The Energy Required to Synthesize Lean and Adipose Tissue in Rats.

Although the energy stored in lean tissue (LT) and adipose tissue (AT) is well known, the energy required to synthesize these tissues is less clear. While elucidating the energy required for AT synthesis may not be so important, the elucidation of the energy required for LT synthesis is important for individuals who aim to increase their skeletal muscle. Theoretically the energy at the point at which ΔLT/Δbody weight (BW) reaches 100% on a regression curve, which indicates the relationship between ΔLT/ΔBW and the energy used to accumulate body tissue, is considered to be the energy expended to synthesize LT. We therefore investigated the relationship using rats. Rats of different ages, and rats in exercised or sedentary states were used because their ΔLT/ΔBW was expected to be different. ΔLT/ΔBW was higher in the 4-wk-old group than in the 8-wk-old group and higher in the exercise group than in the sedentary group. We found a positive correlation between ΔLT/ΔBW and the energy expended to synthesize tissues that accumulated in the body. This energy was lower in the 8-wk-old group, which had a lower ΔLT/ΔBW in comparison to the 4-wk-old group, but was not affected by exercise. The regression curve revealed that the energy expended to synthesize LT was 2.9 kcal/g, while that expended to synthesize AT was 1.1 kcal/g. Therefore, combined with the energy accumulated to the tissues, the energy required to accumulate LT is approximately 4.0 kcal/g, while that required to accumulate AT is approximately 8.5 kcal/g.

MicroRNA-326 negatively regulates CD155 expression in lung adenocarcinoma.

Treatment with immune checkpoint inhibitors induces a durable response in some patients with non-small-cell lung cancer, but eventually gives rise to drug resistance. Upregulation of CD155 expression is implicated as one mechanism of resistance to programmed death receptor-1 (PD-1)/PD-1 ligand (PD-L1) inhibitors, and it is therefore important to characterize the mechanisms underlying regulation of CD155 expression in tumor cells. The aim of this study was to identify microRNAs (miRNAs) that might regulate CD155 expression at the posttranscriptional level in lung cancer. Comprehensive miRNA screening with target prediction programs and a dual-luciferase reporter assay identified miR-346, miR-328-3p, miR-326, and miR-330-5p as miRNAs that bind to the 3'-UTR of CD155 mRNA. Forced expression of these miRNAs suppressed CD155 expression in lung cancer cell lines. Immunohistochemical staining of CD155 in tissue specimens from 57 patients with lung adenocarcinoma revealed the median tumor proportion score for CD155 to be 68%. The abundance of miR-326 in these specimens with a low level of CD155 expression was significantly greater than in specimens with a high level (p < 0.005). Our results thus suggest that miR-326 negatively regulates CD155 expression in lung adenocarcinoma and might therefore play a role in the development of resistance to PD-1/PD-L1 inhibitors.

Impact of increased plasma levels of calreticulin on prognosis of patients with advanced lung cancer undergoing combination treatment of chemotherapy and immune checkpoint inhibitors.

BACKGROUND: Damage-associated molecular pattern (DAMP)-related immunogenic cell death triggers secondary adaptive immune responses. The relationship between DAMP levels and prognosis in patients with non-small cell lung cancer (NSCLC) who undergo a combination therapy of immune checkpoint inhibitors (ICI) and chemotherapy remains unclear. METHODS: Serial plasma samples were prospectively collected from 45 patients treated with ICI combination therapy for advanced NSCLC. Plasma concentrations of high-mobility group box 1 (HMGB1), calreticulin (CRT), annexin A1, and heat shock protein 70 were measured. Associations between increases in plasma DAMP levels and the efficacy of the ICI combination therapy were evaluated. RESULTS: The maximum fold changes in plasma levels differed across individuals but demonstrated a marked increase, especially for CRT (mean ± SEM, 11.61 ± 46.15). Increased plasma DAMP levels were not clearly associated with clinical responses. There was a significant correlation between the maximum fold change in CRT levels and progression-free survival (PFS; r = 0.49, P < 0.001). Median PFS and overall survival (OS) rates were higher in patients with a ≥ 2-fold increase in plasma CRT levels than in those with a < 2-fold increase (PFS, 14.9 versus 6.0 months, hazard ratio (HR), 0.58; P = 0.17; OS, not reached versus 21.6 months, HR, 0.31, P = 0.02). CONCLUSIONS: Plasma CRT level monitoring has the potential to predict the efficacy of ICI combination therapy and shed light on the mechanisms underlying DAMP-related immunogenic cell death.

Effect of the Energy Intake on the Iron Status of Resistance Exercises Performed in Rats.

In many cases, athletes compensate for nutrient deficiencies due to a reduced dietary intake by taking supplements or other means. However, in what ways nutrients are utilized by the body when it is deficient in energy and yet receives adequate amounts of the required nutrients are unclear. We therefore examined the effect of the balance between available energy and iron intake on the iron nutritional status of athletes. The experiment was conducted in two parts. Four-week-old male rats were divided into two groups based on energy and iron sufficiency: Experiment 1 was energy-sufficient and iron-sufficient (ES-FeS) and energy-sufficient and iron-deficient (ES-FeD). Experiment 2 was energy-deficient and iron-sufficient (ED-FeS) and energy-deficient and iron-deficient (ED-FeD) groups. All rats were made to perform climbing exercises 3 days a week at 5 P.M. The results showed that a significantly higher hematocrit, hemoglobin, plasma iron concentration, and TfS were found in the iron-sufficient group than in the iron-deficient group, TIBC was significantly lower in the iron-sufficient group than in the iron-deficient group, and TfS was significantly higher in the iron-sufficient group than in the iron-deficient group, irrespective of energy intake. It was suggested that restricting both iron and energy intake may significantly decrease the amount of iron in the liver and accelerate the metabolic turnover of red blood cells, while restricting iron intake but providing adequate energy intake suggested that resistance exercise-induced tissue iron repartitioning was not altered by iron sufficiency or deficiency.

Immunostimulatory oncolytic activity of coxsackievirus A11 in human malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is an aggressive solid cancer with a poor prognosis, whereas coxsackievirus A11 (CVA11) is a potential oncolytic virus for cancer treatment. We here investigated the oncolytic activity of CVA11 with human MPM cell lines. CVA11 infection was cytotoxic in all six MPM cell lines examined and showed no or minimal cytotoxicity toward normal human normal cell lines. MPM cells with a higher surface level of intercellular adhesion molecule-1 (ICAM-1) expression tended to be more susceptible to CVA11-induced cytotoxicity, and a neutralizing antibody to ICAM-1 attenuated such cytotoxicity. CVA11 infection activated signaling by Akt and extracellular signal-regulated kinase (ERK) pathways, and inhibitors of such signaling also abrogated CVA11-mediated cytotoxicity. Furthermore, CVA11 infection-triggered multiple modes of tumor cell death including apoptosis, pyroptosis, and necroptosis, and such death was accompanied by the release or exposure of the proinflammatory cytokine interleukin-1ß and damage-associated molecular patterns such as calreticulin, high-mobility group box-1, annexin A1, and heat shock protein 70, which are hallmarks of immunogenic cell death. Notably, in vivo treatment of human MPM xenografts with intratumoral CVA11 injection resulted in significant suppression of tumor growth in SCID mice, and all mice infected with CVA11 showed no significant change in body weight. Our findings collectively suggest that the oncolytic activity of CVA11 for MPM is dependent on ICAM-1 as a virus receptor, as well as on Akt and ERK signaling, and that oncolytic virotherapy with CVA11 is a promising treatment modality with immunostimulatory activity for human MPM.

Investigating COVID-19 News Across Four Nations: A Topic Modeling and Sentiment Analysis Approach.

Newspapers are very important for a society as they inform citizens about the events around them and how they can impact their life. Their importance becomes more crucial and indispensable in the times of health crisis such as the current COVID-19 pandemic. Since the starting of this pandemic newspapers are providing rich information to the public about various issues such as the discovery of a new strain of coronavirus, lockdown and other restrictions, government policies, and information related to the vaccine development for the same. In this scenario, analysis of emergent and widely reported topics/themes/issues and associated sentiments from various countries can help us better understand the COVID-19 pandemic. In our research, the database of more than 100,000 COVID-19 news headlines and articles were analyzed using top2vec (for topic modeling) and RoBERTa (for sentiment classification and analysis). Our topic modeling results highlighted that education, economy, US, and sports are some of the most common and widely reported themes across UK, India, Japan, South Korea. Further, our sentiment classification model achieved 90% validation accuracy and the analysis showed that the worst affected country, i.e. the UK (in our dataset) also has the highest percentage of negative sentiment.

Increased plasma levels of damage-associated molecular patterns during systemic anticancer therapy in patients with advanced lung cancer.

BACKGROUND: Immunogenic cell death (ICD) characterized by the release of damage-associated molecular patterns (DAMPs) from dying cancer cells may contribute to the synergistic antitumor effect of cytotoxic chemotherapy combined with an immune checkpoint inhibitor. The kinetics of circulating DAMP levels in cancer patients have remained largely uncharacterized, however. METHODS: We evaluated the possible effects of various systemic anticancer therapy modalities on the kinetics of plasma DAMP concentrations in a prospective observational study of patients with advanced lung cancer. The plasma concentrations of high-mobility group box 1 (HMGB1), calreticulin (CRT), heat shock protein 70 (HSP70), annexin A1, and histone H3 were thus determined in 121 such patients at four time points during the first cycle of treatment. RESULTS: The mean of the maximum fold change in HMGB1, HSP70, or annexin A1 concentration observed during treatment was significantly greater than the corresponding baseline value (P<0.005). The maximum fold changes in HMGB1 and CRT concentrations tended to be associated with clinical response as evaluated by RECIST criteria, although the changes in the levels of these two DAMPs were not correlated, suggestive of differential induction mechanisms. Among the various treatment modalities administered, platinum-based combination or single-agent chemotherapy tended to elicit robust increases in the concentrations of HMGB1 and CRT. CONCLUSIONS: Serial monitoring of plasma revealed that systemic anticancer therapy increased the circulating levels of HMGB1 and CRT and that these changes tended to be associated with clinical response, suggesting that agents capable of releasing these DAMPs into plasma might induce ICD in advanced lung cancer patients.

Effect of Thoracic Gas Volume Changes on Body Composition Assessed by Air Displacement Plethysmography after Rapid Weight Loss and Regain in Elite Collegiate Wrestlers.

We investigated the effect of rapid weight loss (RWL) and weight regain (WR) on thoracic gas volume (VTG) and body composition assessment using air displacement plethysmography (ADP) in male wrestlers. Eight male elite collegiate wrestlers completed a RWL regimen (6% of body mass) over a 53-h period, which was followed by a 13-h WR period. ADP was used at three time points (baseline (T1), post-RWL (T2) and post-WR (T3)) according to the manufacturer's testing recommendations. The total body water and bone mineral content were estimated using the stable isotope dilution method and dual energy X-ray absorptiometry, respectively, at the same time points. Body composition was assessed with two-component (2C) or four-component (4C) models using either the measured VTG (mVTG) or predicted VTG (pVTG). Measured VTG increased from T1 to T2 (0.36 ± 0.31 L, p < 0.05) and decreased from T2 to T3 (-0.29 ± 0.15 L, p < 0.01). However, the changes in fat mass and fat free mass, which were calculated by both 2C and 4C models, were not significantly different when compared between calculations using mVTG and those using pVTG. Our results indicate that VTG significantly changes during RWL and WR, but both measured and predicted VTG can be used to assess changes in body composition during RWL and WR.

Energy Deficit Required for Rapid Weight Loss in Elite Collegiate Wrestlers.

To determine energy density for rapid weight loss (RWL) of weight-classified sports, eight male elite wrestlers were instructed to lose 6% of body mass (BM) within 53 h. Energy deficit during the RWL was calculated by subtracting total energy expenditure (TEE) determined using the doubly labeled water method (DLW) from energy intake (EI) assessed with diet records. It was also estimated from body composition change estimated with the four-component model (4C) and other conventional methods. BM decreased significantly by 4.7 ± 0.5 kg (6.4 ± 0.5%). Total body water loss was the major component of the BM loss (71.0 ± 7.6%). TEE was 9446 ± 1422 kcal, and EI was 2366 ± 1184 kcal during the RWL of 53-h; therefore, the energy deficit was 7080 ± 1525 kcal. Thus, energy density was 1507 ± 279 kcal/kg ∆BM during the RWL, comparable with values obtained using the 4C, three-component model, dual energy X-ray absorptiometry, and stable isotope dilution. Energy density for RWL of wrestlers is lower than that commonly used (7400 or 7700 kcal/kg ΔBM). Although RWL is not recommended, we propose that commonly practiced extreme energy restriction such as 7400 or 7700 kcal/kg ΔBM during RWL appears to be meaningless.

[Bilateral Internal Carotid Artery Dissection Caused by Elongated Styloid Processes:A Case Report].

We report a case of bilateral internal carotid artery(ICA)dissection associated with bilateral elongated styloid processes(ESPs). A 46-year-old man presented with transient aphasia and left visual disturbance at a business meeting. He complained of a foreign body sensation in his throat during swallowing for two years. Magnetic resonance imaging(MRI)demonstrated fresh small infarcts in the left corona radiata. Magnetic resonance angiography(MRA)revealed string signs bilaterally in the cervical ICAs. The patient was diagnosed with bilateral idiopathic ICA dissection and was treated with ozagrel and clopidogrel. Three-dimensional computed tomographic angiogram(3DCTA)indicated bilateral ESPs and bilateral ICA stenosis. 3DCTA with the patient's head tilting and neck extension revealed that each ICA was compressed by the ipsilateral ESP. A follow-up MRA showed complete normalization of bilateral ICAs after neck rest and anti-platelet therapy, following which, clopidogrel was stopped. The patient wore a soft cervical collar until the operation, to avoid contact between the ESPs and ICAs due to changes in head position. Bilateral ESP resection was performed to prevent recurrence of cerebral ischemic events caused by ICA dissection. The patient was discharged one week after the surgery without any neurological deficit. There was no recurrence of symptoms during the next eight months after the operation.

Silicone impression material foreign body in the middle ear: Two case reports and literature review.

We report two cases of impression material foreign body in the middle ear. The first case had been affected with chronic otitis media. The silicone flowed into the middle ear through a tympanic membrane perforation during the process of making an ear mold. About 4 years and 8 months after, the patient had severe vertigo and deafness. We found bone erosion of the prominence of the lateral semicircular canal and diagnosed labyrinthitis caused by silicone impression material. In the second case silicone flowed into the canal wall down mastoid cavity. Both cases required surgery to remove the foreign body. The clinical courses in such cases are variable and timing of surgery is sometimes difficult. In addition to reporting these two cases, we present here a review of the literature regarding impression material foreign bodies.

Ten-year experience of remote medical education in Asia.

BACKGROUND: Moving images are often essential in medical education, to learn new procedures and advanced skills, but, in the past, high-quality movie transmission was technically much more challenging than transmitting still pictures because of technological limitations and cost. MATERIALS AND METHODS: We established a new system, taking advantage of two advanced technologies, the digital video transport system (DVTS) and the research and education network (REN), which enabled satisfactory telemedicine on a routine basis. RESULTS: Between 2003 and 2013, we organized 360 programs connecting 221 hospitals or facilities in 34 countries in Asia and beyond. The two main areas were endoscopy and surgery, with 113 (31%) and 106 (29%) events, respectively. Teleconferences made up 76% of the total events, with the remaining 24% being live demonstrations. Multiple connections were more popular (63%) than one-to-one connections (37%). With continuous technological development, new high-definition H.323 and Vidyo(®) (Hackensack, NJ) systems were used in 47% and 39% of events in 2011 and 2012, respectively. The evaluation by questionnaires was favorable on image and sound quality as well as programs. CONCLUSIONS: Remote medical education with moving images was well accepted in Asia with changing needs and developing technologies.

Effects of resistance exercise on iron absorption and balance in iron-deficient rats.

We have previously reported that resistance exercise improved the iron status in iron-deficient rats. The current study investigated the mechanisms underlying this exercise-related effect. Male 4-week-old rats were divided into a group sacrificed at the start (week 0) (n = 7), a group maintained sedentary for 6 weeks (S) or a group that performed exercise for 6 weeks (E), and all rats in the latter groups were fed an iron-deficient diet (12 mg iron/kg) for 6 weeks. The rats in the E group performed climbing exercise (5 min × 6 sets/day, 3 days/week). Compared to the week 0 rats, the rats in the S and E groups showed lower tissue iron content, and the hematocrit, hemoglobin, plasma iron, and transferrin saturation values were all low. However, the tissue iron content and blood iron status parameters, and the whole body iron content measured using the whole body homogenates of the rats, did not differ between the S group and the E group. The messenger RNA (mRNA) expression levels of hepcidin, duodenal cytochrome b, divalent metal transporter 1, and ferroportin 1 did not differ between the S group and the E group. The apparent absorption of iron was significantly lower in the E group than in the S group. Therefore, it was concluded that resistance exercise decreases iron absorption, whereas the whole body iron content is not affected, and an increase in iron recycling in the body seems to be responsible for this effect.

Basal metabolic rate and body composition of elite Japanese male athletes.

The estimated energy requirement is important for adequate nutritional management in athletes. The energy requirement can be estimated from the basal metabolic rate (BMR). However, there is little data regarding the BMR of Japanese athletes. This study measured the BMR and body composition of 81 elite Japanese male athletes in different sports categories: endurance (E), strength, power and sprint (S) and ball game (B). The factors influencing the BMR were also investigated. The BMR and body composition were measured by indirect calorimetry and an air-displacement plentysmograph device (the BOD POD), respectively. The BMR per lean body mass (LBM) differed significantly among the three groups. The BMR was significantly correlated with the body weight (BW) and LBM in all groups. A multiple-regression analysis showed that the LBM was the most powerful predictor in the E and S groups, whereas the BW was the most powerful predictor in the B group. The BW appears to become an important predictor as the BW of athletes increases. Additionally, height was the second explanatory variable in the S and B groups, thus suggesting that height needs to be considered for the BMR in these groups. Therefore, the BMR in elite athletes needs to be estimated according to their body composition.

Emerging technologies for telemedicine.

This paper focuses on new technologies that are practically useful for telemedicine. Three representative systems are introduced: a Digital Video Transport System (DVTS), an H.323 compatible videoconferencing system, and Vidyo. Based on some of our experiences, we highlight the advantages and disadvantages of each technology, and point out technologies that are especially targeted at doctors and technicians, so that those interested in using similar technologies can make appropriate choices and achieve their own goals depending on their specific conditions.

The effects of resistance exercise and post-exercise meal timing on the iron status in iron-deficient rats.

Resistance exercise increases heme synthesis in the bone marrow and the hemoglobin in iron-deficient rats. Post-exercise early nutrient provision facilitates skeletal muscle protein synthesis compared to late provision. However, the effects of post-exercise nutrition timing on hemoglobin synthesis are unclear. The current study investigated the effect of post-exercise meal timing on the activity of the key enzyme involved in hemoglobin synthesis, δ-aminolevulinic acid dehydratase (ALAD), in the bone marrow and examined the hemoglobin concentration in iron-deficient rats. Male 4-week-old Sprague-Dawley rats were fed an iron-deficient diet containing 12 mg iron/kg and performed climbing exercise (5 min × 6 sets/day, 3 days/week) for 3 weeks. The rats were divided into a group fed a post-exercise meal early after exercise (E) or a group fed the meal 4 h after exercise (L). A single bout of exercise performed after the 3-week training period increased the bone marrow ALAD activity, plasma iron concentration, and transferrin saturation. Although the plasma iron concentration and transferrin saturation were lower in the E group than the L group after a single bout of exercise, the basal hematocrit, hemoglobin, and TIBC after 3 weeks did not differ between the groups. Therefore, resistance exercise increases the bone marrow ALAD activity, while the post-exercise meal timing has no effect on the hemoglobin concentration in iron-deficient rats.

Live surgery and teleconferencing at the 19th World Congress of the International Association of Surgeons, Gastroenterologists and Oncologists (IASGO) in Beijing.

Advanced technologies were introduced for the first time at the 19th World Congress of the Inter-national Association of Surgeons, Gastroenterologists and-Oncologists (IASGO) in Beijing, China. Live surgery and multi-station teleconferencing were performed using the super high-speed inter-net to transmit and preserve the high quality life- like images of surgical operations. This is the first time in the history of IASGO that use has been made of this worldwide academic network and user friendly digital video transport system, which has many advantages over traditional telemedicine systems. Here we briefly report these epoch-making sessions and their future expectations

The SI strain of measles virus derived from a patient with subacute sclerosing panencephalitis possesses typical genome alterations and unique amino acid changes that modulate receptor specificity and reduce membrane fusion activity.

Subacute sclerosing panencephalitis (SSPE) is a fatal sequela associated with measles and is caused by persistent infection of the brain with measles virus (MV). The SI strain was isolated in 1976 from a patient with SSPE and shows neurovirulence in animals. Genome nucleotide sequence analyses showed that the SI strain genome possesses typical genome alterations for SSPE-derived strains, namely, accumulated amino acid substitutions in the M protein and cytoplasmic tail truncation of the F protein. Through the establishment of an efficient reverse genetics system, a recombinant SI strain expressing a green fluorescent protein (rSI-AcGFP) was generated. The infection of various cell types with rSI-AcGFP was evaluated by fluorescence microscopy. rSI-AcGFP exhibited limited syncytium-forming activity and spread poorly in cells. Analyses using a recombinant MV possessing a chimeric genome between those of the SI strain and a wild-type MV strain indicated that the membrane-associated protein genes (M, F, and H) were responsible for the altered growth phenotype of the SI strain. Functional analyses of viral glycoproteins showed that the F protein of the SI strain exhibited reduced fusion activity because of an E300G substitution and that the H protein of the SI strain used CD46 efficiently but used the original MV receptors on immune and epithelial cells poorly because of L482F, S546G, and F555L substitutions. The data obtained in the present study provide a new platform for analyses of SSPE-derived strains as well as a clear example of an SSPE-derived strain that exhibits altered receptor specificity and limited fusion activity.