Sporadic inclusion body myositis-derived myotube culture revealed muscle cell-autonomous expression profiles.

Sporadic inclusion body myositis (sIBM) is a muscle disease in older people and is characterized by inflammatory cell invasion into intact muscle fibers and rimmed vacuoles. The pathomechanism of sIBM is not fully elucidated yet, and controversy exists as to whether sIBM is a primary autoimmune disease or a degenerative muscle disease with secondary inflammation. Previously, we established a method of collecting CD56-positive myoblasts from human skeletal muscle biopsy samples. We hypothesized that the myoblasts derived from these patients are useful to see the cell-autonomous pathomechanism of sIBM. With these resources, myoblasts were differentiated into myotubes, and the expression profiles of cell-autonomous pathology of sIBM were analyzed. Myoblasts from three sIBM cases and six controls were differentiated into myotubes. In the RNA-sequencing analysis of these "myotube" samples, 104 differentially expressed genes (DEGs) were found to be significantly upregulated by more than twofold in sIBM, and 13 DEGs were downregulated by less than twofold. For muscle biopsy samples, a comparative analysis was conducted to determine the extent to which "biopsy" and "myotube" samples differed. Fifty-three DEGs were extracted of which 32 (60%) had opposite directions of expression change (e.g., increased in biopsy vs decreased in myotube). Apolipoprotein E (apoE) and transmembrane protein 8C (TMEM8C or MYMK) were commonly upregulated in muscle biopsies and myotubes from sIBM. ApoE and myogenin protein levels were upregulated in sIBM. Given that enrichment analysis also captured changes in muscle contraction and development, the triggering of muscle atrophy signaling and abnormal muscle differentiation via MYMK or myogenin may be involved in the pathogenesis of sIBM. The presence of DEGs in sIBM suggests that the myotubes formed from sIBM-derived myoblasts revealed the existence of muscle cell-autonomous degeneration in sIBM. The catalog of DEGs will be an important resource for future studies on the pathogenesis of sIBM focusing on primary muscle degeneration.

Thoracic and vertebral deformities in lung transplantation: perioperative complications and long-term prognoses.

BACKGROUND: Lung transplantation (LTx) is a crucial therapeutic strategy for patients suffering from end-stage respiratory diseases, necessitating precise donor-recipient size matching to ensure optimal graft function. While standard allocation protocols rely on predicted lung capacity based on factors such as sex, age, and height, a subset of patients with respiratory diseases presents an additional challenge - thoracic or vertebral deformities. These deformities can complicate accurate volume predictions and may impact the success of lung transplantation. METHODS: In this retrospective cohort study of patients who underwent LTx at Tohoku University Hospital between January 2007 and April 2022, with follow-up until October 2022, the primary objective was to assess the influence of thoracic and vertebral deformities on perioperative complications, emphasizing interventions, such as volume reduction surgery. The secondary objective aimed to identify any noticeable impact on long-term prognoses in recipients with these deformities. RESULTS: Of 129 LTx recipients analyzed, 17.8% exhibited thoracic deformities, characterized by pectus excavatum, while 16.3% had vertebral deformities. Perioperative complications, requiring delayed chest closure, tracheostomy, and volume reduction surgery, were more prevalent in the deformity group. Thoracic deformities were notably associated with the need for volume reduction surgery. However, long-term prognoses did not differ significantly between patients with deformities and those without. Vertebral deformities did not appear to significantly impact perioperative or long-term outcomes. CONCLUSIONS: This study highlights the prevalence of thoracic deformities in LTx recipients, correlating with increased perioperative complications, particularly the potential need for volume reduction surgery. Importantly, these deformities do not exert a significant impact on long-term prognoses. Additionally, patients with vertebral deformities, such as scoliosis and kyphosis, appear to be manageable in the context of LTx.

Gait classification of knee osteoarthritis patients using shoe-embedded internal measurement units sensor.

BACKGROUND: Knee osteoarthritis negatively affects the gait of patients, especially that of elderly people. However, the assessment of wearable sensors in knee osteoarthritis patients has been under-researched. During clinical assessments, patients may change their gait patterns under the placebo effect, whereas wearable sensors can be used in any environment. METHODS: Sixty patients with knee osteoarthritis and 20 control subjects were included in the study. Wearing shoes with an IMU sensor embedded in the insoles, the participants were required to walk along a walkway. The sensor data were collected during the gait. To discriminate between healthy and knee osteoarthritis patients and to classify different subgroups of knee osteoarthritis patients (patients scheduled for surgery vs. patients not scheduled for surgery; bilateral knee osteoarthritis diagnosis vs. unilateral knee osteoarthritis diagnosis), we used a machine learning approach called the support vector machine. A total of 88 features were extracted and used for classification. FINDINGS: The patients vs. healthy participants were classified with 71% accuracy, 85% sensitivity, and 56% specificity. The "patients scheduled for surgery" vs. "patients not scheduled for surgery" were classified with 83% accuracy, 83% sensitivity, and 81% specificity. The bilateral knee osteoarthritis diagnosis vs. unilateral knee osteoarthritis diagnosis was classified with 81% accuracy, 75% sensitivity, and 79% specificity. INTERPRETATION: Gait analysis using wearable sensors and machine learning can discriminate between healthy and knee osteoarthritis patients and classify different subgroups with reasonable accuracy, sensitivity, and specificity. The proposed approach requires no complex gait factors and is not limited to controlled laboratory settings.

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.

Similarities, differences and overlaps between frailty and Parkinson's disease.

Parkinson's disease is a neurodegenerative disorder clinically characterized by bradykinesia, rest tremor, rigidity, and postural and gait disturbances, which are frequently observed in older people. It also shows non-motor symptoms, such as depression, anxiety, cognitive impairment and dementia. The number of patients is gradually increasing worldwide. Aging is a risk factor for the onset of Parkinson's disease, and various physiological effects of aging influence its progression. Frailty is a geriatric syndrome in which the reversible and vulnerable status between robustness and disability is affected by various physiological stressors with aging. Frailty consists of physical, psychological and social aspects. Furthermore, sarcopenia, a syndrome characterized by the loss of muscle mass, strength and function, is also significantly associated with frailty. To maintain the quality of life of older people, frailty, including sarcopenia, should be quickly and appropriately managed. Polypharmacy is an important factor causing the progression of frailty in geriatric syndrome. Although Parkinson's disease and frailty have similar symptoms, and are considered to affect each other, the clinical features and mechanisms of both largely remain unclear. Nevertheless, little literature on the relationship between frailty and Parkinson's disease is currently available. This narrative review aims to clarify the relationships between Parkinson's disease and frailty, not only on the physical, but also on the mental, cognitive, and social aspects and issues regarding polypharmacy in Parkinson's disease explored by previous studies. Geriatr Gerontol Int 2022; 22: 259-270.

Role of preoperative cervical alignment on postoperative dysphagia after occipitocervical fusion.

BACKGROUND: Dysphagia is one of the most serious complications of occipitocervical fusion (OCF). The previous studies have shown that postoperative cervical alignment, documented with occipito (O)-C2 angles, C2-C6 angles, and pharyngeal inlet angles (PIA), impacted the incidence of postoperative dysphagia in patients undergoing OCF. Here, we investigated the relationship of preoperative versus postoperative cervical alignment on the incidence of postoperative dysphagia after OCF. METHODS: We retrospectively reviewed the clinical data/medical charts for 22 patients following OCF (2006- 2019). The O-C2 angles, C2-C6 angles, PIA, and narrowest pharyngeal airway spaces (nPAS) were assessed using plain lateral radiographs of the cervical spine before and after the surgery. The severity of dysphagia was assessed with the functional oral intake scale (FOIS) levels as documented in medical charts; based on this, patients were classified into the nondysphagia (FOIS: 7) versus dysphagia (FOIS: 1-6) groups. RESULTS: Seven patients (35%) experienced dysphagia after OCF surgery. Preoperative PIA and nPAS were smaller in the dysphagia group. Spearman rank correlation showed a positive correlation between preoperative PIA and FOIS and between preoperative nPAS and FOIS. CONCLUSION: This study suggests that preoperative cervical alignment may best predict the incidence of postoperative dysphagia after OCF.

Molecular and Neural Mechanism of Dysphagia Due to Cancer.

Cancer is one of the most common causes of death worldwide. Along with the advances in diagnostic technology achieved through industry-academia partnerships, the survival rate of cancer patients has improved dramatically through treatments that include surgery, radiation therapy, and pharmacotherapy. This has increased the population of cancer "survivors" and made cancer survivorship an important part of life for patients. The senses of taste and smell during swallowing and cachexia play important roles in dysphagia associated with nutritional disorders in cancer patients. Cancerous lesions in the brain can cause dysphagia. Taste and smell disorders that contribute to swallowing can worsen or develop because of pharmacotherapy or radiation therapy; metabolic or central nervous system damage due to cachexia, sarcopenia, or inflammation can also cause dysphagia. As the causes of eating disorders in cancer patients are complex and involve multiple factors, cancer patients require a multifaceted and long-term approach by the medical care team.

Persistence of the Postoperative Change in the Six-minute Walking Distance of Lung Cancer Patients with Chronic Obstructive Pulmonary Disease.

OBJECTIVES: The aim of this prospective follow-up study was to investigate the difference before and after surgery in the six-minute walking distance (6MD) of lung cancer patients with chronic obstructive pulmonary disease (COPD) and to examine the long-term effect of the change in 6MD in the early postoperative period. METHODS: This was a retrospective analysis of 25 COPD patients who underwent lung cancer surgery and perioperative rehabilitation in our department. Assessments of 6WD were carried out preoperatively and at 1, 3, and 6 months postoperatively. The changes in 6MD at 1, 3, and 6 months postoperatively compared with the preoperative value were designated the 1-month Δ6MD, the 3-month Δ6MD, and the 6-month Δ6MD, and the associations between them were investigated. RESULTS: The mean 6MD distance was 412.0±27.3 m (95% confidence interval) preoperatively, 369.0±33.8 m at 1 month, 395.6±32.2 m at 3 months, and 400.0±38.2 m at 6 months, with a significant difference between the preoperative and 1-month values (P<0.01). There were strong correlations between 1-month and 3-month Δ6MDs (r =0.74, P<0.0001) and between 1-month and 6-month Δ6MDs (r =0.88, P<0.0001). CONCLUSIONS: In lung cancer patients with COPD, the 1-month Δ6MD was strongly associated with both the 3-month Δ6MD and the 6-month Δ6MD. These findings suggest that the decrease in exercise tolerance of patients whose 6MD is low at 1 month postoperatively may be prolonged, and such patients may therefore be in greater need of postoperative outpatient rehabilitation.

Appendicular Skeletal Muscle Mass Correlates with Patient-Reported Outcomes and Physical Performance in Patients with Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF), an incurable lung disease of unknown cause, often presents with losses of skeletal muscle mass. IPF requires comprehensive care, but it has not been investigated which skeletal muscle mass index reflects holistic management factors: pulmonary function, patient-reported outcomes (PROs), and physical performance. We compared three representative indices of skeletal muscle mass with holistic management factors in IPF patients. Twenty-seven mild to severe IPF patients (21 male) with the mean age of 76.1 ± 5.9 years were enrolled. The three indices were appendicular skeletal muscle mass index (ASMI), cross-sectional area of pectoralis major (PMCSA), and cross-sectional area of erector spinae muscles (ESMCSA). ASMI is considered as a gold standard for sarcopenia assessment, while PMCSA and ESMCSA are frequently used in IPF. As PROs, we assessed breathlessness with the modified Medical Research Council dyspnea scale (mMRC), symptoms with the chronic obstructive pulmonary disease assessment test (CAT), and health-related quality of life with St. George's Respiratory Questionnaire (SGRQ). For physical performance, peripheral muscle strength and 6-min walk distance (6MWD) were investigated. In this cross-sectional study, ASMI showed the greatest number of significantly correlated indices, such as pulmonary function, peripheral muscle strength, 6MWD, mMRC, and SGRQ. PMCSA showed the next greatest number of correlations, with peripheral muscle strength, 6MWD, and mMRC, whereas ESMCSA showed no significant correlations with any index. Thus, ASMI correlated with both PROs and physical performance, and PMCSA correlated mainly with physical performance. In conclusion, assessing ASMI is helpful for the comprehensive care of patients with IPF.

Role of O-C2 angle in the development of dysphagia in patients with halo-vest fixation.

BACKGROUND: Dysphagia is one of the most serious complications in patients treated with a halo-vest brace. However, the cause of dysphagia development by halo-vest fixation is not yet clear. We therefore investigated the incidence of dysphagia and cervical alignment as well as clinical data from medical charts in patients treated with a halo-vest brace. METHODS: We retrospectively reviewed clinical data from the medical charts of 49 patients who had undergone halo-vest fixation. Occipito (O)-C2 angle, C2-C6 angle, and pharyngeal inlet angle were assessed by lateral plain X-rays of the cervical spine. The impacts of these parameters on incidence and severity of dysphagia were analyzed. RESULTS: Thirteen patients (32%) suffered from dysphagia during halo-vest fixation, and age and length of intensive care unit (ICU) stay were greater in the dysphagia group (p = 0.044 and 0.013, respectively) than in those who did not develop dysphagia. O-C2 angle was smaller in the dysphagia group (p = 0.016). After multivariate logistic analysis, body mass index, ICU stay, and O-C2 angle remained as independent risk factors related to incidence of dysphagia. Spearman rank correlation showed a negative correlation between ICU stay and Food Intake Level Scale (FILS) (p = 0.026), and a positive correlation between O-C2 angle and FILS (p = 0.008). CONCLUSION: This study suggested that O-C2 angle is related to both incidence and severity of dysphagia due to halo-vest fixation.

Alleviation of Dyspnea Sensation by Phototherapy in Healthy Adults.

BACKGROUND: Because both dyspnea and pain have common features from a clinical and physiologic point of view, we hypothesized that stellate ganglion irradiation by using a linear polarized near-infrared ray device, which is often used for pain management, might be applicable for dyspnea relief. To evaluate the use of stellate ganglion irradiation as a novel noninvasive treatment for dyspnea, we investigated the influence of stellate ganglion irradiation on dyspnea. METHODS: Perceptions of dyspnea were examined with or without stellate ganglion irradiation in 28 healthy adults. The sensation of breathing difficulty was induced by a two-way non-rebreathing valves with linear inspiratory resistance (R) of 0, 10, 20, and 30 cm H2O/L/s. Dyspnea was evaluated with the modified Borg scale to determine subjects' discomfort level. Stellate ganglion irradiation was performed by intermittent irradiation near the bilateral stellate ganglion by using a linear polarized near-infrared ray device. RESULTS: There were significant changes from baseline at R = 10 cm H2O/L/s (P = .007), R = 20 cm H2O/L/s (P = .005), and R = 30 cm H2O/L/s (P = .009). For each resistive load, the mean dyspnea sensation score was lower with stellate ganglion irradiation compared with sham irradiation, with significant differences (P = .003 at R = 0 cm H2O/L/s; P < .001 at R = 10, 20, 30 cm H2O/L/s). There was a significantly lower slope of the dyspnea response for the linear regression of the loads and Borg scores in the stellate ganglion irradiation versus sham treatment (P = .003). CONCLUSIONS: Stellate ganglion irradiation significantly alleviated dyspnea induced by an external inspiratory load in healthy adults. Stellate ganglion irradiation might be an option to treat dyspnea in some cases. Further studies in individuals with diverse types of dyspnea and clinical settings are warranted.

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.

Long-acting muscarinic antagonist and long-acting ß2-agonist therapy to optimize chronic obstructive pulmonary disease prior to lung cancer surgery.

Bronchodilators are essential for the perioperative management of patients with chronic obstructive pulmonary disease (COPD) undergoing surgery for lung cancer. The objective of the present study was to examine whether the usage of a long-acting ß2-agonist (LABA) with a long-acting muscarinic antagonist (LAMA) could optimize preoperative lung function and reduce the risk for postoperative pulmonary complications. Thirty-two consecutive patients with moderate-to-severe COPD who underwent a lobectomy for lung cancer and received preoperative LAMA (n=19) or LAMA/LABA (n=13) therapy between January 2005 and December 2015 were enrolled in this retrospective study. The improvement of preoperative pulmonary function and the postoperative morbidity were compared between the patients with preoperative LAMA, and LAMA/LABA therapy. Increases in the forced expiratory volume in one second (FEV1) were significantly larger in the LAMA/LABA group than in the LAMA group (0.26±0.05 l vs. 0.07±0.05 l; P=0.0145). More patients in the LAMA/LABA group than in the LAMA group showed a marked improvement of >10% in %FEV1 after bronchodilators (85 vs. 32%; P=0.0046). The incidence of postoperative pneumonia was significantly lower in the LAMA/LABA group than in the LAMA group (0 vs. 26%; P=0.044). In conclusion, the present study showed that preoperative LAMA/LABA therapy was associated with larger improvements in preoperative pulmonary function and less postoperative pneumonia than LAMA therapy. These results may lead to greater improvements in FEV1 and less postoperative pneumonia by encouraging preoperative LAMA/LABA therapy in this patient population.

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.

[Perioperative Management and Minimally Invasive Pulmonary Resection-early Stage Rehabilitation, Postoperative Early Ambulation].

In chest surgery, minimal invasiveness is an important topic. Video-assisted thoracic surgery and a less radical resection may be effective for decreasing postoperative complications or postoperative mortality rates. Respiratory rehabilitation is useful for preventing postoperative complications, and it is used pre- and postoperatively for patients with lung cancer and chronic obstructive pulmonary disease (COPD) in most hospitals. Although it is well adapted to patients with a lower forced expiratory volume in 1 second, higher stages of COPD, severe emphysematous changes on computed tomography, and performance status ≥2, there are no definitive criteria for rehabilitation. Before initiating respiratory rehabilitation for patients, it is important to evaluate their risk factors, such as sputum production, articular disturbances, or activities. There are many kinds of rehabilitation, but preoperative respiratory rehabilitation is especially effective in inoperable cases to improve respiratory function, to change their status to operable, and to decrease periods of chest-tube drainage or hospital admission. It should be used for minimally invasive chest surgery from now on.

The wish to die among palliative home care clients in Ontario, Canada: A cross-sectional study.

BACKGROUND: In the pursuit to provide the highest quality of person centered palliative care, client preferences, needs, and wishes surrounding end of life should be used to inform the plan of care. During a clinical assessment for care services, clients may voluntarily express a 'wish to die' either directly to the clinician or it may be indirectly reported second-hand to the clinician through an informal caregiver or family member. This is the first study using data gathered from the interRAI Palliative Care Assessment instrument (interRAI PC) to examine socio-demographic, clinical, and psycho-social factors of palliative home care clients with the voluntary expression of a 'wish to die now'. Factors associated with the risk for depression within this group were also identified. Awareness and understanding of clients who express the 'wish to die' is needed to better tailor a person-centered approach to end-of-life care. METHODS: This cross-sectional study included assessment records gathered from 4,840 palliative home care clients collected as part of pilot implementation of the interRAI PC assessment instrument in Ontario, Canada from 2006 through 2011. RESULTS: During the clinical assessment, 308 palliative home care clients (6.7%) had voluntarily expressed a 'wish to die now'. Independent factors emerging from multivariate logistic regression analyses predicting the expression of a 'wish to die' included not being married/widowed, a shorter estimated prognosis, depressive symptoms, functional impairment, too much sleep (excessive amount), feeling completion regarding financial/legal matters, and struggling with the meaning of life. Among persons who expressed a 'wish to die now', those who exhibited depressive symptoms (23.8%, n = 64) were also more likely to exhibit cognitive impairment, have decline in cognition in the last 90 days, exhibit weight loss, have informal caregivers exhibiting distress, 'not have a consistent positive outlook on life' and report 'struggling with the meaning of life'. CONCLUSION: When clients voluntary express a wish to die clinicians should take notice and initiate follow-up to better understand the context of this meaning for the individual. Clients who expressed a 'wish to die' did not all experience pain, depression, and psychological distress suggesting an individualized approach to care management be taken.

Chemical Senses Affecting Cough and Swallowing.

BACKGROUND: Dysfunction of swallowing and coughing leads to life-threatening aspiration pneumonia, especially in the elderly. In order to induce the cough and swallowing reflexes efficiently, sensory inputs to trigger the reflexes are essential. METHODS: Both the cough and swallowing reflexes respond to mechanical and chemical stimuli. However, the mechanisms of action of the two reflexes are not homogeneous. Some substances stimulate both reflexes, but others stimulate one of the reflexes and inhibit the other one. RESULTS: Capsaicin, a TRPV1 agonist, stimulates both the cough and swallowing reflexes. Menthol, a TRPM8 agonist, stimulates the swallowing reflex, but it inhibits the cough reflex, especially if applied to the nose. Acid stimulates the cough reflex but its effect on the swallowing reflex is complicated. Theophylline inhibits the cough reflex by decreasing the excitability of sensory nerves, whereas it stimulates the swallowing reflex by antagonizing adenosine receptors. In smoking, cigarette smoke and nicotine have different effects. Cigarette smoke stimulates the cough reflex, while it inhibits the swallowing reflex. Nicotine inhibits the cough reflex but does not affect the swallowing reflex. CONCLUSION: Whenever you prescribe for an abnormality of one of the reflexes, you should think about the effect of the prescription on the other reflex.

Thermal taste and anti-aspiration drugs: a novel drug discovery against pneumonia.

Despite the development of strong antibiotics, the pneumonia death is increasing all over the world in these decades. Among the people who died of pneumonia, the majority were 65 years old or over. Although pneumonia is recently categorized into several entities, aspiration pneumonia includes all entities. Therefore, targeting dysphagia and aspiration to treat pneumonia is a promising strategy and anti-aspiration drugs will be a part of pneumonia treatment. The swallowing reflex in elderly people was temperature-sensitive and the improvement of swallowing reflex by temperature stimuli could be mediated by the thermosensing TRP channels at pharynx. The administration of capsaicin as an agonist stimulus of TRPV1, a warm temperature receptor, decreased the delay in swallowing reflex. Red wine polyphenols improved swallowing reflex by enhancing TRPV1 response. Food with menthol, agonist of TRPM8 which is a cold temperature receptor, also decreased the delay in swallowing reflex. Olfactory stimulation such as black pepper was useful to improve the swallowing reflex for people with low ADL levels or with decreased consciousness. Thus, recent advancement of geriatrics found several anti-aspiration drugs such as thermosensing TRP channel agonists, black pepper odor, amantadine, cilostazol, theophylline and angiotensin- converting enzymes inhibitors. Thermosensing TRP channel agonists include capsaicin, capsiate, menthol, and red wine polyphenols. Controls of swallowing are mediated by various stages of neural system from peripheral sensory nerves to the entire cerebral cortex. Each anti-aspiration drug acts on various sites of neural axis of swallowing reflex. The combination of various anti-aspiration drugs may improve dysphagia and prevent aspiration pneumonia.

Royal jelly prevents the progression of sarcopenia in aged mice in vivo and in vitro.

Sarcopenia is characterized by the age-related loss of muscle mass and strength. One of the mechanisms of sarcopenia is the loss in the function and number of muscle satellite cells. Royal jelly (RJ) is a health food used worldwide. To obtain better digestion and absorption than RJ, protease-treated RJ (pRJ) has been developed. RJ and pRJ have been suggested to have potential pharmacological benefits such as prolonging the life span and reducing fatigue. Because these effects may improve sarcopenia and the functions of satellite cells, we examined the effects of RJ or pRJ treatment on the skeletal muscles in an animal model using aged mice. In vivo, RJ/pRJ treatment attenuated the decrease in the muscle weight and grip strength and increased the regenerating capacity of injured muscles and the serum insulin-like growth factor-1 levels compared with controls. In vitro, using isolated satellite cells from aged mice, pRJ treatment increased the cell proliferation rate, promoted cell differentiation, and activated Akt intracellular signaling pathway compared with controls. These findings suggest that RJ/pRJ treatment had a beneficial effect on age-related sarcopenia.