Knee extensor muscle strength as a predictor of peak oxygen uptake in patients with heart disease.

[Purpose] The mortality rate increases when peak oxygen uptake is less than 5 metabolic equivalents, and peak oxygen uptake correlates with knee extensor muscle strength. This study aimed to determine the knee extensor muscle strength at peak oxygen uptake corresponding to 5 metabolic equivalents. [Participants and Methods] We enrolled 45 consecutive patients (29 males and 16 females; average age, 63.6 ± 13.7 years) with heart disease receiving outpatient rehabilitation with us. We performed cardiopulmonary exercise testing with a bicycle ergometer to measure peak oxygen uptake. We investigated the relationship between peak oxygen uptake and isometric knee extensor muscle strength divided by the body weight (kgf/kg). The cutoff value for knee extensor muscle strength with peak oxygen uptake corresponding to 5 metabolic equivalents was calculated. [Results] Knee extensor muscle strength was significantly positively associated with peak oxygen uptake. The cutoff value for knee extensor muscle strength at peak oxygen uptake corresponding to 5 metabolic equivalents was 0.46 kgf/kg. [Conclusion] In this study, the cutoff value for knee extensor muscle strength for achieving peak oxygen uptake corresponding to 5 metabolic equivalents in patients with heart disease was 0.46kgf/kg.

Factors influencing trough and 90-minute plasma dabigatran etexilate concentrations among patients with non-valvular atrial fibrillation.

INTRODUCTION: Dabigatran etexilate, a direct oral anti-coagulation agent, is used in the prevention of thromboembolism in patients with non-valvular atrial fibrillation (NVAF). However, for reasons that are not fully understood, plasma dabigatran etexilate concentrations (PDC) vary significantly among patients. METHODS: We measured trough and 90min PDC in 98 patients with NVAF. To elucidate the cause of variations in PDC, we determined correlations between PDC and various factors including renal function, co-administration of a P-glycoprotein inhibitor, and the effects of three single nucleotide polymorphisms (SNPs) of the P-glycoprotein intestinal efflux transporter. To further determine the cause of PDC variations, we examined the relationship between PDC, activated partial prothrombin time (APTT), and D-dimer (DD) levels, which are surrogate markers for thrombotic risk. RESULTS: Multivariate analysis showed significant relations among creatinine, creatinine clearance, and CHA2D2-VaSc scores (p=0.04, p=0.01, and p=0.04, respectively). In addition, creatinine and creatinine clearance were significantly correlated with trough and 90min PDC (p<0.01), respectively. There was a clear linear relation between PDC and APTT, but not DD levels. However, higher DD levels (>0.5µg/mL) were associated with lower trough and 90min PDCs. CONCLUSIONS: Renal function and CHA2D2-VaSc scores affect PDC, suggesting these may be primary factors influencing the wide variation observed in PDCs under these conditions. Variations in APTT can primarily be explained by variations in PDC; patients with lower PDCs may have a higher risk of thromboembolism events.

Dengue Hemorrhagic Fever in a Japanese Traveler with Pre-existing Japanese Encephalitis Virus Antibody.

An adult Japanese man who had just returned from Thailand developed dengue hemorrhagic fever (DHF). A primary infection of dengue virus (DENV) was confirmed, specifically DENV serotype 2 (DENV-2), on the basis of the detection of the virus genome, a significant increase in the neutralizing antibody and the isolation of DENV-2. DHF is often observed following a secondary infection from another serotype of dengue virus, particularly in children, but this case was a primary infection of DENV. Japan is a non-endemic country for dengue disease. In fact, only Japanese encephalitis (JE) is known to be a member of the endemic flavivirus family. In this study, IgG antibody against Japanese encephalitis virus (JEV) was detected. JEV belongs to the family of dengue virus and prevails in Japan, particularly Kyushu. Among many risk factors for the occurrence of DHF, a plausible candidate could be a cross-reactive antibody-dependent enhancement (ADE) mechanism caused by JEV antibody. This indicates that most Japanese travelers who living in dengue non-endemic areas, particularly Kyushu, should be aware of the occurrence of DHF.

The N-terminal fragment of a PB2 subunit from the influenza A virus (A/Hong Kong/156/1997 H5N1) effectively inhibits RNP activity and viral replication.

BACKGROUND: Influenza A virus has a RNA-dependent RNA polymerase (RdRp) that is composed of three subunits (PB1, PB2 and PA subunit), which assemble with nucleoproteins (NP) and a viral RNA (vRNA) to form a RNP complex in the host nucleus. Recently, we demonstrated that the combination of influenza ribonucleoprotein (RNP) components is important for both its assembly and activity. Therefore, we questioned whether the inhibition of the RNP combination via an incompatible component in the RNP complex could become a methodology for an anti-influenza drug. METHODOLOGY/PRINCIPAL FINDINGS: We found that a H5N1 PB2 subunit efficiently inhibits H1N1 RNP assembly and activity. Moreover, we determined the domains and important amino acids on the N-terminus of the PB2 subunit that are required for a strong inhibitory effect. The NP binding site of the PB2 subunit is important for the inhibition of RNP activity by another strain. A plaque assay also confirmed that a fragment of the PB2 subunit could inhibit viral replication. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the N-terminal fragment of a PB2 subunit becomes an inhibitor that targets influenza RNP activity that is different from that targeted by current drugs such as M2 and NA inhibitors.

[The national strategies for suicide prevention by the United Nation/World Health Organization and the present situation of suicide in the East Asia].

We discussed "Prevention of suicide: Guidelines for the formulation and implementation of national strategies" formulated by the United Nations and the World Health Organization in 1996 and the present situation of suicide in the East Asia. Although much public attention has been paid to a high suicide rate of Japan in the world, the increasing tendency of suicide rates have been found in other East Asian countries as well. For example the Republic of Korea shows a recent suicide rate higher than 30 per 100,000, which surpasses the suicide rate of Japan. Facing the fact, various measures for suicide prevention have been conducted. The UN guidelines for suicide prevention point out that these strategies should be discussed to meet each country's need for more appropriate suicide prevention. The Japanese government had the Basic Law on Suicide Prevention enforced in 2006 to implement measures that society must tackle because various social factors are behind suicides. In recent years, some countries in the East Asia also show increasing suicide rates, which attract the society's serious concern. The rapid economic growth and globalization have led to personnel cut, performance-based compensation, and the widening gap between the rich and the poor and the society cannot maintain the conventional employment system. In addition, socio-economic changes have brought collapse of the original societal and familial system, which might have existed behind the increase of suicide in this region.

[Review of a community-based laboratory diagnosis of pandemic influenza A (H1N1) 2009].

We performed a community-based laboratory diagnosis of pandemic influenza A (H1N1) 2009 with the RT-PCR technique using originally constructed primers. Of 30 patients who were suspected to be infected with the influenza virus from May 2009 until January 2010, the A (H1N1) 2009 virus was detected in 13 patients (43.3%). Three cases were immunologically confirmed to be infected with the A (H1N1) 2009 virus, because significant increases in the HI titer were observed in the convalescent sera. We also measured the antibody titers to the A (H1N1) 2009 virus in 13 healthy individuals with the HI assay using originally isolated virus. In most cases, the HI antibody titers were less than 10, except two cases with titers of 40 and 20. Our inspection system organized in the early phase of the A (H1N1) 2009 pandemic contributed to disease control in an outpatient clinic and a hospital in a small city. The process which we used to construct the system would be a good reference for a treatment protocol in the case of a future literal pandemic.

Impaired capsular polysaccharide is relevant to enhanced biofilm formation and lower virulence in Streptococcus pneumoniae.

Streptococcus pneumoniae has been reported to form biofilms. Many different surface molecules, including capsular polysaccharide (CPS), may play a fundamental role in pneumococcal biofilm development. We designed a CPS mutant, TIGR4cps4D(-), from the TIGR4 strain and detected enhanced biofilm formation. The pathogenic diversities of the mutant were also investigated with the in vitro expression levels of pavA, lytA, IgA1, piaA, psaA, ply, and spxB. The mean OD595 of TIGR4cps4D(-) biofilm was 1.77 and 1.74, whereas that of TIGR4 was 0.76 and 0.33 on day 1 and day 2, respectively. Scanning electron microscopy and confocal laser scanning microscopy showed TIGR4cps4D(-) formed a biofilm that was significantly thicker than that formed by TIGR4 (~12.22 vs. ~6.29 µm). Compared to TIGR4, the gene expression of lytA, IgA1, and, psaA in TIGR4cps4D(-) was 1.9 × 10(-5)-, 2.4 × 10(-5)-, and 3.2 × 10(-3) fold lower under the planktonic condition, and 1.9 × 10(-5)- and 9.7 × 10(-5) fold lower in biofilms, respectively. Furthermore, TIGR4cps4D(-) seemed to induce less cell death, compared to the results of TIGR4 (21.38 vs. 33.47 %, after a 5-h exposure; P < 0.05). Our data indicate that impaired pneumococcal CPS may increase biofilm formation and be involved in inhibition of virulence, possibly by influencing the gene expression.

Intrahost emergent dynamics of oseltamivir-resistant virus of pandemic influenza A (H1N1) 2009 in a fatally immunocompromised patient.

The oseltamivir-resistant pandemic influenza virus A (2009 H1N1) with H275Y mutation in neuraminidase (NA) has been sporadically reported, and its wide spread remains a potential threat. Here we detected the uneven distribution of H275Y mutant virus in a patient who received a 21-day long-term administration of oseltamivir. Intrahost variation of the virus showed that the H275Y mutant virus was the predominant population in both nasopharynx and right lung, whereas the oseltamivir-sensitive virus comprised half the population in the left lung. By constructing minimum spanning trees, it is proposed that the H275Y mutant might be generated primarily in the nasopharynx, then spread to the right and left lungs.

Clinical study concerning the relationship between community-acquired pneumonia and viral infection in northern Thailand.

OBJECTIVE: The etiological agents associated with community-acquired pneumonia (CAP) in Thailand have been studied extensively in bacterial pathogens, but not in viral pathogens. To clarify the association of viral pathogens with CAP, we conducted a comprehensive study of viral and bacterial pathogens in patients with CAP. METHODS: We enrolled 119 hospitalized patients with CAP in Nakornping Hospital, Chiang Mai, Thailand between 2006 and 2008. The severity of pneumonia was classified and the risk factors for death were estimated. Bacterial and fungal pathogens were determined from specimens taken from blood and sputum, and viral pathogens were identified from nasopharyngeal specimens by RT-PCR using primers specific for 7 respiratory viruses. RESULTS: Overall, 29 patients were HIV-infected and 90 patients were non-HIV-infected. The microbial pathogens most commonly isolated among HIV-infected patients were: 4 Klebsiella pneumoniae, 4 Mycobacterium tuberculosis and 3 Haemophilus influenzae. Among non-HIV infected patients, predominant microbial pathogens were: 6 Pseudomonas aeruginosa, 5 Haemophilus influenzae and 4 Klebsiella pneumoniae. As for viral pathogens for CAP, influenza virus was identified from 2 HIV-infected patients and 5 non-HIV infected patients. In addition, human rhinovirus (HRV) and respiratory syncytial virus (RSV) were identified from 2 patients each among non-HIV-infected patients. CONCLUSION: Our study demonstrates that the most common viral agent was influenza virus (5%), followed by HRV (2%) and RSV (2%) among CAP patients in northern Thailand. The underlying chronic obstructive pulmonary disease (COPD) seems to be correlated with the severity of illness.

Influence of work duration or physical symptoms on mental health among Japanese visual display terminal users.

The present study examined the relationship of work duration or physical symptoms to the mental health of visual display terminal (VDT) workers in Japan. The mental health status of 2,327 VDT users at an administrative office was investigated using the 12-item General Health Questionnaire (GHQ-12). Subjects were asked about their age, sex, hours of daily VDT use, rest and breaks during VDT work, eyestrain, and musculoskeletal pain. Logistic regression analysis was used to evaluate the associations with mental health status (GHQ-12 scores). The mean age of subjects was 39.5 yr (SD=10.3). Among all subjects, 36.7% could rest during VDT work and 66.9% received breaks during VDT work. The proportion of subjects who reported eyestrain and musculoskeletal pain were 19.6% and 25.7%, respectively. Eighteen percent of subjects were classified into a GHQ-12 high score group. Logistic regression analysis showed that age less than 40 yr, not receiving breaks during VDT work, and the presence of eyestrain and musculoskeletal pain were significantly associated with poor mental health status (high GHQ-12 scores). Using a VDT for more than 5 h/d and being female were also marginally associated with high GHQ scores (p<0.1). In conclusion, the management of physical health as well as work duration is important for good mental health status among VDT users.

Determination of haloperidol and reduced haloperidol in human serum by liquid chromatography after fluorescence labeling based on the Suzuki coupling reaction.

A simultaneous method for the determination of haloperidol (HP) and its metabolite, reduced haloperidol (RHP), in human serum was developed by means of high-performance liquid chromatography (HPLC) with fluorescence detection. Suzuki coupling reaction with a fluorescent arylboronic acid, 4-(4,5-diphenyl-1H-imidazol-2-yl)phenylboronic acid (DPA), was employed to convert HP and RHP into highly fluorescent compounds. HP and RHP were extracted from human serum by liquid-liquid extraction with a mixture of n-hexane and isoamyl alcohol (99:1, v/v) and subsequently labeled by reaction with DPA. Separation of DPA derivatives of HP and RHP was performed on a silica column with a mixture of acetonitrile and H(2)O (90:10, v/v) containing triethylamine and acetic acid as a mobile phase. The proposed method allowed sensitive detection of HP and RHP in human serum with a detection limit (at a signal to noise ratio of 3) of 0.22 and 0.20 ng/mL, respectively. The applicability of the method for therapeutic drug monitoring (TDM) was demonstrated by analyzing human serum samples from schizophrenic patients receiving HP.

Prognostic value of myocardial MIBG scintigraphy findings in patients with cardiomyopathy--importance of background correction for quantification of MIBG activity.

OBJECTIVE: To assess the prognostic value of I-123 metaiodobenzylguanidine (MIBG) scintigraphy findings, and establish the most appropriate method for calculating myocardial MIBG activity in patients with left ventricular dysfunction due to cardiomyopathy (CM). METHODS: Predictors of cardiac death related to progressive heart failure (HF) were examined in 150 patients with CM (80 patients with idiopathic CM and 70 patients with ischemic CM). All patients underwent MIBG scintigraphy at rest and other hemodynamic studies when their clinical status was stable. MIBG scintigrams were obtained 15 minutes and 4 hours after the injection of the isotope. The parameters for quantification of myocardial MIBG activity were heart/mediastinal activity ratio (H/M) and myocardial washout rate (WR). The WR was calculated with and without background (BG) correction. RESULTS: The WR showed better correlation with plasma norepinephrine and left ventricular ejection fraction after BG correction. During a mean follow-up period of 33 +/- 9 (7 to 54) months, 12 patients died due to HF; 7 patients due to progressive HF and 5 patients due to sudden cardiac death. Cox regression analysis indicated, the H/M and the WR with and withoutBG correction, were significant predictors of cardiac death (Wald chi-squared value: H/M [ 15 min] = 9.7, H/M [4 hr] = 19.5, WR with BG correction = 29.9, WR without BG correction = 12.6). WR prognostic value was better after BG correction, and a high WR with BG correction was the only independent predictor of cardiac death (relative risk [RR] = 1.174, p < 0.0001). CONCLUSIONS: Accelerated WR is a powerful predictor of the patient's prognosis and BG correction is essential for calculating WR.

Mental health conditions among atomic bomb survivors in Nagasaki.

To elucidate the effects of the bombing on the atomic bomb survivors' mental health, a mental health survey was conducted using a 12-item version of the General Health Questionnaire (GHQ-12) and a mail survey on atomic bomb exposure conditions and lifestyle using a self-administered questionnaire. A total of 3526 atomic bomb survivors in Nagasaki responded and a high GHQ-12 score, as defined when the responses to four or more items were positive, was observed in 296 (8.4%) subjects. It was indicated that the risk of a high GHQ-12 score will decrease 0.98-fold with every 1-year increase in age, and will increase 1.45-fold and 1.70-fold in those who lost family members due to the bombing and those who had acute symptoms, respectively, compared with those who did not. It was indicated that the atomic bomb exposure has affected survivors' mental health and that the care of their mental health is important.