Complete Regression of Endobronchial Carcinoid Tumor after an Endoscopic Biopsy.

An 80-year-old woman who had been diagnosed with an endobronchial carcinoid tumor visited our hospital for treatment with an endoscopic technique. However, a bronchoscopic examination at our hospital showed spontaneous regression of the tumor at the orifice of the right middle lobar bronchus. Chest computed tomography five months later revealed no local recurrence. This is the second report of an endobronchial carcinoid tumor vanishing after an endoscopic biopsy.

Early administration of durvalumab after chemoradiotherapy increased risk of pneumonitis in patients with locally advanced non-small cell lung cancer.

AIMS: Durvalumab (Durva) administration after chemoradiation therapy (CRT) in locally advanced non-small-cell lung cancer (NSCLC) is the standard of care, associated with relatively prolonged progression-free (PFS) and overall survival. However, pneumonitis occurs in 73.6% of Japanese patients. This retrospective study aimed to identify factors associated with Durva efficacy and safety, specifically, the risk of pneumonitis. METHODS: This study included data from 26 consecutive patients with locally advanced NSCLC who underwent CRT followed by Durva. The rates of adverse events and PFS were examined. RESULTS: The median PFS time was 15.6 months (95% confidence interval [CI]: 8.7-not available). Patients developed pneumonitis of grade 1, 2, 3, and 4 at the rate of 62%, 27%, 12%, and 0%, respectively. The median PFS time was 6.4 months for patients with programmed death ligand 1 (PD-L1) expression level of <50% and not reached for patients with PD-L1 expression level of ≥50% (hazard ratio [HR], 0.19; 95% CI: 0.04-0.89), which was significantly prolonged. The cumulative incidence of pneumonitis grade 2 or above was significantly higher when the time between the last day of thoracic radiotherapy (TRT) and the start of Durva therapy was within 14 days compared to >14 days (HR: 0.19; 95% CI: 0.06-0.59). This association was statistically significant in multivariate analysis. CONCLUSIONS: The initiation of Durva therapy within 14 days after TRT may increase the risk of pneumonitis grade 2 or above. Careful observation and suitable treatment are recommended.

A Case of Mediastinal Localized Malignant Pleural Mesothelioma Successfully Treated by Chemotherapy and Conversion Surgery.

Localized malignant mesothelioma is a rare disease and little is known about its treatment strategy. We herein report a case of localized malignant pleural mesothelioma that had infiltrated into the anterior mediastinum, which was successfully treated using chemotherapy and conversion surgery. A 63-year-old man with a mediastinal tumor was referred to our hospital. Pathologic analysis of the biopsy specimen showed malignant mesothelioma. Significant tumor shrinkage by cisplatin and pemetrexed was observed and he underwent radical surgery via a median sternotomy. The patient has been disease free for 12 months.

Phenolic Acids Induce Nod Factor Production in Lotus japonicus-Mesorhizobium Symbiosis.

In legume-rhizobia symbiosis, partner recognition and the initiation of symbiosis processes require the mutual exchange of chemical signals. Chemicals, generally (iso)flavonoids, in the root exudates of the host plant induce the expression of nod genes in rhizobia, and, thus, are called nod gene inducers. The expression of nod genes leads to the production of lipochitooligosaccharides (LCOs) called Nod factors. Natural nod gene inducer(s) in Lotus japonicus-Mesorhizobium symbiosis remain unknown. Therefore, we developed an LCO detection method based on ultra-high-performance liquid chromatography-tandem-quadrupole mass spectrometry (UPLC-TQMS) to identify these inducers and used it herein to screen 40 phenolic compounds and aldonic acids for their ability to induce LCOs in Mesorhizobium japonicum MAFF303099. We identified five phenolic acids with LCO-inducing activities, including p-coumaric, caffeic, and ferulic acids. The induced LCOs caused root hair deformation, and nodule numbers in L. japonicus inoculated with M. japonicum were increased by these phenolic acids. The three phenolic acids listed above induced the expression of the nodA, nodB, and ttsI genes in a strain harboring a multicopy plasmid encoding NodD1, but not that encoding NodD2. The presence of p-coumaric and ferulic acids in the root exudates of L. japonicus was confirmed by UPLC-TQMS, and the induction of ttsI::lacZ in the strain harboring the nodD1 plasmid was detected in the rhizosphere of L. japonicus. Based on these results, we propose that phenolic acids are a novel type of nod gene inducer in L. japonicus-Mesorhizobium symbiosis.

Lotus Accessions Possess Multiple Checkpoints Triggered by Different Type III Secretion System Effectors of the Wide-Host-Range Symbiont Bradyrhizobium elkanii USDA61.

Bradyrhizobium elkanii, a rhizobium with a relatively wide host range, possesses a functional type III secretion system (T3SS) that is involved in symbiotic incompatibility against Rj4-genotype soybean (Glycine max) and some accessions of mung bean (Vigna radiata). To expand our knowledge on the T3SS-mediated partner selection mechanism in the symbiotic legume-rhizobia association, we inoculated three Lotus experimental accessions with wild-type and T3SS-mutant strains of B. elkanii USDA61. Different responses were induced by T3SS in a host genotype-dependent manner. Lotus japonicus Gifu inhibited infection; L. burttii allowed infection, but inhibited nodule maturation at the post-infection stage; and L. burttii and L. japonicus MG-20 both displayed a nodule early senescence-like response. By conducting inoculation tests with mutants of previously reported and newly identified effector protein genes of B. elkanii USDA61, we identified NopF as the effector protein triggering the inhibition of infection, and NopM as the effector protein triggering the nodule early senescence-like response. Consistent with these results, the B. elkanii USDA61 gene for NopF introduced into the Lotus symbiont Mesorhizobium japonicum induced infection inhibition in L. japonicus Gifu, but did not induce any response in L. burttii or L. japonicus MG-20. These results suggest that Lotus accessions possess at least three checkpoints to eliminate unfavorable symbionts, including the post-infection stage, by recognizing different T3SS effector proteins at each checkpoint.

Assessment of Polygala paniculata (Polygalaceae) characteristics for evolutionary studies of legume-rhizobia symbiosis.

Root nodule (RN) symbiosis is a mutualistic interaction observed between nitrogen-fixing soil bacteria and nodulating plants, which are scattered in only four orders of angiosperms called nitrogen-fixing clade. Most of legumes engage in RN symbiosis with rhizobia. Molecular genetic analyses with legumes and non-leguminous nodulating plants revealed that RN symbiosis utilizes early signalling components that are required for symbiosis with arbuscular mycorrhizal (AM) fungi. However detailed evolutionary processes are still largely unknown. Comparative analyses with non-nodulating species phylogenetically related to legumes could be better strategies to study the evolution of RN symbiosis in legumes. Polygala paniculata is a non-leguminous species that belongs to a family different from legumes but that is classified into the same order, Fabales. It has appropriate characteristics for cultivation in laboratories: small body size, high fertility and short lifecycles. Therefore, we further assessed whether this species is suitable as a model species for comparative studies with legumes. We first validated that the plant we obtained in Palau was truly P. paniculata by molecular phylogenetic analysis using rbcL sequences. The estimated genome size of this species was less than those of two model legumes, Lotus japonicus and Medicago truncatula. We determined conditions for cultivation in vitro and for hairy root formation from P. paniculata seedlings. It would facilitate to investigate gene functions in this species. The ability of P. paniculata to interact with AM fungi was confirmed by inoculation with Rhizophagus irregularis, suggesting the presence of early signalling factors that might be involved in RN symbiosis. Unexpectedly, branching of root hairs was observed when inoculated with Mesorhizobium loti broad host range strain NZP2037, indicating that P. paniculata has the biological potential to respond to rhizobia. We propose that P. paniculata is used as a model plant for the evolutionary study of RN symbiosis.

Severe varus knees result in a high rate of undercorrection of lower limb alignment after opening wedge high tibial osteotomy.

PURPOSE: The purpose of this study was to clarify the indication for opening wedge high tibial osteotomy (OWHTO) in terms of lower limb alignment to achieve satisfactory clinical results. METHODS: Ninety-two patients (98 knees) with medial compartment knee osteoarthritis were investigated in this study. The average follow-up period was 34 months (range, 24-68 months). The average age of the patients at the time of surgery was 63 years (range, 41-77 years). RESULTS: The patients were divided into the following two groups according to the preoperative femorotibial angle (FTA) on anteroposterior full-length radiographs of the lower limbs while weight bearing: 29 knees with a preoperative FTA of ≥185° were defined as those with severe varus (S group), and the remaining 69 knees with a preoperative FTA of <185° were defined as those with mild varus (M group). Knees with a postoperative FTA of >175° were defined as undercorrected. The Lysholm score was used to assess the clinical results. The average postoperative FTA was 175.7° ± 4.1° in the S group and 174.6° ± 3.1° in the M group ( p = 0.013). Significantly, more undercorrected knees were observed in the S than M group ( p = 0.00035). The postoperative Lysholm score was 85.6 ± 8.5 in the S group and 88.5 ± 5.7 in the M group at the last follow-up ( p = 0.0033). CONCLUSION: Based on these results, we recommend that a preoperative FTA of <185° should be included as a criterion for OWHTO alone.

Patellar Dislocation in a Patient with Kabuki Syndrome with Severe Mental Retardation: A Case Report.

BACKGROUND: Kabuki syndrome is a rare congenital syndrome. Individuals with Kabuki syndrome have intellectual disabilities, often combined with skeletal anomalies and joint laxity. We herein report the first case of rehabilitation after reconstruction of the medial patellofemoral ligament in a patient with Kabuki syndrome. CASE: A 27-year-old woman with Kabuki syndrome and severe intellectual disability fell during an epileptic seizure. The right patella dislocated and then spontaneously reduced; similar episodes occurred repeatedly. Reconstruction of the medial patellofemoral ligament and lateral retinacular release were performed. Despite an intensive rehabilitation protocol, the patient's activities of daily living (ADL) did not quickly improve postoperatively because of her severe intellectual impairment and unwillingness to participate in rehabilitation exercises. About 3 months postoperatively, staff encouraged the patient to transfer from a wheelchair to a car, and she was able to get into the car with a little assistance. Subsequently, the patient's ADL gradually improved. By approximately 1 year postoperatively, the patient was able to ambulate independently for a few meters. DISCUSSION: The patient was thought to be interested in cars and in going for drives. Rehabilitation training for ADL improvement in patients with severe developmental disorders should include activities that the patients consider interesting.

Sports and Physical Activities of Elderly Patients with Medial Compartment Knee Osteoarthritis after High Tibial Osteotomy.

OBJECTIVE: We retrospectively investigated the preoperative and postoperative sports and physical activities (SPA) of elderly patients with medial compartment knee osteoarthritis who underwent opening-wedge high tibial osteotomy (OWHTO). METHODS: Fifty-six patients (62 knees) with medial compartment knee osteoarthritis were included in the study. The patients comprised 45 women and 11 men with a mean age at surgery of 71.6 years (range, 65-81 years). The mean follow-up period was 51±7 months. Patients who performed SPA to maintain their health for at least 30 min per session more than once a week were defined as SPA cases. The preoperative and postoperative ratios of SPA cases, the time to resuming or starting postoperative SPA, and the frequency of performing postoperative SPA were investigated. Clinical results were assessed using the Lysholm score. RESULTS: Fifteen patients (26.7%) performed SPA before OWHTO and 14 (25.0%) performed SPA after OWHTO (P=0.21). The mean time to resuming or starting SPA after surgery was 14.1±10.0 months, and the frequency of postoperative SPA sessions was 4.2±2.1 per week. The mean Lysholm score significantly improved from 60.8±8.9 preoperatively to 92.5±2.5 postoperatively (P<0.0001). CONCLUSION: The ratio of patients who performed SPA after OWHTO was still <30% , and it took a comparatively long time for patients to resume or start SPA after surgery.

Whole-Genome Sequence of the Nitrogen-Fixing Symbiotic Rhizobium Mesorhizobium loti Strain TONO.

Mesorhizobium loti is the nitrogen-fixing microsymbiont for legumes of the genus Lotus Here, we report the whole-genome sequence of a Mesorhizobium loti strain, TONO, which is used as a symbiont for the model legume Lotus japonicus The whole-genome sequence of the strain TONO will be a solid platform for comparative genomics analyses and for the identification of genes responsible for the symbiotic properties of Mesorhizobium species.

Genome analysis of a novel Bradyrhizobium sp. DOA9 carrying a symbiotic plasmid.

Bradyrhizobium sp. DOA9 isolated from the legume Aeschynomene americana exhibited a broad host range and divergent nodulation (nod) genes compared with other members of the Bradyrhizobiaceae. Genome analysis of DOA9 revealed that its genome comprised a single chromosome of 7.1 Mbp and a plasmid of 0.7 Mbp. The chromosome showed highest similarity with that of the nod gene-harboring soybean symbiont B. japonicum USDA110, whereas the plasmid showed highest similarity with pBBta01 of the nod gene-lacking photosynthetic strain BTAi1, which nodulates Aeschynomene species. Unlike in other bradyrhizobia, the plasmid of DOA9 encodes genes related to symbiotic functions including nodulation, nitrogen fixation, and type III/IV protein secretion systems. The plasmid has also a lower GC content (60.1%) than the chromosome (64.4%). These features suggest that the plasmid could be the origin of the symbiosis island that is found in the genome of other bradyrhizobia. The nod genes of DOA9 exhibited low similarity with those of other strains. The nif gene cluster of DOA9 showed greatest similarity to those of photosynthetic bradyrhizobia. The type III/IV protein secretion systems of DOA9 are similar to those of nod gene-harboring B. elkanii and photosynthetic BTAi1. The DOA9 genome exhibited intermediate characteristics between nod gene-harboring bradyrhizobia and nod gene-lacking photosynthetic bradyrhizobia, thus providing the evidence for the evolution of the Bradyrhizobiaceae during ecological adaptation. Bradyrhizobium sp. DOA9 isolated from the legume Aeschynomene americana exhibited a broad host range and divergent nodulation (nod) genes compared with other members of the Bradyrhizobiaceae. Genome analysis of DOA9 revealed that its genome comprised a single chromosome of 7.1 Mbp and a plasmid of 0.7 Mbp. The chromosome showed highest similarity with that of the nod gene-harboring soybean symbiont B. japonicum USDA110, whereas the plasmid showed highest similarity with pBBta01 of the nod gene-lacking photosynthetic strain BTAi1, which nodulates Aeschynomene species. Unlike in other bradyrhizobia, the plasmid of DOA9 encodes genes related to symbiotic functions including nodulation, nitrogen fixation, and type III/IV protein secretion systems. The plasmid has also a lower GC content (60.1%) than the chromosome (64.4%). These features suggest that the plasmid could be the origin of the symbiosis island that is found in the genome of other bradyrhizobia. The nod genes of DOA9 exhibited low similarity with those of other strains. The nif gene cluster of DOA9 showed greatest similarity to those of photosynthetic bradyrhizobia. The type III/IV protein secretion systems of DOA9 are similar to those of nod gene-harboring B. elkanii and photosynthetic BTAi1. The DOA9 genome exhibited intermediate characteristics between nod gene-harboring bradyrhizobia and nod gene-lacking photosynthetic bradyrhizobia, thus providing the evidence for the evolution of the Bradyrhizobiaceae during ecological adaptation.

Deformation of the patellofemoral joint caused by synovial hemangioma: a case report.

A 15-year-old girl with synovial hemangioma of the knee joint presented with gait pain and occasional sudden swelling for over 7 years. Plain radiographs showed an irregular joint line and a lateral shift of the patella caused by malformation of the patellar groove. Arthroscopy was performed to resect the tumor and to release the lateral patellar retinaculum. If the synovial hemangioma exists in the patellofemoral joint during the growth period, we propose that early surgical treatment is necessary to avoid the deformation of the joint.

Involvement of a novel genistein-inducible multidrug efflux pump of Bradyrhizobium japonicum early in the interaction with Glycine max (L.) Merr.

The early molecular dialogue between soybean and the bacterium Bradyrhizobium japonicum is crucial for triggering their symbiotic interaction. Here we found a single large genomic locus that is widely separated from the symbiosis island and was conspicuously induced within minutes after the addition of genistein. This locus (named BjG30) contains genes for the multidrug efflux pump, TetR family transcriptional regulator, and polyhydroxybutyrate (PHB) metabolism. The induction of BjG30 by genistein was competitively inhibited by daidzein, although both genistein and daidzein are soybean-derived inducers of nodulation (nod) genes. Such a differential expression pattern is also observed in some legume-derived flavonoids, which structurally differ in the hydroxy/deoxy group at the 5-position. In addition, not only did the induction start far in advance of nodW and nodD1 after the addition of genistein, but the levels showed distinct concentration dependence, indicating that the induction pattern of BjG30 is completely different from that of nod genes. The deletion of genes encoding either the multidrug efflux pump or PHB metabolism, especially the former, resulted in defective nodulation performance and nitrogen-fixing capability. Taken together, these results indicate that BjG30, and especially its multidrug efflux pump, may play a key role in the early stage of symbiosis by balancing the dual functions of genistein as both a nod gene inducer and toxicant.

Effect of medial epicondylar osteotomy on soft tissue balancing in total knee arthroplasty.

Balancing and surgical exposure of a severe varus knee during total knee arthroplasty (TKA) can be difficult. Use of a medial epicondylar osteotomy to solve these problems has been reported. This study compared knee stability in cadaveric specimens after TKA, after medial epicondylar osteotomy, and after conventional subperiosteal release of the medial collateral ligament (MCL). Five cadaveric knees were tested after TKA, after medial epicondylar osteotomy, and after repair of the osteotomy to compare the results to 5 cadaveric knees that underwent complete subperiosteal release of the MCL. A retrospective review of clinical cases also was performed of 118 varus knees exposed using the standard medial parapatellar approach and subperiosteal release of the MCL to compare results to the literature using a medial epicondylar osteotomy. Coronal and transverse plane laxity increased significantly at 60° and 90° flexion in the knees after medial epicondylar osteotomy. Suture repair of the osteotomy did not affect stability. The knees with MCL release had a significantly lower degree of coronal and transverse plane laxity at 60° and 90° than knees with an epicondylar osteotomy. The retrospective case review found satisfactory exposure and correct ligament balance was achieved in all cases. The findings of this study question the need for an epicondylar osteotomy in severe varus osteoarthritic knees. Because the knee remains unstable in flexion after this technique, an implant with higher constraint should be used.

Hijacking of leguminous nodulation signaling by the rhizobial type III secretion system.

Root-nodule symbiosis between leguminous plants and nitrogen-fixing bacteria (rhizobia) involves molecular communication between the two partners. Key components for the establishment of symbiosis are rhizobium-derived lipochitooligosaccharides (Nod factors; NFs) and their leguminous receptors (NFRs) that initiate nodule development and bacterial entry. Here we demonstrate that the soybean microsymbiont Bradyrhizobium elkanii uses the type III secretion system (T3SS), which is known for its delivery of virulence factors by pathogenic bacteria, to promote symbiosis. Intriguingly, wild-type B. elkanii, but not the T3SS-deficient mutant, was able to form nitrogen-fixing nodules on soybean nfr mutant En1282. Furthermore, even the NF-deficient B. elkanii mutant induced nodules unless T3SS genes were mutated. Transcriptional analysis revealed that expression of the soybean nodulation-specific genes ENOD40 and NIN was increased in the roots of En1282 inoculated with B. elkanii but not with its T3SS mutant, suggesting that T3SS activates host nodulation signaling by bypassing NF recognition. Root-hair curling and infection threads were not observed in the roots of En1282 inoculated with B. elkanii, indicating that T3SS is involved in crack entry or intercellular infection. These findings suggest that B. elkanii has adopted a pathogenic system for activating host symbiosis signaling to promote its infection.

Commonalities and differences among symbiosis islands of three Mesorhizobium loti strains.

To shed light on the breadth of the host range of Mesorhizobium loti strain NZP2037, we determined the sequence of the NZP2037 symbiosis island and compared it with those of strain MAFF303099 and R7A islands. The determined 533 kb sequence of NZP2037 symbiosis island, on which 504 genes were predicted, implied its integration into a phenylalanine-tRNA gene and subsequent genome rearrangement. Comparative analysis revealed that the core regions of the three symbiosis islands consisted of 165 genes. We also identified several NZP2037-specific genes with putative functions in nodulation-related events, suggesting that these genes contribute to broaden the host range of NZP2037.

LjMATE1: a citrate transporter responsible for iron supply to the nodule infection zone of Lotus japonicus.

Symbiotic nitrogen fixation by intracellular rhizobia within legume root nodules requires the exchange of nutrients between host plant cells and their resident bacteria. While exchanged molecules imply nitrogen compounds, carbohydrates and also various minerals, knowledge of the molecular basis of plant transporters that mediate those metabolite exchanges is still limited. In this study, we have shown that a multidrug and toxic compound extrusion (MATE) protein, LjMATE1, is specifically induced during nodule formation, which nearly paralleled nodule maturation, in a model legume Lotus japonicus. Reporter gene experiments indicated that the expression of LjMATE1 was restricted to the infection zone of nodules. To characterize the transport function of LjMATE1, we conducted a biochemical analysis using a heterologous expression system, Xenopus oocytes, and found that LjMATE1 is a specific transporter for citrate. The physiological role of LjMATE1 was analyzed after generation of L. japonicus RNA interference (RNAi) lines. One RNAi knock-down line revealed limited growth under nitrogen-deficient conditions with inoculation of rhizobia compared with the controls (the wild type and an RNAi line in which LjMATE1 was not suppressed). It was noteworthy that Fe localization was clearly altered in nodule tissues of the knock-down line. These results strongly suggest that LjMATE1 is a nodule-specific transporter that assists the translocation of Fe from the root to nodules by providing citrate.

Rhizobial measures to evade host defense strategies and endogenous threats to persistent symbiotic nitrogen fixation: a focus on two legume-rhizobium model systems.

The establishment and maintenance of rhizobium-legume symbioses require a sequence of highly regulated and coordinated events between the organisms. Although the interaction is mutually beneficial under nitrogen-limited conditions, it can resemble a pathogenic infection at some stages. Some host legumes mount defense reactions, including the production of reactive oxygen species (ROS) and defensin-like antimicrobial compounds. To subvert these host defenses, the infecting rhizobial cells can use measures to passively protect themselves and actively modulate host functions. This review first describes the establishment and maintenance of active nodules, as well as the external and endogenous attack and threat stages. Next, recent studies of ROS scavenging enzymes, the BacA protein originally found in Sinorhizobium meliloti, and the type III/IV secretion systems are discussed, with a focus on two legume-rhizobium model systems.

Evaluation of rotational instability in the anterior cruciate ligament deficient knee using triaxial accelerometer: a biomechanical model in porcine knees.

PURPOSE: To measure the acceleration in multiple directions of the rotational instability in ACL deficient models using porcine knees. METHODS: Ten porcine knees were tested with ACL intact and tear models. The pivot shift test was performed manually, and the acceleration of the pivot shift phenomenon was recorded by the use of a triaxial accelerometer. Tests were repeated in four different ACL states: (1) intact; (2) partial AM deficient; (3) complete AM deficient, and (4) complete ACL (AM and PL) deficient. The acceleration in three directions and the magnitude of acceleration were measured to evaluate rotational instability and compare between different ACL conditions. RESULTS: Significantly increased accelerations were observed in the complete deficient ACL model, while the partial ACL tear models demonstrated a slight increase without statistical significance. The accelerometer detected stepwise increases in the acceleration with the extent of ACL tear. Additionally, the PL bundle exhibited the largest contribution for rotational instability (80.4%) when compared with the AM (19.5%) bundles. CONCLUSION: Triaxial accelerometer could serve as a quantitative evaluation of rotational instability. The present study demonstrated that PL bundle has the most important contribution for rotational instability (80.4%) when compared to IM bundle (0.01%) and AM bundle (19.5%) in porcine knee model.