Correction: 'Transition mechanism for a periodic bar-and-joint framework with limited degrees of freedom controlled by uniaxial load and internal stiffness' (2018), by Tanaka et al.

[This corrects the article DOI: 10.1098/rsos.180139.][This corrects the article DOI: 10.1098/rsos.180139.].

Abrupt Deterioration of COVID-19 Patients and Spreading of SARS COV-2 Virions in the Lungs.

A unique feature of COVID-19 interstitial pneumonia is an abrupt progression to respiratory failure. Our calculation shows that this abrupt deteriorate may be caused by a sudden shift in the spread of virus-laden bioaerosols through the airways to many different regions of the lungs from the initial site of infection.

Transition mechanism for a periodic bar-and-joint framework with limited degrees of freedom controlled by uniaxial load and internal stiffness.

A specific periodic bar-and-joint framework with limited degrees of freedom is shown to have a transition mechanism when subjected to an external force. The static nonlinear elasticity of this framework under a uniaxial load is modelled with the two angular variables specifying the rotation and distortion of the linked square components. Numerically exploring the equilibrium paths then reveals a transition state of the structure at a critical value of the internal stiffness. A simplified formulation of the model with weak nonlinear terms yields an exact solution of its transition state. Load-displacement behaviour and stability for the two systems with or without approximation are analysed and compared.

Forebrain-specific ablation of phospholipase Cγ1 causes manic-like behavior.

Manic episodes are one of the major diagnostic symptoms in a spectrum of neuropsychiatric disorders that include schizophrenia, obsessive-compulsive disorder and bipolar disorder (BD). Despite a possible association between BD and the gene encoding phospholipase Cγ1 (PLCG1), its etiological basis remains unclear. Here, we report that mice lacking phospholipase Cγ1 (PLCγ1) in the forebrain (Plcg1f/f; CaMKII) exhibit hyperactivity, decreased anxiety-like behavior, reduced depressive-related behavior, hyperhedonia, hyperphagia, impaired learning and memory and exaggerated startle responses. Inhibitory transmission in hippocampal pyramidal neurons and striatal dopamine receptor D1-expressing neurons of Plcg1-deficient mice was significantly reduced. The decrease in inhibitory transmission is likely due to a reduced number of γ-aminobutyric acid (GABA)-ergic boutons, which may result from impaired localization and/or stabilization of postsynaptic CaMKII (Ca2+/calmodulin-dependent protein kinase II) at inhibitory synapses. Moreover, mutant mice display impaired brain-derived neurotrophic factor-tropomyosin receptor kinase B-dependent synaptic plasticity in the hippocampus, which could account for deficits of spatial memory. Lithium and valproate, the drugs presently used to treat mania associated with BD, rescued the hyperactive phenotypes of Plcg1f/f; CaMKII mice. These findings provide evidence that PLCγ1 is critical for synaptic function and plasticity and that the loss of PLCγ1 from the forebrain results in manic-like behavior.

Adsorption efficiency of natural materials for low-concentration cesium in solution.

In this study, several natural materials were investigated in order to clarify their potential use as cesium (Cs) adsorbents in situ. Four materials--carbonized rice hull, beech sawdust, oak sawdust, and charcoal (Japanese cedar)--which were previously shown to have Cs adsorption capabilities, were examined. Cs adsorption experiments were conducted using different initial Cs and adsorbent concentrations. The physical properties, adsorption isotherms, and adsorption processes were then examined, so as to exploit the Cs adsorption characteristics in the field. Based on these findings, carbonized rice hull and beech sawdust were selected as effective Cs adsorbents. It was found that these materials show continuous and stable Cs adsorption rates for different initial Cs concentrations. The adsorption efficiency of these two adsorption materials in combination was considered, and it was shown that the adsorption isotherms for carbonized rice hull and beech sawdust follow the Freundlich model. Furthermore, the beech sawdust adsorption process exhibited better agreement with the calculated values obtained via the adsorption rate model and the adsorption kinetics model than did the carbonized rice hull adsorption.

Pim-2 kinase is an important target of treatment for tumor progression and bone loss in myeloma.

Pim-2 kinase is overexpressed in multiple myeloma (MM) cells to enhance their growth and survival, and regarded as a novel therapeutic target in MM. However, the impact of Pim-2 inhibition on bone disease in MM remains unknown. We demonstrated here that Pim-2 expression was also upregulated in bone marrow stromal cells and MC3T3-E1 preosteoblastic cells in the presence of cytokines known as the inhibitors of osteoblastogenesis in MM, including interleukin-3 (IL-3), IL-7, tumor necrosis factor-α, transforming growth factor-ß (TGF-ß) and activin A, as well as MM cell conditioned media. The enforced expression of Pim-2 abrogated in vitro osteoblastogenesis by BMP-2, which suggested Pim-2 as a negative regulator for osteoblastogenesis. Treatment with Pim-2 short-interference RNA as well as the Pim inhibitor SMI-16a successfully restored osteoblastogenesis suppressed by all the above inhibitory factors and MM cells. The SMI-16a treatment potentiated BMP-2-mediated anabolic signaling while suppressing TGF-ß signaling. Furthermore, treatment with the newly synthesized thiazolidine-2,4-dione congener, 12a-OH, as well as its prototypic SMI-16a effectively prevented bone destruction while suppressing MM tumor growth in MM animal models. Thus, Pim-2 may have a pivotal role in tumor progression and bone loss in MM, and Pim-2 inhibition may become an important therapeutic strategy to target the MM cell-bone marrow interaction.

The effects of dexmedetomidine on inflammatory mediators after cardiopulmonary bypass.

Cardiac surgery with cardiopulmonary bypass is associated with the development of a systemic inflammatory response that can often lead to dysfunction of major organs. We hypothesised that the highly selective α2-adrenergic agonist, dexmedetomidine, attenuates the systemic inflammatory response. Forty-two patients were randomly assigned to receive dexmedetomidine or saline after aortic cross-clamping). The mean (SD) levels of the nuclear protein plasma high-mobility group box 1 increased significantly from 5.1 (2.2) ng ml(-1) during (16.6 (7.3) ng ml(-1) ) and after (14.3 (8.2) ng ml(-1) ) cardiopulmonary bypass in the saline group. In the dexmedetomidine group, the levels increased significantly only during cardiopulmonary bypass (4.0 (1.9) ng ml(-1) baseline vs. 10.8 (2.7) ng ml(-1) ) but not after (7.4 (3.8) ng ml(-1) ). Dexmedetomidine infusion also suppressed the rise in mean (SD) interleukin-6 levels after cardiopulmonary bypass (a rise of 124.5 (72.0) pg ml(-1) vs. 65.3 (30.9) pg ml(-1)). These suppressive effects of dexmedetomidine might be due to the inhibition of nuclear factor kappa B activation and suggest that intra-operative dexmedetomidine may beneficially inhibit inflammatory responses associated with ischaemia-reperfusion injury during cardiopulmonary bypass.

Endothelin B receptor expression correlates with tumour angiogenesis and prognosis in oesophageal squamous cell carcinoma.

BACKGROUND: The endothelin axis has been shown to have a pivotal role in several human malignancies. The aim of this study was to clarify the clinical importance of endothelin receptor type B (ETBR) in human oesophageal squamous cell carcinoma (OSCC). METHODS: We evaluated ETBR expression in 107 patients with OSCC by immunohistochemistry. Microvessel density (MVD) and lymphatic vessel density were assessed by CD31 and D2-40 immunostaining, respectively. Furthermore, CD4, CD8, and CD45RO+ tumour-infiltrating lymphocytes (TILs) were immunohistochemically analysed. RESULTS: Sixty-one (57%) cases showed high expression of ETBR. Endothelin receptor type B expression was correlated with several clinicopathological factors including tumour differentiation, tumour depth, and lymph node metastasis. The overall and disease-specific survival rates were significantly lower in patients with high ETBR expression than patients with low expression. Furthermore, multivariate analysis revealed that ETBR status was an independent prognostic factor for patient survival. Mechanistic analysis indicated that MVD was significantly higher in tumour tissues with high ETBR expression compared with those with low expression, suggesting that angiogenesis may be a key mechanism in tumour progression and metastasis of OSCC mediated by ETBR expression. By contrast, there were no significant correlations between TILs and ETBR expression. CONCLUSION: Endothelin receptor type B has a pivotal role in oesophageal cancer and may be therapeutic target for this intractable malignancy.

Embryonal rhabdomyosarcoma of the uterus in a 35-year-old woman: case report and review of the literature.

Embryonal rhabdomyosarcoma (RMS) is a rare sarcoma that characteristically occurs in children. The current treatment protocols are based on trials performed in patients under 21 years of age. Embryonal RMS in women over 20 years of age is rare, and studies on treatments and outcomes are limited. The authors here in report a case of a 35-year-old woman with ectocervical RMS who was treated with radical hysterectomy followed by chemotherapy. She is currently disease-free. Based on a literature review, the authors recommend a surgical approach in combination with chemotherapy for treatment of embryonal RMS in adult patients.

Effects of macronutrient intake on thigh muscle mass during home-based walking training in middle-aged and older women.

We examined whether post-exercise macronutrient supplementation during a 5-month home-based interval walking training (IWT) accelerated exercise-induced increases in skeletal muscle mass and strength in healthy middle-aged and older women. Thirty-five women (41-78 years) were randomly divided into two groups: IWT alone (CNT, n = 18) or IWT plus post-exercise macronutrient (7.6 g protein, 32.5 g carbohydrate, and 4.4 g fat) supplementation (NUT, n = 17). For IWT, all subjects were instructed to repeat five or more sets of 3-min low-intensity walking at 40% peak aerobic capacity (Vo2 peak ), followed by a 3-min high-intensity walking above 70% Vo2 peak per day for 4 or more days per week. We determined Vo2 peak , thigh muscle tissue area by computer tomography, and thigh muscle strength in all subjects before and after IWT. We found that an increase in hamstring muscle tissue area was 2.8 ± 1.2% in NUT vs -1.0 ± 0.7% in CNT and that in isometric knee flexion force was 16.3 ± 3.7% in NUT vs 6.5 ± 3.0% in CNT; both were significantly higher in NUT than in CNT (both, P < 0.001). Thus, post-exercise macronutrient supplementation enhanced the increases in thigh muscle mass and strength, although partially, in home-based IWT in middle-aged and older women.

Flotillin-2 deficiency leads to reduced lung metastases in a mouse breast cancer model.

Flotillin microdomains, specialized lipid raft domains in cell membranes, serve as physical platforms for many different molecules important in crucial intracellular signaling pathways. Flotillin-2 (Flot2), together with flotillin-1, is a marker for lipid raft microdomains distinct from caveolar lipid rafts, and has been implicated in the progression of cancer and metastasis formation. Based largely on studies in xenograft models, flotillin-2 has been implicated in the progression of multiple types of human tumors, including breast cancer. In our studies, we identified flotillin-2 as highly amplified in a high-throughput comparative genomic hybridization screen of human breast cancer cell lines and breast tumor samples. Short hairpin RNA-mediated reduction of flotillin-2 protein levels significantly reduced the tumorigenicity and metastatic capability of a human breast cancer cell line in vivo. We generated mice deficient for flotillin-2 and also found a reduction of flotillin-1 protein levels and complete absence of flotillin-specific membrane microdomains in these mice. To examine the role of Flot2 in mammary tumorigenesis and lung metastasis, we used an in vivo molecular genetics approach, crossing a well-characterized transgenic mouse model of breast cancer, the MMTV-PyMT (mouse mammary tumor virus-polyoma middle T antigen) mouse, with gene-targeted Flot2(-/-) mice. Flotillin-2 deficiency lead to a striking reduction in the number of lung metastasis observed, but had no influence on primary tumor formation in this model. Our results indicate, using a novel in vivo animal model approach, that Flot2 is an important regulator of mammary tumor-derived lung metastasis.

Epithelioid sarcoma on the foot masquerading as an intractable wound for > 18 years.

Slow-growing sarcomas may give rise to intractable wounds, which may be attributed to commoner causes. A 57-year-old man with diabetes mellitus presented with a 24-year history of a chronic wound that originated on his left great toe. Because of the long history, the nonspecific histological findings and the complication of ulcerative colitis, we misdiagnosed his ulcer as pyoderma gangrenosum. The wound was eventually diagnosed correctly by histological examination of a skin biopsy and the use of immunohistochemistry to detect cytokeratin, epithelial membrane antigen and vimentin. Specimens obtained 16 years earlier showed the same staining pattern. Radiological examinations revealed no metastasis. The patient received a below-knee amputation without further chemotherapy or radiotherapy. When patients have intractable ulcers, appropriate biopsies and immunohistochemical examinations are sometimes necessary to exclude a malignancy even if the history and symptoms do not suggest a diagnosis of sarcoma.

Branched-chain amino acid supplementation attenuates muscle soreness, muscle damage and inflammation during an intensive training program.

AIM: The aim of this paper was to assess the effects of branched-chain amino acid (BCAA) supplementation on muscle soreness, muscle damage and inflammation during an intensive training program. METHODS: Twelve long-distance runners (20 + or - 1 year-old) participated in a double-blinded crossover designed study conducted during two intensive training periods (three-day). The subjects were provided either a drink containing BCAA (0.8% BCAA in a 3.5% carbohydrate solution; 2,500 mL/day) or an isocaloric placebo drink during each training period. All subjects completed the same training program (total running distance: males: 86 km, females: 64 km), and ate the same meals during the training period. Whole body muscle soreness and fatigue sensation were measured in the morning before and during the training period by Visual Analogue Scale method. Plasma creatine kinase (CK), lactate dehydrogenase (LDH), and granulocyte elastase (GEL) levels were measured as indicators of muscle damage and inflammation before and after the training period. RESULTS: Muscle soreness and fatigue sensation during the training period in the BCAA trial were lower than those in the placebo trial (-32% and -24%, respectively; P<0.05). The plasma CK, LDH, and GEL levels after the training program in the BCAA trial were lower than those in the placebo trial (-21%, -6%, and -15%, respectively; P<0.05). CONCLUSIONS: These results demonstrate that BCAA supplementation during an intensive training program effectively reduces the muscle soreness and fatigue sensation, and that the perceived changes could be attributed to the attenuation of muscle damage and inflammation.

A small-molecule compound targeting CCR5 and CXCR3 prevents airway hyperresponsiveness and inflammation.

Asthma is associated with increased numbers of T-cells in the lung. CC chemokine receptor (CCR)5 and CXC chemokine receptor (CXCR)3 have been reported to play important roles in the lung T-cell homing pathway, and may be potential targets for asthma therapy. The aim of the present study was to investigate the role of CCR5 and CXCR3 in allergen-induced acute asthma and to determine whether a novel small-molecule compound, TAK-779, targeting CCR5 and CXCR3 can attenuate allergic airway responses. Mice were sensitised with ovalbumin (OVA). mRNA expression of chemokine receptors in the lung were measured after the challenge with either aerosolised phosphate-buffered saline or OVA. OVA-sensitised mice were also treated with TAK-779. Respiratory function was measured, bronchoalveolar lavage was performed, and blood and lung samples were obtained. OVA challenge increased CCR3, CCR5 and CXCR3 expression in the lung. Treatment with TAK-779 significantly attenuated altered respiratory function and pulmonary allergic inflammation. The beneficial effect was associated with reduced expression of CCR5 and CXCR3 in the lung. These data demonstrate that blockade of CC chemokine receptor 5 and CXC chemokine receptor 3 using TAK-779, a synthetic nonpeptide compound, can prevent the development of asthma features in a mouse model. Thus, CC chemokine receptor 5 and CXC chemokine receptor 3 may be potential targets for asthma therapy.

Surface discharge of heavy metals from low farmland.

Runoff heavy metals from farmland were examined using the field data for the summer of 2005. The observation farmland is located on lowland where the irrigation water was contaminated with the drained water from the upstream farmlands. The area of the farmland is 11.2 ha, of which 6.0 ha and 4.5 ha have been used for rice paddy fields and soybean cultivation, respectively. During the observation, heavy metal concentrations at the downstream end were usually found to be higher than those in the irrigation water. That is, the heavy metal concentrations increased due to the passage of the water through the farmland. This increase in the heavy metal concentrations is not equal to the discharge of the heavy metal because the evaporation on the surface of the paddy field and the absorption by plants makes the surface water volume small. The discharged load from the farmland generally indicates the gross surface load from the farmland. When the effects of circulation irrigation on the heavy metal concentrations are estimated, the discharged load from the farmland should be calculated as the net surface load. When the runoff heavy metals from the circulation irrigation farmland are estimated, it is important to consider the inflowing heavy metals with irrigation water. All the heavy metal types observed in this study were discharged from the farmland. The net surface loads of Cr, Fe, Cd, and Pb were 371 microg m(-2) day(-1), 14.9 mg m(-2) day(-1), 0.26 microg m(-2) day(-1), and 3.3 microm( -2) day(-1), respectively.