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Objectives: A major regulatory peptide in iron metabolism, hepcidin, has been shown to predict mortality in HIV-infected tuberculosis patients. The aim of this study was to evaluate whether plasma hepcidin levels on admission can be used to predict the treatment outcome of patients with smear-positive pulmonary tuberculosis (PTB) without HIV co-infection. Methods: In this prospective observational study, a total of 35 PTB patients with Mycobacterium tuberculosis-positive sputum smears were enrolled. The relationship between plasma hepcidin levels on admission and the time period to sputum culture-negative was explored. Results: Plasma hepcidin levels of PTB patients were significantly higher than those of healthy subjects (p

Objective This retrospective cohort study investigated whether the three components of the blood cell count have prognostic implications in HIV-negative Japanese adult inpatients with smear-positive pulmonary tuberculosis. Methods We reviewed patients who were treated by the isoniazid, rifampicin, pyrazinamide, and ethambutol regimen or by the isoniazid, rifampicin, and ethambutol regimen. The association between the patient data on admission and the survival outcome was evaluated. Results We reviewed 367 consecutive patients (male, 60.5%) with a median age of 72 [interquartile range (IQR), 54-82] years. While the white blood cell count did not differ between the two groups, (discharged alive: 7,000/μL; IQR, 5,500-9,300; died in hospital: 7,200/μL; IQR, 5,600-9,400; p=0.797), hemoglobin level (discharged alive: 11.5 g/dL; IQR, 10.0-13.1; died in hospital: 9.9 g/dL; IQR, 8.6-11.3; p

Objective Onodera's Prognostic Nutritional Index (PNI), determined as "10× albumin (g/dL) + 0.005× lymphocyte count (/μL)," was originally designed to determine the risk of complications following gastrointestinal surgery. This single-center, retrospective observational study was designed to investigate whether or not the PNI can predict the treatment outcome. Methods We consecutively reviewed HIV-negative pulmonary tuberculosis adults in an isolation ward. Most patients were being treated with standard three- or four-drug regimens. Patients were discharged after consecutive negative smears/cultures were confirmed. The risk of all-cause death was assessed using a multivariable Cox proportional hazard model and a log-rank trend test. Results During the observation period, we observed 371 consecutive patients with a median age of 72 (interquartile range [IQR]: 54-82) years. In our cohort, 295 (79.5%) patients were discharged alive, and 76 (20.5%) died in-hospital. Patients who died in-hospital had a lower PNI [median 21.2 (IQR: 18.5-25.9)] than those who were discharged alive [median 35.1 (IQR: 28.0-43.3); p

We conducted a single-center retrospective cohort study to evaluate whether the HbA1c level on admission could predict the in-hospital treatment outcome of smear-positive non-multi-drug-resistant HIV-negative culture-proven pulmonary tuberculosis inpatients. Our standard regimens under the direct observation were HRZE or HRE for the first two months followed by combination therapy with isoniazid and rifampicin. Our cohort consisted of consecutive 239 patients consisted of 147 men and 92 women with a median age of 73 years. The HbA1c level of patients whose HbA1c was above 7.0% on admission showed clear declining trends after admission. HbA1c on admission had no Spearman’s rank correlation with time to discharge alive (r = 0.17) and time to becoming non-infective (r = 0.17). By Kaplan-Meier curves and a log-rank trend test, HbA1c quartile subgroups showed no association with times to discharge alive (p = 0.431), becoming non-infective (p = 0.113), and in-hospital death (p = 0.427). Based on multi-variate Cox analysis, HbA1c on admission had no significant impact on time to discharge alive (hazard ratio = 1.03, 95% CI 0.89–1.20, p = 0.659), becoming non-infective (hazard ratio = 0.93, 95% CI 0.80–1.06, p = 0.277), and in-hospital death (hazard ratio = 0.68, 0.43–1.07, p = 0.097). In conclusion, the HbA1c level on admission did not seem to affect in-hospital tuberculosis treatment outcomes in Japanese cohort.

Background Occasionally, patients who complain of chest pain after the onset of coughing are diagnosed with rib fractures. We investigated the characteristics of cough-induced rib fractures. Methods Between April 2008 and December 2013, 17 patients were referred to our hospital with chest pain after the onset of coughing. Rib radiography was performed, focusing on the location of the chest pain. When the patient had other signs and symptoms such as fever or persistent cough, computed tomography of the chest was carried out. We analyzed the data retrospectively. Results Rib fractures were found in 14 of the 17 patients. The age of the patients ranged from 14 to 86 years (median 39.5 years). Ten patients were female and 4 were male. Three patients had chronic lung disease. There was a single rib fracture in 9 patients, and 5 had two or more fractures. The middle and lower ribs were the most commonly involved; the 10th rib was fractured most frequently. Conclusions Cough-induced rib fractures occur in every age group regardless of the presence or absence of underlying disease. Since rib fractures often occur in the lower and middle ribs, rib radiography is useful for diagnosis.

Currently, an anti-glycopeptidolipid (GPL)-core IgA antibody assay kit for diagnosing Mycobacterium avium complex (MAC) is commercially available. We conducted this systematic review and meta-analysis to reveal the precise diagnostic accuracy of anti-GPL-core IgA antibodies for MAC pulmonary disease (MAC-PD). We systematically searched reports that could provide data for both sensitivity and specificity by anti-GPL-core IgA antibody for clinically diagnosed MAC-PD. Diagnostic test accuracy was estimated using the bivariate model. Of the 257 articles that we had found through primary search, we finally included 16 reports consisted of 1098 reference positive subjects and 2270 reference negative subjects. The diagnostic odds ratio was 24.8 (95% CI 11.6–52.8, I2 = 5.5%) and the area under the hierarchical summary receiver operating characteristic curves was 0.873 (95% CI 0.837–0.913). With a cutoff value of 0.7 U/mL, the summary estimates of sensitivity and specificity were 0.696 (95% CI 0.621–0.761) and 0.906 (95% CI 0.836–0.951), respectively. The positive and negative likelihood ratios were 7.4 (95% CI 4.1–13.8) and 0.34 (95% CI 0.26–0.43), respectively. The demanding clinical diagnostic criteria may be a cause of false positive of the index test. The index test had good overall diagnostic accuracy and was useful to ruling in MAC-PD with the cutoff value.

Diagnostic test accuracy of the loop-mediated isothermal amplification (LAMP) assay for culture proven tuberculosis is unclear. We searched electronic databases for both cohort and case-control studies that provided data to calculate sensitivity and specificity. The index test was any LAMP assay including both commercialized kits and in-house assays. Culture-proven M. tuberculosis was considered a positive reference test. We included 26 studies on 9330 sputum samples and one study on 315 extra-pulmonary specimens. For sputum samples, 26 studies yielded the summary estimates of sensitivity of 89.6% (95% CI 85.6–92.6%), specificity of 94.0% (95% CI 91.0–96.1%), and a diagnostic odds ratio of 145 (95% CI 93–226). Nine studies focusing on Loopamp MTBC yielded the summary estimates of sensitivity of 80.9% (95% CI 76.0–85.1%) and specificity of 96.5% (95% CI 94.7–97.7%). Loopamp MTBC had higher sensitivity and lower specificity for smear-positive sputa compared to smear-negative sputa. In-house assays showed higher sensitivity and lower specificity compared to Loopamp MTBC. LAMP promises to be a useful test for the diagnosis of TB, however there is still need to improve the assay to make it simpler, cheaper and more efficient to make it competitive against other PCR methods already available.

Summary Nucleic acid amplification tests are a major diagnostic tool for pulmonary tuberculosis (PTB). Recently, digital PCR (dPCR) assay has improved sensitivity for the detection of small copy numbers of target molecules. The aim of this study is to explore the utility of dPCR for detecting Mycobacterium tuberculosis (MTB) DNA in PTB patient plasma. Total DNA was purified from plasma samples of newly diagnosed sputum smear-positive PTB patients. Copy numbers of MTB-specific genes in the samples were quantified with dPCR assays targeted for IS6110 or gyrB . A total of 33 PTB patients were enrolled. Significant differences between PTB patients and controls were observed in copy numbers of both targets: IS6110 mean ± SD, 144.8 ± 538.3 vs 0.44 ± 0.49 (copies/20 μL, p = 0.004; Mann–Whitney U test) and gyrB mean ± SD, 359.0 ± 2116 vs 0.07 ± 0.28 (copies/20 μL, p = 0.011; Mann–Whitney U test), respectively. This test had sensitivities of 65% or 29% and a specificity of 93% or 100% with the IS6110 -targeted or gyrB -targeted assays, respectively. A dPCR assay successfully detected MTB DNA in PTB patient plasma. This minimally invasive and accurate method has potential to become an alternative diagnostic option.

Currently, amrubicin is permitted for relapsed small-cell lung carcinoma (SCLC) only in Japan. The efficacy and adverse effects of amrubicin as reported by previous studies varied greatly. The inclusion criterion was a prospective study that was able to provide data for efficacy and safety by the AMR single agent regimen as second-line chemotherapy for a patient with SCLC. Binary data were meta-analyzed with the random-model generic inverse variance method. We included nine articles consisted of 803 patients. The pooled three-, six- and nine-month progression-free survival were 63% (95% CI 57–69%, I2 = 53%), 28% (95% CI 21–35%, I2 = 71%) and 10% (95% CI 6–14%, I2 = 41%), respectively. The pooled six-, 12- and 18-month overall survival were 69% (95% CI 61–78%, I2 = 83%), 36% (95% CI 28–44%, I2 = 80%) and 15% (95% CI 8–21%, I2 = 81%), respectively. Amrubicin seemed much more beneficial for Japanese patients. However, compared to the efficacy of topotecan presented in a previous meta-analysis, amrubicin may be a better treatment option than topotecan for both Japanese and Euro-American. Adverse effects by amrubicin were almost exclusively observed to be hematological. Notably, grade III/IV neutropenia incidence was 70% and febrile neutropenia incidence was 12%.

Since 2010, studies on the diagnostic accuracy of COBAS TaqMan MTB (CTM) have been frequently reported with an unignorable discrepancy. The key inclusion criterion for this systematic review was original studies that could provide sufficient data for calculating the sensitivity and the specificity of CTM for M tuberculosis (TB) or M tuberculosis complex. The reference test was Mycobacterium culture. We used bivariate model for meta-analyses. Of the 201 candidate articles, we finally identified 17 eligible articles.Concerning the respiratory specimens, 1900 culture positive specimens and 20983 culture negative specimens from 15 studies were assessed. This provided the summary estimate sensitivity of 0.808 (95% CI 0.758–0.850) and the summary estimate specificity of 0.990 (95% CI 0.981–0.994). The area under curve was 0.956. The diagnostic odds ratio was 459 (95% CI 261–805, I2 26%). For the smear positive respiratory specimens, the sensitivity was 0.952 (95% CI 0.926–0.969) and the specificity was 0.916 (95% CI 0.797–0.968). For the smear negative respiratory specimens, the sensitivity and the specificity were 0.600 (95% CI 0.459–0.726) and 0.989 (95% CI 0.981–0.993), respectively. The diagnostic accuracy was poorer for the non-respiratory specimens, than for the respiratory specimens, but was acceptable. We believe that the information obtained from this study will aid physicians’ decision making.

Topotecan is the most reliable chemotherapy regimen for relapsed small-cell lung carcinoma (SCLC). The efficacy and adverse effects of topotecan as reported by previous studies varied greatly. The inclusion criterion was a prospective study that was able to provide data for 6-month over-all survival (OS) rate, 1-year OS rate, objective responses, and/or adverse effects of single agent topotecan as a second line chemotherapy for SCLC, written in English language as a full article. Any topotecan regimen were allowed. Binary data were meta-analyzed with the random-model generic inverse variance method. We included 14 articles consisted of 1347 patients. Pooled values were estimated as follows. Six-month OS rate: 37% (95% CI: 28–46%). One-year OS rate: 9% (95% CI: 5–13%). Response rate: 5% (95% CI: 1–8%). Six-month OS rate: 57% (95% CI: 50–64%). One-year OS rate: 27% (95% CI: 22–32%). Response rate: 17% (95% CI: 11–23%). Grade III/IV neutropenia 69% (95% CI: 58–80%). Grade III/IV thrombopenia 41% (95% CI: 34–48%). Grade III/IV anemia 24% (95% CI: 17–30%). Non-hematorogical events were rare. Chemotherapy-related death 2% (95% CI: 1–3%). In conclusion, Topotecan provided a possibly promising outcome for sensitive-relapse SCLC and poor outcome for refractory relapse SCLC. Adverse events were mainly hematological.

The rat embryonic brain was probed with anti-d-aspartic acid (d-Asp) antiserum at different stages of development. At gestational day (E) 12, weak immunoreactivity (IR) of d-Asp was apparent at the hindbrain, midbrain and caudal forebrain, whereas it became more intense and extended over the whole brain at E20. However, IR markedly decreased after parturition. In the region of the immature forebrain at an early stage of development (E12), IR was mainly a characteristic of the cytoplasm of the neuronal cells, while in the more mature hindbrain it was localized in the axonal zone. In the more differentiated forebrain at a later stage of development (E18), the IR became restricted to zones which mainly consisted of axons and processes. Consequently, in the rat central nervous system, d-Asp first emerges during embryonic development as a feature of the cytoplasm and thereafter spreads into the axonal regions of neuronal cells, before disappearing almost completely after parturition.

In the current study, localization of D-aspartic acid (D-Asp) in rat testis was studied by immunohistochemical and biochemical techniques. Immunohistochemical staining of this tissue using specific polyclonal antibody to D-Asp revealed D-Asp immunoreactivity (IR) in the cytoplasm of germ cells, especially around the region rich in elongate spermatids, the most mature of the germ cells. Weak IR was also noted in cytoplasm of spermatocytes and round spermatids; however, it was negligible in interstitial cells and Sertoli cells. The intensity of immunostaining in each seminiferous tubule differed according to its distinct germ cell composition. In testis of young rats, seminiferous tubules lack elongated spermatids, and D-Asp was found to be localized in spermatocytes, the most mature population of germ cells at that age. We used various toxicants to destroy specific testicular cell populations and to confirm the localization of D-Asp in rat testis. Administration of ethane dimethane sulfonate induced a selective destruction of all Leydig cells in this tissue. This resulted in a significant decrease in the D-Asp level, which was probably due to a drop in testosterone brought about by this treatment, and this was followed by a modulation of spermatogenesis. Three days after treatment with methoxyacetic acid (MAA), many seminiferous tubules were found to lack or to have severe depletions of pachytene spermatocytes, but not of elongate spermatids. This caused reductions in protein content and in the total amount of L-Asp, but not that of D-Asp. Twenty days after treatment with MAA, the depleted population of germ cells progressed through the spermatogenic cycle from pachytene spermatocytes to elongate spermatids. At this time, the level of D-Asp decreased significantly, as did that of L-Asp and protein, consistent with D-Asp localization in elongate spermatids. This decrease in the D-Asp level was also seen with immunostaining.

Developmental changes in cellular localization of D-aspartic acid (D-Asp) were investigated in rat adrenal gland with polyclonal anti-D-Asp antibody. At 1 and 3 weeks of age, immunoreactivity (IR) toward this amino acid was intense in the cytoplasm of cells in the zona fasciculata (ZF) and zona reticularis (ZR) of the adrenal cortex but was less so in the zona glomerulosa (ZG). Conversely at 8 weeks of age, intense IR was observed in the ZG and less in the ZF and ZR. In the adrenal medulla, IR was evident in large clusters of cells which were identified as adrenaline-storing cells. The emergence of D-Asp in specific types of cells at distinct periods of development of rat adrenal gland suggests that this amino acid may have a physiological role in the maturation of the organ.

A snake-like robot is a robot imitating a real snake. A snake-like robot is developed in order to achieve excellent locomotion characterization of a real snake. It is necessary for a snake-like robot to move even in geographical features like a slope for adapting to various environment. The purpose of this study is the verification of slope climbing movement of the snake-like robot. In previous our study, a developed robot was affected seriously by cable tension. Hence, we have to realize wireless control of the snake-like robot for solving the problem. In this paper, we make a wireless system for transmitting the sensor information from the robot and commands from a computer. The wireless system behavior is verified by simulations.

Rat pituitary gland and retina were probed with anti-D-aspartate (D-Asp) antibody previously prepared in this laboratory [Lee et al., Biochem. Biophys. Res. Commun., 231 (1997) 505-508]. D-Asp immunoreactivity (IR) was observed only in the posterior lobe of the pituitary gland of 3-day-old rats, whereas the anterior and posterior lobes were also positive in 3-week and 6-week-old rats, respectively. In the anterior lobe, intense IR was scattered throughout the lobe and the D-Asp-positive cells appeared to be prolactin-containing cells or some other very closely related type of cell. In the retina, D-Asp IR was observed only in the ganglion cell and nerve fiber region of 3-day-old rats. In contrast, during the transient increase in D-Asp levels in 7-day-old rats, D-Asp IR was additionally evident in regions where differentiating bipolar cells had begun to make contact with other types of cells. The functional relevance of D-Asp localization in these tissues is discussed.

We studied the distribution of phosphorylated tau (p-tau) in neonatal and adult rat cerebrum using monoclonal antibodies that recognize distinct tau epitopes in a phosphorylation-dependent manner. In neonatal cortex, p-tau was detected in the apical dendrites and somata of pyramidal neurons as well as in axons. In adults, p-tau was present predominantly in neuronal somata and dendrites and, to a lesser extent, in axons, whereas tau-1, that recognizes a dephosphorylated tau epitope, immunolabeled neuropil and axons, and not the neuronal somata and dendrites. These results suggest that tau phosphorylated at multiple sites is present in somatodendritic compartments of rat cortical neurons throughout life, and that phosphorylation may be one of the determinants for the compartmentalization of tau in the brain.

Specific polyclonal antibody was raised against D-aspartate (D-Asp) which had been conjugated to glutaraldehyde and was purified by affinity chromatography. Immunohistochemical staining of rat pineal gland with the antibody demonstrated the presence of D-Asp in the cytoplasm of pinealocytes, the predominant cell type in this gland. D-Asp immunoreactivity was more evident in the distal region than in the proximal region of the gland. Pinealocytes in the distal region are presumably involved in the synthesis and secretion of the pineal hormone, melatonin, and the results of staining may indicate some yet unknown role of D-Asp in the regulation of melatonin secretion.