[Physiology of the Vagus Nerve: Basic Medical Research from the Past to the Present].

The vagus nerve, which is the 10th cranial nerve, exits from the medulla and distributes widely to the visceral organs. Although it contains the motor, somatic, and sympathetic nerves, the main component is the parasympathetic nerve, which acts as the core of homeostasis. The vagal efferent regulates the cardiac muscle, striated muscle and glands, while the vagal afferent sends the information from the visceral organs to the brain. The vagus nerve is also responsible for the gut-brain axis.

Metabolic indices related to leaf marginal necrosis associated with potassium deficiency in tomato using GC/MS metabolite profiling.

To clarify the physiological factors associated with the development of tomato leaf marginal necrosis associated with potassium deficiency, tomato leaf blades prior to development of the symptoms were collected, and profiles of water-soluble metabolites were analyzed using gas chromatography-mass spectrometry. Multivariate analysis was conducted to screen for a component that was related to potassium deficiency-induced leaf necrosis among the 60 metabolites detected in tomato leaves. Polyamines, sugars, and branched amino acids were ranked highly. Putrescine was most strongly and negatively correlated with potassium concentration and exhibited an exponential response, regardless of the site or plant body. In addition to putrescine, glucose, xylose and l-isoleucine are known to play important roles in stress response and ion balance control, and it is thought that changes in metabolite profiles are linked to tomato leaf marginal necrosis associated with a decrease in endogenous potassium concentration. These findings will be useful for cultivation management to mitigate this physiological disorder of tomato.

Impact of comorbidity and relative dose intensity on outcomes in diffuse large B-cell lymphoma patients treated with R-CHOP.

BACKGROUND: Comorbidity and relative dose intensity (RDI) have been associated with survival in diffuse large B-cell lymphoma (DLBCL) patients, but both relationships remain unaddressed in the same patients. METHODS: A retrospective review of consecutive DLBCL patients treated from January 2010 to October 2018 was performed. Data for the clinical characteristics of the patients, including the Charlson Comorbidity Index (CCI) and RDI, on their outcomes were evaluated. RESULTS: A total of 211 patients with a median age of 72 years (range 19-90 years) were analyzed. CCI ≥ 2 was associated with poor event-free survival (EFS) and overall survival (OS). RDI < 70% was associated with worse EFS and OS. A multivariate analysis revealed that RDI < 70% was only a poor risk factor for the reduction of OS in elderly DLBCL patients (65 years <) and independent from the presence of CCI. The relationship between CCI and RDI in elderly patients was analyzed in four groups, based on CCI ≥ 2 or less and RDI ≥ 70% or less. The group with CCI ≥ 2 and RDI < 70% had a poorer OS and EFS, as compared to the other three groups. The group with CCI < 2 and RDI ≥ 70% had a superior OS but an identical EFS, as compared to the two groups with CCI < 2 and RDI < 70% and CCI ≥ 2 and RDI ≥ 70%. CONCLUSIONS: CCI ≥ 2 was associated with a poorer outcome, but maintaining RDI ≥ 70% may improve the outcome, especially in elderly DLBCL patients.

Association between Comorbidity and Relative Dose Intensity in Patients with Diffuse Large B-Cell Lymphoma.

BACKGROUND: Comorbidities among cancer patients are becoming more common. Comorbidity and relative dose intensity (RDI)are 2 major host-dependent prognostic factors for diffuse large B-cell lymphoma(DLBCL), but the clinical evidence demonstrating a relationship between those 2 factors is limited. METHODS: We retrospectively analyzed the clinical records of patients with de novo DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone(R-CHOP) therapy at the Okitama Public General Hospital between January 2010 and October 2018 to evaluate the relationship between comorbidity and RDI. RESULTS: A total of 104 patients with a median age of 73 years(range, 36-90 years)were included. More than half of the patients(n=58, 55.8%)had at least one comorbidity. 3-year progression-free survival(p=0.043)and 3- year overall survival(p=0.049)were lower in the comorbidity group than in the no comorbidity group. The RDI was also lower in the comorbidity group than in the no comorbidity group(p=0.011). Univariate analysis of various factors influencing the RDI revealed that the presence of comorbidity was associated with insufficient RDI(p=0.016), but multivariate analysis revealed that only age ≥75(p<0.001)was independently associated with insufficient RDI. CONCLUSIONS: Our results demonstrated that the presence of comorbidity was associated with insufficient RDI and poor treatment outcome in DLBCL patients treated with R-CHOP. To optimize the RDI maintenance to achieve better outcomes for DLBCL patients, further investigation of comorbidities is required.

Somatosensory regulation of resting muscle blood flow and physical therapy.

Somatosensory stimulation can affect skeletal muscle blood flow (MBF) at rest in anesthetized animals via pressor reflex response or antidromic and local vasodilation. Increase in MBF due to reflex pressor response occurs generally in the skeletal muscles of the entire body, while antidromic and local vasodilation are limited to the peripheral stimulation site. Since increased MBF improves several disorders (muscle stiffness, pain, etc.), it is reasonable to further explore the effective use of somatic stimulation in physical therapies, such as massage, acupuncture, anma, and shiatsu or acupressure, in treating skeletal muscle disorders.

Enhancement of ERK phosphorylation and photic responses in Vc/C1 neurons of a migraine model.

Although it is well known that migraine pain is enhanced by photic stimulation of the eye, the mechanisms underlying this response are not yet understood. Noxious stimulation to the dura is known to activate trigeminal spinal subnucleus caudalis and upper cervical spinal cord (Vc/C1) neurons, causing migraine pain. Intense photic stimulation to the eye is also known to activate certain Vc/C1 neurons, thus increasing migraine pain. In this study, we hypothesized that Vc/C1 neurons receiving noxious dural input would be further activated by intense photic stimulation, resulting in the enhancement of migraine pain. However, mechanisms underlying the interactions between dural and photic sensory information in Vc/C1 neurons is unknown. To evaluate the above hypothesis, we studied phosphorylated extracellular signal-regulated kinase (pERK) -immunoreactive (IR) cells in Vc/C1 in dural mustard oil (DMO)-administrated rats. The change in neuronal excitability of Vc/C1 nociceptive neurons receiving input from the dura in DMO rats was examined and tested if those neurons were modulated by intense flush light stimulation. There were many pERK-IR cells in the lateral portion of Vc/C1 after MO administration to the dura. Flashlight presentation to the eye in DMO rats caused an enhancement of ERK phosphorylation in Vc/C1 neurons and pERK-IR cells were significantly suppressed after intracisternal administration of MEK1 inhibitor PD98059. Dura-light sensitive (DL) neurons were recorded in the lateral portion of Vc/C1 and photic responses of DL neurons were significantly enhanced following dural MO administration. These findings indicate that DL Vc/C1 neurons in DMO rats intensified their responses to intense photic stimulation and that ERK phosphorylation in Vc/C1 neurons receiving noxious dural input increased with intense photic stimulation, suggesting that Vc/C1 nociceptive neurons are involved in the enhancement of dural nociception associated with intense light stimulation.

Somatoautonomic reflexes in acupuncture therapy: A review.

Oriental therapies such as acupuncture, moxibustion, or Anma, have been used to treat visceral disorders since ancient times. In each of these therapies, stimulation of the skin or underlying muscles leads to excitation of afferent nerves. The sensory information is carried to the central nervous system, where it is transferred to autonomic efferents, thus affecting visceral functions. This neuronal pathway, known as the "somatoautonomic reflex", has been systematically studied by Sato and his colleagues for over a half century. Nearly all their studies were conducted in anesthetized animals, whereas human patients are conscious. Responses in patients or the events following therapeutic somatic stimulation may differ from those observed in anesthetized animals. In fact, it is increasingly apparent that the responses in patients and animals are not always coincident, and the differences have been difficult for clinicians to reconcile. We review the mechanism of the "somatoautonomic reflex" as described in anesthetized animals and then discuss how it can be applied clinically.

Usefulness of Oral Care-related Information Provision at Drugstores to Prevent Pneumonia.

Although the removal of bacteria in the oral cavity is regarded as an important preventive measure against pneumonia, the majority of elderly individuals are rarely provided with oral care-related information. This study examined the usefulness of oral care-related information provision for the elderly by pharmacists working at drugstores. A questionnaire survey was conducted, involving 387 pharmacists working at drugstores and 51 elderly individuals who visited such stores. Oral care-related information had been actively provided by 14.5% of the pharmacists, and 62.5% of all oral care products were being sold as care products. When focusing on the elderly, 70.6% showed interest in oral care, but the proportion of those who had performed self-care to promote such health was limited to 5.9%. After being provided with oral care-information, 97.6% answered "I wish to regularly perform oral self-care", and 86.3% regarded oral care-related information provision by pharmacists as "very useful". The results of this study demonstrate the usefulness of information provision by pharmacists at drugstores to promote oral self-care among the elderly.

High Serum Adiponectin Level Is a Risk Factor for Anemia in Japanese Men: A Prospective Observational Study of 1,029 Japanese Subjects.

Erythroid abnormalities including anemia and polycythemia are often observed in the general clinical setting. Because recent studies reported that adiponectin negatively affects hematopoiesis, we performed a prospective observational study to assess the relationship between anemia and adiponectin, as well as other parameters, in 1029 Japanese subjects (477 men and 552 women) 40 years of age and older. Body measurements, blood tests, and nutrition intake studies were performed at baseline, and 5 to 7 years later (follow-up). Hemoglobin (Hb) and hematocrit (Hct) levels in men with high serum adiponectin levels were lower at follow-up than at baseline. Multiple regression analysis showed that age, body mass index, adiponectin, and glutamic-pyruvic transaminase were significantly associated with erythroid-related variables (red blood cells, Hb, and Hct) in both men and women (P <0.05). In a logistic regression analysis, adiponectin, fasting blood glucose, and ß-natriuretic peptide were significant risk factors for anemia in men, and blood urea nitrogen and amylase were significant risk factors in women. Physical features and nutrient intake were not risk factors for anemia. Our study demonstrates, both clinically and epidemiologically, that a high serum adiponectin level decreases the amounts of erythroid-related variables and is a risk factor for anemia in Japanese men.

Successful high-dose dexamethasone treatment of acquired pure red cell aplasia following ABO major mismatched allogeneic hematopoietic stem cell transplantation.

A 46-year-old man was diagnosed with acute myelomonocytic leukemia involving inv(16)(p13.1q22) in August 2007. He received a human leukocyte antigen-identical, ABO major-mismatched (donor: A, recipient: O) bone marrow transplantation from an unrelated donor in June 2009. Cyclosporin A (CsA) and short-course methotrexate were used for graft versus host disease prophylaxis. Although granulocyte and platelet engraftment were achieved, the patient exhibited persistent anemia and was dependent on red blood cell (RBC) transfusions. Bone marrow aspiration on day 63 revealed the near absence of erythroid precursors, a finding consistent with pure red cell aplasia. No CBFß-MYH11 transcripts were detected. The recipient's anti-A IgM antibody titer was 1:64, and his anti-A IgG antibody titer was 1:1024. The discontinuation of CsA, and the initiation of rituximab and donor lymphocyte infusions were all ineffective against his anemia. He was treated with high-dose dexamethasone (DEXA) (40 mg/day DEXA, days 657-660, days 757-760; 20 mg/day DEXA, days 764-767, days 772-775) in April 2010. A follow-up examination performed at 7 months after the high-dose DEXA treatment showed the patient's anti-A antibody titer to have dropped to an undetectable level. His hemoglobin levels also returned to normal (Hb: 13.4 g/dl), and he no longer required RBC transfusions.

Carbonaceous aerosol tracers in ice-cores record multi-decadal climate oscillations.

Carbonaceous aerosols influence the climate via direct and indirect effects on radiative balance. However, the factors controlling the emissions, transport and role of carbonaceous aerosols in the climate system are highly uncertain. Here we investigate organic tracers in ice cores from Greenland and Kamchatka and find that, throughout the period covered by the records (1550 to 2000 CE), the concentrations and composition of biomass burning-, soil bacterial- and plant wax- tracers correspond to Arctic and regional temperatures as well as the warm season Arctic Oscillation (AO) over multi-decadal time-scales. Specifically, order of magnitude decreases (increases) in abundances of ice-core organic tracers, likely representing significant decreases (increases) in the atmospheric loading of carbonaceous aerosols, occur during colder (warmer) phases in the high latitudinal Northern Hemisphere. This raises questions about causality and possible carbonaceous aerosol feedback mechanisms. Our work opens new avenues for ice core research. Translating concentrations of organic tracers (µg/kg-ice or TOC) from ice-cores, into estimates of the atmospheric loading of carbonaceous aerosols (µg/m(3)) combined with new model constraints on the strength and sign of climate forcing by carbonaceous aerosols should be a priority for future research.

[Correlates of mental health in Japanese caseworkers employed at social welfare offices].

OBJECTIVES: The aim of this study was to evaluate the correlation between the mental health status of caseworkers at welfare offices and factors affecting mental health (i.e., working conditions, participation in training courses and workshops, lifestyle habits, presence of illness, social support, and self-efficacy). METHODS: The welfare offices in Japan (1,230 locations) were arranged in descending order according to their establishment and region. Systematic sampling was then conducted to select 20% (n =246) of the welfare institutions for this study. A total of 1,230 caseworkers on welfare (five from each institution) were administered anonymous self-completed questionnaires. The questionnaires involved the General Health Questionnaire (GHQ)-28 Japanese version and questions regarding basic attributes, working conditions, social support (i.e., family, friends, superiors, and colleagues), participation in training courses and workshops, presence of illness, lifestyle habits, mental health, and self-efficacy. Subjects were divided into the following 2 groups: low-score group (GHQ-28 score ≤5) and high-score group (GHQ-28 score ≥6). Data were analyzed using a t-test, χ(2) test, and Fisher's exact test. The GHQ-28 high- and low-score groups were considered gender-specific dependent variables due to the sex differences observed in the univariate analysis. Significant variables in the univariate analysis were considered independent variables in the multiple logistic regression analysis (forward stepwise selection). RESULTS: Five hundred and six people (410 male and 96 female) provided valid responses. Most respondents had poor mental health (66%, high-score group; 34%, low-score group). Both men and women who worked ≥10 hours/day had significantly poorer mental health than individuals who worked ≤9 hours/day. Individuals with low self-efficacy had significantly poorer mental health compared to people with high self-efficacy. Men who were able to maintain moderate hours of sleep and received support from colleagues, friends, and family had good mental health. Among women, mental health deteriorated with age. Furthermore, women who devoted most work time to home visit had good mental health. CONCLUSION: The mental health of caseworkers at welfare offices can be improved by reducing overtime work hours, ensuring sufficient hours of sleep for each worker, and fostering supportive communication and self-efficacy in the workplace. Furthermore, sex differences should be considered when assessing the mental health of workers at welfare offices in Japan.

Applying spatial epidemiology to hematological disease using R: a guide for hematologists and oncologists.

"Spatial statistics" is an academic field that deals with the statistical analysis of spatial data, and has been applied to econometrics and various other policy fields. These methods are easily applied by hematologists and oncologists using better and much less expensive software. To encourage physicians to use these methods, this review introduces the methods and demonstrates the analyses using R and FleXScan, which can be freely downloaded from the website, with sample data. It is demonstrated that spatial analysis can be used by physicians to analyze hematological diseases. In addition, applying the technique presented to the investigation of patient prognoses may enable generation of data that are also useful for solving health policy-related problems, such as the optimal distribution of medical resources.

Management of erythropoiesis: cross-sectional study of the relationships between erythropoiesis and nutrition, physical features, and adiponectin in 3519 Japanese people.

Although erythroid abnormalities (anemia and polycythemia) are commonly observed pathological conditions, not much information about borderline abnormalities is available. In this study, a cross-sectional study to analyze the relationships between erythropoiesis and nutrition, physical features, and laboratory test findings was conducted in middle-aged and older men and women. The study included 3519 Japanese people (1579 men and 1940 women), age 40 years and over. Analysis of variance showed that the group with a tendency to anemia was older, had a lower body mass index and diastolic blood pressure, and had higher serum adiponectin and creatinine. Multiple regression analysis showed that adiponectin, triglycerides, and total protein were common factors that affected erythropoiesis in both men and women. Hepatic, renal, and cardiac functions were also factors involved in erythropoiesis in men and in postmenopausal women. In addition, nutrient factors such as alcohol, vitamins, and carbohydrates were also significantly involved in erythropoiesis in men, but there were no significant nutrient factors involved in erythropoiesis in either premenopausal or postmenopausal women. This study showed that factors that influence erythropoiesis differ between men, premenopausal women, and postmenopausal women, and it suggested that appropriately modifying erythropoiesis management for each group of people is essential.

Lymphomatosis cerebri with intramedullary spinal cord involvement.

Lymphomatosis cerebri (LC) is a rare form of primary central nervous system lymphoma (PCNSL). Little is known about cases of LC with spinal cord involvement. Among the 11 PCNSL patients treated in our hospital during a four-year period, we identified two cases of LC with spinal cord lesions. One showed a spinal cord lesion followed by leukoencephalopathy. The other showed a spinal cord lesion after LC. In both cases, the histopathology was diffuse large B-cell lymphoma. It is possible that LC may affect the entire central nerve system, and tumor infiltration to the brain and spinal cord in LC may occur more frequently than has been previously considered.

Effects of exercise on the prevention of conditions leading to the need for long-term care.

BACKGROUND: Intervention strategies for 'prevention of conditions leading to the need for long-term care' (prevention of long-term care status) that have physically and mentally proven effects are needed. OBJECTIVE: The aim of this randomized controlled trial was to clarify the physical and psycho-social effects of an exercise program, easily performed at home and in communities using inexpensive equipments for prevention of long-term care status. METHODS: A cluster of 196 participants was randomly assigned to the intervention group that performed the exercise for 8 weeks and the control group. Both groups received tests for physical strength and endurance and interview surveys at baseline and 9 weeks later. The exercise consisted of six types of stretching exercises, six types of muscle strength training, two types of balance training and toe stretching in order to improve ambulatory, balance and stability ability of elderly. The physical aspects of the subjects were assessed by balance assessment, activities of daily living (ADL), timed up-and-go test (TUG), functional reach test (FRT), sit and reach. The psycho-social aspects were assessed by the fall prevention self-efficacy scale (FPSE), instrumental activities of daily living (IADL), degree of houseboundness, and assessment at the end of intervention. RESULTS: The intervention and control groups consisted of 101 and 81 persons at the baseline and 92 and 74 after intervention, respectively. The intervention group showed significantly higher values than the control group after exercise in the FRT, the FPSE and degree of houseboundness. CONCLUSION: This exercise program can promote physical and psycho-social aspects of the health in the elderly, and may reduce the amount of care that the elderly require.

Increased blood serotonin concentrations are correlated with reduced tension/anxiety in healthy postpartum lactating women.

The serotonin (5-HT) system in the brain plays an important role in mood regulation. The postpartum period is considered a high-risk time for mood and anxiety disorders. We assessed changes in 5-HT levels in whole blood (as an indicator of brain 5-HT concentrations) and mood states before and after delivery in 28 healthy, lactating postpartum women. Mood states were evaluated using Profile of Mood States questionnaires (POMS). Measurements were done on the same day in early (first week) and late (third-fourth and sixth-seventh weeks) postpartum, and compared with those in the third trimester and in age-matched, healthy, non-pregnant women. Mean 5-HT concentrations were significantly higher and mean tension/anxiety scores of POMS were significantly lower in late (but not early) postpartum than in the third trimester or non-pregnant controls. 5-HT concentrations correlated with tension/anxiety in the third trimester and late postpartum, indicating an important role for the 5-HT system in the regulation of tension/anxiety in healthy postpartum women. The mechanism underlying the changes in the 5-HT system may be rapid inhibition induced by the marked decrease in estradiol after delivery and gradual excitation caused by lactation-induced brain oxytocin release during the postpartum period.

Involvement of ERK phosphorylation of trigeminal spinal subnucleus caudalis neurons in thermal hypersensitivity in rats with infraorbital nerve injury.

To evaluate the involvement of the mitogen-activated protein kinase (MAPK) cascade in orofacial neuropathic pain mechanisms, this study assessed nocifensive behavior evoked by mechanical or thermal stimulation of the whisker pad skin, phosphorylation of extracellular signal-regulated kinase (ERK) in trigeminal spinal subnucleus caudalis (Vc) neurons, and Vc neuronal responses to mechanical or thermal stimulation of the whisker pad skin in rats with the chronic constriction nerve injury of the infraorbital nerve (ION-CCI). The mechanical and thermal nocifensive behavior was significantly enhanced on the side ipsilateral to the ION-CCI compared to the contralateral whisker pad or sham rats. ION-CCI rats had an increased number of phosphorylated ERK immunoreactive (pERK-IR) cells which also manifested NeuN-IR but not GFAP-IR and Iba1-IR, and were significantly more in ION-CCI rats compared with sham rats following noxious but not non-noxious mechanical stimulation. After intrathecal administration of the MEK1 inhibitor PD98059 in ION-CCI rats, the number of pERK-IR cells after noxious stimulation and the enhanced thermal nocifensive behavior but not the mechanical nocifensive behavior were significantly reduced in ION-CCI rats. The enhanced background activities, afterdischarges and responses of wide dynamic range neurons to noxious mechanical and thermal stimulation in ION-CCI rats were significantly depressed following i.t. administration of PD98059, whereas responses to non-noxious mechanical and thermal stimulation were not altered. The present findings suggest that pERK-IR neurons in the Vc play a pivotal role in the development of thermal hypersensitivity in the face following trigeminal nerve injury.

Acute kidney injury and inflammatory immune reconstitution syndrome in mixed genotype (A/E) hepatitis B virus co-infection in HIV-associated lymphoma.

We report a first case of HIV-associated lymphoma (HAL) presenting with acute kidney injury (AKI) and inflammatory immune reconstitution syndrome (IRIS). A 39-year-old male, treated with nonsteroidal anti-inflammatory drugs (NSAIDs) for one month prior to admission, developed AKI, left testicular tumor, and recurrent swelling of the right parotid gland. A resected testicular tumor exhibited features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Renal biopsy showed hydro-degeneration of renal tubules, interstitial inflammatory cells, and a small number of lymphoma cells in the sub-capsule, compatible with acute interstitial nephritis. His renal dysfunction rapidly recovered following chemotherapy and combination antiretroviral therapy (cART). He developed pneumonia concomitantly with a decrease in HIV-RNA level and an increase in CD4+ cells after the first cycle of chemotherapy, which spontaneously resolved after the second cycle of chemotherapy without additional anti-infection drugs; thus, his pneumonia fulfilled the diagnostic criteria for IRIS. We suggest that IRIS may frequently develop during chemotherapy for HAL, but may be overlooked. He was coinfected with hepatitis B virus (HBV), which genotypes known as is associated with liver-related mortality and response to antiviral therapy; recently, an intimate interplay between HIV and HBV in the onset of lymphoma has been reported. Therefore, we addressed the HBV genotype in the patient. The analysis revealed that he exhibited a mixed genotype (A/E) not native to Japan and primarily found in Europe and North America or West Africa. These findings suggest that universal vaccination for juveniles against HBV is warranted in Japan.