Evolution of secondary metabolites, morphological structures and associated gene expression patterns in galls induced by four closely related aphid species on a host plant species.

Gall-forming insects induce various types of galls on their host plants by altering gene expression in host plant organs, and recent studies have been conducted for gene expression in galls. However, the evolutionary trajectories of gene expression patterns and the resulting phenotypes have not yet been studied using multiple related species. We investigated the speciation and the diversification process of galls induced by four closely related aphid species (Hormaphidini) on a host plant species (Hamamelis japonica) by examining the phylogenetic congruence between the geographical divergences of aphids and the host plant, and by comparing their gene expression patterns and resulting phenotypes. Phylogenetic analysis of aphids and the host plant showed that geographical isolation among host plant populations has interrupted gene flow in aphids and accelerated the speciation process. The concentration of phenolics and the complexity of the internal structure of galls were correlated with the expression levels of genes for the biosynthesis of phenolics and morphogenesis respectively. These results suggest that the expression levels of genes for the biosynthesis of phenolics and morphogenesis have evolutionarily increased in galls accelerated by the speciation process of aphids due to the distribution change of the host plant, leading to the related phenotypic evolution. Our study showed the evolutionary process of phenotypic traits in galls in the wild from both gene expression and actual phenotype levels.

Basal Coronary Microvascular Resistance Predicting Death and Heart Failure in Patients Without Functional Coronary Stenosis.

BACKGROUND: Abnormal coronary microcirculation is linked to poor patient prognosis, so the aim of the present study was to assess the prognostic relevance of basal microvascular resistance (b-IMR) in patients without functional coronary stenosis.Methods and Results: Analyses of 226 patients who underwent intracoronary physiological assessment of the left anterior descending artery included primary endpoints of all-cause death and heart failure, as well as secondary endpoints of cardiovascular death and atherosclerotic vascular events. During a median follow-up of 2 years, there were 12 (5.3%) primary and 21 (9.3 %) secondary endpoints. The optimal b-IMR cutoff for the primary endpoints was 47.1 U. Kaplan-Meier curve analysis demonstrated worse event-free survival of the primary endpoints in patients with a b-IMR below the cutoff (χ2=21.178, P<0.001). b-IMR was not significantly associated with the secondary endpoints (P=0.35). A low coronary flow reserve (CFR; <2.5) had prognostic value for both endpoints (primary endpoints: χ2=11.401, P=0.001; secondary endpoints: (χ2=6.015; P=0.014), and high hyperemic microvascular resistance (≥25) was associated only with the secondary endpoints (χ2=4.420; P=0.036). Incorporating b-IMR into a clinical model that included CFR improved the Net Reclassification Index and Integrated Discrimination Improvement for predicting the primary endpoints (P<0.001 and P=0.034, respectively). CONCLUSIONS: b-IMR may be a specific marker of the risk of death and heart failure in patients without functional coronary stenosis.

Prediction of human serum concentration-time profiles of therapeutic monoclonal antibodies using common marmosets (Callithrix jacchus): Initial assessment with canakinumab, adalimumab, and bevacizumab.

1. Cynomolgus monkeys and human FcRn transgenic mice are generally used for pharmacokinetic predictions of therapeutic monoclonal antibodies (mAbs). In the present study, the application of the common marmoset, a small nonhuman primate, as a potential animal model for prediction was evaluated for the first time.2. Canakinumab, adalimumab, and bevacizumab, which exhibited linear pharmacokinetics in humans, were selected as the model compounds. Marmoset pharmacokinetic data were reportedly available only for canakinumab, and those for adalimumab and bevacizumab were acquired in-house.3. Four pharmacokinetic parameters for a two-compartment model (i.e., clearance and volume of distribution in the central and peripheral compartments) in marmosets were extrapolated to the values in humans with allometric scaling using the average exponents of the three mAbs. As a result, the observed human serum concentration-time curves of the three mAbs following intravenous administration and those of canakinumab and adalimumab following subcutaneous injections (with an assumed absorption rate constant and bioavailability) were reasonably predicted.4. Although further prediction studies using a sufficient number of other mAbs are necessary to evaluate the versatility of this model, the findings indicate that marmosets can be an alternative to preceding animals for human pharmacokinetic predictions of therapeutic mAbs.

[Community Care Meetings Co-Managed by a University and Local Government].

The Long-Term Care Insurance System, revised in 2015, obliged utmost efforts to enforce community-based care meetings to establish the Community-based Integrated Care System. In Toyoake in Aichi Prefecture, Japan, the"Multidisciplinary Joint Care Conference,"a monthly community-based care meeting, has been held since April 2016. All participants have an equal relationship since no advisors are appointed. This conference is designed to share helpful knowledge about methods that can be applied in similar future cases instead of just reviewing the support methods used in previous cases. Continuing to hold this conference is expected to yield various satisfactory outcomes. Exchanging knowledge with experts in different fields has led to technology transfer among professions. Furthermore, sharing knowledge in areas where information was insufficient has allowed individuals to determine what they could contribute from their standpoint. They have cogitated about selecting cases and how the host progressed the conference. Because local governments' employees are often reshuffled, accurately taking over duties from their predecessors is a significant concern. As a result, to reduce such risks, the municipality decided to cooperate and manage the conference with a local university engaged in solving local problems. An online provision system was established early to continue conducting the meeting during the COVID-19 pandemic. Currently, this system is beneficial in accepting observation members from municipalities and professionals nationwide. We aspire to continue engaging in the Multidisciplinary Joint Care Conference. This allows individuals connected to the communities to share strategies and methods for achieving their goals and unite as a single problem-solving team.

Origin and diversification of pheretimoid megascolecid earthworms in the Japanese Archipelago as revealed by mitogenomic phylogenetics.

Megascolecid earthworms of the pheretimoid group are dominant detritivores of soil ecosystems in the Japanese Archipelago and East Asia. However, their diversity and phylogenetic relationships are poorly understood. We assembled whole mitogenome sequences for 197 megascolecid earthworms collected throughout Japan to study the phylogenetic relationships, phylogeography, divergence times, and diversification of important morphological characteristics among pheretimoid earthworms. Using 197 mitogenome sequences and 24 published mitogenome sequences from the East Asian mainland (221 sequences in total), we constructed a maximum likelihood tree and found that the pheretimoid earthworms currently assigned to Amynthas, Metaphire, Duplodicodrilus, and Manus are involved in the most senior genus Amynthas; thus, Amynthas can be treated as the sole genus encompassing all of the above genera. Within the Amynthas group, we identified three major lineages that led to four groups of endemic species in Japan. These lineages originated from different lineages on the East Asian mainland and Taiwan Island, indicating multiple colonization events from the East Asian mainland by different ancestral lineages, possibly after the Miocene. We also assembled nuclear ribosomal DNA sequences encompassing the 18S to 28S rRNA genes. The nuclear gene tree showed major groups consistent with the mitogenome tree except for different (and not well-resolved) relationships among major clades. Our molecular data covered 115-158 native and 7 non-native Amynthas group species in Japan in terms of DNA-based species delimitation. Our findings provide a basis for understanding the evolutionary relationships among diversified megascolecid earthworms in the Amynthas group in Japan and adjacent regions.

Synthesis and Properties of Rubicene-Based Aromatic π-Conjugated Compounds as Five-Membered Ring Embedded Planar Nanographenes.

Polycyclic aromatic hydrocarbons consisting of two or three rubicene substructures were designed as π-conjugated compounds embedding five-membered rings. The target compounds with t-butyl groups were synthesized by the Scholl reaction of precursors consisting of 9,10-diphenylanthracene units, even though a partially precyclized precursor was required for the synthesis of the trimer. These compounds were isolated as stable and dark blue solids. Single-crystal X-ray analysis and DFT calculations revealed the planar aromatic framework of these compounds. In the electronic spectra, the absorption and emission bands were considerably red-shifted compared with those of the reference rubicene compound. In particular, the emission band of the trimer extended to the near-IR region while retaining the emissive property. The narrowed HOMO-LUMO gap with the extension of the π-conjugation was confirmed by cyclic voltammetry and DFT calculations.

Supratentorial multifocal gliomas associated with Ollier disease harboring IDH1 R132H mutation: A case report.

Somatic mosaicism of isocitrate dehydrogenase 1/2 (IDH1/2) mutation is a cause of Ollier disease (OD), characterized by multiple enchondromatosis. A 35-year-old woman who was diagnosed with OD at age 24 underwent resection surgery for multifocal tumors located at the right and left frontal lobes that were discovered incidentally. No apparent spatial connection was observed on preoperative magnetic resonance imaging. Pathological examinations revealed tumor cells with a perinuclear halo in the left frontal lobe tumor, whereas astrocytic tumor cells were observed in the right frontal lobe tumor. Based on positive IDH1 R132H immunostaining and the result of 1p/19q fluorescent in situ hybridization, pathological diagnoses were IDH mutant and 1p/19q-codeleted oligodendroglioma in the right frontal lobe tumor and IDH mutant astrocytoma in the left frontal lobe tumor, respectively. The DNA sequencing revealed IDH1 R132H mutation in the peripheral blood sample and frontal lobe tumors. This case suggested that in patients with OD, astrocytoma and oligodendroglioma can co-occur within the same individual simultaneously, and IDH1 R132H mutation was associated with supratentorial development of gliomas.

Improved responsiveness for JKOOS+ compared to KOOS in Japanese patients undergoing total knee arthroplasty.

BACKGROUND: Existing knee related patient reported outcome measurements (PROMs) have overwhelmingly been developed and validated in western chair-based societies, suggesting a potential for a western bias in PROMs evaluation of patients with knee conditions. We, therefore, endeavor to evaluate the responsiveness of the previously developed culturally relevant Japanese version of the knee injury and osteoarthritis outcome score (JKOOS+). METHODS: We enrolled 114 patients scheduled for total knee arthroplasty (TKA) across 8 knee clinics in Japan. Patients completed the Oxford Knee Score (OKS) and JKOOS + both at the time of enrollment and again 1-year post-TKA. Responsiveness was evaluated using effect size and standardized response mean (SRM). An effect size or SRM >0.8 is considered adequately responsive. We further tested the difference in responsiveness between the original Japanese language KOOS activities of daily living (ADL) domain and the novel Japanese ADL (JADL) domain using the modified Jacknife test. RESULTS: All domains were adequately responsive with the exception of the KOOS sports and recreation domain, which has previously been ignored by TKA researchers due to its lack of applicability to elderly patients undergoing TKA. The JADL domain outperformed the ADL domain in both effect size (1.51 v. 1.45) and SRM (1.67 v. 1.57) (p < 0.001). The novel Knee Flexion (KF) domain was adequately responsive, though less responsive than other domains except sports and recreation (p < 0.01 v. all other PROMs domains). CONCLUSIONS: The JKOOS+ JADL domain is significantly more responsive than the Europe-developed ADL domain to TKA in Japanese knee patients suffering from knee osteoarthritis (OA). The KF domain, unique to the JKOOS+ and intended to assess difficulty with knee flexion, is adequately responsive to TKA in Japanese patients suffering from OA.

PIEZO1 promotes ATP release from periodontal ligament cells following compression force.

OBJECTIVES: Orthodontic mechanical force on the periodontal ligament induces extracellular adenosine triphosphate (ATP) release. However, mechanosensitive molecules have not been confirmed functionally in periodontal ligament cells. In the present study, we examined the roles of mechanosensitive PIEZO channels in the mechanically stimulated release of ATP in human periodontal ligament fibroblasts (HPdLFs). MATERIALS AND METHODS: To examine PIEZO expression in HPdLFs, we performed reverse transcription-quantitative polymerase chain reaction, fluorescent immunostaining, and Ca2+ imaging. ATP concentrations were measured in culture medium after applications of the PIEZO1 agonist Yoda1 and compression force in a newly developed in vitro weight-loaded cell model (IVWLC) using balance weights and a 48-well plate. The mechanosensitive channel inhibitor GsMTx4 and the ATP-releasing route inhibitors clodronic acid, meclofenamic acid, and probenecid were used. To suppress PIEZO1 expression, short interference RNA (siRNA) treatment of the PIEZO1 gene was performed. RESULTS: PIEZO1 mRNA was expressed more abundantly than PIEZO2 mRNA in HPdLFs. HPdLF cell bodies were immunoreactive to anti-PIEZO1 antibody. Yoda1 increased intracellular Ca2+ and extracellular ATP concentrations in a dose-dependent manner. ATP release was inhibited by GsMTx4 and inhibitors of ATP release routes. In the IVWLC, HPdLFs released ATP in response to compression force but not in response to hypoxic stimulation that was simultaneously applied to cells. Mechanically stimulated ATP release was inhibited by GsMTx4, inhibitors of ATP-releasing routes and siRNA treatment of PIEZO1. CONCLUSIONS: PIEZO1 on the cell membranes of HPdLFs is activated by compression force and then induces ATP release via intracellular Ca2+-dependent exocytosis and ATP-permeable channels.

Global dispersal and diversification in ground beetles of the subfamily Carabinae.

The origin and diversification process of lineages of organisms that are currently widely distributed among continents is an interesting subject for exploring the evolutionary history of global species diversity. Ground beetles of the subfamily Carabinae are flightless except for one lineage, but nevertheless occur on all continents except Antarctica. Here, we used sequence data from ultraconserved elements to reconstruct the phylogeny, divergence time, biogeographical history, ancestral state of hind wings and changes in the speciation rate of Carabinae. Our results show that Carabinae originated in the Americas and diversified into four tribes during the period from the late Jurassic to the late Cretaceous, with two in South America (Celoglossini) and Australasia (Pamborini) and two in Laurasia (Cychrini and Carabini). The ancestral Carabinae were inferred to be winged; three of four tribes (Cychrini, Ceglossini and Pamborini) have completely lost their hind wings and flight capability. The remaining tribe, Carabini, diverged into the subtribes Carabina (wingless) and Calosomina (winged) in the Oligocene. Carabina originated in Europe, spread over Eurasia and diversified into approximately 1000 species, accounting for around 60% of all Carabinae species. Calosomina that were flight-capable dispersed from North America or Eurasia to South America, Australia, and Africa, and then flightless lineages evolved on oceanic islands and continental highlands. The speciation rate increased in the Cychrini and Carabini clades in Eurasia. Within Carabini, the speciation rate was higher for wingless than winged states. Our study showed that the global distribution of Carabinae resulted from ancient dispersal before the breakup of Gondwana and more recent dispersal through flight around the world. These patterns consequently illustrate the causal relationships of geographical history, evolution of flightlessness, and the global distribution and species diversity of Carabinae.

Selection of the candidate compound at an early stage of new drug development: retrospective pharmacokinetic and metabolic evaluations of valsartan using common marmosets.

Valsartan is an antihypertensive drug that was developed using common marmosets (Callithrix jacchus) in pivotal toxicity studies as a non-rodent species. The aim of the present study was to investigate the utility of marmosets in the candidate selection of this drug from a pharmacokinetic and metabolic viewpoint.Valsartan, as well as three other angiotensin II type-I receptor blockers, assumed as competitive candidates, were administered to common marmosets. Human pharmacokinetic parameters predicted by single-species allometric scaling and Wajima superposition suggested that valsartan may exhibit promising pharmacokinetic properties in humans.In vitro metabolic studies of valsartan using isolated rat, dog, marmoset, cynomolgus monkey, and human hepatocytes revealed that the marmoset was the most relevant animal species to humans presenting with the most abundant human metabolite, 4-hydroxyvalsartan. Oral administration of an elevated dose of valsartan to a common marmoset demonstrated that the level of 4-hydroxyvalsartan in the plasma was comparable to that in clinical practice and suggested that safety of the human metabolite might have been confirmed in the toxicity studies using common marmosets.These results suggest that common marmosets, the small, non-human primates, had been a suitable species for the development of valsartan.

Self-administration of gender-affirming hormones and supratherapeutic dosing are relatively common in Japanese transgender women.

AIM: This study was performed to determine the proportion of transgender women with self-adjusted hormone administration and excess dosing. METHODS: The medical records of 87 transgender women who visited our gender clinic from 2010 through 2019 were reviewed. The complete blood count and serum concentrations of D-dimer, gonadotropins, and sex steroids were compared between transgender women who were self-administering gender-affirming hormones and women not using such hormones. RESULTS: Fifty-eight of 87 (66.7%) transgender women had contravened the guideline and self-adjusted their hormone administration. The hormonal data of one woman with hypopituitarism were eliminated from the analyses. The serum gonadotropin and testosterone levels were significantly lower in the self-administration group than in the hormone-naïve group. Gonadotropin levels below the lower limit of normal were found in 32/86 (37.2%) transgender women. The testosterone levels in six transgender women were not analyzed because these women had undergone sex reassignment surgery before visiting our hospital. Testosterone levels below the lower limit of normal men were found in 36/80 (45.0%) transgender women. Unexpectedly, 29/36 (80.6%) transgender women who were classified as having suppressed serum testosterone levels had testosterone levels of <0.6 ng/mL, which corresponds to the levels in cisgender women. The white blood cell count and hemoglobin concentration were significantly different between the groups. CONCLUSION: Self-initiated hormonal treatments seem to affect the serum concentrations of gonadotropin and sex steroids and the complete blood count. The prevalence of transgender women with self-adjusted use of gender-affirming hormones is high, and an excess dose of hormones occasionally occurs.

Applicability of neutral electrolyzed water for cleaning contaminated fixed orthodontic appliances.

INTRODUCTION: We investigated whether water jet washing with neutral electrolyzed water (NW) can be an easy and safe self-performed cleaning method for oral environments of fixed orthodontic appliance-wearing patients. In line with this, we examined the bactericidal effects and dissolution behaviors of metal elements released from appliances. METHODS: A metal or resin bracket ligated with a metal wire and metal bracket adhered to an apatite-pellet were used as specimens. The bacteria and plaque removal effects of the 30 seconds of NW (30, 100 ppm) jet washing for contaminated specimens were examined via an agar-plate method and the observation of the residual plaque, comparing with other treatments (brushing and flow washing), those treatments with tap water (TW), and flow washings with commercial mouthwashes, Listerine Total Care + (LS) and ConCool F (CC). The amounts of metal released from metal specimens during the 1-week immersion in NW were analyzed and compared with those in TW, LS, and CC. RESULTS: NW jet washing produced larger decreases of surviving bacteria than the treatments with TW and CC (P <0.05) and equal or larger decreases than the treatment with LS (P <0.05). NW jet washing yielded the highest plaque removal level. The amounts of nickel and chromium released from metal specimens after the 1-week immersion in NW (30 ppm) were less than or equal to those with LS. CONCLUSIONS: NW jet washing could be applicable for cleaning fixed orthodontic appliances because of its higher bactericidal effects than the treatments with commercial mouthwashes, inducing no or a slight metal release in actual usage time.

CD70 expression correlates with a worse prognosis in malignant pleural mesothelioma patients via immune evasion and enhanced invasiveness.

Diffuse malignant mesothelioma of the pleura (MPM) is a highly aggressive tumour that typically is associated with short survival. CD70 and CD27 belong to the tumour necrosis factor (TNF) and the TNF receptor (TNFR) superfamily, respectively. Under physiological conditions, the tightly regulated interaction between CD70 and CD27 plays a co-stimulatory role in promoting T-cell expansion and differentiation through the NFκB pathway. Aberrantly high CD70 expression has been documented in haematological and solid malignancies in association with immune evasion in malignant cells. In this study, 172 well-characterised primary diffuse MPM tumours including epithelioid (n = 145), biphasic (n = 15), and sarcomatoid (n = 12) histotypes were evaluated immunohistochemically for CD70, CD27, CD3, CD4, CD8, CD56, PDCD1 (PD-1), and FOXP3 expression. Twenty per cent (34/172) of the mesothelioma cells expressed CD70 on the cell membrane. Overall survival was significantly decreased in the cohort of patients with CD70-expressing tumour cells (p < 0.01). Patients with MPM containing a higher number of CD3+ (p < 0.01), CD4+ (p < 0.01), CD8+ (p < 0.01), or FOXP3+ (p < 0.01) tumour-infiltrating lymphoid cells (TILs) showed significantly worse clinical outcomes. As potential independent risk factors for MPM patients, multivariate Cox proportional hazards regression analysis revealed CD70 expression on mesothelioma cells [hazard ratio (HR) 2.25; p = 0.010], higher FOXP3+ TILs (HR 2.81; p = 0.004), and higher CD3+ TIL accumulation (HR 6.12; p < 0.001). In contrast, as a potential independent favourable factor, higher CD27+ TIL accumulation (HR 0.48; p = 0.037) was identified. In vitro experiments and an immunodeficient mouse model revealed that CD70 enhances the invasiveness of MPM cells through MET-ERK axis activation. Further analyses in syngeneic mouse models demonstrated possible roles for CD70 in immune evasion. Collectively, these findings suggest that the CD70-CD27 pathway enhances the malignant phenotypes of MPM and diminishes anti-tumor immune response in patients with these neoplasms. These markers might be useful in MPM for prognostic evaluations as well as targeted therapeutics. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Artificial intelligence supported anemia control system (AISACS) to prevent anemia in maintenance hemodialysis patients.

Anemia, for which erythropoiesis-stimulating agents (ESAs) and iron supplements (ISs) are used as preventive measures, presents important difficulties for hemodialysis patients. Nevertheless, the number of physicians able to manage such medications appropriately is not keeping pace with the rapid increase of hemodialysis patients. Moreover, the high cost of ESAs imposes heavy burdens on medical insurance systems. An artificial-intelligence-supported anemia control system (AISACS) trained using administration direction data from experienced physicians has been developed by the authors. For the system, appropriate data selection and rectification techniques play important roles. Decision making related to ESAs poses a multi-class classification problem for which a two-step classification technique is introduced. Several validations have demonstrated that AISACS exhibits high performance with correct classification rates of 72%-87% and clinically appropriate classification rates of 92%-98%.

Human total clearance values and volumes of distribution of typical human cytochrome P450 2C9/19 substrates predicted by single-species allometric scaling using pharmacokinetic data sets from common marmosets genotyped for P450 2C19.

Common marmosets (Callithrix jacchus) are small non-human primates that genetically lack cytochrome P450 2C9 (CYP2C9). Polymorphic marmoset CYP2C19 compensates by mediating oxidations of typical human CYP2C9/19 substrates.Twenty-four probe substrates were intravenously administered in combinations to marmosets assigned to extensive or poor metaboliser (PM) groups by CYP2C19 genotyping. Eliminations from plasma of cilomilast, phenytoin, repaglinide, tolbutamide, and S-warfarin in the CYP2C19 PM group were significantly slow; these drugs are known substrates of human CYP2C8/9/19.Human total clearance values and volumes of distribution of the 24 test compounds were extrapolated using single-species allometric scaling with experimental data from marmosets and found to be mostly comparable with the reported values.Human total clearance values and volumes of distribution of 15 of the 24 test compounds similarly extrapolated using reported data sets from cynomolgus or rhesus monkeys were comparable to the present predicted results, especially to those based on data from PM marmosets.These results suggest that single-species allometric scaling using marmosets, being small, has advantages over multiple-species-based allometry and could be applicable for pharmacokinetic predictions at the discovery stage of drug development.

Remnant preservation provides good clinical outcomes after anterior cruciate ligament reconstruction.

PURPOSE: To evaluate the association of remnant preservation (RP) and non-RP (NRP) with patient-reported outcome measures and subsequent graft rupture at a minimum 2-year follow-up after anterior cruciate ligament (ACL) reconstruction. METHODS: Patients in this retrospective study underwent primary isolated ACL reconstruction by the RP or NRP technique with a four- to five-strand hamstring tendon graft. Multivariate linear or logistic regression and Cox regression analyses were performed to compare the physical and psychological outcomes by the International Knee Documentation Committee subjective knee form (IKDC-SKF) and the Japanese Anterior Cruciate Ligament questionnaire 25 (JACL-25), respectively; satisfaction rate; and prognosticators of graft rupture. RESULTS: In total, 120 patients (mean age, 30.6 ± 12.7 years; 54 RP, 66 NRP) with a mean follow-up of 3.2 ± 1.6 years were enrolled in this study. At the latest postoperative follow-up, the RP group showed a mean IKDC-SKF score of 92.3 ± 8.5 and mean JACL-25 score of 13.2 ± 11.2, while these scores in the NRP group were 86.4 ± 12.2 and 24.4 ± 19.5, respectively (P = 0.016 and 0.007, respectively). No significant differences were found in the return-to-sports rate (RP vs. NRP, 79.5% vs. 67.5%) or satisfaction rate (RP vs. NRP, 89.2% vs. 74.4%) (n.s.); however, a significant difference was found in the rate of return to the preinjury sports level (RP vs. NRP, 64.1% vs. 37.5%; P = 0.014). The graft rupture rate was significantly higher in the NRP than RP group (9/66 vs. 1/54; hazard ratio 9.29; 95% confidence interval 1.04-82.81). Younger age (≤ 18 years) was the other important risk factor for graft rupture (hazard ratio 8.67; 95% confidence interval 2.02-37.13). CONCLUSION: Patients who underwent ACL reconstruction with the RP technique obtained somewhat better physical and psychological results than those who underwent ACL reconstruction with the NRP technique. With respect to clinical relevance, patients treated with the RP technique may obtain better outcomes in terms of graft rupture and return to the preinjury sports level than those treated with the NRP technique, but with no differences in overall return to sports or satisfaction. LEVEL OF EVIDENCE: IV.

Validation and defining the minimal clinically important difference of the Japanese version of the IKDC Subjective Knee Form.

BACKGROUND: This study aimed to validate and determine the minimal clinically important difference (MCID) in the Japanese version of the International Knee Documentation Committee Subjective Knee Form (Japanese IKDC-SKF) for patients with anterior cruciate ligament (ACL) injuries. METHODS: This prospective study was performed using the COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) guideline to assess the measurement properties of reliability, responsiveness, validity, and interpretability of the Japanese IKDC-SKF. RESULTS: A total of 152 patients were enrolled in the study. The Japanese IKDC-SKF had excellent internal consistency [Cronbach's alpha (95% confidence interval, CI) was 0.90 (0.88-0.92), and the test-retest reliability [intraclass correlation coefficient, ICC2,1 (95% CI)] was 0.97 (0.94-0.98). The content validity (r), which was interpretable between the Japanese IKDC-SKF and the Japanese Anterior Cruciate Ligament questionnaire 25 was -0.87 (P < 0.001). The construct validity for the IKDC-SKF was 86% (six of seven hypotheses were consistent with the results), also indicating high validity. Responsiveness of the Japanese IKDC-SKF was confirmed, with an acceptable area under the curve of 0.81 and a large effect size (Cohen's d of 0.8). There were no floor or ceiling effects. The MCID for the Japanese IKDC-SKF for ACL injury was 10.7. CONCLUSIONS: Our results indicate that the Japanese version of the IKDC-SKF is a reliable, valid, and responsive measurement instrument with which to evaluate the physical function of patients with ACL injuries.

Assessment of prognosis in immunoglobulin light chain amyloidosis patients with severe heart failure: a predictive value of right ventricular function.

Although the benefit of updated therapeutic regimens, including bortezomib, on the survival of immunoglobulin light chain (AL) amyloidosis patients with heart failure (HF) has been reported, predictors of mortality in the patients treated with the updated therapy remain unclear. We retrospectively enrolled AL amyloidosis patients who had severe HF at the time of diagnosis and received the updated therapy, including bortezomib (n = 19, 61 ± 6 years old, 68% male). Severe HF was defined as the presence of both NYHA functional class III or IV and BNP > 200 pg/ml or NT-pro-BNP > 900 pg/ml. One-year mortality rate during follow-up after commencement of the treatment was 37%. Left ventricular morphological parameters and indexes of left ventricular diastolic function on admission were similar in the non-survivors and survivors. However, non-survivors had higher incidences of atrial fibrillation and ventricular tachycardia, higher serum total bilirubin levels (1.34 ± 0.55 vs. 0.61 ± 0.29 mg/dl), higher right atrial volume index (RAVI 49.7 ± 29.9 vs. 27.3 ± 6.8 ml/m2), lower tricuspid annular peak velocities during systole (RVs' 8.0 ± 1.8 vs. 11.6 ± 3.7 cm/sec) and late diastole (RVa' 3.4 ± 0.9 vs. 11.4 ± 5.3 cm/sec), and larger inferior vena cava dimension (22.7 ± 6.4 vs. 16.3 ± 4.9 mm) than those in survivors. Kaplan-Meier curve analyses showed that larger RAVI and lower RVs' and RVa', but not left ventricular systolic/diastolic dysfunction, predicted higher mortality during 1-year follow-up. The present results suggest that the presence of right-sided heart abnormality on admission is associated with high 1-year mortality in AL amyloidosis patients with severe HF under the updated therapeutic regimens.

The Role of Overriding Preseptal Orbicularis Oculi Muscle in Development of Involutional Lower Eyelid Entropion: Microscopic Viewpoints.

The aim of this study was to demonstrate the extent of preseptal orbicularis oculi muscle (OOM) override onto the pretarsal OOM in the lower eyelids. In this experimental microscopic study, 22 exenterated specimens from 22 Japanese cadavers were prepared as full-thickness sagittal sections. All exenterated specimens were devoid of lower eyelid entropion. The tarsal dimension and distance from the lower tarsal edge to the tip of overriding OOM were microscopically measured. The rotation axis of the tarsus was presumed to pass through the tarsal centroid and the distance from an estimated tarsal centroid to the lower tarsal edge was calculated. Consequently, 2 eyelids did not exhibit any overriding of the OOM. In the remaining 20 eyelids with OOM override, the average distance of the overriding OOM was found at a level covering 48.0% of the whole tarsal height. In 15 out of the 20 eyelids, the tip of the overriding OOM was located lower than the centroid. These microscopic findings suggest that overriding of the preseptal OOM does not always produce an inward rotational force on the tarsus.