Effect of X-ray tube on image quality and pancreatic ductal adenocarcinoma conspicuity in pancreatic protocol dual-energy CT.

AIM: To compare the radiation dose, image quality, and conspicuity of pancreatic ductal adenocarcinoma (PDAC) in pancreatic protocol dual-energy computed tomography (CT) between two X-ray tubes mounted in the same CT machine. MATERIAL AND METHODS: This retrospective study comprised 80 patients (median age, 73 years; 45 men) who underwent pancreatic protocol dual-energy CT from January 2019 to March 2022 using either old (Group A, n=41) or new (Group B, n=39) X-ray tubes mounted in the same CT machine. The imaging parameters were completely matched between the two groups, and CT data were reconstructed at 70 and 40 keV. The CT dose-index volume (CTDIvol); CT attenuation of the abdominal aorta, pancreas, and PDAC; background noise; and qualitative scores for the image noise, overall image quality, and PDAC conspicuity were compared between the two groups. RESULTS: The CTDIvol was lower in Group B than Group A (7.9 versus 9.2 mGy; p<0.001). The CT attenuation of all anatomical structures at 70 and 40 keV was comparable between the two groups (p=0.06-0.78). The background noise was lower in Group B than Group A (12 versus 14 HU at 70 keV, p=0.046; and 26 versus 30 HU at 40 keV, p<0.001). Qualitative scores for image noise and overall image quality at 70 and 40 keV and PDAC conspicuity at 40 keV were higher in Group B than Group A (p<0.001-0.045). CONCLUSION: The latest X-ray tube could reduce the radiation dose and improve image quality in pancreatic protocol dual-energy CT.

Comprehensive validation of early diagnostic algorithms for myocardial infarction in the emergency department.

OBJECTIVE: To comprehensively evaluate diagnostic algorithms for myocardial infarction using a high-sensitivity cardiac troponin I (hs-cTnI) assay. PATIENTS AND METHODS: We prospectively enrolled patients with suspected myocardial infarction without ST-segment elevation from nine emergency departments in Japan. The diagnostic algorithms evaluated: (i) based on hs-cTnI alone, such as the European Society of Cardiology (ESC) 0/1-h or 0/2-h and High-STEACS pathways; or (ii) used medical history and physical findings, such as the ADAPT, EDACS, HEART, and GRACE pathways. We evaluated the negative predictive value (NPV), sensitivity as safety measures, and proportion of patients classified as low or high-risk as an efficiency measure for a primary outcome of type 1 myocardial infarction or cardiac death within 30 days. RESULTS: We included 437 patients, and the hs-cTnI was collected at 0 and 1 hours in 407 patients and at 0 and 2 hours in 394. The primary outcome occurred in 8.1% (33/407) and 6.9% (27/394) of patients, respectively. All the algorithms classified low-risk patients without missing those with the primary outcome, except for the GRACE pathway. The hs-cTnI-based algorithms classified more patients as low-risk: the ESC 0/1-h 45.7%; the ESC 0/2-h 50.5%; the High-STEACS pathway 68.5%, than those using history and physical findings (15-30%). The High-STEACS pathway ruled out more patients (20.5%) by hs-cTnI measurement at 0 hours than the ESC 0/1-h and 0/2-h algorithms (7.4%). CONCLUSIONS: The hs-cTnI algorithms, especially the High-STEACS pathway, had excellent safety performance for the early diagnosis of myocardial infarction and offered the greatest improvement in efficiency.

Lactobacillus gasseri PA-3 directly incorporates purine mononucleotides and utilizes them for growth.

Lactococcus lactis has been reported unable to directly incorporate mononucleotides but instead requires their external dephosphorylation by nucleotidases to the corresponding nucleosides prior to their incorporation. Although Lactobacillus gasseri PA-3 (PA-3), a strain of lactic acid bacteria, has been found to incorporate purine mononucleotides such as adenosine 5'-monophosphate (AMP), it remains unclear whether these bacteria directly incorporate these mononucleotides or incorporate them after dephosphorylation to the corresponding nucleosides. This study evaluated whether PA-3 incorporated radioactively-labeled mononucleotides in the presence or absence of the 5'-nucleotidase inhibitor α,ß-methylene ADP (APCP). PA-3 took up 14C-AMP in the presence of APCP, as well as incorporating 32P-AMP. Furthermore, radioactivity was detected in the RNA/DNA of bacterial cells cultured in the presence of 32P-AMP. Taken together, these findings indicated that PA-3 incorporated purine mononucleotides directly rather than after their dephosphorylation to purine nucleosides and that PA-3 utilizes these purine mononucleotides in the synthesis of RNA and DNA. Although additional studies are required to identify purine mononucleotide transporters in PA-3, this study is the first to show that some lactic acid bacteria directly incorporate purine mononucleotides and use them for growth.

Prevalence and associated risk factors of drug-resistant tuberculosis in Thailand: results from the fifth national anti-tuberculosis drug resistance survey.

OBJECTIVE: To assess the prevalence and risk factors of drug-resistant tuberculosis (TB), the fifth national anti-TB drug resistance survey was conducted in Thailand. METHODS: A cross-sectional study was conducted by stratified cluster sampling with probability proportional to size of TB cases from public health facilities in 100 clusters throughout Thailand from August 2017 to August 2018. Susceptibility testing of TB isolates to first- and second-line anti-TB drugs was performed on Löwenstein-Jensen medium using the indirect proportion method. Multiple imputation was done for handling missing data using Stata 16. The proportion of TB cases with drug resistance was determined. The odds ratio was used to evaluate risk factors associated with drug-resistant TB. RESULTS: Among 1501 new TB and 69 previously treated TB cases, 14.0% [95% confidence interval (CI): 12.1-16.1] and 33.4% (95% CI: 23.6-44.8), respectively, had resistance to any anti-TB drug. Multidrug-resistant TB accounted for 0.8% (95% CI: 0.5-1.4) of new TB cases and 13.0% (95% CI: 6.5-24.4) of previously treated TB cases. Drug-resistant TB was associated with prior TB treatment [odds ratio (OR), 2.9; 95% CI: 1.6-5.0], age at 45-54 years (OR, 1.6; 95% CI: 1.0-2.4), male (OR, 1.5; 95% CI: 1.0-2.1) and human immunodeficiency virus (HIV) infection (OR, 1.6; 95% CI: 1.0-2.4). CONCLUSIONS: The burden of drug-resistant TB remains high in Thailand. Intensified prevention and control measures should be implemented to reduce the risks of drug-resistant TB in high-risk groups previously treated, especially individuals of late middle age, males and those with coinfection of TB and HIV.

Enhancing the fungicidal activity of amphotericin B via vacuole disruption by benzyl isothiocyanate, a cruciferous plant constituent.

Amphotericin B (AmB), a typical polyene macrolide antifungal agent, is widely used to treat systemic mycoses. In the present study, we show that the fungicidal activity of AmB was enhanced by benzyl isothiocyanate (BITC), a cruciferous plant-derived compound, in the budding yeast, Saccharomyces cerevisiae. In addition to forming a molecular complex with ergosterol present in fungal cell membranes to form K+ -permeable ion channels, AmB has been recognized to mediate vacuolar membrane disruption resulting in lethal effects. BITC showed no effect on AmB-induced plasma membrane permeability; however, it amplified AmB-induced vacuolar membrane disruption in S. cerevisiae. Furthermore, the BITC-enhanced fungicidal effects of AmB significantly decreased cell viability due to the disruption of vacuoles in the pathogenic fungus Candida albicans. The application of the combinatorial antifungal effect of AmB and BITC may aid in dose reduction of AmB in clinical antifungal therapy and consequently decrease side effects in patients. These results also have significant implications for the development of vacuole-targeting chemotherapy against fungal infections.

Validation of the Japanese version of the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities.

BACKGROUND: Dementia in people with intellectual disabilities (IDs) is difficult to detect because of preexisting cognitive deficits. An effective screening method is required. The Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID) was developed as an observer rating tool to screen dementia in people with ID. The aim of this study was to verify the screening accuracy of the DSQIID for Japanese people with ID. METHODS: Four-hundred ninety-three subjects with ID participated in this study. Caregivers who had observed the participants for more than 2 years scored the Japanese version of the DSQIID (DSQIID-J) of the participants. Three doctors examined participants directly and diagnosed dementia using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. To identify the key screening items that predict dementia, the specificities of a single and pairs of items with 100% sensitivity were evaluated relative to the dementia diagnosis. RESULTS: Of 493 participants, 34 were people with Down syndrome (DS), and 459 were people without DS. Seventeen participants were diagnosed with dementia. The suitable cut-off score of the DSQIID-J was 10/11 (sensitivity 100% and specificity 96.8%) for screening dementia. The inter-rater reliability, test-retest reliability and internal consistency of the DSQIID-J were excellent. Regarding key items, there was no single item with 100% sensitivity, and the best two-item combination was the pair of 'Cannot dress without help' and 'Walks slower' (sensitivity 100% and specificity 93.5%). CONCLUSIONS: We identified several important question items of the DSQIID-J related to the diagnosis of dementia in people with ID. The DSQIID-J is a useful screening tool for dementia in adults with ID.

Species-dependent patterns of incorporation of purine mononucleotides and nucleosides by lactic acid bacteria.

Although most lactic acid bacteria do not directly incorporate purine nucleotides, the strain Lactobacillus gasseri PA-3 was found to incorporate purine mononucleotides. To determine whether the direct uptake of purine mononucleotides is dependent on the species or strain of lactic acid bacteria, incorporation of purine mononucleotides was assessed in L. gasseri, Lactcoccus lactis sbsp. lactis, Streptococcus thermophilus and other species of lactic acid bacteria. Each bacterial strain was incubated with 32P-AMP or 14C-adenosine and the incorporation of each purine was evaluated by measuring their radioactivity. All investigated strains of L. gasseri incorporated 32P-AMP, whereas strains of S. thermophilus and most strains of L. lactis did not. Incorporation of 32P-AMP into strains of Pediococcus was dependent on the strain or species of that genus of bacteria. All investigated strains, except for one strain of L. gasseri, incorporated 14C-adenosine, with S. thermophilus, L. lactis and Pediococcus generally displaying greater incorporation of 14C-adenosine than L. gasseri. Although most lactic acid bacteria such as S. thermophiles and L. lactis do not incorporate purine mononucleotides, some species such as L. gasseri directly incorporate purine mononucleotides. These findings indicate that the preferential incorporation of purine mononucleotides or nucleosides by lactic acid bacteria is dependent on the species or strain.

Indo-Oceanic Mycobacterium tuberculosis strains from Thailand associated with higher mortality.

SETTING: This study was conducted among tuberculosis (TB) patients in a highly endemic Thai province.OBJECTIVE: To evaluate the association between different Mycobacterium tuberculosis lineages and clinical characteristics, especially mortality.DESIGN: We enrolled 1,304 TB patients registered from 2002-2011 with culture isolates whose lineages were identified by specific regions of deletion. Data on mortality within 1 year of follow-up were extracted from the registration system and hospital records. Mortality-associated risk factors, including bacterial lineages, as independent variables were analysed using Cox regression models.RESULTS: Of 1,304 isolates, 521 (40.0%) and 582 (44.6%) belonged to Indo-Oceanic and East-Asian lineages, respectively. Indo-Oceanic strains significantly increased the mortality risk compared with East-Asian strains (adjusted hazard ratio [aHR] 1.42, 95%CI 1.02-1.99) or modern lineages (aHR 1.49, 95%CI 1.08-2.06) in the 172 patients who died within 1 year after TB diagnosis. The former also caused significantly higher mortality than modern lineages among patients who died within 6 months after TB diagnosis (aHR 1.62, 95%CI 1.12-2.35). No significant association was found between drug resistance and death.CONCLUSION: In Thailand, the Indo-Oceanic lineage of M. tuberculosis increased mortality risk compared with modern lineages or the East-Asian lineage, the latter being considered highly virulent in previous studies.

Tissue Thickness Effects on Immunohistochemical Staining Intensity of Markers of Cancer.

High-quality patient samples are required for reliable immunohistochemistry test outcomes that provide a significant benefit for patient care. Among the preanalytic variables in tissue handling, tissue thickness is thought to be easily controlled; however, whether the thickness of the tissue effects the staining intensity for antibody immunohistochemistry has not been quantitatively demonstrated. To investigate, we cut multiblock tissue sections of tonsil, liver, and kidney at 2, 4, 6, and 8 µm thicknesses. Interferometry measurements of the sectioned paraffin showed a <1 µm variation within a preset microtome thickness. Sections were then immunostained with antibodies targeting different cellular localizations; Ki-67 and BCL6 (nuclear), CD7 (membranous), and cytokeratin (cytoplasmic). A pathologist annotated regions of interest for each marker and performed brightfield and whole-slide visual scoring. Then a pixel-wise processing algorithm determined intensity of each pixel in these regions of interest and binned them into predetermined 0, 1+, 2+, or 3+ intensities. Visual scores from brightfield and whole-slide images were highly correlated to the percentage of pixels in each intensity bin. A stepwise increase was observed in pathologist scores and algorithmically defined percentage of pixels in each bin with increasing thickness demonstrating that changes in preset section thickness impacts staining intensity. The use of tissue thickness outside vendors' recommendations might change the intensity including the proportion of positive and negative cells and eventually the overall diagnosis outcome. Therefore, we recommend that tissue be consistently cut within the middle of thickness range specified by the assay manufacturer.

Sleep during low-frequency repetitive transcranial magnetic stimulation is associated with functional improvement in upper limb hemiparesis after stroke.

Many studies have reported that repetitive transcranial magnetic stimulation (rTMS) is beneficial for post-stroke patients with upper limb hemiparesis. It was reported that application of rTMS during sleep could possibly strengthen neural plasticity. The purpose of this study was to investigate the relationship between sleep during low-frequency rTMS session and improvement of motor function in affected upper limb in post-stroke patients after inpatient rehabilitation combined with rTMS using the bispectral index (BIS) monitor. During 15-day hospitalization, each patient received rTMS and intensive occupational therapy. Low-frequency rTMS with 1 Hz was applied over the contralesional motor cortex. During rTMS session, adhesive sensor was put on each patient's forehead and connected to the BIS monitor. The mean score for the maximum change of BIS values during each rTMS session (ΔBIS) was calculated. We regarded the patients with and over 10 of mean ΔBIS as Asleep group and under 10 as Awake group. Fugl-Meyer assessment (FMA) and Action Research Arm Test (ARAT) were evaluated on admission and discharge. Awake group included six patients and Asleep group included seven patients. There was no significant difference in clinical characteristics and in increase of FMA between two groups. Asleep group was significantly superior to Awake group in the increase of ARAT (p < 0.05). There was a significant correlation between the mean of ΔBIS and increase of ARAT (ρ = 0.78, p = 0.002). Sleep during low-frequency rTMS may contribute to improvement of motor function in the affected upper limb.

Transition of Spleen Volume Long After Pediatric Living Donor Liver Transplantation for Biliary Atresia.

PURPOSE: After undergoing the Kasai procedure for biliary atresia (BA), most patients develop severe splenomegaly that tends to be improved by liver transplantation. However, fluctuations in splenic volume long after transplantation remain to be elucidated. PATIENTS AND METHODS: Seventy-one consecutive patients who had undergone pediatric living donor liver transplantation (LDLT) for BA were followed up in our outpatient clinic for 5 years. They were classified into 3 groups according to their clinical outcomes: a good course group (GC, n = 41) who were maintained on only 1 or without an immunosuppressant, a liver dysfunction group (LD, n = 18) who were maintained on 2 or 3 types of immunosuppressants, and a vascular complication group (VC, n = 11). Splenic and hepatic volumes were calculated by computed tomography in 464 examinations and the values compared before and after the treatment, especially in the VC group. RESULTS: Splenic volume decreased exponentially in the GC group, with splenic volume to standard spleen volume ratio (SD) being 1.59 (0.33) 5 years after liver transplantation. Splenic volume to standard spleen volume ratios were greater in the VC and LD groups than in the GC group. Patients in the VC group with portal vein stenosis developed liver atrophy and splenomegaly, whereas those with hepatic vein stenosis developed hepatomegaly and splenomegaly. Interventional radiation therapy tended to improve the associated symptoms. CONCLUSIONS: Fluctuations in splenic volume long after pediatric LDLT for BA may reflect various clinical conditions. Evaluation of both splenic and hepatic volumes can facilitate understanding clinical conditions following pediatric LDLT.

Lactobacillus gasseri PA-3, but not L. gasseri OLL2996, reduces the absorption of purine nucleosides in rats.

Lactobacillus gasseri PA-3 (PA-3) is a bacterial strain with a strong ability to degrade purine nucleosides. We previously showed that PA-3 incorporates purines in vitro and that oral administration of PA-3 and purines to rats attenuated their absorption of purines. It remains unclear whether these effects of PA-3 depend on bacterial strains. This study therefore compared the abilities of PA-3 and another bacterial strain of L. gasseri, OLL2996, which has shown decreased ability to degrade purine nucleosides in vitro, to incorporate purine nucleosides and to inhibit the absorption of purines fed to rats. Each bacterial strain was incubated in the presence of 14C-adenosine or 14C-inosine and the incorporation of each purine was evaluated by measuring their radioactivity. In vivo, rats were fed 14C-labeled purines along with PA-3 or OLL2996 and the absorption of these 14C-labeled purines was evaluated by analyzing radioactivity of blood samples. PA-3 incorporated about twice as much 14C-adenosine and 14C-inosine as OLL2996. The elevation of radioactivity levels in blood was 10-20% lower in rats treated with PA-3 than in control rats, after feeding with both 14C-adenosine and 14C-inosine as purines. In contrast, treatment with OLL2996 did not have statistically significant effects on radioactivity compared with the control group. These results indicate that the magnitude of bacterial inhibition of purine absorption is dependent on bacterial strain, correlating at least partly with the ability to incorporate and degrade purines.

Lactobacillus gasseri PA-3 utilizes the purines GMP and guanosine and decreases their absorption in rats.

Excessive intake of purine-rich foods elevates serum uric acid levels, making it a risk factor for hyperuricemia. We hypothesized that lactic acid bacteria ingested with food might utilize purines and contribute to their decreased absorption in the intestines, thereby preventing hyperuricemia. We previously reported that Lactobacillus gasseri PA-3 (PA-3) incorporates adenosine/inosine and related purines and that oral ingestion of PA-3 reduced the absorption of these purines in rats. However, it is unclear whether PA-3 also decreases the absorption of other purines, such as guanosine 5'-monophosphate (GMP) and guanosine. This study investigated whether PA-3 incorporates GMP and guanosine and reduces their absorption in rats. PA-3 incorporated both purines, with 14C-GMP uptake being greater than that of 14C-guanosine. Radioactivity in rat blood was significantly lower 30, 45, and 60 minutes after administration of 14C-GMP plus PA-3 than after administration of 14C-GMP alone and was significantly lower 15 minutes after administration of 14C-guanosine plus PA-3 than after administration of 14C-guanosine alone. PA-3 incorporates GMP and guanosine in vitro. Oral administration of PA-3 with GMP and guanosine reduces the intestinal absorption of these purines in vivo. These findings, together with those of previous studies, indicate that PA-3 reduces the absorption of major purines contained in foods. PA-3 may also attenuate the excessive absorption of dietary purines in humans, protecting these individuals against hyperuricemia.

Endotoxin Metabolism Reflects Hepatic Functional Reserve in End-Stage Liver Disease.

BACKGROUND: The hepatic clearance of endotoxin (Et) may reflect hepatic functional reserve and ischemic injury to hepatocytes. Therefore, we examined the relationships between Et activity (EA) and the metrics Pediatric End-Stage Liver Disease (PELD)/Model of End-Stage Liver Disease (MELD) score and alanine transaminase (ALT) levels in the postoperative period. METHODS: We performed 8 living-donor liver transplantations (LDLTs) for biliary atresia at our center from April 2012 to December 2012. EA was measured by means of an Et activity assay (EAA) in samples collected from a vein 1 day before LDLT, from the portal vein during the intraoperative anhepatic phase, from an artery 1 hour after reperfusion, from an artery on postoperative day (POD) 1, and from an artery or vein at PODs 7 and 14. RESULTS: EAs generally remained at low levels. EA at the reperfusion period was significantly lowest. The correlation coefficient for the preoperative MELD/PELD score and the EAA was 0.837, and the corresponding P value was .009; thus, there was a significant relationship between the preoperative MELD/PELD score and the EAA. The correlation coefficients for ALT at POD 1 and EA during the anhepatic phase, at 1 hour after reperfusion, and at POD 1 were 0.64, 0.43, and 0.38, respectively, and the P values for these correlations were .08, .67, and .34. Thus, we observed that ALT and EA generally tended to be somewhat directly correlated, but no significant relationships between these 2 metrics were observed. CONCLUSIONS: Endotoxin metabolism reflects the hepatic functional reserve capacity of end-stage liver disease.

Optimal human and system performance during neonatal resuscitation.

Performance in the delivery of care to sick neonates in need of resuscitation has long been defined primarily in terms of the extent of the knowledge possessed and hands-on skill demonstrated by physicians and other healthcare professionals. This definition of performance in neonatal resuscitation is limited by its focus solely on the human beings delivering care and a perceived set of the requisite skills to do so. This manuscript will expand the definition of performance to include all of the skill sets that humans must use to resuscitate newborns as well as the often complex systems in which those humans operate while delivering that care. It will also highlight how the principles of human factors and ergonomics can be used to enhance human and system performance during patient care. Finally, it will describe the role of simulation and debriefing in the assessment of human and system performance.

Antibody Drug Treatment for Steroid-Resistant Rejection After Pediatric Living Donor Liver Transplantation: A Single-Center Experience.

BACKGROUND: Antibody drugs have been used to treat steroid-resistant rejection (SRR) after liver transplantation. Although anti-thymocyte globulin has been used for SRR after liver transplantation in place of muromonab-CD3 since 2011 in Japan, the effectiveness of anti-thymocyte globulin after pediatric living-donor liver transplantation (LDLT) has not yet been reported. The aim of this study was to evaluate the effectiveness of antibody drug treatment for SRR after pediatric LDLT in our single center. METHODS: Between May 2001 and December 2013, 220 pediatric LDLTs were performed. Initial immunosuppression after LDLT included tacrolimus and methylprednisolone therapy. Acute rejection was diagnosed by use of a liver biopsy and the administration of steroid pulse treatment, and SRR was defined as acute rejection refractory to the steroid pulse treatment. RESULTS: Acute rejection and SRR occurred in 74 (33.6%) and 16 patients (7.3%), respectively. The graft survival rates of non-SRR and SRR were 92.4% and 87.5%, respectively (P = .464). The median concentration of alanine aminotransferase before and after the administration of antibody drug was 193.5 mU/mL (range, 8-508) and 78 mU/mL (range, 9-655), respectively (P = .012). The median rejection activity index before and after the administration of antibody drugs was 5 (range, 2-9) and 1 (range, 0-9), respectively (P = .004). After antibody drug treatment, 12 patients had cytomegalovirus infections, 2 patients had Epstein-Barr virus infections, 3 patients had respiratory infections, and 1 patient had encephalitis. The cause of death in 1 patient with SRR was recurrence of infant fulminant hepatic failure. CONCLUSIONS: Antibody drug treatment for SRR after pediatric LDLT is safe and effective.

Effect of interlamellar interactions on shear induced multilamellar vesicle formation.

Shear-induced multilamellar vesicle (MLV) formation has been studied by coupling the small-angle neutron scattering (SANS) technique with neutron spin echo (NSE) spectroscopy. A 10% mass fraction of the nonionic surfactant pentaethylene glycol dodecyl ether (C12E5) in water was selected as a model system for studying weak inter-lamellar interactions. These interactions are controlled either by adding an anionic surfactant, sodium dodecyl sulfate, or an antagonistic salt, rubidium tetraphenylborate. Increasing the charge density in the bilayer induces an enhanced ordering of the lamellar structure. The charge density dependence of the membrane bending modulus was determined by NSE and showed an increasing trend with charge. This behavior is well explained by a classical theoretical model. By considering the Caillé parameters calculated from the SANS data, the layer compressibility modulus B¯ is estimated and the nature of the dominant inter-lamellar interaction is determined. Shear flow induces MLV formation around a shear rate of 10 s-1, when a small amount of charge is included in the membrane. The flow-induced layer undulations are in-phase between neighboring layers when the inter-lamellar interaction is sufficiently strong. Under these conditions, MLV formation can occur without significantly changing the inter-lamellar spacing. On the other hand, in the case of weak inter-lamellar interactions, the flow-induced undulations are not in-phase, and greater steric repulsion leads to an increase in the inter-lamellar spacing with shear rate. In this case, MLV formation occurs as the amplitude of the undulations gets larger and the steric interaction leads to in-phase undulations between neighboring membranes.

Strain-based HLA association analysis identified HLA-DRB1*09:01 associated with modern strain tuberculosis.

Tuberculosis (TB) occurs as a result of complex interactions between the host immune system and pathogen virulence factors. Human leukocyte antigen (HLA) class II molecules play an important role in the host immune system. However, no study has assessed the association between HLA class II genes and susceptibility to TB caused by specific strains. This study investigated the possible association of HLA class II genes with TB caused by modern and ancient Mycobacterium tuberculosis (MTB). The study included 682 patients with TB and 836 control subjects who were typed for HLA-DRB1 and HLA-DQB1 alleles. MTB strains were classified using a large sequence polymorphism typing method. Association analysis was performed using common HLA alleles and haplotypes in different MTB strains. HLA association analysis of patients infected with modern MTB strains showed significant association for HLA-DRB1*09:01 (odds ratio [OR] = 1.82; P-value = 9.88 × 10-4 ) and HLA-DQB1*03:03 alleles (OR = 1.76; P-value = 1.31 × 10-3 ) with susceptibility to TB. Haplotype analysis confirmed that these alleles were in strong linkage disequilibrium and did not exert an interactive effect. Thus, the results of this study showed an association between HLA class II genes and susceptibility to TB caused by modern MTB strains, suggesting the importance of strain-specific analysis to determine susceptibility genes associated with TB.

Identification of ecdysteroidogenic enzyme genes and their expression during pupal diapause in the cabbage armyworm, Mamestra brassicae.

In this study, we identified ecdysteroidogenic enzymes in the cabbage armyworm, Mamestra brassicae, and demonstrated reduced expression of these genes during diapause. Some insects employ a temporary developmental arrest, diapause, to survive in severe environments. The titres of the moulting hormone ecdysteroid were reduced in diapause pupae of M. brassicae; therefore, ecdysteroidogenesis might be suppressed by a diapause-specific mechanism. To clarify expression changes of ecdysteroidogenic enzyme genes during diapause in M. brassicae, we first identified the genes for seven ecdysteroidogenic enzymes: Neverland, Non-molting glossy (Nm-g), CYP307A1 (Spook), CYP306A1 (Phantom), CYP302A1 (Disembodied), CYP315A1 (Shadow) and CYP314A1 (Shade). Enzymatic assays using heterologous expression in Drosophila Schneider 2 (S2) cells and analysis of mRNA distribution indicated that the identified genes were ecdysteroidogenic enzymes of M. brassicae. Expression levels of these ecdysteroidogenic enzyme genes were compared between prothoracic glands in different pupal stages throughout diapause. Immediately after pupation, diapause-destined pupae showed similar expression levels of ecdysteroidogenic enzyme genes to those of nondiapause pupae. All of these genes showed reduced gene expression after diapause initiation. Expression was immediately increased in diapause-destined pupae at the postdiapause quiescence phase. These results indicate that reduced expression of ecdysteroidogenic enzyme genes suppresses ecdysteroidogenesis and maintains developmental arrest during diapause.

Hotspots of MLV integration in the hematopoietic tumor genome.

Extensive research has been performed regarding the integration sites of murine leukemia retrovirus (MLV) for the identification of proto-oncogenes. To date, the overlap of mutations within specific oligonucleotides across different tumor genomes has been regarded as a rare event; however, a recent study of MLV integration into the oncogene Zfp521 suggested the existence of a hotspot oligonucleotide for MLV integration. In the current review, we discuss the hotspots of MLV integration into several genes: c-Myc, Stat5a and N-myc, as well as ZFP521, as examined in tumor genomes. From this, MLV integration convergence within specific oligonucleotides is not necessarily a rare event. This short review aims to promote re-consideration of MLV integration within the tumor genome, which involves both well-known and potentially newly identified and novel mechanisms and specifications.