selectivity among the internal thoracic and coronary arteries. The results also indicated that the use of ADPJ may enhance safe procedures to harvest grafts during coronary artery bypass grafting.