Establishment of a post-disaster healthcare information booklet for the Turkey-Syrian earthquake, based on past disasters.

The scientific evidence based on experiences with past disasters points to the possibility of the occurrence of future mental health issues among those who were affected by the recent Turkey-Syria earthquake. However, post-disaster care information on factors that could give rise to mental health issues among those affected have yet to be provided. In March 2011, Tohoku University compiled and published a booklet with post-disaster healthcare information based on the experiences with the Great East Japan Earthquake. This study aimed to promote the introduction and use of this booklet for post-disaster care in Turkey and Syria by presenting the results of a satisfaction survey conducted with relevant Japanese organizations about the booklet. A total of 505 Japanese organizations participated in the satisfaction survey of, and evaluated, the booklet. The results indicated the need to consider the ease of understanding for the general public when providing information on post-disaster care through booklets. We hope that this study leads to the appropriate provision of easy-to-understand, post-disaster healthcare information to the victims of the Turkey-Syria earthquake and future disasters.

Effects of body postures on respiratory muscle force and coughing in healthy people.

The respiratory muscle force determines the intensity of cough force. A greater cough force for cleaning the airways is essential for preventing and managing pneumonia. Body posture can affect the onset of aspiration pneumonia. However, the effects of body posture on the respiratory muscle and cough forces remain unclear. Thus, we aimed to explore the influence of the four body postures on respiratory muscle force, cough pressure, subjective ease of coughing, and pulmonary function in healthy individuals. Twenty healthy individuals were included in this study. Body postures were 0-degree supine, 30- and 60-degree semi-recumbent, and 90-degree sitting. The maximal inspiratory and expiratory pressures, maximal cough pressure, subjective ease of coughing, and pulmonary function, including peak expiratory flow, were evaluated. We set the measured values in the supine posture to 100% and showed the relative values. The 60-degree posture showed stronger inspiratory (125.1 ± 3.9%, mean ± standard error [SE]) and expiratory (116.4 ± 3.0%) muscle force, cough pressure, more subjective ease of coughing, and greater peak expiratory flow (113.4 ± 3.0%) than the supine posture. The sitting posture also showed greater inspiratory muscle force and peak expiratory flow than the supine posture. The correlation coefficient for the 60-degree posture showed that the maximal inspiratory pressure was moderately correlated with the maximal expiratory pressure (r = 0.512), cough pressure (r = 0.495), and peak expiratory flow (r = 0.558). The above findings suggest the advantage of keeping a 60-degree posture and avoiding the supine posture to generate a greater cough force in the prevention and management of pneumonia.

Geriatric Nutritional Risk Index Predicts High Activities of Daily Living at Discharge in Older Patients with Heart Failure after Cardiac Rehabilitation.

BACKGROUND: Hospitalization often leads to a decline in activities of daily living (ADL) in older patients with heart failure. Although cardiac rehabilitation (CR) improves ADL, it can be difficult to perform CR due to the deconditioning of these patients. This study aimed to examine the factors associated with ADL at discharge in older patients with heart failure who underwent CR. METHODS: A total of 86 of 110 older heart failure patients aged ≥ 75 years (average age, 86.9 ± 5.7 years) transferred to our institution for CR were enrolled and classified into high ADL at discharge (n = 54) and low ADL at discharge (n = 32) groups. Physical characteristics, comorbidities, medications, blood test data, echocardiographic data, and nutritional status (Geriatric Nutritional Risk Index [GNRI]) were retrospectively examined from medical records. ADL were assessed using the Barthel Index (BI) at admission and discharge. Considering multicollinearity, the relationship between high ADL (BI ≥ 60) at discharge and these assessments at admission was analyzed using multiple logistic regression analysis. The receiver operating characteristic curve was analyzed to calculate the cutoff values for the parameters identified by the multiple logistic regression analysis. RESULTS: The GNRI was the only independent factor predicting high ADL at discharge (p = 0.041; odds ratio [OR], 1.125; 95% confidence interval [CI], 1.005-1.260). The area under the receiver operating characteristic curve for the GNRI was 0.770 (95% CI, 0.664-0.876). The cutoff value for the GNRI was 83.4 (sensitivity, 85.2%; specificity, 62.5%). CONCLUSION: These findings suggest that the GNRI score at admission predicts high ADL at discharge in older patients with heart failure who underwent CR.

Importance of Skeletal Muscle and Interdisciplinary Team Approach in Managing Pneumonia in Older People.

Pneumonia is the most frequent lower respiratory tract disease and a major cause of morbidity and mortality globally [...].

Impacts of body positions on the geniohyoid muscle contraction and swallowing difficulty in healthy adults.

BACKGROUND: Body positions affect swallowing and gastroesophageal reflux. Swallowing impairment is one of the main causes of aspiration pneumonia. To prevent pneumonia, evaluation of body positions on gastroesophageal reflux recommended 30 degrees or higher semi-recumbent positions. The geniohypoid muscle and tongue play central roles in swallowing. However, the effects of body positions on contracting rates in the geniohyoid muscle and tongue pressure are unclear. Moreover, correlations between geniohyoid muscle contracting rates and subjective swallowing difficulties are unclear. AIMS: This study aimed to identify the proper body positions on contracting rates in the geniohyoid muscle, tongue pressure, and subjective swallowing difficulties. MATERIALS & METHODS: Twenty healthy adults swallowed 15- or 50 ml of water at 90 degrees sitting, 60- and 30 degrees semi-recumbent, and 0 degrees supine positions. We scored the subjective swallowing difficulties and measured the tongue pressure and the number of swallows. An ultrasound evaluated the geniohyoid muscle size and contracting rates. RESULTS: At sitting and 60 degrees semi-recumbent positions, the geniohyoid muscle showed greter contracting rates than at 30 degrees semi-recumbent and supine postions (P < 0.05), which resulted in easier swalloiwng. Greater tongue pressure was weakly correlated with fewer swallows (r = -0.339, P = 0.002), whereas the body positions did not affect. CONCLUSION: Considering swallowing and gastroesophageal reflux together, a trunk angle of 60 degrees or more might be beneficial for reducing the risk of aspiration.

Anatomy and function of the lymphatic vessels in the parietal pleura and their plasticity under inflammation in mice.

Inflammatory pleuritis often causes pleural effusions, which are drained through lymphatic vessels (lymphatics) in the parietal pleura. The distribution of button- and zipper-like endothelial junctions can identify the subtypes of lymphatics, the initial, pre-collecting, and collecting lymphatics. Vascular endothelial growth factor receptor (VEGFR)-3 and its ligands VEGF-C/D are crucial lymphangiogenic factors. Currently, in the pleura covering the chest walls, the anatomy of the lymphatics and connecting networks of blood vessels are incompletely understood. Moreover, their pathological and functional plasticity under inflammation and the effects of VEGFR inhibition are unclear. This study aimed to learn the above-unanswered questions and immunostained mouse chest walls as whole-mount specimens. Confocal microscopic images and their 3-dimensional reconstruction analyzed the vasculatures. Repeated intra-pleural cavity lipopolysaccharide challenge induced pleuritis, which was also treated with VEGFR inhibition. Levels of vascular-related factors were evaluated by quantitative real-time polymerase chain reaction. We observed the initial lymphatics in the intercostals, collecting lymphatics under the ribs, and pre-collecting lymphatics connecting both. Arteries branched into capillaries and gathered into veins from the cranial to the caudal side. Lymphatics and blood vessels were in different layers with an adjacent distribution of the lymphatic layer to the pleural cavity. Inflammatory pleuritis elevated expression levels of VEGF-C/D and angiopoietin-2, induced lymphangiogenesis and blood vessel remodeling, and disorganized the lymphatic structures and subtypes. The disorganized lymphatics showed large sheet-like structures with many branches and holes inside. Such lymphatics were abundant in zipper-like endothelial junctions with some button-like junctions. The blood vessels were tortuous and had various diameters and complex networks. Stratified layers of lymphatics and blood vessels were disorganized, with impaired drainage function. VEGFR inhibition partially maintained their structures and drainage function. These findings demonstrate anatomy and pathological changes of the vasculatures in the parietal pleura and their potential as a novel therapeutic target.

Association between Low Forced Vital Capacity and High Pneumonia Mortality, and Impact of Muscle Power.

Impaired % predicted value forced vital capacity (% FVC) is related to higher all-cause mortality in aged adults, and strong muscle force may improve this relationship. A muscle disease, sarcopenia, causes higher mortality. We aimed to identify the unknown disease that relates impaired % FVC with higher mortality in aged adults among the three major leading causes of death, and the effect of strong leg force on this relationship. Cox proportional hazard model analyzed the longitudinal Tsurugaya cohort that registered 1048 aged Japanese for 11 years. The primary outcome was the relationship between % FVC and mortality by cancer, cardiovascular disease, or pneumonia. Exposure variables were % FVC or leg force divided by 80% or median values, respectively. The secondary outcome was the effects of leg force on the relationship. Among the diseases, % FVC < 80% was related only to higher pneumonia mortality (hazard ratio [HR], 4.09; 95% CI, 1.90-8.83) relative to the % FVC ≥ 80% group before adjustment. Adding the leg force as an explanatory variable reduced the HR to 3.34 (1.54-7.25). Weak leg force might indicate sarcopenia, and its prevention may improve higher pneumonia mortality risk related to impaired % FVC, which we may advise people in clinical settings.

Anatomy and pathology of lymphatic vessels under physiological and inflammatory conditions in the mouse diaphragm.

The lymphatic vessels in the parietal pleura drain fluids. Impaired drainage function and excessive fluid entry in the pleural cavity accumulate effusion. The rat diaphragmatic lymphatics drain fluids from the pleura to the muscle layer. Lymphatic subtypes are characterized by the major distribution of discontinuous button-like endothelial junctions (buttons) in initial lymphatics and continuous zipper-like junctions (zippers) in the collecting lymphatics. Inflammation replaced buttons with zippers in tracheal lymphatics. In the mouse diaphragm, the structural relationship between the lymphatics and blood vessels, the presence of lymphatics in the muscle layer, and the distributions of initial and collecting lymphatics are unclear. Moreover, the endothelial junctional alterations and effects of vascular endothelial growth factor receptor (VEGFR) inhibition under pleural inflammation are unclear. We subjected the whole-mount mouse diaphragms to immunohistochemistry. The lymphatics and blood vessels were distributed in different layers of the pleural membrane. Major lymphatic subtypes were initial lymphatics in the pleura and collecting lymphatics in the muscle layer. Chronic pleural inflammation disorganized the stratified layers of the lymphatics and blood vessels and replaced buttons with zippers in the pleural lymphatics, which impaired drainage function. VEGFR inhibition under inflammation maintained the vascular structures and drainage function. In addition, VEGFR inhibition maintained the lymphatic endothelial junctions and reduced the blood vessel permeability under inflammation. These findings may provide new targets for managing pleural effusions caused by inflammation, such as pleuritis and empyema, which are common pneumonia comorbidities.

High Mortality in an Older Japanese Population with Low Forced Vital Capacity and Gender-Dependent Potential Impact of Muscle Strength: Longitudinal Cohort Study.

Generally, weak muscle power is associated with high mortality. We aimed to evaluate the unknown association between % predicted value forced vital capacity (FVC% predicted) and mortality in asymptomatic older people, and the impact of muscle power on this association. We analyzed the Tsurugaya cohort that enrolled Japanese people aged ≥70 for 15 years with Cox proportional hazards model. Exposure variables were FVC% predicted and leg power. The outcome was all-cause mortality. The subjects were divided into quartiles by FVC% predicted or leg power, or into two groups by 80% for FVC% predicted or by the strongest 25% for leg power. Across 985 subjects, 262 died. The males with lower FVC% predicted exhibited higher mortality risks. The hazard ratio (HR) was 2.03 (95% CI 1.30−3.18) at the lowest relative to the highest groups. The addition of leg power reduced the HR to 1.78 (95% CI 1.12−2.80). In females, FVC% predicted under 80% was a risk factor and the HR was 1.67 (95% CI 1.05−2.64) without the effect of leg power. In FVC% predicted <80% males HRs were 2.44 (95% CI 1.48−4.02) in weak and 1.38 (95% CI 0.52−3.64) in strong leg power males, relative to ≥80% and strong leg power males. Low FVC% predicted was associated with high mortality with potential unfavorable effects of weak leg power in males.

Frequent Onsets of Cellulitis in Lower Limbs with Lymphedema Following COVID-19 mRNA Vaccination.

Four patients with secondary lower limb lymphedema developed cellulitis at their lymphedema lesion following COVID-19 mRNA vaccinations. They did not develop adverse effects at their vaccination site. All the patients were Japanese females aged <60 years. Three patients developed cellulitis following the first vaccination. The date of onset of cellulitis following the first vaccination varied from 0 to 21 days. Two received BNT162b2 mRNA vaccines and the others received mRNA-1273 vaccines. All the patients were treated with oral antibiotics and recovered. Two patients had repeated cellulitis. The patients with the repeated development of cellulitis could not perform good skincare. One patient had joint contractures in their lower limbs and could not reach her lymphedema lesions, and the other patient could not master the skincare. According to previous studies, the development of cellulitis following vaccination was rare. In this study, four patients aged <60 years developed cellulitis among the eight patients that regularly visited our hospital for rehabilitation for their lower limb lymphedema. In patients with lymphedema, prolonged inflammation may impair lymphatic functions and worsen edema. Therefore, at the time of vaccination, we should keep in mind the prevention and immediate management of cellulitis using intensive skincare and antibiotic treatment.

Characteristics of aspiration pneumonia patients in acute care hospitals: A multicenter, retrospective survey in Northern Japan.

BACKGROUND: Pneumonia is a common cause of illness and death of the elderly in Japan. Its prevalence is escalating globally with the aging of population. To describe the latest trends in pneumonia hospitalizations, especially aspiration pneumonia (AP) cases, we assessed the clinical records of pneumonia patients admitted to core acute care hospitals in Miyagi prefecture, Japan. METHODS: A retrospective multi-institutional joint research was conducted for hospitalized pneumonia patients aged ≥20 years from January 2019 to December 2019. Clinical data of patients were collected from the medical records of eight acute care hospitals. RESULTS: Out of the 1,800 patients included in this study, 79% of the hospitalized pneumonia patients were aged above 70 years. The most common age group was in the 80s. The ratio of AP to total pneumonia cases increased with age, and 692 out of 1,800 patients had AP. In univariate analysis, these patients had significantly older ages, lower body mass index (BMI), a lower ratio of normal diet intake and homestay before hospitalization, along with more AP recurrences and comorbidities. During hospitalization, AP patients had extended fasting periods, more swallowing assessments and interventions, longer hospitalization, and higher in-hospital mortality rate than non-AP patients. A total of 7% and 2% AP patients underwent video endoscopy and video fluorography respectively. In multivariate analysis, lower BMI, lower C-reactive protein, a lower ratio of homestay before hospitalization, a higher complication rate of cerebrovascular disease, dementia, and neuromuscular disease were noted as a characteristic of AP patients. Swallowing interventions were performed for 51% of the AP patients who had been hospitalized for more than two weeks. In univariate analysis, swallowing intervention improved in-hospital mortality. Lower AP recurrence before hospitalization and a lower ratio of homestay before hospitalization were indicated as characteristics of AP patients of the swallowing intervention group from multivariate analysis. Change in dietary pattern from normal to modified diet was observed more frequently in the swallowing intervention group. CONCLUSION: AP accounts for 38.4% of all pneumonia cases in acute care hospitals in Northern Japan. The use of swallowing evaluations and interventions, which may reduce the risk of dysphagia and may associate with lowering mortality in AP patients, is still not widespread.

Respiratory Muscle Weakness as a Risk Factor for Pneumonia in Older People.

INTRODUCTION: The respiratory muscle strength regulates the effectiveness of coughing, which clears the airways and protects people from pneumonia. Sarcopenia is an aging-related loss of muscle mass and function, the worsening of which is associated with malnutrition. The loss of respiratory and swallowing muscle strength occurs with aging, but its effect on pneumonia is unclear. This study aimed to determine the risks of respiratory muscle weakness on the onset and relapse of pneumonia in older people in conjunction with other muscle-related factors such as malnutrition. METHODS: We conducted a longitudinal study with 47 pneumonia inpatients and 35 non-pneumonia controls aged 70 years and older. We evaluated the strength of respiratory and swallowing muscles, muscle mass, and malnutrition (assessed by serum albumin levels and somatic fat) during admission and confirmed pneumonia relapse within 6 months. The maximal inspiratory and expiratory pressures determined the respiratory muscle strength. Swallowing muscle strength was evaluated by tongue pressure. Bioelectrical impedance analysis was used to evaluate the muscle and fat mass. RESULTS: The respiratory muscle strength, body trunk muscle mass, serum albumin level, somatic fat mass, and tongue pressure were significantly lower in pneumonia patients than in controls. Risk factors for the onset of pneumonia were low inspiratory respiratory muscle strength (odds ratio [OR], 6.85; 95% confidence interval [CI], 1.56-30.11), low body trunk muscle mass divided by height2 (OR, 6.86; 95% CI, 1.49-31.65), and low serum albumin level (OR, 5.46; 95% CI, 1.51-19.79). For the relapse of pneumonia, low somatic fat mass divided by height2 was a risk factor (OR, 20.10; 95% CI, 2.10-192.42). DISCUSSION/CONCLUSIONS: Respiratory muscle weakness, lower body trunk muscle mass, and malnutrition were risk factors for the onset of pneumonia in older people. For the relapse of pneumonia, malnutrition was a risk factor.

Questionnaire survey on pharyngolaryngeal sensation evaluation regarding dysphagia in Japan.

OBJECTIVE: The objective is to conduct a questionnaire survey regarding pharyngolaryngeal sensation evaluation in dysphagia to understand the current situation in Japan. METHOD: The questionnaire was sent to the councilor of the Society of Swallowing and Dysphagia of Japan and the Japanese Society of Dysphagia Rehabilitation-Certified Clinician. The prospective questionnaire survey included the questions listed below: Q1: What do you think of the importance of pharyngolaryngeal sensory evaluation? Q2: Select one of the essential swallowing sensations. Q3: Select one of the following regarding the frequency of sensory examination of the larynx. Q4: Select the proportion of cases the sensory test results affect. Q5: As a pharyngolaryngeal sensory evaluation method in swallowing function evaluation, please fill in the table below for the frequency, difficulty, and effectiveness of the following tests, such as gag reflex, touching the larynx by endoscopy, touching the larynx by the probe with endoscopy, cough reflex test, swallowing provocation test. RESULTS: The essential swallowing sensations of mechanical stimulation, chemical stimulation, thermal stimulation were 84.9%, 5.4%, and 9.7%, respectively. The frequency of touching the larynx by endoscopy in the otolaryngology group and cough reflex test in dentistry was significantly higher than the other groups (p < 0.05). The correlation between the frequency and difficulty or effectiveness of the sensory tests indicated that the frequency and difficulty are significantly correlated between each item. CONCLUSION: Our results aid in increasing understanding and selection of pharyngolaryngeal sensation evaluation for dysphagia patients.

Association between sarcopenia and pneumonia in older people.

Pneumonia is a major cause of death in older people, and the number of such deaths is increasing. Present guidelines for pneumonia management are based on a pathogen-oriented strategy that relies on the optimal application of antibiotics. Older pneumonia inpatients show the high incidence of aspiration pneumonia. The main cause of aspiration pneumonia is an impairment in the swallowing and cough reflexes. These facts suggest a limitation of present management strategies and a requirement for new strategies for aspiration pneumonia. Sarcopenia is the loss of muscle strength and mass, and declining physical function with aging. Recently, a decrease in the mass or strength of the swallowing muscles was suggested to be associated with reduced swallowing function. Accordingly, dysphagia caused by sarcopenia of the systemic and swallowing-related muscles was named sarcopenic dysphagia. Presently, few studies have shown associations between aspiration pneumonia and sarcopenic dysphagia. As for the cough reflex, strong cough prevents aspiration pneumonia, and its strength is regulated by respiratory muscles. A few studies have reported a relationship between muscles and pneumonia in older people. Sarcopenia is a risk factor for pneumonia in older people, and aspiration pneumonia inpatients with low muscle mass show high mortality rates. Aspiration pneumonia induced muscle atrophy in respiratory, swallowing, and skeletal muscles in an animal model and humans. Associations between respiratory muscle strength and pneumonia are currently under investigation. Evaluation and management of sarcopenia could potentially become a new strategy to prevent and treat pneumonia in older patients, and research has only recently been launched. Geriatr Gerontol Int 2020; 20: 7-13.

Axl kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas.

Axl receptor tyrosine kinase is involved in the growth and metastasis and is an indicator of poor prognosis in several cancers including lung cancers. Although a mitogen-activated protein kinase (MAPK) pathway and an epithelial-to-mesenchymal transition (EMT) program are critical, molecular mechanisms underlying the Axl-driven cancer progression have not been fully elucidated. We aimed to identify molecules up-regulated by Axl kinase in lung adenocarcinomas. Through the global gene expression analysis and the functional annotation clustering, we found that AXL expression positively correlated with mRNA expressions of immune checkpoint molecules and chemokine receptors in non-small-cell lung cancers. Validation cohorts including our biobank confirmed that the AXL expression significantly correlated with expression of genes encoding programmed death-ligand1 (PD-L1) and CXC chemokine receptor 6 (CXCR6) in lung adenocarcinoma, especially in epidermal growth factor receptor (EGFR) mutation-positive adenocarcinoma. Pharmacological inhibition of Axl kinase activity decreased mRNA expressions of PD-L1 and CXCR6 in EGFR mutation-positive cell lines. Our data indicates the novel role of Axl kinase as a driver of immune checkpoint molecules and chemokine signalling pathways in the progression of lung adenocarcinomas. This study also highlights the necessity of clinical trials in order to test the efficacy of Axl kinase inhibition in the Axl-highly expressing subset of lung adenocarcinomas. .

Beneficial effects of sunitinib on tumor microenvironment and immunotherapy targeting death receptor5.

Tumor-associated blood vessels and lymphatics are abnormal and dysfunctional. These are hallmarks of the tumor microenvironment, which has an immunosuppressive nature, such as through hypoxia. Treatment with anti-death receptor5 (DR5) monoclonal antibody MD5-1, which induces tumor cell death, is a potent anti-tumor immunotherapy. Generally, MD5-1 induces cell death mainly via antigen presenting cells (APCs) and generates tumor-specific effector T cells. To date, the effects of a simultaneous functional improvement of abnormal blood vessels and lymphatics on the immune microenvironment are largely unknown. A combination therapy using sunitinib, vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor inhibitor, and MD5-1 substantially inhibited tumor growth. Sunitinib improved pericyte coverage on endothelial cells and the expression levels of regulator of G-protein signaling 5, suggesting blood vessel normalization. Sunitinib also increased lymph flow from tumors to central lymph nodes, suggesting improved lymphatic function. In concordance with improved vasculature functions, sunitinib alleviated the tumor hypoxia, suggesting an improved tumor microenvironment. Indeed, the combination therapy induced strong activation of CD8+ T cells and dendritic cells in draining lymph nodes. The combination therapy reduced the ratio of immune-suppressive T regulatory cells in the tumors and draining lymph nodes. The combination therapy enhanced the numbers and activation of tumor-infiltrating CD8+ T cells. CD4 and/or CD8 depletion, or APC inhibiting experiments showed the contribution of CD8+ T cells and APCs to the combination therapy. These findings suggest that targeting blood vessels and lymphatics may have potential benefits for immunotherapy mediated by CD8+ T cells and APCs.

Ultrasonography to detect age-related changes in swallowing muscles.

PURPOSE: Sarcopenia of swallowing muscles is a potential cause of dysphagia. We investigated age-related changes in mass and quality of swallowing muscles by ultrasonography as a non-invasive and convenient examination in subjects without dysphagia. METHODS: A total of 104 subjects (34 males, 70 females) participated in this study. Age, physical status, and mass and strength of skeletal and swallowing muscles were investigated. Ultrasonography was performed to measure cross-sectional area and brightness of the geniohyoid muscle as a swallowing muscle. Calf circumference was measured to evaluate skeletal muscle mass. Hand grip strength was measured to evaluate skeletal muscle strength. Subjects were divided into two groups: young (< 65 years old) and old (≥ 65 years old). We performed univariate and multivariate analyses to analyze the differences between the groups. RESULTS: The number of subjects in the young group was 35, and 69 in the old group. The mean ± SD of measurements in each group was as follows (young/old): age, 35.4 ± 13.9/74.5 ± 5.5 years old; calf circumference, 37.4 ± 4.1/33.9 ± 2.7 cm (p < 0.001); hand grip strength, 35.6 ± 10.2/25.8 ± 7.6 kg (p < 0.001); cross-sectional area of geniohyoid muscle, 229.5 ± 52.2/174.1 ± 40.7 mm2 (p < 0.001); and brightness of geniohyoid muscle, 46.6 ± 11.1/59.6 ± 10.8 (p < 0.001). The old group had a significantly smaller geniohyoid muscle area and significantly greater geniohyoid muscle brightness than the young group (p < 0.01). Age and calf circumference were independent explanatory factors for geniohyoid muscle area (p < 0.01). Age and sex were independent explanatory factors for geniohyoid muscle brightness (p < 0.01). CONCLUSIONS: Ultrasonography revealed a smaller area and greater brightness, which suggested smaller mass and greater infiltration of fat, in the geniohyoid muscle in old people than in young people.

TLR7 agonist attenuates acetylcholine-induced, Ca2+ -dependent ionic currents in swine tracheal submucosal gland cells.

NEW FINDINGS: What is the central question of this study? Does Toll-like receptor 7 (TLR7) have any direct effects on Ca2+ -dependent physiological function of tracheal submucosal gland cells? What is the main finding and its importance? TLR7 is co-localized with SERCA2 in tracheal submucosal gland cells and causes a rapid attenuation of acetylcholine (ACh)-induced, Ca2+ -dependent ionic currents through the activation of SERCA2-dependent Ca2+ clearance. TLR7 is abundantly expressed in the airways of both swine and healthy human subjects, but is significantly downregulated in chronic obstructive pulmonary disease (COPD) airways. These findings suggest that a dysfunction of TLR7 in COPD removes the brake on ACh-induced serous secretion during viral infections, resulting in prolonged airway hypersecretion, and that it is one of the triggers of COPD exacerbations. ABSTRACT: Airway surface fluids are mainly secreted from submucosal glands (SMGs) and play important roles in the defence of airways via the activation of mucociliary transport. Toll-like receptor 7 (TLR7) recognizes and eliminates single stranded RNA (ssRNA) viruses through the induction of innate immunity. However, there is no obvious connection between TLR7 and mucus secretion, aside from TLR7 recognizing ssRNA viruses, which are often associated with airway hypersecretion in chronic obstructive pulmonary disease (COPD). Here, we investigated whether TLR7 has any direct effects on the Ca2+ -dependent physiological function of tracheal SMG cells. Patch-clamp analyses revealed that TLR7 ligand inhibited the acetylcholine (ACh)-induced ionic currents in isolated tracheal SMG cells. Intracellular calcium assays and pharmacological analyses revealed that TLR7 attenuated the transient rises in the intracellular calcium concentration evoked by ACh by activating sarco/endoplasmic reticulum Ca2+ -ATPase 2 (SERCA2). Immunofluorescence staining and immunohistochemical staining revealed that TLR7 was co-localized with SERCA2. These findings suggest that the activation of TLR7 during viral infections contributes to the rapid attenuation of ACh-induced ionic currents through an increase in SERCA2-dependent Ca2+ clearance in healthy airway SMG cells. Our study also revealed that TLR7 expression was significantly downregulated in COPD airways. Based on these findings, we speculate that a dysfunction of TLR7 may not only have an adverse effect on the elimination of these viruses but also remove the brake on ACh-induced serous secretion, resulting in prolonged hypersecretion and acting as one of the triggers of COPD exacerbations.

Aspiration pneumonia induces muscle atrophy in the respiratory, skeletal, and swallowing systems.

BACKGROUND: Repetition of the onset of aspiration pneumonia in aged patients is common and causes chronic inflammation. The inflammation induces proinflammatory cytokine production and atrophy in the muscles. The proinflammatory cytokines induce muscle proteolysis by activating calpains and caspase-3, followed by further degradation by the ubiquitin-proteasome system. Autophagy is another pathway of muscle atrophy. However, little is known about the relationship between aspiration pneumonia and muscle. For swallowing muscles, it is not clear whether they produce cytokines. The main objective of this study was to determine whether aspiration pneumonia induces muscle atrophy in the respiratory (the diaphragm), skeletal (the tibialis anterior, TA), and swallowing (the tongue) systems, and their possible mechanisms. METHODS: We employed a mouse aspiration pneumonia model and computed tomography (CT) scans of aged pneumonia patients. To induce aspiration pneumonia, mice were inoculated with low dose pepsin and lipopolysaccharide solution intra-nasally 5 days a week. The diaphragm, TA, and tongue were isolated, and total RNA, proteins, and frozen sections were stored. Quantitative real-time polymerase chain reaction determined the expression levels of proinflammatory cytokines, muscle E3 ubiquitin ligases, and autophagy related genes. Western blot analysis determined the activation of the muscle proteolysis pathway. Frozen sections determined the presence of muscle atrophy. CT scans were used to evaluate the muscle atrophy in aged aspiration pneumonia patients. RESULTS: The aspiration challenge enhanced the expression levels of proinflammatory cytokines in the diaphragm, TA, and tongue. Among muscle proteolysis pathways, the aspiration challenge activated caspase-3 in all the three muscles examined, whereas calpains were activated in the diaphragm and the TA but not in the tongue. Activation of the ubiquitin-proteasome system was detected in all the three muscles examined. The aspiration challenge activated autophagy in the TA and the tongue, whereas weak or little activation was detected in the diaphragm. The aspiration challenge resulted in a greater proportion of smaller myofibers than in controls in the diaphragm, TA, and tongue, suggesting muscle atrophy. CT scans clearly showed that aspiration pneumonia was followed by muscle atrophy in aged patients. CONCLUSIONS: Aspiration pneumonia induced muscle atrophy in the respiratory, skeletal, and swallowing systems in a preclinical animal model and in human patients. Diaphragmatic atrophy may weaken the force of cough to expectorate sputum or mis-swallowed contents. Skeletal muscle atrophy may cause secondary sarcopenia. The atrophy of swallowing muscles may weaken the swallowing function. Thus, muscle atrophy could become a new therapeutic target of aspiration pneumonia.