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Spreading depolarization (SD) develops after stroke and traumatic brain injury and may contribute to secondary brain damage. These diseases are often accompanied by intracranial hypertension, but little is known about the effects of intracranial pressure (ICP) on SD. Here, we study the effect of increased ICP on hemodynamic and metabolic response to SD in rats. SDs were triggered at different ICPs and cerebral perfusion pressures (CPP). The regional cerebral blood flow (rCBF), partial pressure of brain tissue oxygen (PbtO 2 ), cerebral extracellular glucose and lactate concentrations were recorded. Fluoro-Jade staining was used to quantify neuronal injury in cortex. At high ICP (50 mmHg) with low CPP (30 mmHg), rCBF and PbtO2 were monophasically decreased in contrast to a monophasically increased pattern under normal conditions. Neuronal death increased in both hemispheres but much more on the side where SDs were triggered. At high ICP (50 mmHg) with normal CPP (70 mmHg), CBF and metabolism during SD did not differ from baseline, and neuronal death did not increase even on the side of SD induction. These data suggest that maintaining CPP at 70 mmHg, even when the ICP is as high as 50 mmHg, preserves normal blood flow and metabolism during SD events and prevents neuronal degeneration., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: First-time traumatic anterior shoulder dislocation (FASD) is a common trauma associated with shoulder dysfunction. Although several randomized controlled trials have compared conservative and surgical treatments for FASD, the comparative efficacy of these treatments is poorly understood. In this network meta-analysis (NMA), we compared the available evidence on the efficacy of various interventions in patients with FASD., Methods: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases in March 2023. This NMA included randomized controlled trials comparing conservative and surgical treatments for FASD, including arthroscopic Bankart repair, arthroscopic lavage, external rotation (ER) immobilization, and internal rotation (IR) immobilization. The primary outcomes were redislocation rates, Western Ontario Shoulder Instability Index (WOSI) scores, and adverse events (AEs). We conducted random-effects NMA within the frequentist framework. To rank the treatments, the Surface Under the Cumulative Ranking curve was calculated using a Bayesian framework. We evaluated confidence in each outcome using the CINeMA tool., Results: Of the 2999 reviewed studies, 15 were included and analyzed. Regarding the primary outcomes, arthroscopic Bankart repair likely results in a large reduction in redislocation rates compared to IR immobilization (risk ratio [RR], 0.15; 95% confidence interval [CI], 0.07-0.33). Both arthroscopic lavage (RR, 0.47; 95% CI, 0.20-1.11) and ER immobilization (RR 0.70; 95% CI, 0.50-1.00) may reduce the redislocation rates slightly compared with IR immobilization. According to these results, arthroscopic Bankart repair ranked first in terms of reducing the redislocation rate, followed by arthroscopic lavage, ER and IR immobilization. Regarding the WOSI score, no substantial differences were observed in the WOSI scores among the four treatments. AEs showed that ER immobilization tended to cause greater shoulder stiffness than IR immobilization, and postoperative erythema, swelling, and adhesive capsulitis were observed after arthroscopic Bankart repair and lavage. However, a meta-analysis was not performed because the definitions of AEs differed between the studies., Conclusion: Arthroscopic Bankart repair showed a significant effect in reducing the redislocation rate compared to IR immobilization. Although both arthroscopic lavage and ER immobilization seemed to be effective in reducing the redislocation rates, it was not statistically significant. Moreover, these four treatments may result in little to no difference in disease-specific quality of life and there is no clear evidence of AEs., (Copyright © 2024 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Skeletal muscle and bone interact to maintain their structure and function. Physical exercise is the most effective and easily applicable strategy to maintain their functions; however, exercise-induced interactions by soluble factors remained elusive. Our study aimed to identify exercise-induced interactions between muscle and bone by examining (1) the effects of myokine on bone and (2) the effects of osteocalcin (OCN) on skeletal muscle. To understand the effects of exercise-induced myokines on bone, we examined the effects of FNDC5 for aerobic exercise and IGF-1 for resistance exercise using a muscle-specific myokine overexpression model. To examine OCN effects on muscle, mice were intraperitoneally administered OCN-neutralizing antibody during long-term exercise. Our result showed that aerobic exercise tended to increase serum HA-tag protein attached to FNDC5 in muscle-specific overexpression groups. In addition, osteoblastic activation was increased only after aerobic exercise with HA/FNDC5 overexpression. Resistance exercise did not alter circulating HA-tag (muscle-derived IGF-1) and bone metabolism after IGF-1/HA overexpression. In the OCN study, aerobic exercise enhanced endurance capacity by restoring muscle glycogen content; however, OCN neutralization returned these to baseline. After resistance exercise, OCN suppression inhibited muscle hypertrophy and strength gains by preventing protein synthesis. Our results suggest that aerobic exercise following FNDC5 muscle overexpression promotes osteoblast activity, which may be partially caused by muscle-derived FNDC5 secretion. In addition, OCN was necessary for muscle adaptation in both aerobic and resistance exercises., Competing Interests: Declaration of competing interest All authors have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Amyotrophic lateral sclerosis (ALS) is a refractory neurodegenerative disease characterized by the degeneration and loss of motor neurons, typically resulting in death within five years of onset. There have been few effective treatments, making the development of robust therapies an urgent challenge. Genetic mutations have been identified as contributors to ALS, with mutations in superoxide dismutase 1 ( SOD1 ), which neutralizes the harmful reactive oxygen species superoxide, accounting for approximately 2% of all ALS cases. To counteract the toxic gain of function caused by SOD1 mutations, therapeutic strategies aimed at suppressing SOD1 gene expression have shown promise. Antisense oligonucleotide (ASO) is an artificially synthesized, short, single-stranded DNA/RNA molecule that binds to target RNA to alter gene expression, representing a next-generation therapeutic approach. In 2023, tofersen became the first ASO drug approved by the FDA for ALS. Administered intrathecally, tofersen specifically binds to SOD1 mRNA, inhibiting the production of toxic SOD1 protein, thereby improving biomarkers of ALS. The long-term efficacy and safety of tofersen require further validation, and the development of more optimized treatment protocols is essential. A series of studies and therapeutic developments related to SOD1 mutations have advanced the understanding of ALS pathophysiology and significantly contributed to treatment strategies for central nervous system disorders. This review focuses on an overview of SOD1 mutations and the development process of tofersen, aiming to deepen the understanding of advancements in ALS research and discuss future challenges and directions for ASO therapy.

To our knowledge, this is the first report of percutaneous endoscopic intragastric surgery (PEIGS) for gastric metastases from other organs. A 70-year-old male with a history of renal cell carcinoma (RCC) was referred to our department for the treatment of gastric metastasis of RCC. Partial gastrectomy was performed using single-incision PEIGS. Two years after the surgery, a follow-up esophagogastroduodenoscopy revealed a tumor located on the middle greater curvature of the stomach. The diagnosis was metastatic renal cell carcinoma, prompting a similar surgery. No recurrence was observed after the second surgery. PEIGS is a minimally invasive option for the treatment of metastatic gastric tumors., (© 2024 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Microbes have evolved intricate communication systems that enable individual cells of a population to send and receive signals in response to changes in their immediate environment. In the fission yeast Schizosaccharomyces pombe, the oxylipin nitrogen signaling factor (NSF) is part of such communication system, which functions to regulate the usage of different nitrogen sources. Yet, the pathways and mechanisms by which NSF acts are poorly understood. Here, we show that NSF physically interacts with the mitochondrial sulfide:quinone oxidoreductase Hmt2 and that it prompts a change from a fermentation- to a respiration-like gene expression program without any change in the carbon source. Our results suggest that NSF activity is not restricted to nitrogen metabolism alone and that it could function as a rheostat to prepare a population of S. pombe cells for an imminent shortage of their preferred nutrients., (© 2024. The Author(s).)

Background: Moderate mechanical stress generated by normal joint loading and movements helps maintain the health of articular cartilage. Despite growing interest in the pathogenesis of cartilage degeneration caused by reduced mechanical stress, its reversibility by mechanical reloading is less understood. This study aimed to investigate the response of articular cartilage exposed to mechanical reloading after unloading in vivo and in vitro., Methods and Results: Disuse atrophy was induced in the knee joint cartilage of adult mice through hindlimb unloading by tail suspension. For in vivo experiments, mice were subjected to reloading with or without daily exercise intervention or surgical destabilization of the knee joint. Microcomputed tomography and histomorphometric analyses were performed on the harvested knee joints. Matrix loss and thinning of articular cartilage due to unloading were fully or partially restored by reloading, and exercise intervention enhanced the restoration. Subchondral bone density decreased by unloading and increased to above-normal levels by reloading. The severity of cartilage damage caused by joint instability was not different even with prior non-weight bearing. For in vitro experiments, articular chondrocytes isolated from the healthy or unloaded joints of the mice were embedded in agarose gel. After dynamic compression loading, the expression levels of anabolic (Sox9, Col2a1, and Acan) and catabolic (Mmp13 and Adamts5) factors of cartilage were analyzed. In chondrocytes isolated from the unloaded joints, similar to those from healthy joints, dynamic compression increased the expression of anabolic factors but suppressed the expression of catabolic factors., Conclusion: The results of this study indicate that the morphological changes in articular cartilage exposed to mechanical unloading may be restored in response to mechanical reloading by shifting extracellular matrix metabolism in chondrocytes to anabolism., (© 2024. The Author(s).)

Background: Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is a rare malignant gastrointestinal tumor. The prognosis of patients with MiNEN is poor because of the high frequency of recurrence and metastases. We report a case of esophagogastric junction MiNEN (EGJ-MiNEN) with a long-term recurrence-free survival of 5.5 years., Case Presentation: A 58-year-old male patient underwent thoracoscopic esophagectomy for esophagogastric junction adenocarcinoma. The patient's postoperative course was uneventful. R0 resection was achieved, and the pathological diagnosis of the surgical specimen was pT3N2M0 Stage IIIA (according to the Japanese Classification of Gastric Cancer, 4th edition). Based on the pathology results, the patient was treated with postoperative adjuvant therapy with oral S-1. The patient maintained recurrence-free survival for 5.5 years postoperatively. However, 6 years postoperatively, the patient visited our department with cachexia. Computed tomography (CT) revealed a large amount of ascites and pleural effusion. He rapidly developed a poor circulatory and respiratory status and died 16 days after admission. An autopsy revealed severe bloody ascites and pleural effusion, as well as numerous nodules on the pleura and mesentery. Immunohistochemistry of the nodules revealed positivity for chromogranin A, Synaptophysin A, neural cell adhesion molecule (NCAM or CD56), and insulinoma-associated protein 1 (INSM1). The specimen showed a mixture of adenocarcinoma and neuroendocrine cell carcinoma and was diagnosed as MiNEN. Retrospective immunostaining of the surgical specimen showed similar results, and we diagnosed the patient with recurrence of EGJ-MiNEN., Conclusion: MiNEN has a poor prognosis; however, in some cases, long-term recurrence-free survival is achieved with radical resection and adjuvant chemotherapy., (© 2024. The Author(s).)

Background: Maintaining intrinsic articular cartilage homeostasis is essential for the health of cartilage. However, the impact of aerobic exercise of varying intensities on the articular cartilage homeostasis has never been studied. This study aims to elucidate the influence of different aerobic exercise intensities on the anabolic and catabolic processes within articular cartilage., Methods: Forty-eight male C57BL/6J mice, aged 7 weeks, were divided into 4 aerobic exercise groups and 1 control group. The aerobic exercise groups were subjected to both acute and chronic exercise protocols with varying intensities of 8, 12, 16, 20, and 24 m min-1. Total RNA from the knee joint cartilage was extracted in both phases to quantify mRNA of anabolic (Sox9, Col2a1, and Acan) and catabolic (MMP-13 and ADAMTS5) markers. In the chronic exercise, articular cartilage thickness and chondrocyte density were histologically assessed. Additionally, immunohistochemical staining quantified relevant molecules involved in cartilage metabolism., Results: In the acute exercise, the 8 m min-1 group exhibited reduced ADAMTS5 expression compared to the control, 16 m min-1, and 24 m min-1 groups. Chronic exercise showed enhanced articular cartilage thickness in both the 8 and 12 m min-1 groups relative to the control group. Moreover, the 8 m min-1 group demonstrated elevated aggrecan levels in comparison to both the control and 24 m min-1 groups. Additionally, the 24 m min-1 group exhibited significantly higher ADAMTS5 levels than the control group., Conclusion: Our findings suggest that consistent low-intensity aerobic exercise suppresses catabolic molecule expression in articular cartilage, thereby fostering anabolic activity. Conversely, continuous high-intensity aerobic exercise can potentially disrupt cartilage homeostasis by enhancing catabolic processes. This dichotomy underscores the need for balanced exercise regimens to maintain cartilage health.

Background & Aims: Body weight is one of the essential indicators of nutritional status, and body weight management is vital in nutritional care. In addition, low body mass index (BMI) was included as a phenotypic criterion in the Global Leadership Initiative on Malnutrition (GLIM) criteria. Furthermore, low BMI has been used in grading the severity of malnutrition (moderate or severe malnutrition) in the GLIM criteria. A recent cross-sectional study reported that muscle mass of the quadriceps in older inpatients with severely low BMI is less than those of older inpatients with moderately low BMI and non-low BMI. However, the longitudinal relationship between body weight and muscle mass of the quadriceps in older inpatients in each BMI category according to the GLIM criteria remains unclear. This study aimed to examine the longitudinal relationship between body weight and muscle mass of the quadriceps in older inpatients in each BMI category according to the GLIM criteria., Methods: This retrospective cohort study included 179 older inpatients (aged ≥ 70 years) (median [IQR] age: 84.0 [79.0-89.0]). The period of this study was between January 2017 and March 2020. In accordance with the cut-off value of a low BMI for patients aged ≥ 70 years in the Asian population according to the GLIM criteria, the participants were divided into the following three groups: the severely low BMI group (< 17.8 kg/m 2 ) (n = 47), moderately low BMI group (≥ 17.8 to < 20.0 kg/m 2 ) (n = 38), and non-low BMI group (≥ 20.0 kg/m 2 ) (n = 94). The medians (IQR) of the length of hospital stay of the severely low BMI, moderately low BMI, and non-low BMI groups were 71.0 (49.0-98.0) days, 71.0 (50.0-98.0) days, and 50.5 (36.5-103.0) days, respectively. The primary outcome was a change in muscle mass of the quadriceps. The muscle mass of the quadriceps was examined using ultrasound images (i.e., quadriceps thickness). The changes in quadriceps thickness and body weight were calculated by subtracting the quadriceps thickness and body weight at admission from those values at discharge. Multiple linear regression analysis adjusting for confounding factors was used to determine whether the change in body weight was independently and significantly related to the change in quadriceps thickness in the severely low BMI, moderately low BMI, and non-low BMI groups., Results: The means (SD) of the change in quadriceps thickness of the severely low BMI group, moderately low BMI group, and non-low BMI group were 0.0 ± 0.3 cm, 0.1 ± 0.3 cm, and 0.1 ± 0.5 cm, respectively. The means of the change in body weight in those groups were 0.4 ± 2.8 kg, - 1.1 ± 2.7 kg, and - 1.3 ± 4.3 kg, respectively. In the severely low BMI group, the change in body weight (β = 0.34, p = 0.006) and quadriceps thickness at admission (β = -0.62, p < 0.001) were significantly and independently related to the change in quadriceps thickness (R 2  = 0.645, f 2  = 1.817, statistical power = 1.000). In the moderately low BMI and non-low BMI groups, there were no factors that were significantly and independently related to the change in quadriceps thickness., Conclusions: The results of this study suggest that change in body weight is positively related to the change in muscle mass of the quadriceps in older inpatients with severely low BMI according to the GLIM criteria. These results imply the importance of body weight management for older inpatients with severely low BMI perspective from the muscle mass of the quadriceps., (© 2024. The Author(s).)

To regulate the effective photon energy with a constant tube voltage and to perform enhanced K-edge x-ray imaging, we built a prototype fully digitalized triple-energy x-ray computed tomography (TECT) scanner utilizing beam hardening. An object on the turntable is irradiated by a 0.1-mm-focus x-ray tube at 1.4-time-magnification. 720 raw radiograms are obtained using a flat panel detector, and 512 tomograms are reconstructed. With an increasing digital amplification factor, the gray raw-density projections obtained using low-energy-photon absorption disappeared at a constant maximum raw density, and the effective energy was increased by x-ray beam hardening. TECT was performed at digital amplifier factors below 3.0, and the effective energy increased with increasing amplification factors. In particular, fine blood vessels were visible using gadolinium-K-edge CT., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

TGF-β is an immunosuppressive cytokine and plays a key role in progression of cancer by inducing immunosuppression in tumor microenvironment. Therefore, inhibition of TGF-β signaling pathway may provide a potential therapeutic intervention in treating cancers. Herein, we report the discovery of a series of novel thiazole derivatives as potent inhibitors of ALK5, a serine-threonine kinase which is responsible for TGF-β signal transduction. Compound 29b was identified as a potent inhibitor of ALK5 with an IC 50 value of 3.7 nM with an excellent kinase selectivity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Masaaki Sawa is a Chief Scientific Officer of Carna Biosciences, Inc. and owns stocks of Carna Biosciences, Inc. Kazuhito Naka receives research funding from Carna Biosciences, Inc. All the other authors were full time employees of Carna Biosciences, Inc. and have no competing/conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Ocular health has emerged as one of the major issues of global health concern with a decline in quality of life in an aging population, in particular and rise in the number of associated morbidities and mortalities. One of the chief reasons for vision impairment is oxidative damage inflicted to photoreceptors in rods and cone cells by blue light as well as UV radiation. The scenario has been aggravated by unprecedented rise in screen-time during the COVID and post-COVID era. Lutein and Zeaxanthin are oxygenated carotenoids with proven roles in augmentation of ocular health largely by virtue of their antioxidant properties and protective effects against photobleaching of retinal pigments, age-linked macular degeneration, cataract, and retinitis pigmentosa. These molecules are characterized by their characteristic yellow-orange colored pigmentation and are found in significant amounts in vegetables such as corn, spinach, broccoli, carrots as well as fish and eggs. Unique structural signatures including tetraterpenoid skeleton with extensive conjugation and the presence of hydroxyl groups at the end rings have made these molecules evolutionarily adapted to localize in the membrane of the photoreceptor cells and prevent their free radical induced peroxidation. Apart from the benefits imparted to ocular health, lutein and zeaxanthin are also known to improve cognitive function, cardiovascular physiology, and arrest the development of malignancy. Although abundant in many natural sources, bioavailability of these compounds is low owing to their long aliphatic backbones. Under the circumstances, there has been a concerted effort to develop vegetable oil-based carriers such as lipid nano-emulsions for therapeutic administration of carotenoids. This review presents a comprehensive update of the therapeutic potential of the carotenoids along with the challenges in achieving an optimized delivery tool for maximizing their effectiveness inside the body.

Background: Understanding how healthy articular cartilage responds to mechanical loading is critical. Moderate mechanical loading has positive effects on the cartilage, such as maintaining cartilage homeostasis. The degree of mechanical loading is determined by a combination of intensity, frequency, and duration; however, the best combination of these parameters for knee cartilage remains unclear. This study aimed to determine which combination of intensity, frequency, and duration provides the best mechanical loading on healthy knee articular cartilage in vitro and in vivo., Methods and Results: In this study, 33 male mice were used. Chondrocytes isolated from mouse knee joints were subjected to different cyclic tensile strains (CTSs) and assessed by measuring the expression of cartilage matrix-related genes. Furthermore, the histological characteristics of mouse tibial cartilages were quantified using different treadmill exercises. Chondrocytes and mice were divided into the control group and eight intervention groups: high-intensity, high-frequency, and long-duration; high-intensity, high-frequency, and short-duration; high-intensity, low-frequency, and long-duration; high-intensity, low-frequency, and short-duration; low-intensity, high-frequency, and long-duration; low-intensity, high-frequency, and short-duration; low-intensity, low-frequency, and long-duration; low-intensity, low-frequency, and short-duration. In low-intensity CTSs, chondrocytes showed anabolic responses by altering the mRNA expression of COL2A1 in short durations and SOX9 in long durations. Furthermore, low-intensity, low-frequency, and long-duration treadmill exercises minimized chondrocyte hypertrophy and enhanced aggrecan synthesis in tibial cartilages., Conclusion: Low-intensity, low-frequency, and long-duration mechanical loading is the best combination for healthy knee cartilage to maintain homeostasis and activate anabolic responses. Our findings provide a significant scientific basis for exercise and lifestyle instructions., (© 2024. The Author(s).)

To observe fine blood vessels as uneven tomographic images at a high contrast, we performed tentative experiments on embossed x-ray computed tomography (CT). We constructed a cone-beam CT scanner and carried out dual-energy CT with tube voltages of 60 and 100 kV. X-ray photons penetrating through an object were detected using an indirect-conversion flat panel detector, and radiograms were produced and sent to a personal computer to reconstruct tomograms. Embossed CT was performed using pixel-shifted dual-energy subtraction, and blood vessels filled with Gd medium were observed as uneven images at high contrast and spatial resolutions. Using 1.4-time magnification imaging in combination with a 0.1-mm-focus x-ray tube, the diameter of the object visible on the embossed CT was below 100 μm., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Knee malalignment is a risk factor for patellar instability and patellofemoral osteoarthritis (PFOA), but etiologies remain unknown. We investigated the potential effects of decreased weight loading during growth on knee alignments and patellofemoral (PF) joint pathology. Hindlimb suspension (HS) was performed in 4-week-old female rats for 2, 4, and 8 weeks (HS groups). Age-matched rats were used as controls. Three-dimensional reconstructed images of the knee were obtained using X-ray computed tomography. Tibial tubercle-trochlear groove (TT-TG) distance, patellar tilt angle, and bisect offset were measured as indices of knee alignment. Histological analysis was also performed to evaluate the changes in cartilage and synovium in the PF joints. At Week 8, TT-TG distance, patella tilt angle, and bisect offset were significantly larger in the HS group than in the control group, respectively, indicating tibial external rotation, outward patellar tilt, and external displacement of the patella. Lateral patellar dislocation was frequently found in the HS group at Week 8 (five of eight knee joints, p < 0.05). Degenerative changes in the cartilage of the trochlear groove were observed at Week 8, and synovial changes such as hypertrophy and synovitis were observed at Weeks 4 and 8. Correlation analyses revealed significant relationships between the Mankin score and bisect offset, and between the OARSI synovitis score and all knee alignments indices. These results suggest that decreased weight loading on the lower extremities in growing rats resulted in knee malalignments characterized by external rotation of tibia and high incidence of lateral patellar dislocation with concomitant PFOA., (© 2024 Orthopaedic Research Society.)

Exercise can induce beneficial improvements in cognition. However, the effects of different modes and intensities of exercise have yet to be explored in detail. This study aimed to identify the effects of different exercise modes (aerobic and resistance) and intensities (low and high) on cognitive performance, adult hippocampal neurogenesis and synaptic plasticity in mice. A total of 40 C57BL/6J mice were randomised into 5 groups (n = 8 mice per group): control, low-intensity aerobic exercise, high-intensity aerobic exercise, low-intensity resistance exercise, and high-intensity resistance exercise. The aerobic exercise groups underwent treadmill training, while the resistance exercise groups underwent ladder climbing training. At the end of the exercise period, cognitive performance was assessed by the Y-maze and Barnes maze. In addition, adult hippocampal neurogenesis was evaluated immunohistochemically by 5-bromo-2'-deoxyuridine (BrdU)/ neuronal nuclei (NeuN) co-labeling. The levels of synaptic plasticity-related proteins in the hippocampus, including synaptophysin (SYP) and postsynaptic density protein 95 (PSD-95), were analyzed by western blotting. Our results showed no significant differences in cognitive performance among the groups. However, high-intensity aerobic exercise significantly increased hippocampal adult neurogenesis relative to the control. A trend towards increased adult neurogenesis was observed in the low-intensity aerobic group compared to the control group. No significant changes in synaptic plasticity were observed among all groups. Our results indicate that high-intensity aerobic exercise may be the most potent stimulator of adult hippocampal neurogenesis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We report here the whole-genome sequence of the Chlamydia psittaci NRM&#95;5 strain isolated from the fecal samples of wild Indian ring-necked parakeet ( Psittacula krameri manillensis ) in Japan. The sequence type is ST35, which is known to be associated with pigeons and doves, indicating the potential for transmission among bird species., Competing Interests: The authors declare no conflict of interest.

Numerous surgical techniques for median cleft lip repair have been described; however, most cause excessively sharp peaks or the collapse of Cupid's bow. We report a technique for median cleft lip repair using a mucosal skin flap and full-thickness skin graft and 15 years of follow-up. Our technique provides acceptable formation of the columella, philtrum, and the two peaks of Cupid's bow. In this paper, we cite our previously reported techniques and add new findings and discussion based on the long-term postoperative outcomes of this procedure. Advantages and disadvantages of this technique are discussed, and a possible solution to achieve a more satisfactory result is suggested. Advantages and disadvantages of this new technique are discussed, and a possible solution to achieve a more satisfactory result is suggested., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Talaromyces spp. have a worldwide distribution, are ecologically diverse and have been isolated from numerous different substrates. Talaromyces spp. are considered biotechnologically important due to their ability to produce a range of enzymes and pigments. Talaromyces pinophilus, belonging to genus Talaromyces and family Trichocomaceae, is known for producing several important bioactive metabolites. Here we report the isolation and characterisation of a partitivirus from T. pinophilus which we have nominated Talaromyces pinophilus partitivirus-1 (TpPV-1). TpPV-1 possesses a genome consisting of three double stranded (ds) RNA segments i.e., dsRNAs1-3, 1824 bp, 1638 bp and 1451 bp respectively, which are encapsidated in icosahedral particles 35 nm in diameter. Both dsRNA1 and dsRNA2 contain a single open reading frame (ORF) encoding respectively a 572 amino acid (aa) protein of 65 kDa and a 504 aa protein of 50 kDa. The third segment (dsRNA3) is potentially a satellite RNA. Phylogenetic analysis revealed that the TpPV-1 belongs to the family Partitiviridae in the proposed genus Zetapartitivirus. TpPV-1 infection decreases the mycelial growth rate of the host fungus and alters pigmentation as indicated by time course experiments performed on a range of different solid media comparing virus-infected and virus-free isogenic lines. This is the first report of mycovirus infection in T. pinophilus and may provide insights into understanding the effect of the mycovirus on the production of enzymes and pigments by the host fungus., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: The use of robotic platform for gastrectomy for gastric cancer is rapidly increasing. This study aimed to describe the perioperative outcomes of 12 patients who underwent robotic gastrectomy for gastric cancer using the hinotori™ surgical robot system (hinotori), a novel robot-assisted surgical platform, and compare the outcomes with the existing system, the da Vinci ® Surgical System (DVSS). Methods: This study included 12 consecutive patients with gastric cancer who underwent robotic gastrectomy for gastric cancer using the hinotori between March 2023 and September 2023 at our institution. The comprehensive perioperative outcomes of these patients were retrospectively analyzed and compared to 11 patients who underwent robotic gastrectomy using the DVSS during the same period. Results: The median age and body mass index were 71 years (range: 56-86) and 22.7 kg/m 2 (range: 16.1-26.7). Distal and total gastrectomy were performed in 8 and 4 patients, respectively. The median console time and operation times were 187 (range: 112-270) and 252 minutes (range: 173-339), respectively. The median blood loss was 3 mL (range: 2-5). No intra- or postoperative complications were observed. There were no significant differences in perioperative outcomes between the hinotori and the DVSS. Conclusions: Robotic gastrectomy for gastric cancer using the hinotori is a feasible procedure and achieved perioperative outcomes similar to that using the DVSS. Clinical Trial Registration number: 114167-1.

Background/aim: Anastomotic leakage is one of the most common and serious postoperative complications following esophagectomy. This study analyzed the effect of risk factors, such as the degree of arteriosclerosis, comorbidities, and patient characteristics on the incidence of reconstruction-related complications including anastomotic leakage. Furthermore, the usefulness of tailor-made reconstruction methods was clarified using wide gastric conduit., Patients and Methods: Patients who underwent esophagectomy with a gastric conduit for esophageal cancer between 2011 and 2018 were enrolled. In the initial group that underwent esophagectomy between August 2011 and February 2016, gastrointestinal reconstruction was performed using a narrow gastric conduit. In the latter group, reconstruction using subtotal gastric conduit was selected for high-risk patients between March 2016 and March 2018. Postoperative complications including reconstruction-related complications were assessed., Results: The occurrence of anastomotic leakage was significantly associated with the patient's risk in the initial group. The rates of anastomotic leakage and reconstruction-related complications were significantly lower in the latter group than in the initial group (3.2% vs. 23.0%, p=0.001; 27.0% vs. 44.3%, p=0.044). The incidence of all complications was significantly lower in the latter group than in the initial group (28.6% vs. 59.0%, p=0.001). The change in bodyweight loss one year after the operation was significantly lower in the latter group than in the initial group (p=0.042)., Conclusion: Tailor-made reconstruction using wide gastric conduit for high-risk cases of esophageal cancer could reduce the occurrence of anastomotic leakage and promote a better quality of life after surgery., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Patients receiving long-term oxygen therapy are in a state of progressive respiratory dysfunction and have high mortality. However, the predictors of mortality in these patients have not yet been established. Objectives: This prospective observational study aimed to identify the predictors of two-year mortality in patients receiving long-term oxygen therapy. Design, Setting/Subjects: This two-year prospective observational study included 96 patients who received long-term oxygen therapy in the outpatient department of the National Hospital Organization Nishiniigata Chuo Hospital in Japan. Measurements: The updated Charlson Comorbidity Index, body mass index, handgrip strength, modified British Medical Research Council scale (mMRC), Barthel Index (BI), and Montreal Cognitive Assessment (MoCA) were collected in 2019 as a baseline. Outcome was defined as mortality due to chronic respiratory disease during the two-year follow-up period, and predictors were estimated using age- and sex-adjusted Cox proportional hazards model. Results: The 83 patients that were followed up, 30 (36%) died. The Cox proportional hazards model estimated handgrip strength (adjusted hazard ratio [HR]: 0.89; 95% confidence interval [CI]: 0.84-0.94; p  < 0.01; Wald: 14.38.), mMRC (adjusted HR: 1.96; 95% CI: 1.36-2.83; p  < 0.01; Wald: 13.16.), BI (adjusted HR: 0.95; 95% CI: 0.93-0.98; p  < 0.01; Wald: 17.07.), and MoCA (adjusted HR: 2.17; 95% CI: 1.31-3.59; p  < 0.01; Wald: 9.06) as predictors. Conclusions: This study indicated that handgrip strength, dyspnea, activities of daily living, and cognitive function were predictors of two-year mortality in patients receiving long-term oxygen therapy.

This case-control study examined cognitive function in patients with mild idiopathic pulmonary fibrosis (IPF), in comparison with controls or moderate-to-severe IPF. Ten mild IPF, 10 moderate-to-severe IPF, and 16 controls were enrolled, and performance on seven different cognitive function tests was compared in each group. IPF showed decreased cognitive function compared to controls in verbal memory, cognitive flexibility and information processing speed. As the scores were lower even in mild IPF, this study suggests that cognitive function declines early in the disease process of IPF. Thus, occupational therapy for IPF should require an assessment of cognitive function and assistance appropriate to the client's function.

Introduction: Exercise intensity determines the benefits of aerobic exercise. Our objectives were, in aerobic exercise at different intensities, to determine (1) changes in bone metabolism-related genes after acute exercise and (2) changes in bone mass, strength, remodeling, and bone formation-related proteins after long-term exercise., Materials and Methods: Total 36 male C57BL/6J mice were divided into a control group and exercise groups at 3 different intensities: low, moderate, or high group. Each exercise group was assigned to acute- or long-term exercise groups. Tibias after acute exercise were evaluated by real-time PCR analysis. Furthermore, hindlimbs of long-term exercise were assessed by micro-CT, biomechanical, histological, and immunohistochemical analyses., Results: Acute moderate-intensity exercise decreased RANKL level as bone resorption marker, whereas low- and high-intensity exercise did not alter it. Additionally, only long-term exercise at moderate intensity increased bone mass and strength. Moderate-intensity exercise promoted osteoblast activity and suppressed osteoclast activity. After low- and high-intensity exercise, osteoblast and osteoclast activity were unchanged. An increase in the number of β-catenin-positive cells and a decrease in sclerostin-positive cells were observed in the only moderate group., Conclusion: These results showed that moderate-intensity exercise can inhibit bone resorption earlier, and long-term exercise can increase bone mass and strength through promoted bone formation via the Wnt/β-catenin activation. High-intensity exercise, traditionally considered better for bone, may fail to stimulate bone remodeling, leading to no change in bone mass and strength. Our findings suggest that moderate-intensity exercise, neither too low nor high, can maintain bone health., (© 2024. The Japanese Society Bone and Mineral Research.)

Reflux of gastroduodenal contents into the esophagus leads to the development of esophagitis and inflammation-associated pathologies, such as Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). The role of the lipoxygenase (LOX) pathway in carcinogenesis has been recently reported; however, its involvement in esophageal carcinogenesis remains unclear. To address this, the present study investigated the potential of pranlukast, a cysteinyl leukotriene receptor-1 antagonist, to suppress the progression of BE and EAC in a rat duodenogastroesophageal reflux (DGER) model. Male Wistar rats that underwent DGER were divided into two groups. One group was fed commercial chow (control group), and the other was fed experimental chow containing pranlukast (pranlukast group). The rats were sacrificed at 10, 20, 30 and 40 weeks after surgery, and their esophagi were examined. Expression levels of 5-LOX, CD68, IL-8, VEGF and Ki-67 were investigated using immunohistochemistry, and apoptosis was analyzed using the TUNEL method. In the pranlukast group, esophagitis was milder, and the incidence of BE and EAC was significantly lower (P<0.05) compared with that in the control group at 40 weeks after surgery. The number of cells positive for IL-8 and VEGF were significantly lower in the pranlukast group compared with the control group. Proliferative activity was also lower in the pranlukast group compared with the control group (P<0.05). Pranlukast treatment increased apoptosis (P<0.05). Overall, Pranlukast suppressed esophageal carcinogenesis in a rat DGER model, decreasing inflammatory cytokines such as IL-8 and VEGF., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Kohno et al.)

Background: The surgical difficulty of laparoscopic cholecystectomy (LC) for acute cholecystitis varies from case to case, and appropriate intraoperative evaluation would help prevent bile duct injury (BDI)., Methods: We analyzed 178 patients who underwent LC for acute cholecystitis. Expert surgeons and trainees individually evaluated the surgical difficulty. The inter-rater agreement was analyzed using Conger's κ and Gwet's agreement coefficient (AC). Furthermore, we analyzed the predictive surgical difficulty item for performing subtotal cholecystectomy (STC)., Results: Regarding the inter-rater agreement between expert surgeons and trainees, 15 of the 17 surgical difficulty items had a Gwet's AC of 0.5 or higher, indicating "moderate" agreement or higher. Furthermore, the highest and total surgical difficulty scores were deemed "substantial" agreement. Scarring and dense fibrotic changes around the Calot's triangle area with easy bleeding with/without necrotic changes were predictive of whether STC should be performed., Conclusions: This surgical difficulty grading system is expected to be a tool that can be used by any surgeon with LC experience. STC should be performed to prevent BDI according to the changes around the Calot's triangle area., (© 2023 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Radical cystectomy for locally advanced colorectal cancer with urinary bladder invasion significantly reduces the quality of life in exchange for a cure. We performed preoperative chemotherapy with FOLFOXIRI plus bevacizumab for 3 patients with locally advanced colorectal cancer with urinary bladder invasion to avoid radical cystectomy and to achieve local control for urinary bladder preservation. Grade 3 neutropenia was observed in 2 patients as an adverse reaction to the preoperative chemotherapy, but all 3 patients showed good tumor regression. All 3 patients underwent laparoscopic high anterior rectal resection and partial cystectomy, and all were able to undergo R0 resections with urinary bladder preservation. One patient had anastomotic leakage as a postoperative complication. One patient had local recurrence in the urinary bladder, and 2 had recurrence with peritoneal dissemination during their postoperative courses. Preoperative chemotherapy(FOLFOXIRI plus bevacizumab)for locally advanced colorectal cancer with urinary bladder invasion is considered to be a useful treatment option because of its potential for tumor shrinkage and bladder preservation.

Background: Recent studies reported that an increase in intramuscular adipose tissue of the quadriceps in older patients negatively affects the recovery of activities of daily living (ADL) more than the loss of muscle mass. However, whether intramuscular adipose tissue of the quadriceps in older patients with aspiration pneumonia is related to ADL recovery remains unclear. This study aimed to determine the relationship between intramuscular adipose tissue of the quadriceps and ADL recovery in older patients with aspiration pneumonia., Methods: Thirty-nine older inpatients who were diagnosed with aspiration pneumonia participated in this prospective study. The main outcome of this study was ADL at discharge. ADL were assessed using the Barthel Index (BI). The intramuscular adipose tissue and muscle mass of the quadriceps were evaluated at admission using echo intensity and muscle thickness observed on ultrasound images. A multiple linear regression analysis was performed to confirm whether the quadriceps echo intensity was related to the BI score at discharge, even after adjusting for confounding factors., Results: The medians [interquartile range] of the BI score at admission and discharge were 15.0 [0.0-35.0] and 20.0 [5.0-55.0], respectively. The BI score at discharge was significantly higher than that at admission (p = 0.002). The quadriceps echo intensity (β =  - 0.374; p = 0.036) and BI score at admission (β = 0.601; p < 0.001) were independently and significantly related to the BI score at discharge (R 2  = 0.718; f 2  = 2.546; statistical power = 1.000). In contrast, the quadriceps thickness (β =  - 0.216; p = 0.318) was not independently and significantly related to the BI score at discharge., Conclusions: Increased intramuscular adipose tissue of the quadriceps at admission is more strongly and negatively related to ADL recovery at discharge than the loss of muscle mass among older patients with aspiration pneumonia. Interventions targeting the intramuscular adipose tissue of the quadriceps may improve ADL among these patients., (© 2024. The Author(s).)

Introduction: Total knee arthroplasty (TKA) reduces pain and improves physical function; however, not all patients have successful outcomes after surgery. To identify these patients would be critical information for improving rehabilitation programs. The purpose of this study was to clarify the cut-off values of lower extremity muscle strength for predicting postoperative good walking ability., Materials and Methods: Timed Up and Go test of 105 patients was measured at 6 months postoperatively, and participants were divided into good (< 9.1 s) and poor (≥ 9.1 s) walking ability. Both sides of knee extensor strength (KES) and hip abductor strength (HAS) were measured using hand-held dynamometer preoperatively. Receiver operating characteristic (ROC) curve analysis was used to identify cut-off values for classifying the participants into the two groups., Results: Of the 105 patients, 54 were allocated in the poor walking ability group, whereas 51 were allocated in the good walking ability group. KES and HAS were significantly greater in the good walking ability group than in the poor walking ability group. ROC curve analysis revealed that the cut-off value for KES was 0.79 Nm/kg (area under the curve (AUC) 0.68; sensitivity 64.7%; specificity 68.5%) on the involved side and 0.86 Nm/kg (AUC 0.73; sensitivity 84.6%; specificity 55.6%) on the uninvolved side, and for HAS was 0.57 Nm/kg (AUC 0.71; sensitivity 60.8%; specificity 71.7%) on the involved side and 0.61 Nm/kg (AUC 0.76; sensitivity 66.7%; specificity 77.4%) on the uninvolved side., Conclusion: The cut-off values of preoperative KES and HAS for predicting good walking ability after TKA are 0.79 Nm/kg on the involved side and 0.86 Nm/kg on the uninvolved side, and 0.57 Nm/kg on the involved side and 0.61 Nm/kg on the uninvolved side, respectively. We should provide enhanced pre- and post-operative rehabilitation programs for patients with muscle strength lower than these values., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Agrobacterium tumefaciens ( Rhizobium radiobacter ) is used for the transient expression of foreign genes by the agroinfiltration method, but the introduction of foreign genes often induces transcriptional and/or post-transcriptional gene silencing (TGS and/or PTGS). In this study, we characterized the structural features of T-DNA that induce TGS during agroinfiltration. When A. tumefaciens cells harboring an empty T-DNA plasmid containing the cauliflower mosaic virus (CaMV) 35S promoter were infiltrated into the leaves of Nicotiana benthamiana line 16c with a GFP gene over-expressed under the control of the same promoter, no small interfering RNAs (siRNAs) were derived from the GFP sequence. However, siRNAs derived from the CaMV 35S promoter were detected, indicating that TGS against the GFP gene was induced. When the GFP gene was inserted into the T-DNA plasmid, PTGS against the GFP gene was induced whereas TGS against the CaMV 35S promoter was suppressed. We also showed the importance of terminator sequences in T-DNA for gene silencing. Therefore, depending on the combination of promoter, terminator and coding sequences on T-DNA and the host nuclear genome, either or both TGS and/or PTGS could be induced by agroinfiltration. Furthermore, we showed the possible involvement of three siRNA-producing Dicers (DCL2, DCL3 and DCL4) in the induction of TGS by the co-agroinfiltration method. Especially, DCL2 was probably the most important among them in the initial step of TGS induction. These results are valuable for controlling gene expression by agroinfiltration., Competing Interests: Conflict of interestThe authors have declared that no competing interests exist., (© 2023 Japanese Society for Plant Biotechnology.)

A 56-year-old female was referred to our hospital for further examination and treatment because of her increasing right axillary mass for 1 year. Based on histological examination diagnosing the right axillary mass as carcinoma and radiological examination showing no evidence of distal metastasis, we decided to perform a radical resection. The patient underwent right axillary mass resection, axillary lymph node dissection, and latissimus dorsi musculocutaneous flap reconstruction. Right-sided breast cancer was diagnosed based on histopathological examination. The diagnosis was similar to that of breast cancer. The patient underwent adjunctive chemotherapy and is currently undergoing endocrine therapy. The incidence of accessory breast cancer is 0.2-0.6% among all breast cancers and is relatively rare. Postoperative adjuvant pharmacotherapy has no consensus. However, endocrine therapy, chemotherapy, and molecular target therapy are performed in cases of conventional breast cancer. Herein, we describe a case of right axillary accessory breast cancer with skin invasion successfully treated with radical resection.

The patient is a 51-year-old female with comorbidity of schizophrenia. At the age of 41, she underwent surgery for bilateral breast cancer. Both sides were of the Luminal type, with Stage ⅢC on the right and Stage 0 on the left. She started to receive adjuvant chemotherapy but it was interrupted according to her wish. Approximately 3 years ago, she developed carcinomatous pleuritis, multiple liver metastases, and bone metastases. Despite receiving chemotherapy, her condition worsened. A BRACAnalysis revealed pathogenic variants in BRCA2. Upon initiating treatment with olaparib, both her liver metastases and carcinomatous pleuritis have shown reductions, and her tumor markers have also started to decline. Approximately 5 months after treatment with olaparib, it has been possible to continue without any side effects. Olaparib has shown good results in patients with germline BRCA1/2 mutation-positive HER2-negative advanced/recurrent breast cancer who have a history of receiving anthracycline and taxane-based therapies. It was considered that even in recurrent breast cancer, the presence or absence of BRCA1/2 mutations should be actively sought even in advanced cases, and the administration of olaparib should be considered.

A 55-year-old man was referred for the close examination of an abdominal mass noted on abdominal ultrasonography during a physical examination. A contrast-enhanced computed tomography(CT)scan of his abdomen revealed a 36-mm heterogeneously contrast-enhanced mass on the left side of the aorta. He was referred for laparoscopic tumor resection without preoperative histological examination. The tumor was identified from the dorsal aspect of the mesentery of the transverse colon and was resected only because it was detachable from the duodenum. A temporary abnormal hypertension was observed intraoperatively. However, he exhibited a favorable postoperative course and was discharged on the 8th postoperative day. Grossly, it was a nodular tumor with a diameter of 38 mm. Histopathological examination revealed that the tumor cells having abundant cytoplasm formed large foci and were surrounded by sinusoidal vessels. Immunohistochemistry results were positive for chromogranin A, synaptophysin, and neural cell adhesion molecule; thus, paraganglioma was diagnosed. Herein, we report a case of laparoscopic resection of an asymptomatic paraganglioma.

Background & Aim: Several randomized controlled trials indicated that an increase in protein intake decreases intramuscular adipose tissue of the thigh in mobility-limited or pre-frail older persons and stroke patients. However, whether the increase in protein intake in older inpatients is related to decreasing intramuscular adipose tissue remains unclear. The aim of this study was to examine the longitudinal relationship between intramuscular adipose tissue of the quadriceps and protein intake in older inpatients., Methods: This longitudinal study included 193 older inpatients (aged ≥65 years) (median [IQR] age: 83.0 [77.0-88.0]). The primary outcomes were changes in intramuscular adipose tissue of the quadriceps and protein intake. Intramuscular adipose tissue and muscle mass of the quadriceps were examined using ultrasound images (i.e., quadriceps echo intensity and thickness). The changes in quadriceps echo intensity and protein intake were calculated by subtracting the quadriceps echo intensity and protein intake at admission from those values at discharge. Multiple linear regression analysis adjusting for confounding factors was used to determine whether the change in protein intake was independently and significantly related to changes in quadriceps echo intensity and thickness., Results: Quadriceps echo intensity at discharge (81.3 ± 20.6 [a.u.]) was significantly lower than at admission (84.0 ± 20.5 [a.u.]). Protein intake at discharge (1.2 [1.0-1.4] g/kg/day) was significantly higher than at admission (1.2 [0.9-1.4] g/kg/day). Change in protein intake was negatively and significantly related to the change in quadriceps echo intensity. In contrast, change in protein intake was not independently and significantly related to change in quadriceps thickness., Conclusions: Our results indicate that an increase in protein intake is related to a decrease in intramuscular adipose tissue of the quadriceps in older inpatients. Nutritional intervention for increasing protein intake in older inpatients may be essential for decreasing intramuscular adipose tissue of the quadriceps., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Osteoporosis-related fractures are a major public health problem. Mechanobiological stimulation utilizing low-intensity pulsed ultrasound (LIPUS) is the most widely accepted modality for accelerating fracture healing. However, recent evidence has demonstrated the ineffectiveness of LIPUS, and the biophysical mechanisms of ultrasound-induced bone formation also remain elusive. Here, we demonstrate that ultrasound at a higher intensity than LIPUS effectively accelerates fracture healing in a mouse osteoporotic fracture model. Higher-intensity ultrasound promoted chondrogenesis and hypertrophic differentiation of chondrocytes in the fracture callus. Higher-intensity ultrasound also increased osteoblasts and newly formed bone in the callus, resulting in accelerated endochondral ossification during fracture healing. In addition, we found that accelerated fracture healing by ultrasound exposure was attenuated when the mechanosensitive ion channel Piezo1 was inhibited by GsMTx4. Ultrasound-induced new bone formation in the callus was attenuated in fractured mice treated with GsMTx4. Similar results were also confirmed in a 3D osteocyte-osteoblast co-culture system, where osteocytic Piezo1 knockdown attenuated the expression of osteoblastic genes after ultrasound exposure. Together these results demonstrate that higher-intensity ultrasound than clinically used LIPUS can accelerate endochondral ossification after fractures. Furthermore, our results suggest that mechanotransduction via Piezo1 mediates ultrasound-stimulated fracture healing and bone formation., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: The Western corn rootworm (WCR), Diabrotica virgifera virgifera, is a highly adaptable insect pest that has evolved resistance to a variety of control strategies, including insecticides. Therefore, it is interesting to examine how housekeeping proteins in WCR have been changed under WCR-controlling strategies. In this study, we focused on one of such proteins in WCR, a ubiquitous enzyme 5'-triphosphate nucleotidohydrolase (dUTPase). In the thymidine synthetic pathway, dUTPase hydrolyzes deoxyuridine triphosphate (dUTP) and supplies the substrate, deoxyuridine monophosphate, for the thymidylate synthase (TS). It decreases the cellular content of uracil, reducing uracil misincorporation into DNA. Suppressing the dUTPase activity, therefore, contributes to thymineless death. In this study, we investigated the enzymatic properties of dUTPase., Results: The WCR dUTPase gene (DUT) was synthesized with the addition of His-tag corresponding DNA sequence and then cloned and expressed in Escherichia coli, and the protein product was purified. The product of WCR DUT hydrolyzed dUTP and was designated as dUTPase. WCR dUTPase did not hydrolyze dATP, dTTP, dCTP, or dGTP. WCR dUTPase was analyzed via size-exclusion chromatography and exhibited a molecular weight corresponding to that of trimer. The present format can be interpreted as nuclear trimer type. Possible isomers will be examined once transcriptome analyses are conducted., (© 2023. The Author(s).)

Paeciliomyces variotii is a thermo-tolerant, ubiquitous fungus commonly found in food products, indoor environments, soil and clinical samples. It is a well-known biocontrol agent used against phytopathogenic fungi and its metabolites have many industrial applications. Rare reports of P. variotii- related human infections have been found in the medical literature. In this study, we report for the first time the infection of P. variotii isolated from a soil sample collected in a rice field with a double-stranded RNA virus, Paeciliomyces variotii partitivirus 1 (PvPV-1) in the family Partitiviridae. P. variotii harboured icosahedral virus particles 30 nm in diameter with two dsRNA segments 1758 and 1356 bp long. Both dsRNA1 and dsRNA2 have a single open reading frame encoding proteins of 63 and 40 kDa, respectively. These proteins have significant similarity to the RNA-dependent RNA polymerase and capsid protein encoded by the genomic segments of several viruses from the family Partitiviridae . Phylogenetic analysis revealed that PvPV-1 belongs to the family Partitiviridae but in an unclassified group/genus, tentatively nominated Zetapartitivirus. PvPV-1 was found to increase the growth rate of the host fungus, as indicated by time course experiments performed on a range of different media for virus-infected and virus-free isogenic lines. Further, dual-culture assays performed for both isogenic lines confirmed the antagonistic potential of P. variotii against other phytopathogenic fungi. The findings of this study assist us in understanding P. variotii as a potential biocontrol agent, together with plant-fungus-virus interactions.

Background: The membrane components of cardiomyocytes are rich in polyunsaturated fatty acids, which are easily oxidized. Thus, an efficient glutathione-based lipid redox system is essential for maintaining cellular functions. However, the relationship between disruption of the redox system during ischemia-reperfusion (IR), oxidized lipid production, and consequent cell death (ferroptosis) remains unclear. We investigated the mechanisms underlying the disruption of the glutathione-mediated reduction system related to ferroptosis during IR and developed intervention strategies to suppress ferroptosis., Methods: In vivo fluctuations of both intra- and extracellular metabolite levels during IR were explored via microdialysis and tissue metabolome analysis. Oxidized phosphatidylcholines were assessed using liquid chromatography high-resolution mass spectrometry. The areas at risk following IR were assessed using triphenyl-tetrazolium chloride/Evans blue stain., Results: Metabolomic analysis combined with microdialysis revealed a significant release of glutathione from the ischemic region into extracellular spaces during ischemia and after reperfusion. The release of glutathione into extracellular spaces and a concomitant decrease in intracellular glutathione concentrations were also observed during anoxia-reperfusion in an in vitro cardiomyocyte model. This extracellular glutathione release was prevented by chemical inhibition or genetic suppression of glutathione transporters, mainly MRP1 (multidrug resistance protein 1). Treatment with MRP1 inhibitor reduced the intracellular reactive oxygen species levels and lipid peroxidation, thereby inhibiting cell death. Subsequent in vivo evaluation of endogenously oxidized phospholipids following IR demonstrated the involvement of ferroptosis, as levels of multiple oxidized phosphatidylcholines were significantly elevated in the ischemic region 12 hours after reperfusion. Inhibition of the MRP1 transporter also alleviated intracellular glutathione depletion in vivo and significantly reduced the generation of oxidized phosphatidylcholines. Administration of MRP1 inhibitors significantly attenuated infarct size after IR injury., Conclusions: Glutathione was released continuously during IR, primarily in an MRP1-dependent manner, and induced ferroptosis. Suppression of glutathione release attenuated ferroptosis and reduced myocardial infarct size following IR., Competing Interests: Disclosures None.

A 78-year-old male was diagnosed with a primary gastric B-cell malignant lymphoma and metastatic lung tumor 10 years ago. He underwent chemotherapy at another hospital, achieved complete remission, and was actively undergoing follow- up. He presented to our hospital with a 1-month history of a bulge in his right lower abdomen. CT revealed thickening of the ascending colon and dilatation of the oral intestine. He was diagnosed with ascending colon cancer and underwent right hemicolectomy. The subsequent pathological examination revealed a collision tumor involving diffuse, large B-cell lymphoma and well-differentiated adenocarcinoma. He was discharged from our hospital and received chemotherapy at another institution. Unfortunately, the patient died of interstitial pneumonia 31 months postoperatively. This report describes the resection of a collision tumor involving ascending colon cancer and malignant lymphoma. Surgical treatment combined with postoperative chemotherapy improved this patient's long-term survival.

Purpose: Patients undergoing long-term oxygen therapy (LTOT) are predisposed to progressive cognitive decline; however, the association between cognitive decline progression and activities of daily living (ADL) decline has not been described. We aimed to describe the association between cognitive decline progression and ADL decline in patients undergoing LTOT., Materials and Methods: In this prospective observational pilot study, data were collected at baseline and 1-year following the ambulatory recruitment of patients in the Department of Respiratory Medicine at the National Hospital Organization Nishiniigata Chuo Hospital. We recruited 96 patients with chronic respiratory disease undergoing LTOT, and 55 patients who completed a 1-year follow-up were finally included., Results: Multivariate logistic regression analysis revealed that Montreal Cognitive Assessment score reduction (a measure of cognitive decline) was associated with Barthel index score reduction (a measure of ADL) at 1-year follow-up (odds ratio: 3.98; 95% confidence interval: 1.16 - 13.69; p  = 0.02)., Conclusion: A progression of cognitive decline in patients undergoing LTOT may affect ADL decline. An early detection of cognitive decline in patients undergoing LTOT is essential for ADL maintenance in rehabilitation practice.IMPLICATIONS FOR REHABILITATIONPatients undergoing long-term oxygen therapy (LTOT) present with progressive cognitive decline.Cognitive decline progression is associated with a decline in activities of daily living in patients undergoing LTOT.A periodic cognitive assessment is important in rehabilitation practice for the early detection of progressive cognitive decline in patients undergoing LTOT.

Two endornaviruses, Phytophthora endornavirus 2 (PEV2) and Phytophthora endornavirus 3 (PEV3), have been discovered in pathogens targeting asparagus. In this study, we analyzed the nick structure in the RNA genomes of PEV2 and PEV3 in the host oomycetes. Northern blot hybridization using positive and negative strand-specific RNA probes targeting the 5' and 3' regions of PEV2 and PEV3 RNA genomes revealed approximately 1.0 kilobase (kb) RNA fragments located in the 5' regions of the two genomes. 3' RACE analysis determined that the size of the RNA fragments were 958 nucleotides (nt) for PEV2 and 968 nt for PEV3. We have successfully constructed full-length cDNA clones of the entire RNA genomes of PEV2 and PEV3 using a homologous recombination system in the yeast, Saccharomyces cerevisiae . These full-length cDNA sequences were ligated downstream of a constitutive expression promoter ( TDH3 ) or a galactose-inducing promoter ( GAL1 ) in the shuttle vector to enable the production of the full-length RNA transcripts of PEV2 and PEV3 in yeast cells. Interestingly, a 1.0 kb RNA fragment from the PEV3 positive-strand transcript was also detected with a 5'-region RNA probe, indicating that site-specific cleavage also occurred in yeast cells. Further, when PEV2 or PEV3 mRNA was overexpressed under the GAL1 promoter, yeast cell growth was suppressed. A fusion protein combining EGFP to the N-terminus of the full-length PEV2 ORF or C-terminus of the full-length PEV3 ORF was expressed, and allowed PEV2 and PEV3 ORFs to be successfully visualized in yeast cells. Expression of the fusion protein also revealed presence of heterogeneous bodies in the cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sakuta, Uchida, Fukuhara, Komatsu, Okada and Moriyama.)

Background: Malignant esophageal stenosis is a common and severe complication of advanced esophageal cancer that can be a serious problem in the continuation of chemotherapy and other anticancer treatments. The impact of chemotherapy regimens on the degree of improvement in esophageal stenosis is unknown. In this study, we focused on the impacts of chemotherapy on the direct anticancer effects, and in the improvement of malignant stenosis., Methods: Patients who underwent radical esophagectomy after chemotherapy, either adjuvant 5-fluorouracil and cisplatin (FP) or docetaxel, cisplatin, and 5-fluorouracil (DCF) regimen, were included. We assessed the length of the cancerous stenosis, the width of the narrowest segment, and the size of the intraluminal area in the stenotic segment by fluoroscopy, and compared the differences before and after chemotherapy. In addition, we evaluated the dysphagia score (Mellow-Pinkas scoring system) as the evaluation of patients' symptoms. The antitumor effects of chemotherapy were also investigated., Results: A total of 81 patients were enrolled: 50 were treated with FP, and 31 were treated with DCF. The expansion rate in the length of the narrowest part was significantly increased in the DCF group compared with the FP group. Furthermore, the stenosis index (intraluminal stenotic area/stenotic length) was significantly increased in the DCF group compared with the FP group (112% vs 96%, P = 0.038). Dysphagia score after chemotherapy significantly improved in the DCF group compared to the FP group (P = 0.007). The response rates were 60% in the FP group and 67.7% in the DCF group. Effective histopathological response (improvement to grade 2 or 3) was 24% in the FP group and 38.8% in the DCF group., Conclusion: DCF therapy is more effective than FP treatment in the improvement of malignant esophageal stenosis., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The degree of difficulty in the overall procedure and forceps handling encountered by surgeons is greatly influenced by the positional relationship of intrathoracic organs in minimally invasive esophagectomy. This study aimed to identify the anatomical factors associated with the difficulty of minimally invasive esophagectomy assessed by intraoperative injuries and postoperative outcomes., Methods: Minimally invasive esophagectomy in the left-decubitus position was performed in 258 patients. We defined α (mm) as the anteroposterior distance between the front of the vertebral body and aorta, β (mm) as the distance between the center of the vertebral body and center of the aorta, and γ (degree) as the angle formed at surgeon's right-hand port site by insertion of lines from the front of aorta and from the front of vertebrae in the computed tomography slice at the operator's right-hand forceps hole level. We retrospectively analyzed the correlations among clinico-anatomical factors, surgeon- or assistant-caused intraoperative organ injuries, and postoperative complications., Results: Intraoperative injuries significantly correlated with shorter α (0.2 vs. 3.9), longer β (33.0 vs. 30.5), smaller γ (3.0 vs. 4.3), R1 resection (18.5% vs. 8.3%), and the presence of intrathoracic adhesion (46% vs. 26%) compared with the non-injured group. Division of the median values into two groups showed that shorter α and smaller γ were significantly associated with organ injury. Longer β was significantly associated with postoperative tachycardia onset, respiratory complications, and mediastinal recurrence. Furthermore, the occurrence of intraoperative injuries was significantly associated with the onset of postoperative pulmonary complications., Conclusions: Intrathoracic anatomical features greatly affected the procedural difficulty of minimally invasive esophagectomy, suggesting that preoperative computed tomography simulation and appropriate port settings may improve surgical outcomes., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Nonocclusive mesenteric ischemia (NOMI), an ischemic bowel disease without a disruption of the mesenteric blood flow or strangulation of the mesentery or intestine, may cause a lethal clinical course. We report a very rare case of jejunal necrosis caused by NOMI in the pedicled mesentery of the reconstructed jejunum after remnant gastric tube resection for heterochronous gastric tube cancer after esophagectomy., Case Presentation: An 80-year-old man visited our department with chief complaints of fever and appetite loss after 4 months from gastric tube resection and digestive reconstruction with pedicled jejunum. Contrast-enhanced computed tomography (CT) revealed impaired blood flow without torsion of the mesentery, severe wall thickness, and micro-penetration in the reconstructed jejunum and combined pyothorax in the right thoracic cavity. Esophagogastroduodenoscopy demonstrated extensive mucosal necrosis confined to the jejunum, which was elevated in the thoracic cavity. The jejunal necrosis due to NOMI occurring in the reconstructed jejunum was suspected, and lifesaving small bowel resection with right thoracotomy was considered necessary. However, radical operation with right thoracotomy was considered to be excessively invasive and not valid due to the patient's poor physical status, advanced age, and presence of left adrenal metastasis from the remnant gastric cancer. Therefore, we selected the conservative treatment with fasting, transnasal drainage, and administration of antibiotics due to the patient's intention. CT-guided right thoracic drainage for the intrathoracic abscess was needed 10 days after starting treatment and the inflammatory response rapidly improved. Follow-up CT and esophagogastroduodenoscopy revealed the improvement in the ischemic changes in jejunal mucosa without perforation. Intake was initiated at 20 days after symptom onset, and the patient was discharged at 40 hospital days without any complications and sequelae., Conclusions: To the best of our knowledge, this is the first case of NOMI occurring in the reconstructed jejunum after remnant gastric tube resection that was successfully treated with a conservative treatment. For NOMI, it is important to make appropriate diagnosis based on imaging findings and perform proper assessment of the patient's condition. Conservative treatments may be also useful depending on the patient's condition., (© 2023. Japan Surgical Society.)