Genetic structure of Enyalius capetinga (Squamata, Leiosauridae) in Central Cerrado and transitional areas between the Cerrado and the Atlantic forest, with updated geographic distribution.

The Brazilian Cerrado is considered a biodiversity hotspot highly threatened by human activities. Recently, many studies have demonstrated how underestimated is Cerrado's biodiversity considering squamate species, and the identification of divergent and cryptic lineages is essential for the formulation of effective conservation strategies. The transition areas between the Cerrado and the Atlantic Forest are even less known and, consequently, often dismissed in conservation policies. As previous studies suggested the presence of cryptic diversity within E. capetinga, we investigated patterns and processes in the geographic distribution of its genealogical lineages. We used DNA sequences from individuals collected in six localities and sequences publicly available from three mitochondrial markers (CYT-B, 16S and ND4) and one nuclear marker (C-Mos). We tested if the core and ecotone regions of the Cerrado show differences in biotic and abiotic characteristics that could promote genetic structure and divergence among lineages within E. capetinga. We found evidence for divergent lineages within the species, but not congruent with our hypothesis. Similar divergent patterns were observed in other Cerrado lizards, including interspecific divergences within the Enyalius genus. Molecular characterization of field-collected individuals (previously identified as E. bilineatus), allowed us to update the geographic distribution of the species to include the ecotone between the Cerrado and the Atlantic Forest, an area where species distribution overlap.

Etiology of acute ischaemic cerebrovascular disease associated with rheumatoid arthritis: changes with progression of anti-inflammatory therapy.

BACKGROUND AND PURPOSE: In patients with rheumatoid arthritis (RA), the serum C-reactive protein (CRP) level is associated with ischaemic cerebrovascular disease (iCVD). Acute iCVD patients with RA were investigated, assessing changes of clinical characteristics and CRP with progress in RA treatment. METHODS: Patients hospitalized for acute iCVD from August 2002 to February 2018 were divided into two groups at February 2010. Patients with RA were retrospectively identified. The incidence of RA, the occurrence of acute exacerbation of inflammation due to causes other than synovitis preceding iCVD (non-synovitis AEI) and serum CRP were compared. RESULTS: In the first and second periods, 23/1203 patients (1.9%) and 22/1094 patients (2.0%) respectively had acute iCVD with RA. Non-synovitis AEI was significantly less frequent in the second period (5%, n = 1) than in the first period (35%, n = 8) (P < 0.05). CRP was significantly lower at iCVD onset in the second period [median and interquartile range 2.72 (0.89-4.5) mg/dl vs. 0.34 (0.12-1.19) mg/dl, P < 0.01]. Excluding nine patients with non-synovitis AEI, CRP was still lower in the second period [1.21 (0.47-2.72) mg/dl vs. 0.33 (0.11-0.98) mg/dl, P < 0.01]. CRP levels before both iCVD and non-synovitis AEI tended to be lower in the second period [1.53 (0.3-2.78) mg/dl vs. 0.69 (0.06-1.28) mg/dl, P = 0.059]. Two patients using tocilizumab developed iCVD despite persistently low CRP levels. CONCLUSIONS: With progress in treatment, RA-related inflammation was better suppressed and CRP decreased, but the prevalence of RA amongst acute iCVD patients was unchanged. Strategies for tighter control of inflammation are needed, and a new biomarker may be required in patients using tocilizumab.

Comparative evaluation of new and conventional classifications of magnifying endoscopy with narrow band imaging for invasion depth of superficial esophageal squamous cell carcinoma.

A new classification of magnifying endoscopy with narrow band imaging (ME-NBI) for diagnosing and staging superficial esophageal squamous cell carcinoma (SESCC) was proposed by the Japan Esophageal Society in 2011. This study aimed to compare the new classification with the conventional classifications (Inoue's classification and Arima's classification). This was a prospective analysis of data from a single cancer center involving 151 consecutive patients with 156 SESCCs that were endoscopically or surgically resected. Initially, only ME-NBI images were selected and reviewed independently by three experienced endoscopists. White light imaging (WLI) was then evaluated separately after an interval. The diagnostic performance of each classification and interobserver agreement were assessed, and the WLI findings that affect the diagnosis by the new classification were identified. The specificity for classifying invasive depth as epithelium (EP)/lamina propria mucosae (LPM) confined was higher with the new classification than with Inoue's classification (0.512 vs. 0.349; P = 0.02) and Arima's classification (0.512 vs. 0.279; P < 0.01). However, the sensitivity was lower (0.902 vs. 1.000; P < 0.01) compared with Arima's classification. The concordance rates of three evaluators (κ values) were 0.52 for the new classification, 0.50 for Inoue's classification, and 0.23 for Arima's classification. On multivariate analysis, thickness on WLI independently affected the accuracy of diagnosis with the new classification (OR 3.23; 95%CI, 1.30-8.03). The new classification is superior to conventional classifications with respect to specificity for diagnosing SESCC with depth EP/LPM. Thickness on WLI was a factor negatively affecting the diagnostic performance of the new classification.

Enhanced loading regimen of teicoplanin is necessary to achieve therapeutic pharmacokinetics levels for the improvement of clinical outcomes in patients with renal dysfunction.

We evaluated the clinical efficacy and safety of teicoplanin according to the pharmacokinetics (PK) therapeutic level achieved in patients with renal dysfunction. Target trough concentration (Cmin) was ≥15-30 µg/ml which has been recommended in patients with normal renal function. Adult patients (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)) who were treated by teicoplanin were included in the study. We adopted two types of regimen for the initial 3 days: the conventional regimen, and the enhanced loading regimen (10 mg/kg twice daily on the 1st day, followed by 6.7-10 mg/kg once daily for the 2nd and 3rd days]. Two hundred and eighty-eight patients were evaluated for safety, and 106 patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were evaluated for clinical efficacy. A significantly higher success rate was obtained in patients who achieved the target initial Cmin compared with those that did not (75.0 % vs 50.0 %, p = 0.008). In a multivariate analysis, initial Cmin ≥15 µg/ml was an independent factor for clinical success (adjusted odds ratio: 4.20, 95 % confidence interval: 1.34-13.15). In patients with 15-30 µg/ml of maximal Cmin during therapy, nephrotoxicity occurred in 13.1 %, and hepatotoxicity in 2.6 %, and these incidences were not significantly higher compared with those patients with <15 µg/ml. In conclusion, achievement of Cmin of 15-30 µg/ml without delay was necessary to improve clinical outcomes for the treatment by teicoplanin in patients with renal dysfunction. Further investigation is required regarding the optimal loading regimen to achieve the therapeutic levels in those patients.

The relationship between the daily step counts and low back pain during pregnancy.

PURPOSE: To investigate the relationship between the change of daily step counts and low back pain (LBP) during pregnancy. Materials and METHODS: Pregnant women at less than eight weeks of gestation (WG) were recruited. Daily step counts were measured with a pedometer. To assess LBP, the Oswestry disability index (ODI) score was recorded. Thirty-six individuals were divided into the LBP and non-LBP groups. The effect of step counts on LBP between the two groups was analyzed. RESULTS: At 16-19 WG, step counts were not considerably changed in the non-LBP group but were significantly increased in the LBP group. At 24-27 and 32-35 WG, step counts were increased in the non-LBP group but were significantly decreased in the LBP group. CONCLUSIONS: Acute increase of daily step counts in early pregnancy is a risk for LBP, and gradual increases of step counts after mid-pregnancy is recommended for women.

Optogenetic control of insulin secretion by pancreatic ß-cells in vitro and in vivo.

The present study assessed the ability of optogenetics techniques to provide a better understanding of the control of insulin secretion, particularly regarding pancreatic ß-cell function in homeostasis and pathological conditions such as diabetes mellitus (DM). We used optogenetics to investigate whether insulin secretion and blood glucose homeostasis could be controlled by regulating intracellular calcium ion concentrations ([Ca(2+)]i) in a mouse pancreatic ß-cell line (MIN6) transfected with the optogenetic protein channelrhodopsin-2 (ChR2). The ChR2-transfected MIN6 (ChR2-MIN6) cells secreted insulin following irradiation with a laser (470 nm). The increase in [Ca(2+)]i was accompanied by elevated levels of messenger RNAs that encode calcium/calmodulin-dependent protein kinase II delta and adenylate cyclase 1. ChR2-MIN6 cells suspended in matrigel were inoculated into streptozotocin-induced diabetic mice that were then subjected to a glucose tolerance test. Laser irradiation of these mice caused a significant decrease in blood glucose, and the irradiated implanted cells expressed insulin. These findings demonstrate the power of optogenetics to precisely and efficiently controlled insulin secretion by pancreatic ß-cells 'on demand', in contrast to techniques using growth factors or chemical inducers. Optogenetic technology shows great promise for understanding the mechanisms of glucose homeostasis and for developing treatments for metabolic diseases such as DM.

Observation of a p-wave one-neutron halo configuration in (37)Mg.

Cross sections of 1n-removal reactions from the neutron-rich nucleus (37)Mg on C and Pb targets and the parallel momentum distributions of the (37)Mg residues from the C target have been measured at 240 MeV/nucleon. A combined analysis of these distinct nuclear- and Coulomb-dominated reaction data shows that the (37)Mg ground state has a small 1n separation energy of 0.22(-0.09)(+0.12) MeV and an appreciable p-wave neutron single-particle strength. These results confirm that (37)Mg lies near the edge of the "island of inversion" and has a sizable p-wave neutron halo component, the heaviest such system identified to date.

Deformation-driven p-wave halos at the drip line: 31Ne.

The halo structure of 31Ne is studied using 1n-removal reactions on C and Pb targets at 230 MeV/nucleon. A combined analysis of the cross sections of these nuclear and Coulomb dominated reactions that feed directly the 30Ne ground-state reveals 31Ne to have a small neutron separation energy, 0.15(-0.10)(+0.16) MeV, and spin-parity 3/2-. Consistency of the data with reaction and large-scale shell-model calculations identifies 31Ne as deformed and having a significant p-wave halo component, suggesting that halos are more frequent occurrences at the neutron drip line.

Prospective evaluation of a transnasal endoscopy utilizing flexible spectral imaging color enhancement (FICE) with the Valsalva maneuver for detecting pharyngeal and esophageal cancer.

BACKGROUND/AIMS: This study evaluated the efficacy and safety of transnasal endoscopy (TNE) with flexible spectral imaging color enhancement (FICE) for detection of superficial cancer in the pharyngeal and esophageal regions for high-risk populations. METHODOLOGY: Patients who previously had head and neck or esophageal squamous cell carcinoma were enrolled. Screening was conducted using TNE with conventional white-light endoscopy (WLE) followed by FICE chromoendoscopy. For observation of the pharyngeal region, the Valsalva maneuver was employed. RESULTS: 99 patients were eligible. Six esophageal cancers were detected in four patients (4.0%). The sensitivity, specificity, and accuracy for the detection of cancer were 25.0% (95% CI, 3.4- 71.0), 97.8% (95% CI, 92.1-99.8), and 94.9 % (95% CI, 88.4-98.1), respectively for WLE; 100% (95% CI, 45.4%- 100%), 96.8% (95% CI, 90.7%-99.3%), and 96.9% (95% CI, 89.3%-99.1%), respectively for FICE chromoendoscopy. Pain in the nose and nasal hemorrhage were observed in 3 (3.0%) and 2 patients (2.0%), respectively. Following the Valsalva maneuver, endoscopic scores significantly increased from a mean of 1.1 (0.8-1.4) to 2.0 (1.3-2.6) (p<0.05). CONCLUSIONS: TNE with the Valsalva maneuver is a promising screening method for the pharyngeal and esophageal regions. TNE with FICE chromoendoscopy for detecting pharyngeal and esophageal cancer was more sensitive than WLE.

Expression of dihomo-γ-linolenic acid and FADS1/2 and ELOVL2/5 in term rabbit placentas.

Long-chain polyunsaturated fatty acids (LCPUFAs) are essential for both fetal and placental development. We characterized the FA composition and gene expression levels of FA-metabolizing enzymes in rabbit placentas. Total FA compositions from term rabbit placentas (n = 7), livers, and plasma (both n = 4) were examined: among LCPUFAs with more than three double bonds, dihomo-γ-linolenic acid (DGLA) was the most abundant (11.4 ± 0.69 %, mean ± SE), while arachidonic acid was the second-most rich component (6.90 ± 0.56 %). DGLA was barely detectable (<1 %) in livers and plasma from term rabbits, which was significantly lower than in placentas (both p < 0.0001). Compared with the liver, transcript levels of the LCPUFA-metabolizing enzymes FADS2 and ELOVL5 were 7- and 4.5-fold higher in placentas (both p < 0.05), but levels of FADS1 and ELOVL2 were significantly lower (both p < 0.01). Our results suggest a placenta-specific enzyme expression pattern and LCPUFA profile in term rabbits, which may support a healthy pregnancy.

N = 16 spherical shell closure in 24O.

The unbound excited states of the neutron drip-line isotope 24O have been investigated via the 24O(p,p')23O + n reaction in inverse kinematics at a beam energy of 62 MeV/nucleon. The decay energy spectrum of 24O* was reconstructed from the momenta of 23O and the neutron. The spin parity of the first excited state, observed at E(x) = 4.65±0.14 MeV, was determined to be J(π) = 2+ from the angular distribution of the cross section. Higher-lying states were also observed. The quadrupole transition parameter ß2 of the 2(1)+ state was deduced, for the first time, to be 0.15±0.04. The relatively high excitation energy and small ß2 value are indicative of the N = 16 shell closure in 24O.

Is the 7/2(1)- isomer state of 43S spherical?

We report on the spectroscopic quadrupole moment measurement of the 7/2(1)(-) isomeric state in (16)(43)S(27) [E*=320.5(5) keV, T(1/2)=415(3) ns], using the time dependent perturbed angular distribution technique at the RIKEN RIBF facility. Our value, |Q(s)|=23(3) efm(2), is larger than that expected for a single-particle state. Shell model calculations using the modern SDPF-U interaction for this mass region reproduce remarkably well the measured |Q(s)|, and show that non-negligible correlations drive the isomeric state away from a purely spherical shape.

Male death resulting from hybridization between subspecies of the gypsy moth, Lymantria dispar.

We explored the origin of all-female broods resulting from male death in a Hokkaido population of Lymantria dispar through genetic crosses based on the earlier experiments done by Goldschmidt and by testing for the presence of endosymbionts that are known to cause male killing in some insect species. The mitochondrial DNA haplotypes of the all-female broods in Hokkaido were different from those of normal Hokkaido females and were the same as those widely distributed in Asia, including Tokyo (TK). Goldschmidt obtained all-female broods through backcrossing, that is, F1 females obtained by a cross between TK females (L. dispar japonica) and Hokkaido males (L. dispar praeterea) mated with Hokkaido males. He also obtained all-male broods by mating Hokkaido females with TK males. Goldschmidt inferred that female- and male-determining factors were weakest in the Hokkaido subspecies and stronger in the Honshu (TK) subspecies. According to his theory, the females of all-female broods mated with Honshu males should produce normal sex-ratio broods, whereas weaker Hokkaido sexes would be expected to disappear in F1 or F2 generations after crossing with the Honshu subspecies. We confirmed both of Goldschmidt's results: in the case of all-female broods mated with Honshu males, normal sex-ratio broods were produced, but we obtained only all-female broods in the Goldschmidt backcross and obtained an all-male brood in the F1 generation of a Hokkaido female crossed with a TK male. We found no endosymbionts in all-female broods by 4,'6-diamidino-2-phenylindole (DAPI) staining. Therefore, the all-female broods observed in L. dispar are caused by some incompatibilities between Honshu and Hokkaido subspecies.

Epstein-Barr virus load for early detection of lymphoproliferative disorder in pediatric renal transplant recipients.

AIM: The aims of this study were to establish a protocol for monitoring Epstein-Barr virus (EBV) infection for identification of pediatric renal transplant recipients with a high risk of developing posttransplant lymphoproliferative disorder (PTLD) and to predict the development of PTLD. SUBJECTS AND METHODS: Peripheral blood mononuclear cells (PBMCs) and plasma EBV loads were measured by nested PCR (n-PCR) and real-time PCR (r-PCR) every 1 - 3 months after grafting in 17 pediatric recipients who were seronegative for EBV before grafting (4 with EBV-associated symptoms, including 2 with PTLD (Group A); 6 with asymptomatic persistent high EBV loads in PBMCs of > 1,000 copies/µgDNA for over 6 months (Group B); and 7 with neither EBV-associated symptoms nor persistent high EBV loads in PBMCs (Group C)). RESULTS: n-PCR revealed EBV-DNA in PBMCs from all patients. The EBV genome was present in plasma in 3 (75%), 1 (17%), and 0 (0%) in Groups A, B and C (p < 0.01 for A vs. B and A vs. C). EBV loads detected by r-PCR in PBMCs were significantly higher in Groups A (p < 0.05) and B (p < 0.01) compared to Group C. EBV genomes in plasma were detected by n- and r-PCR in only the 2 cases with PTLD. One patient with lymphadenitis in Group A and 1 patient in Group B had EBV-DNA in plasma based on n-PCR, but the viral loads using r-PCR were < 250 copies/ml. CONCLUSION: EBV loads in PBMCs alone are insufficient for predicting EBV-associated symptoms including PTLD. Plasma EBV loads (over 250 copies/ml) estimated by r-PCR may be useful to distinguish PTLD from other EBV-associated diseases or asymptomatic viremia.

Implementation of a hospital-wide project for appropriate antimicrobial prophylaxis.

The aim of this study was to confirm the effect of implementing a hospital-wide project for appropriate use of antimicrobial prophylaxis (AMP) to reduce the rate of antibiotic-resistant organisms. Fifteen different manuals for each surgical department have been simultaneously implemented since February 2007. Compliance rate was compared between pre- and postintervention periods (3 months for each period). As an effect of this intervention, we analyzed changes in the rates of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus among organisms isolated postoperatively. The number of operations was 1,627 in both periods. Among patients whose surgeries were longer than 3 h in duration, 75% received an additional intraoperative antimicrobial dose in the postintervention period and 23% in the preintervention period (P < 0.001). Although most patients received postoperative AMP with an interval of q12 h in the preintervention period, 63% of the patients received AMP with an interval of q8 h in the postintervention period. The duration of AMP use was reduced from 2.4 ± 1.9 to 1.6 ± 1.5 days (P < 0.001). Forty-seven percent of patients discontinued AMP within 24 h and 81% within 48 h. Isolation rates of P. aeruginosa among all gram-negative organisms significantly decreased from 13% (68/538 patients) to 7.3% (37/509 patients) (P = 0.004). Execution of a hospital-wide project to promote the appropriate use of AMP, including shortening the duration of AMP use, was useful to decrease the rate of P. aeruginosa isolated postoperatively.

Halo structure of the island of inversion nucleus 31Ne.

The cross sections for single-neutron removal from the very neutron-rich nucleus 31Ne on Pb and C targets have been measured at 230 MeV/nucleon using the RIBF facility at RIKEN. The deduced large Coulomb breakup cross section of 540(70) mb is indicative of a soft E1 excitation. Comparison with direct-breakup model calculations suggests that the valence neutron of 31Ne occupies a low-l orbital (most probably 2p(3/2)) with a small separation energy (S(n) approximately < 0.8 MeV), instead of being predominantly in the 1f(7/2) orbital as expected from the conventional shell ordering. These findings suggest that 31Ne is the heaviest halo system known.

Anti-oncogenic and oncogenic potentials of interferon regulatory factors-1 and -2.

Interferon regulatory factor-1 (IRF-1), a transcriptional activator, and IRF-2, its antagonistic repressor, have been identified as regulators of type I interferon and interferon-inducible genes. The IRF-1 gene is itself interferon-inducible and hence may be one of the target genes critical for interferon action. When the IRF-2 gene was overexpressed in NIH 3T3 cells, the cells became transformed and displayed enhanced tumorigenicity in nude mice. This transformed phenotype was reversed by concomitant overexpression of the IRF-1 gene. Thus, restrained cell growth depends on a balance between these two mutually antagonistic transcription factors.

Experimental evaluation of photocrosslinkable chitosan hydrogel as injection solution for endoscopic resection.

BACKGROUND AND STUDY AIMS: Saline as an injection solution for endoscopic resection techniques has several disadvantages such as a short-lasting effect leading to a potentially higher risk of bleeding and perforation. The new substance of photocrosslinkable chitosan hydrogel in a DMEM/F12 medium (PCH) can be converted into an insoluble hydrogel by ultraviolet irradiation for 30 s, and was evaluated in two sets of animal experiments. METHODS: 18 pigs were used in the two parts of the study. First, mucosal resections were done with either PCH or hypertonic saline; the effects of both agents on wound healing were examined endoscopically and histologically. Second, in vivo degradation of PCH was examined using six pig stomachs. RESULT: PCH injection led to a longer-lasting elevation with clearer margins, compared with hypertonic saline, thus enabling precise endoscopic submucosal dissection (ESD) along the margins of the elevated mucosa. The endoscopic appearance after ESD was similar in both groups. PCH biodegradation was completed within 8 weeks according to endoscopic and histologic analyses. CONCLUSION: PCH is a promising agent for submucosal injection prior to various techniques of endoresection. It should be evaluated in clinical trials after biocompatibility testing for PCH is completed.

Effect of oral mizoribine pulse therapy for frequently relapsing steroid-dependent nephrotic syndrome.

AIM: To evaluate the efficacy of oral mizoribine (MZB) pulse therapy given twice a week for frequently relapsing steroid-dependent nephrotic syndrome (FR-SDNS). SUBJECTS: 16 patients with FR-SDNS with a median age of 11.6 years (range 5.1 â 17.8 years) were enrolled in the study. This study was a Phase II trial. METHODS: The dose of MZB was adjusted to achieve a peak blood level of about 3 microg/ml (10.0-19.7 mg/kg/d, maximum total dose 750 mg) in two divided doses given 2 days a week before a meal. The therapeutic benefits of MZB pulse therapy were assessed based on a comparison of the incidence of relapse (times/year) and the required daily dosage of prednisolone (PSL) before and after therapy. RESULTS: The incidence of relapse after therapy was significantly lower than that before therapy (2.4 A+/- 1.6 vs. 3.4 A+/- 1.1 times/year, p < 0.05), and the required daily dosage of PSL after therapy was lower than that before therapy (0.39 A+/- 0.26 vs. 0.47 A+/- 0.24 mg/kg/d; not significant). During the follow-up period, discontinuation of PSL was possible in 6 of 12 patients who showed a decreased rate of relapse after therapy. The age at entry into the study and the peak blood concentration of MZB of these patients were significantly higher than in four patients who did not show a decreased rate of relapse (12.3 A+/- 4.3 vs. 7.9 A+/- 2.6 years, p < 0.05; 3.00 A+/- 0.93 vs. 1.97 A+/- 0.36 microg/ml, p < 0.005, respectively). No adverse effects were observed in any patients. CONCLUSION: Our results show that MZB pulse therapy is effective in decreasing the frequency of relapse and reducing the required PSL dosage in older pediatric patients with FR-SDNS.