How staying in a gymnasium affects sleep and bed climate in children.

BACKGROUND: We investigated the relationship between sleep, ambient climate, and bed climate in school-aged children during a one-night stay in a simulated shelter in a gymnasium to demonstrate the effect of ambient climate, and bed climate on sleep. METHODS: We obtained measurements during a one-night stay in a school gymnasium (C), days before C (BC), on the day after (A1), and on the second day after C (A2) in 13 healthy school-aged children during summer. Sleep was evaluated using an actigraph, and the temperature and humidity of the bedrooms in the participants' homes and in the gymnasium were monitored for 3 days before and after C. The bed climate of the chest and foot areas was measured for two nights before and after C. The participants were asked to report on their subjective sleep estimations and thermal sensations two nights before and after C. RESULTS: The ambient temperature in C was significantly higher than that in BC at the initial 180 min, while it significantly decreased compared to A1 and A2 in the last 100 min. The ambient humidity was significantly higher in both C and BC compared to A1 and A2. The sleep efficiency index decreased significantly in C (43±4.8%) compared to other conditions. Sleep time was significantly shorter in C than in other conditions during the initial 195 min. The increase in the bed climate temperature of the chest area in C was significantly delayed compared to that in the other conditions, around the initial 30 min after the lights were off. Subjective estimation revealed that in C, 85% of the participants were out of their sleeping bag at sleep onset, and their sleep was disturbed by heat (77%). CONCLUSIONS: Our study revealed that the disturbed sleep patterns observed with children in a simulated shelter may be related to a delayed increase in bed climate temperature in the chest area. This delayed increase could be related to the children not entering the sleeping bag and a delayed chest skin temperature increase during the sleep onset period.

Novel Virus Air Sampler Based on Electrostatic Precipitation and Air Sampling of SARS-CoV-2.

The assessment of airborne viruses in air is a critical step in the design of appropriate prevention and control measures. Hence, herein, we developed a novel wet-type electrostatic air sampler using a viral dissolution buffer containing a radical scavenging agent, and verified the concentration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in the air of hospital rooms inhabiting coronavirus disease 2019 (COVID-19) patients and public areas. RNA damage caused by corona discharge was negligible when Buffer AVL was used as the collecting electrode. The viral RNA concentration in the air of the room varied by patient: 3.9 × 103 copy/m3 on the 10th day after onset in a mild case and 1.3 × 103 copy/m3 on the 18th day in a severe case. Viral RNA levels were 7.8 × 102 and 1.9 × 102 copy/m3 in the air of the office and food court, respectively, where people removed their masks when eating and talking, but it remained undetected in the station corridor where all the people were wearing masks. The assessment of airborne SARS-CoV-2 RNA using the proposed sampler can serve as a basis for the safe discontinuation of COVID-19 isolation precautions to identify exposure hotspots and alert individuals at increased infection risks.

Sleep Habits in Pairs of Japanese High School Students and Their Mothers in Summer and Autumn.

This study aimed to examine the sleep habits in pairs of Japanese high school students and their mothers in the summer and autumn. Nineteen pairs of high school students and their mothers participated in this study. Wrist actigraphy, subjective sleep evaluations, and bedroom environmental measurements (temperature, humidity, and light) were performed for a duration of one week. The results of a split-plot analysis of variance revealed no significant difference in the actigraphically evaluated time spent in bed (TIB) between the seasons and between the mothers and students. The TIB was approximately 6 h on weekdays, and significantly lengthened to approximately 7 h on weekends (p < 0.05). The average sleep efficiency values recorded were higher than 90%. The mothers showed significantly advanced sleep phases compared to those of the students (p < 0.05). In addition, the waking time on Monday morning was significantly correlated between the mothers and students in the summer and autumn (p < 0.05). A perceived sleep loss "almost every day" or "several times per week" was reported by approximately half of the mothers and students in each season. The students occasionally fell into nocturnal sleep with the room light turned on. These results suggest that sleep hygiene education considering life habit characteristics is required to ensure sufficient sleep time.

Machine learning-based exceptional response prediction of nivolumab monotherapy with circulating microRNAs in non-small cell lung cancer.

Immune checkpoint inhibitors (ICIs) have significantly improved the survival of advanced non-small cell lung cancer (NSCLC). Detecting NSCLC patients with exceptional response to ICIs is necessary to improve the treatment. This case control study profiled circulating microRNA expressions of 213 NSCLC patients treated with nivolumab monotherapy to identify patients with exceptional response. Based on the response and progression-free survival, patients were divided into 3 groups: Exceptional-responder (n = 27), Resistance (n = 161), and Others (n = 25). Resistance group was further randomly partitioned into six non-overlapping sets (n = 26 or 27), while each partition was combined with Exceptional-responder and Others to make balanced datasets. We built machine learning models optimized for identifying Exceptional-responder via 3-group classification and constructed a panel of 45 microRNAs and 3 fields of clinical information. Machine learning models based on the selected panel achieved 0.81-0.89 (median 0.85) sensitivity and 0.52-0.71 (median 0.59) precision for Exceptional-responder in 3-group classification with 5-fold cross validation in all six datasets constructed, while conventional method relying on tumor PD-L1 immunohistochemistry achieved 0.44-0.44 sensitivity and 0.55-0.67 (median 0.62) precision. This study demonstrated the machine learning models achieved much higher sensitivity and accuracy in identifying Exceptional-responder to nivolumab monotherapy when comparing to conventional method only using companion PD-L1 testing.

Developing high-affinity decoy receptors to treat multiple myeloma and diffuse large B cell lymphoma.

Disease relapse and treatment-induced immunotoxicity pose significant clinical challenges for patients with hematological cancers. Here, we reveal distinctive requirements for neutralizing TNF receptor ligands APRIL and BAFF and their receptor activity in MM and DLBCL, impacting protein translation and production in MM cells and modulating the translation efficiency of the ATM interactor (ATMIN/ACSIZ). Therapeutically, we investigated the use of BCMA decoy receptor (sBCMA-Fc) as an inhibitor of APRIL and BAFF. While wild-type sBCMA-Fc effectively blocked APRIL signaling in MM, it lacked activity in DLBCL due to its weak BAFF binding. To expand the therapeutic utility of sBCMA-Fc, we engineered an affinity-enhanced mutant sBCMA-Fc fusion molecule (sBCMA-Fc V3) 4- and 500-fold stronger in binding to APRIL and BAFF, respectively. The mutant sBCMA-Fc V3 clone significantly enhanced antitumor activity against both MM and DLBCL. Importantly, we also demonstrated an adequate toxicity profile and on-target mechanism of action in nonhuman primate studies.

Novel Screening System of Virulent Strains for the Establishment of a Mycobacterium avium Complex Lung Disease Mouse Model Using Whole-Genome Sequencing.

The establishment of animal models reflecting human Mycobacterium avium complex (MAC) lung disease (LD) pathology has the potential to expand our understanding of the disease pathophysiology. However, inducing sustained infection in immunocompetent mice is difficult since MAC generally shows less virulence and higher genetic variability than M. tuberculosis. To overcome this hurdle, we developed a screening system for identifying virulent MAC strains using whole-genome sequencing (WGS). We obtained nine clinical strains from Mycobacterium avium complex lung disease (MAC-LD) patients and divided them into two groups to make the mixed strain inocula for infection. Intranasal infection with the strain mixture of both groups in BALB/c mice resulted in progressive infection and extensive granuloma formation in the lungs, suggesting the existence of highly pathogenic strains in each group. We hypothesized that the change in the abundance of strain-specific single-nucleotide variants (SNVs) reflects the change in bacterial number of each strain in infected lungs. Based on this hypothesis, we quantified individual strain-specific SNVs in bacterial DNA from infected lungs. Specific SNVs for four strains were detected, suggesting the pathogenicity of these four strains. Consistent with these results, individual infection with these four strains induced a high lung bacterial burden, forming extensive peribronchial granuloma, while the other strains showed a decreased lung bacterial burden. The current method combining mixed infection and WGS accurately identified virulent strains that induced sustained infection in mice. This method will contribute to the establishment of mouse models that reflect human MAC-LD and lead to antimycobacterial drug testing. IMPORTANCE To promote research on Mycobacterium avium complex (MAC) pathogenicity, animal models reflecting human progressive MAC lung disease (MAC-LD) are needed. Because there is high genetic and virulence diversity among clinical MAC strains, choosing a suitable strain is an important process for developing a mouse model. In this study, we developed a screening system for virulent strains in mice by combining mixed infection and whole-genome sequencing analysis. This approach is designed on the hypothesis that in vivo virulence of MAC strains can be examined simultaneously by comparing changes in the abundance of strain-specific single-nucleotide variants in the mouse lungs after infection with mixed strains. The identified strains were shown to induce high bacterial burdens and cause extensive peribronchial granuloma resembling the pulmonary pathology of human MAC-LD. The current method will help researchers develop mouse models that reflect human MAC-LD and will lead to further investigation of MAC pathogenicity.

A case of allergic fungal rhinosinusitis caused by Schizophyllum commune identified in both patient's nasal sputum and veranda's soil samples.

This is a case report of allergic fungal rhinosinusitis caused by Schizophyllum commune (S. commune) identified in a patient's nasal mucus and environmental soil sample using (r)DNA sequencing. Although filamentous basidiomycetes, including S. commune, are known as environmental pathogens causing allergic respiratory diseases worldwide, many patients with infections caused by S. commune have not been correctly diagnosed. Repeated exposures to environmental floating fungi supposedly make an easy sensitization and colonization of fungi in the nasal passages, resulting in the onset of allergic fungal rhinosinusitis due to S. commune in our living environments. This report indicates the importance of reconsidering allergic respiratory diseases associated with our living environments.

Napping Behaviors and Extracurricular Club Activities in Japanese High School Students: Associations with Daytime Sleep Problems.

Although engaging in evening naps and extracurricular activities are popular among Japanese high school students, the associations between these behaviors and daytime sleep problems were unclear. A questionnaire on daily life and sleeping habits was administered to 1314 high school students, aged between 15-17 years. The respondents were categorized by their after-school napping habits (did not nap, napped 1-2 days/week, napped ≥3 days/week), and their extracurricular activities (no activity, cultural club, athletic club). The mean nocturnal sleep duration on weekdays (± standard deviation (SD)) was 390 ± 56 min. This was significantly shorter in those students with a higher number of days/week spent napping (p < 0.001), and slightly longer for those in the athletic club (p < 0.001). Sleep problems-including subjective insufficient sleep, excessive sleepiness during class ≥3 days/week, and falling asleep during class ≥3 days/week-were reported by 64%, 55%, and 33% of respondents, respectively. A multiple logistic regression analysis showed significantly higher risks for excessive sleepiness among students taking naps ≥3 days/week, and who belonged to athletic clubs. In addition to those factors, students in cultural clubs revealed significantly higher risks for falling asleep during classes. Future studies are required to decrease daytime sleep problems associated with evening naps and extracurricular activities among high school students.

Effects of the environment of a simulated shelter in a gymnasium on sleep in children.

Effects of the environment of a simulated shelter in a gymnasium on sleep were investigated in 20 healthy school-aged children. Measurements were obtained during a one-night stay in a school gymnasium during the summer (C). Activity levels were monitored using a wrist actigraph, and temperature and humidity of the bedrooms in the subjects' homes were monitored from 3 days before to 3 days after C. The subjects were asked to provide information regarding subjective sleep estimations and thermal sensations. The results for the days before C (BC), C, the first day after C (A1), and the second day after C (A2) were compared. The bedroom temperature was significantly lower on BC than on the other nights. No significant difference was observed in bedtime, whereas wake-up time was significantly earlier on C and later on A1 than on the other nights. Total sleep time was significantly decreased on C (3.6 h) and increased on A1 when compared to the other nights. Daytime nap was significantly increased on A1 when compared to the other days. Subjective estimation of sleep quality was decreased and sweat sensation before sleep was increased on C when compared to the other nights. The main reason for sleep disturbances on C was heat. These results indicate that the environment of the simulated shelter in the gymnasium severely disturbed sleep in children. The resulting loss of sleep was compensated for by increased nocturnal sleep time and daytime napping on the next day.

Sleep and Skin Temperature in Preschool Children and Their Mothers.

The purpose of this study was to investigate and compare sleep and skin temperature (Tsk) of preschool children with those of their mothers. The subjects included 18 pairs of preschool children and their mothers. The actigraphic measurement of sleep, Tsk, heart rate, bedroom climate, and the microclimate temperature and humidity (bed climate) were measured. Proximal and distal Tsk, the temperature gradient of distal and proximal Tsk (DPG), and bed climate temperature were significantly lower in the children. Approximately 70% of the children slept without bed covering. Heat dissipation during sleep in preschool children may primarily rely on the proximal Tsk. The lower Tsk than adults, and behavioral thermoregulation, may be important for sleep in preschoolers.

Difference in Antibody Responses to Mycobacterium tuberculosis Antigens in Japanese Tuberculosis Patients Infected with the Beijing/Non-Beijing Genotype.

The Beijing genotype Mycobacterium tuberculosis (MTB), notorious for its virulence and predisposition to relapse, could be identified by spoligotyping based on genetic heterogeneity. The plasma samples from 20 cases of Beijing and 16 cases of non-Beijing MTB infected individuals and 24 healthy controls (HCs) were collected, and antibodies against 11 antigens (Rv0679c142Asn, Rv0679c142Lys, Ag85B, Ag85A, ARC, TDM-M, TDM-K, HBHA, MDP-1, LAM, and TBGL) were measured by ELISA. Compared to the HCs, the MTB infected subjects showed higher titers of anti-Ag85B IgG (positivity 58.2%) and anti-ACR IgG (positivity 48.2%). Of note, anti-ACR IgG showed higher titer in Beijing MTB infected tuberculosis (TB) patients than in HC (Kruskal-Wallis test, p < 0.05), while the levels of anti-Ag85B, anti-TBGL, anti-TDM-K, and anti-TDM-M IgG were higher in non-Beijing TB patients than in HC. Moreover, anti-Ag85B IgG showed higher response in non-Beijing TB patients than in Beijing TB patients (p < 0.05; sensitivity, 76.9% versus 44.4%). The sensitivity and specificity analysis showed that 78.8% Beijing infected individuals were negative in anti-TBGL-IgG or/and anti-Ag85B-IgG, while 75.0% of those were positive in anti-TBGL-IgA or/and anti-ACR-IgG tests. These results indicate the possibility of developing antibody-based test to identify Beijing MTB.

Immunological Roles of Elevated Plasma Levels of Matricellular Proteins in Japanese Patients with Pulmonary Tuberculosis.

Elevated matricellular proteins (MCPs), including osteopontin (OPN) and galectin-9 (Gal-9), were observed in the plasma of patients with Manila-type tuberculosis (TB) previously. Here, we quantified plasma OPN, Gal-9, and soluble CD44 (sCD44) by enzyme-linked immunosorbent assay (ELISA), and another 29 cytokines by Luminex assay in 36 patients with pulmonary TB, six subjects with latent tuberculosis (LTBI), and 19 healthy controls (HCs) from Japan for a better understanding of the roles of MCPs in TB. All TB subjects showed positive results of enzyme-linked immunospot assays (ELISPOTs). Spoligotyping showed that 20 out of 36 Mycobacterium tuberculosis (MTB) strains belong to the Beijing type. The levels of OPN, Gal-9, and sCD44 were higher in TB (positivity of 61.1%, 66.7%, and 63.9%, respectively) than in the HCs. Positive correlations between OPN and Gal-9, between OPN and sCD44, and negative correlation between OPN and ESAT-6-ELISPOT response, between chest X-ray severity score of cavitary TB and ESAT-6-ELISPOT response were observed. Instead of OPN, Gal-9, and sCD44, cytokines G-CSF, GM-CSF, IFN-α, IFN-γ, IL-12p70, and IL-1RA levels were higher in Beijing MTB-infected patients. These findings suggest immunoregulatory, rather than inflammatory, effect of MCPs and can advance the understanding of the roles of MCPs in the context of TB pathology.

Sleep in a Gymnasium: A Study to Examine the Psychophysiological and Environmental Conditions in Shelter-Analogue Settings.

We aimed to examine sleep in shelter-analogue settings to determine the sleep and environmental conditions in evacuation shelters. A summer social/educational event was conducted in an elementary school, wherein children and their parents (n = 109) spent one night in the school gymnasium; a total of 15 children and 7 adults completed the study. Data were recording using wrist actigraphy and questionnaires, from two days before the event to two days after the event. During the night in the gymnasium, sleep initiation in the children was found to be significantly delayed, whereas adults did not show any significant change in actigraphic sleep parameters. Although 57% of adults complained of stiffness of the floor, only 7% of children had the same complaint. The nocturnal noise recorded at four locations in the gymnasium showed that the percentage of 1-min data epochs with a noise level >40 dB ranged from 53% to 74% during lights-out. The number of subjects that woke up during the night showed a similar pattern with the changes in the noise level. The changes in sleep might represent event-specific responses, such as to a noisy environment, and the different complaints between adults and children could be useful in shelter management.

Rapid Cancer Fluorescence Imaging Using A γ-Glutamyltranspeptidase-Specific Probe For Primary Lung Cancer.

BACKGROUND: We set out to examine the activity of γ-glutamyltranspeptidase (GGT) in lung cancer and the validity of γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) for intraoperative imaging of primary lung cancer. METHODS: GGT activities and mRNA expression levels of GGT1 (one of the GGT subtypes) in five human lung cancer cell lines were examined by fluorescence imaging and quantitative reverse transcription polymerase chain reaction. In vivo imaging of an orthotopic A549 xenograft model in nude mice was performed to confirm its applicability to intraoperative imaging. Furthermore, ex vivo imaging of 73 specimens from lung cancer patients were performed and analyzed to calculate the sensitivity/specificity of gGlu-HMRG for lung cancer diagnosis. RESULTS: GGT activities and mRNA expression levels of GGT1 are diverse depending on cell type; A549, H441, and H460 showed relatively high GGT activities and expression levels, whereas H82 and H226 showed lower values. In the in vivo mouse model study, tiny pleural dissemination and hilar/mediastinal lymph node metastasis (less than 1 mm in diameter) were clearly detected 15 minutes after topical application of gGlu-HMRG. In the ex vivo study of specimens from patients, the sensitivity and specificity of gGlu-HMRG were calculated to be 43.8% (32/73) and 84.9% (62/73), respectively. When limited to female patients, never smokers, and adenocarcinomas, these values were 78.9% (15/19) and 73.7% (14/19), respectively. CONCLUSIONS: Although GGT activity of lung cancer cells vary, gGlu-HMRG can serve as an intraoperative imaging tool to detect small foci of lung cancer when such cells have sufficient GGT activity.

Nanomedicines Eradicating Cancer Stem-like Cells in Vivo by pH-Triggered Intracellular Cooperative Action of Loaded Drugs.

Nanomedicines capable of control over drug functions have potential for developing resilient therapies, even against tumors harboring recalcitrant cancer stem cells (CSCs). By coordinating drug interactions within the confined inner compartment of core-shell nanomedicines, we conceived multicomponent nanomedicines directed to achieve synchronized and synergistic drug cooperation within tumor cells as a strategy for enhancing efficacy, overcoming drug resistance, and eradicating CSCs. The approach was validated by using polymeric micellar nanomedicines co-incorporating the pan-kinase inhibitor staurosporine (STS), which was identified as the most potent CSC inhibitor from a panel of signaling-pathway inhibitors, and the cytotoxic agent epirubicin (Epi), through rationally contriving the affinity between the drugs. The micelles released both drugs simultaneously, triggered by acidic endosomal pH, attaining concurrent intracellular delivery, with STS working as a companion for Epi, down-regulating efflux transporters and resistance mechanisms induced by Epi. These features prompted the nanomedicines to eradicate orthotopic xenografts of Epi-resistant mesothelioma bearing a CSC subpopulation.

Effect of cardboard under a sleeping bag on sleep stages during daytime nap.

Fourteen healthy male subjects slept from 13:30 to 15:30 under ambient temperature and relative humidity maintained at 15 °C and 60%, respectively. They slept under two conditions: in a sleeping bag on wooden flooring (Wood) and in a sleeping bag with corrugated cardboard between the bag and the flooring (CC). Polysomnography, skin temperature (Tsk), microclimate, bed climate, and subjective sensations were obtained. The number of awakenings in the CC had significantly decreased compared to that in the Wood. The mean, back, and thigh Tsk, and bed climate temperature were significantly higher in the CC than that in the Wood. Subjective thermal sensations were warmer in the CC than in the Wood. These results suggest that using corrugated cardboard under a sleeping bag may reduce cold stress, thereby decreasing the number of awakenings and increasing subjective warmth; the mean, back, and thigh Tsk; and bed climate temperature.

Detection of Mycobacterium tuberculosis (MTB) in Fecal Specimens From Adults Diagnosed With Pulmonary Tuberculosis Using the Xpert MTB/Rifampicin Test.

Background. The Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF) is a fully automated diagnostic test that allows for the detection of MTB including its RIF resistance. Although the test is used for the diagnosis of tuberculosis (TB) in sputum samples worldwide, studies using fecal specimens are scarce. We therefore evaluated the efficacy of the Xpert MTB/RIF test for detection of MTB in fecal specimens obtained from adult pulmonary TB patients, confirmed by culture and/or molecular diagnostic methods. Methods. We conducted a retrospective case-control study to provide proof-of-concept regarding the efficacy of the Xpert MTB/RIF test using fecal samples for diagnosing pulmonary TB via detection of MTB in adult patients (≥20 years) at the Fukujuji Hospital in Tokyo, Japan. Results. Fecal specimens were obtained from 56 active pulmonary TB patients (including 48 sputum smear-positive and 8 sputum smear-negative patients), 10 non-TB patients (including 4 Myocobacterium avium complex infections), and 27 healthy individuals who were exposed to active pulmonary TB patients. The sensitivity of the fecal Xpert MTB/RIF was 100% (81.7%-100%) for detection of MTB in specimens from sputum smear-positive (1+ to 3+) patients, 81.0% (58.1%-94.6%) in specimens from sputum smear scanty positive patients, and 50.0% (15.7%-84.3%) in specimens from sputum smear-negative patients. Meanwhile, each of the fecal specimens from the non-TB group was negative for MTB (specificity 100%; 95% confidence interval, 86.2-100). Conclusions. The fecal Xpert MTB/RIF test could detect MTB in a large proportion of smear-positive pulmonary TB patients, without frequent false-positive results at a TB referral hospital in Japan.

Monoglucosyl-rutin as a potential radioprotector in mammalian cells.

In the present study, the role of monoglucosyl­rutin as a potential radioprotector was investigated using mammalian cell culture models. Cell survival and DNA damage were assessed using colony formation, sister chromatid exchange and γH2AX assays. It was demonstrated that monoglucosyl­rutin was able to increase cell survival when exposed to ionizing radiation, possibly by decreasing the amount of base damage experienced by the cell. However, the present study also demonstrated that, despite monoglucosyl­rutin exhibiting radioprotective effects at low doses, high doses of monoglucosyl­rutin led to a decrease in plating efficiency and an increased doubling time. This effect may be due to double­strand breaks caused by high concentrations of monoglucosyl­rutin.

Optimization of the microscopic observation drug susceptibility assay for four first-line drugs using Mycobacterium tuberculosis reference strains and clinical isolates.

OBJECTIVE: The aim of this study is to determine the appropriate cut-off value and turnaround time of the microscopic observation drug susceptibility assay (MODS) for isoniazid (INH), rifampicin (RMP), streptomycin (STR), and ethambutol (EMB). DESIGN: A total of 39 Mycobacterium tuberculosis strains with confirmed drug susceptibility (reference strains) were tested with a range of drug concentrations to determine the optimal cut-off values for INH, RMP, STR, and EMB by MODS. Standard drug susceptibility testing (DST) results were evaluated relative to the Löwenstein-Jensen (L-J) proportion method. Following which, the performance of MODS was evaluated again using 36 sputum samples from patients with tuberculosis (TB) using the cut-off values determined in the aforementioned process. RESULTS: With 39 reference strains, DST identified the following cut-off values: 0.8µg/ml INH (sensitivity, 96.0%; specificity, 92.9%), 2.0µg/ml RMP (sensitivity, 100%; specificity, 95.5%), 4.0µg/ml STR (sensitivity, 90.5%; specificity, 93.8%), and 4.0µg/ml EMB (sensitivity, 100%; specificity, 91.7%). When these cut-off values were used to analyze the 36 clinical isolates, the sensitivity and specificity of MODS were 100% and 93.1% for INH, 100% and 93.8% for RMP, 87.5% and 96.4% for STR, and 100% and 88.2% for EMB, respectively. The turnaround time for these clinical specimens was 9.0days by MODS (95% CI: 5.3-12.7), compared with 11.7days (95% CI: 9.5-13.9) for smear negative specimens. CONCLUSION: Our study identified the optimal cut-off values of the four first-line drugs for MODS based on a wide concentration range. With the optimal cut-off values determined in this study, MODS showed high discriminatory efficiency for DST. This study also demonstrated that MODS is useful for rapid diagnosis of drug-resistant TB even for a smear negative specimen, despite the fact that it generally uses smear positive specimens as direct DST.

[Clinical evaluation of a line probe assay kit for the identification of Mycobacterium species and detection of drug-resistant Mycobacterium tuberculosis].

BACKGROUND: Multidrug resistance (MDR) involves resistance to both isoniazid and rifampicin, which makes the treatment of tuberculosis very difficult. Extensive drug resistance (XDR) occurs when, in addition to isoniazid and rifampicin resistance, the microorganisms are resistant to a fluoroquinolone and an injectable agent (e.g., kanamycin, amikacin, or capreomycin). Generally, drug susceptibility testing takes more than 3-4 weeks after the initial cultivation. There is an urgent need to identify methods that can rapidly detect both the presence of Mycobacterium tuberculosis and the status of drug resistance. PURPOSE: This study was aimed at evaluating the line probe assay (LiPA; Nipro Co.), for the identification of Mycobacterium species and detection of mutations associated with antituberculous drugs. RESULTS: We found that LiPA enabled the rapid identification of M. tuberculosis, M. avium, M. intracellulare, and M. kansasii. When the results of the LiPA and conventional drug susceptibility tests were compared, there was no difference in the susceptibility to rifampicin, pyrazinamide, and levofloxacin; however, there was a difference in the susceptibility to isoniazid. CONCLUSION: Thus, LiPA can be used for the rapid identification of Mycobacterium species and the determination of susceptibility to drugs, which can help in the early initiation of appropriate treatment, leading to a reduction in infectiousness.