The efficiency of Levofloxacin Containing Sequential Therapy with or without Bismuth, in Helicobacter Pylori Eradication, in Non-ulcer Dyspepsia.
The aim of this study is to determine the efficiency of levofloxacin containing sequential therapy with or without bismuth in Helicobacter pylori (Hp) eradication in nonulcer dyspepsia. One hundred and ninety Hp-positive patients with the pre-diagnosis of nonulcer dyspepsia were included in this study. Patients were randomized into 2 groups and 95 individuals were included in each group. The first group was administered levofloxacin containing sequential therapy with bismuth, whereas the second group was administered only levofloxacin containing sequential therapy. Rates of therapy discontinuation and eradication success were compared between the 2 groups. Furthermore, symptomatic healing rates were com-pared between patients in whom Hp eradication was achieved and in whom it was not achieved. Ninety-one patients from each group applied for follow-up after treatment. It was found that 7/91(7.6%) patients from the first group and 5/91(5.4%) patients from the second group did not complete the therapy (p >0.05). In patients who completed therapy, Hp eradication was achieved in 72 out of the 84 patients (85.2%) from the first group and 71 out of 86 patients (82.6%) from the second group (p > 0.05). In addition, symptomatic healing occurred in 125 out of 143 patients (87.4%) in whom Hp was eradicated and 12 out of 27 (44.4%) patients in whom Hp was not eradicated (p < 0.001). Levofloxacin containing sequential therapy for 14 days is quite effective and well-tolerated choice for Hp eradication. However, adding bismuth to sequential therapy does not significantly improve Hp eradication success rates. Therefore, Hp eradication is beneficial and necessary in patients with nonulcer dyspepsia.


Comparative clinical trial of regional anticoagulation for hemodialysis.
The regional anticoagulating effects of FUT-175 (protease inhibitor), and regional or low dose heparinization (RH or LH) were examined comparatively by randomized controlled protocol on 157 hemodialysis (HD) patients with hemorrhagic complications. Increases in bleeding because of HD were milder in FUT as compared with RH and LH, and the bleeding time after needle removal was significantly shorter in FUT than that in heparin. During HD, the prolongation of celite activated coagulation time (CCT) of the intracorporeal blood was significantly milder in FUT than in heparin and that of blood passing through the dialyzer was increased in FUT compared with LH. FUT showed no prolongation of CCT after HD. These results indicate that FUT is a more useful and safer anticoagulant for HD patients with hemorrhagic complications than any regional anticoagulating method using heparin (RH or LH).


Pig Urinary Concentration of Mycotoxins and Metabolites Reflects Regional Differences, Mycotoxin Intake and Feed Contaminations.
The determination of mycotoxin and metabolite concentrations in human and animal urine is currently used for risk assessment and mycotoxin intake measurement. In this study, pig urine (n = 195) was collected at slaughterhouses in 2012 by the Swedish National Food Agency in three counties representing East, South and West regions of Sweden. Urinary concentrations of four mycotoxins, (deoxynivalenol (DON), zearalenone (ZEA), fumonisin B1 (FB1), and ochratoxin A (OTA)), and four key metabolites, (deepoxy-deoxynivalenol (DOM-1), aflatoxin M1 (AFM1, biomarker of AFB1), α-zearalenol (α-ZOL), and β-zearalenol (β-ZOL)) were identified and measured by UPLC-MS/MS. Statistically significant regional differences were detected for both total DON (DON + DOM-1) and total ZEA (ZEA + α-ZOL + β-ZOL) concentrations in pig urine from the three regions. These regional differences were in good agreement with the occurrence of Fusarium graminearum mycotoxins (DON + ZEA) in cereal grains harvested in 2011 in Sweden. There were no statistically significant differences in FB1, AFM1 and OTA urinary concentrations in pigs from the three regions. The overall incidence of positive samples was high for total ZEA (99-100%), total DON (96-100%) and OTA (85-95%), medium for FB1 (30-61%) and low for AFM1 (0-13%) in the three regions. Urinary mycotoxin biomarker concentrations were used to estimate mycotoxin intake and the level of mycotoxins in feeds consumed by the monitored pigs. The back-calculated levels of mycotoxins in feeds were low with the exception of seven samples that were higher the European limits.


(Fe,N-codoped carbon nanotube)/(Fe-based nanoparticle) nanohybrid derived from Fe-doped g-C3N4: A superior catalyst for oxygen reduction reaction.
Transition metal- and N-codoped carbon nanotubes (CNTs) have superior catalytic activity because the curling surface enhances the bonding ability of atoms within CNTs to other species. However, it is a great challenge to prepare CNTs with transition metal- and N-doped at high level during the growth of CNTs. Here, (Fe,N-codoped CNT)/(Fe-based nanoparticle) (Fe,N-CNT/FeNP) hybrid nanostructures are for the first time prepared through the carbonization of Fe-doped g-C3N4. The doping of Fe and N is simultaneously realized during the formation of CNTs. Meanwhile, the abundant and homogeneous Fe and N in Fe-doped g-C3N4 ensure high-level and uniform doping of Fe and N in CNTs. The Fe,N-CNT/FeNP hybrid nanostructures have several types of active components, including homogeneously distributed coordinating Fe moieties (FeCxNy or FeNx) and CFe15.1 nanoparticles embedded in Fe,N-CNTs, towards oxygen reduction reaction (ORR). A superior ORR electrocatalytic performance is therefore obtained on the Fe,N-CNT/FeNP nanohybrids. Our preparation method opens an avenue to preparation of CNTs with transition metal- and N-doping at high-level, and the superior performance of Fe,N-CNT/FeNP nanostructures for ORR will be very helpful to the development of fuel cells and metal-air batteries.


Duodenal haematoma in association with coeliac axis stenosis.
Duodenal haematoma is now a well-established clinical entity. The aetiology, however, is not always clear. Trauma or bleeding due to anticoagulant therapy is the cause in most cases. It is suspected that unreported minor trauma may cause the remainder. A case is reported in which the pancreaticoduodenal circulation was markedly dilated and tortuous because of severe coeliac axis stenosis. It is suggested that no trauma is required in this situation to cause bleeding, which may be due to spontaneous repture of the smaller vasa recta.


Improved contractility with tepid modified full blood cardioplegia compared with cold crystalloid cardioplegia in a piglet model.
Experience regarding warm blood cardioplegia according to Calafiore results from its broad use in adult patients. In this experimental study, tepid (28°C) modified full blood cardioplegia (MBC) was adopted for paediatric use and compared with cold crystalloid cardioplegia (CCC). Twenty male piglets (mean weight: 11.1 ± 1.0 kg) were operated on cardiopulmonary bypass (CPB) in moderate hypothermia (28°C) and randomized to MBC (n = 8) or CCC (n = 12) for 60 min aortic cross-clamping. Blood levels of myocardial proteins [N-terminal pro-brain natriuretic peptide (NT-pro-BNP), myoglobin, creatine kinase type MB and troponin-I] were investigated at the beginning of the experiment and after CPB. Haemodynamic measurements included thermodilution and conductance-catheter technique inserted through the left ventricle-apex. Pressure-volume loop analysis was performed with dobutamine-stress test and inflow occlusion, enabling preload independent evaluation of myocardial performance. Changes of measured data post-CPB were calculated in relation to baseline-levels (%). Baseline and operative data in both groups were similar. During the experiment, cardiac markers showed no significant variations between groups. Pressure-volume loop analysis during stress test revealed a significantly higher preload independent contractility (slope of end-systolic pressure-volume relation: Ees) with MBC compared with CCC (MBC: 123 ± 35% [confidence interval (CI95): 93-153] vs CCC: 78 ± 34% [CI95: 54-102]; P = 0.042), whereas cardiac output was not significantly different between groups {MBC: 122 ± 16% [95% confidence interval (CI95): 109-135] vs CCC: 105 ± 17% [CI95: 93-116]; P = 0.069}. This randomized animal study proves feasibility and safety of MBC for paediatric use. Haemodynamic evaluation and cardiac markers did not show inferiority to standard CCC. Moreover, MBC seems to be associated with superior contractility post bypass, which encourages us to use MBC in paediatric patients in the near future.


The amino acid sequence of the insulin from a primitive vertebrate, the atlantic hagfish (Myxine glutinosa).
Insulin has been isolated and purified from the islet organs of the cyclostome, Myxine glutinosa, by means of acid-ethanol extraction, fractional precipitation, and gel filtration. The complete amino acid sequence of the hormone has been determined by Edman degradation of the S-carboxymethylated or performic acid-oxidized A and B chains, and of various tryptic peptides derived from the chains. The 52-residue hagfish insulin has many structural features in common with other vertebrate insulins including the locations of the 6 half-cystine residues, the NH2-terminal 7 residues and the COOH-terminal 6 residues of the A chain, and several shorter sequences in the B chain that are known to comprise the dimer interface in porcine insulin crystals. Of the 24 residues which are invariant among the other known insulins, 23 are identical in hagfish int 16 of these sites it contains residues not previously observed in vertebrate insulins. The B chain also contains an additional COOH-terminal residue of methionine, making it 1 residue longer than the usual 30-residue mammalian B chains. Several features of the tertiary and quaternary structure of hagfish insulin, including the probable absence of a metal ion-stabilized hexameric form, are discussed on the basis of these findings. The results suggest that the conformation of the insulin molecule has been well conserved throughout the entire evolution of the vertebrates.


Predicting augmented renal clearance using estimated glomerular filtration rate in critically-ill children .
Measured glomerular filtration rate (mGFR) is often used to identify augmented renal clearance (ARC). However, in the clinical setting, estimated GFR (eGFR) is obtained more quickly and inexpensively. We aimed to determine whether eGFR can identify ARC by evaluating the correlation between the eGFR and vancomycin trough level (VTL). We retrospectively reviewed the records of patients aged ≤ 18 years who underwent vancomycin therapeutic drug monitoring at our tertiary hospital from July 2009 to June 2014. VTL, serum creatinine concentration, eGFR, and clinical factors affecting VTL were analyzed. Of 101 patients, 76 (75.25%) had a subtherapeutic VTL. Patient age (p = 0.006), the daily vancomycin dose (p = 0.041) and dosing interval (p = 0.006), and eGFR (p < 0.001) affected the VTL. Multivariate analysis showed a significant relationship between eGFR and VTL (adjusted R2, 0.812; p < 0.001). An increased eGFR (odds ratio, 1.002; 95% confidence interval, 1.001 - 1.003; p = 0.001) was a risk factor for a subtherapeutic vancomycin level. The cutoff eGFR value predicting a subtherapeutic vancomycin level was 110.51 mL/min/1.73m2 (area under the curve, 0.753). The eGFR correlates with the VTL, and the eGFR cutoff value can predict a subtherapeutic vancomycin level. eGFR is a reliable and efficient alternative to mGFR for identifying ARC. .


Activity-based probes for functional proteomics.
Achieving an understanding of the functional role of all proteins expressed by a complex organism will require the development of methods that enable the rapid monitoring of protein function on a global scale. Current genomics and proteomics technologies fall short of this goal since they measure only the relative abundance of transcripts and proteins, respectively. Recent efforts in several laboratories have led to the development of tagged chemical probes that selectively react with families of active enzymes based on shared mechanistic features. These activity-based probes (ABPs) permit the quantitation and comparison of multiple protein activities simultaneously in complex proteomes. In this paper, the general properties and design features of ABPs will be discussed with an emphasis on the use of ABPs for activity-based proteome analysis.


MR image-guided delivery of cisplatin-loaded brain-penetrating nanoparticles to invasive glioma with focused ultrasound.
Systemically administered chemotherapeutic drugs are often ineffective in the treatment of invasive brain tumors due to poor therapeutic index. Within gliomas, despite the presence of heterogeneously leaky microvessels, dense extracellular matrix and high interstitial pressure generate a "blood-tumor barrier" (BTB), which inhibits drug delivery and distribution. Meanwhile, beyond the contrast MRI-enhancing edge of the tumor, invasive cancer cells are protected by the intact blood-brain barrier (BBB). Here, we tested whether brain-penetrating nanoparticles (BPN) that possess dense surface coatings of polyethylene glycol (PEG) and are loaded with cisplatin (CDDP) could be delivered across both the blood-tumor and blood-brain barriers with MR image-guided focused ultrasound (MRgFUS), and whether this treatment could control glioma growth and invasiveness. To this end, we first established that MRgFUS is capable of significantly enhancing the delivery of ~60nm fluorescent tracer BPN across the blood-tumor barrier in both the 9L (6-fold improvement) gliosarcoma and invasive F98 (28-fold improvement) glioma models. Importantly, BPN delivery across the intact BBB, just beyond the tumor edge, was also markedly increased in both tumor models. We then showed that a CDDP loaded BPN formulation (CDDP-BPN), composed of a blend of polyaspartic acid (PAA) and heavily PEGylated polyaspartic acid (PAA-PEG), was highly stable, provided extended drug release, and was effective against F98 cells in vitro. These CDDP-BPN were delivered from the systemic circulation into orthotopic F98 gliomas using MRgFUS, where they elicited a significant reduction in tumor invasiveness and growth, as well as improved animal survival. We conclude that this therapy may offer a powerful new approach for the treatment invasive gliomas, particularly for preventing and controlling recurrence.


Environmental sustainability in an agricultural development project: a system dynamics approach.
Regional agricultural projects based on water resource development have many potential impacts on social and natural environments. In this research, potential long-term environmental problems of the Southeastern Anatolian Project (GAP) related to water resources, land use, land degradation, agricultural pollution and demography are analysed from a systems perspective. The analysis focuses on the totality of environmental, social and economic issues. For this purpose, a system dynamics simulation model (GAPSIM) has been developed as an experimental platform for policy analysis. GAPSIM was validated, first 'structurally', using the tests suggested by the literature and then the model 'behaviour' was tested and calibrated with respect to available data. The reference behaviour of GAPSIM reveals that, as the irrigated lands are developed, GAP faces significant water scarcity because of the increased intensity of cotton, the crop with the highest demands for water. Simulation results also indicate that two key environmental factors, pesticide and fertilizer consumption may reach undesirable levels. Alternative irrigation water release strategies, development rates of irrigated fields and farm rotation practices appear as important policy tools in achieving long-term environmental sustainability. GAPSIM promises to be not only a useful laboratory for policy makers of GAP, but also a useful generic structure applicable to other similar regional development projects.


Chordal tissue in endomyocardial biopsies.
The incidence of chordal tissue in endomyocardial biopsies from heart transplant recipients and the possibility of an association between this incidence and tricuspid regurgitation or tricuspid valvular abnormalities were prospectively investigated. The biopsies were performed to detect rejection. Postoperative echocardiography and Doppler were done according to routine schedule and always when chordal tissue was found histologically, for specific evaluation of the tricuspid valve function. Chordal tissue was detected in 24 of 1,265 bites at 206 biopsies during the study period. Echocardiographically there was no significant increase in tricuspid regurgitation and no major valvular abnormality in any patient after biopsy showing chordal tissue. The presence of chordal tissue in biopsy specimens implies that the tricuspid valve is potentially at risk in biopsy. Our results, however, also showed that occasional capture of chordal tissue by the bioptome did not necessarily result in tricuspid valve dysfunction.


Optimal conditions for synthesizing complementary DNA in the HIV-1 endogenous reverse transcriptase reaction.
Concentration of monovalent and divalent cations, anionic detergent, reducing agent and nucleotides, as well as pH, temperature, and incubation time were optimized for high levels of HIV-1 endogenous reverse transcriptase activity. In addition, mellitin, a peptide substitute for anionic detergent, and oligo(dT)12-18 were found to stimulate nucleic acid synthesis. This HIV-1 endogenous reaction demonstrated RNA- and DNA-dependent DNA polymerase activities. Nucleic acid intermediates and final products included RNA:DNA hybrids as well as single- and double-stranded DNA. The complementary DNA products formed were representative of all regions of the HIV-1 genome.


Myotonic dystrophy presenting as atrial flutter in childhood.
A 12-year-old boy presented with tachycardia and cardiomegaly. An electrocardiogram showed atrial flutter with a ventricular rate of 170 beats/min. The echocardiogram showed left ventricular dilation, with decreased contractility. Electromyography confirmed the diagnosis of myotonic dystrophy. The atrial flutter was converted to sinus rhythm by electroversion, leading to restoration of normal cardiac function. Our case illustrates that atrial flutter can be an early sign of the cardiac complications of myotonic dystrophy in childhood.


The insulin gradient phenomenon: a manifestation of the effects of body weight on blood pressure and insulin resistance.
The relationship between hyperinsulinemia and hypertension is frequently observed in overweight patients; however, population studies have not confirmed an independent association. A population study was conducted to assess whether differences in body mass index and levels of insulinemia modify cardiovascular hemodynamics and arterial pressure. In all, 322 healthy adults underwent a medical evaluation including insulin sensitivity and cardiac performance assessment with echocardiography. A direct relationship between body mass index and blood pressure (r=0.36; P<.01) was shown along with increments in fasting insulin levels. The underlying and progressive rise in insulin levels during blood pressure increase is named the insulin gradient. Left ventricular systolic indexes were significantly greater in the higher-insulin quartile. These findings suggest that body weight increases accompany a rise in systolic pressure and a drop in insulin sensitivity related to the insulin gradient. Increments in ejection fraction and cardiac output with normal total peripheral resistance are related to the blood pressure shift in these persons.


Long-term safety and efficacy of human bone morphogenetic protein (HBMP) in the treatment of resistant non-unions and failed arthrodesis.
The bone morphogenetic protein (BMP) has emerged as a suitable alternative to autogenous cancellous bone grafting and despite current knowledge about its mechanism; few studies provide evidence about the long-term safety of BMP. The aim of this investigation is to determine if BMP implantation is a safe and effective agent in a long-term setting for the treatment of patients with resistant non-unions and failed arthrodesis. This study is a retrospective case series study that was conducted on 55 patients who had received BMP. Collected data included all related surgical history, and clinical and X-ray data both pre-operatively and post-operatively. All patients were scheduled for follow-up evaluations at one week and 1, 3, 6, and 12 months post-operatively. Seven patients (13%) experienced adverse events related to their surgery with hBMP. Six patients (11%) experienced persistent non-union; five of these underwent further revision surgery. One patient (2%) developed an infected non-union. No patients experienced tumor induction, allergic reaction to hBMP. The remaining 48 patients achieved osseous union within six months of hBMP implantation. This study differs from previous studies that the use of hBMP is a safe and efficacious treatment method for resistant non-unions and failed arthrodesis in the long-term setting.


Interactive effect of Gm and Km allotypes on cellular immune responses to streptococcal cell wall antigen.
Serum samples from 121 unrelated, healthy Japanese individuals were typed for several Gm and Km(1) allotypes. Peripheral blood lymphocytes from these subjects were cultured with streptococcal cell wall (SCW) antigen and the incorporation of 3H-thymidine into T lymphoblasts was measured. Log-linear analysis showed a significant interactive effect of Gm1,17;13,16,21 and Km(1) on the cellular immune response to group A SCW antigen.


Different internal fixation methods for Hoffa-like fractures of the tibial plateau: a finite element analysis.
Due to the low incidence of posteromedial tibial plateau fractures and limited clinical data available, the optimal treatment for this type of fracture remains to be established. This type of fracture, also known as Hoffa-like fracture of the tibial plateau, shares a similar mechanism of injury with the Hoffa fracture of the femoral condyle. In the field of orthopedics, finite element analysis is considered a valuable method to guide clinical decision-making. In this study, four methods used for internal fixation of Hoffa-like fractures of the tibial plateau were compared using computer simulation and applying a finite element method (FEM). The methods compared were lateral L-plate fixation alone (Model A); lateral L-plate combined with posterior anti-slip plate (reconstruction plate/T-plate) fixation (Model B); lateral L-plate combined with posterior hollow nail fixation of the fracture block (Model C); and lateral L-plate combined with anterior hollow nail fixation of the fracture (Model D). The maximum displacement of the model and the maximum stress of the internal fixation material were analyzed by applying an axial load of 2,500 N. The results showed that, in the normal bone model, the maximum displacement of the fracture in Model A was 0.60032 mm, with improved stability through the addition of posterior lateral plate fixation in Model B and reduction of the displacement to 0.38882 mm. The maximum displacement in Model C and Model D was comparable, amounting to 0.42345 mm and 0.42273 mm, respectively. Maximum stress was 1235.6 MPa for Model A, 84.724 MPa for Model B, 99.805 MPa for Model C, and 103.19 MPa for Model D. In the internal fixation analysis of the osteoporotic fracture model, we observed patterns similar to the results of the normal bone model. The results indicated that Model B yielded the overall best results in the treatment of Hoffa-like fractures of the tibial plateau. The orthopedic surgeon may wish to implement these insights into the perioperative algorithm, thereby refining and optimizing clinical patient care. In addition, our findings pave the way for future research efforts.


Inhibition of IL-6/STAT3 signaling in human cancer cells using Evista.
Persistent activation of IL-6/STAT3 signaling pathway has been frequently detected in human cancer including breast cancer, colon cancer and multiple myeloma. IL-6/STAT3 can be a promising target for cancer prevent and treatment. However, few STAT3 inhibitors with high efficiency, specificity and safety is available for present clinical cancer therapy. Evista (Raloxifene·HCl) is known as selective estrogen receptor modulator which has been used for the prevention and treatment of osteoporosis and was approved for reducing the risk of invasive breast cancer. Our previous study found that Raloxifene inhibited IL-6/GP130 interaction, resulting in blockade of STAT3 phosphorylation. In our present study, we examined the effect on IL-6/GP130/STAT3 signaling pathway and cancer cell viability with Evista. We first demonstrated Evista inhibited constitutive activation of STAT3 in breast cancer cell line MDB-MB-231, colon cancer cell line HCT116 and multiple myeloma cancer cell line U266. Evista also inhibited phosphorylation of STAT3 induced by IL-6 in MCF-7, HT29 and MM.1S cancer cell lines. Induction of apoptosis was exerted in MDA-MB-231, HCT116 and U266 as evidenced by increased caspase-3 cleavage. However, Evista did not inhibit STAT1, STAT2, STAT4 or STAT6 phosphorylation elicited by IFN-α, IFN-γ and IL-4, nor phosphorylation of STAT3 induced by LIF in MCF-7 cell lines. Evista attenuated STAT3 phosphorylation, decreased STAT3 transcriptional activity but much less in pGL3 and AP1 transcriptional luciferase activity, and decreased cell viability in vitro. These results suggest that it may be possible for Evista to emerge as a chemoprevention agent for breast cancer and other cancers such as colon cancer or multiple myeoloma by targeting IL-6/STAT3 signaling.


Cognitive improvement effects of Tian Wang Bu Xin Dan (Cheonwangbosimdan) in patients with mild cognitive impairment: protocol for a randomized placebo-controlled pilot clinical trial.
It is important to develop effective treatments to prevent the progress of mild cognitive impairment to Alzheimer's disease. Cheonwangbosimdan has been widely prescribed for palpitation, anxiety, insomnia, and memory decline. We aimed to obtain clinical trial data concerning the safety and efficacy of Cheonwangbosimdan for mild cognitive impairment. This clinical trial would be a single-center, double-blinded, parallel-arm, prospective, randomized controlled trial. Forty-eight participants with mild cognitive impairment would be randomly allocated evenly to the placebo or Cheonwangbosimdan groups. Participants will be educated on self-management and exercise at baseline and will receive the trial medication (Cheonwangbosimdan group, Cheonwangbosimdan; placebo group, placebo) once daily for 24 weeks. Primary outcome would include the changes in the Montreal Cognitive Assessment scale scores at the end of the intervention. Secondary outcomes would include the changes in the Montreal Cognitive Assessment scale scores at 12 weeks following the first intervention and changes in the scores of the Alzheimer's Disease Assessment Scale-cognitive subscale-3, the European Quality of Life Five Dimension Five Level scale, Korean Instrumental Activities of Daily Living, Korean Activities of Daily Living, and Geriatric Depression Scale at 12 and 24 weeks following the first intervention. The results of our trial would provide clinical trial data concerning the usefulness, safety, and efficacy of Cheonwangbosimdan in the management of mild cognitive impairment. Clinical Research Information Service (Date: November 26, 2021; Registration No. KCT0006787; https://cris.nih.go.kr/cris/search/detailSearch.do?search_lang=E&search_page=M&pageSize=10&page=undefined&seq=20869&status=5&seq_group=20869).


Thyroid cancer with concurrent breast tubular cancer: A case report and literature review.
Here one concurrent case of a patient with both thyroid and breast cancers was discussed with a comprehensive literature review. On March 21, 2016, a 42-year-old female patient was admitted into our hospital because of right neck mass and left breast mass for 1 week during a routine health examination. On March 22, the combined procedures of complete resection of right thyroid gland plus isthmus with dissection of lymph nodes in right VI region plus left breast regional lumpectomy were performed under endotracheal anesthesia. Final diagnosis: Mammary cancer (right thyroid gland), PT1aN1aM0 (stage I); ductal breast cancer (left breast), PT1NxM0 (re-operation within two weeks). For either disease, a practicing clinician should stay on a high alert for individual and familial endocrine diseases. And breast molybdenum target imaging and type B ultrasound should be performed regularly for screening. It is always prudent to catch and treat diseases as early as possible. The conclusion is as follows.


Parental Self-Efficacy to Support Teens During a Suicidal Crisis and Future Adolescent Emergency Department Visits and Suicide Attempts.
This study of adolescents seeking emergency department (ED) services and their parents examined parents' self-efficacy beliefs to engage in suicide prevention activities, whether these beliefs varied based on teens' characteristics, and the extent to which they were associated with adolescents' suicide-related outcomes. Participants included 162 adolescents (57% female, 81.5% Caucasian), ages 13-17, and their parents. At index visit, parents rated their self-efficacy to engage in suicide prevention activities and their expectations regarding their teen's future suicide risk. Adolescents' ED visits for suicide-related concerns and suicide attempts were assessed 4 months later. Parents endorsed high self-efficacy to engage in most suicide prevention activities. At the same time, they endorsed considerable doubt in being able to keep their child safe if the teen has thoughts of suicide and in their child not attempting suicide in the future. Parents whose teens experienced follow-up suicide-related outcomes endorsed, at clinically meaningful effect sizes, lower self-efficacy for recognizing suicide warning signs, for obtaining the teen's commitment to refrain from suicide, and for encouraging their teen to cope, as well as lower confidence that their teen will not attempt suicide; self-efficacy to recognize warning signs was at trend level. Despite endorsing high self-efficacy for the majority of suicide prevention activities, parents of high-risk teens expressed less confidence in their capacity to influence their teen's suicidal behavior, which could undermine parents' effort to implement these strategies. The relationship between parental self-efficacy and youth suicide-related outcomes points to its potential value in guiding clinical decision making and interventions.


Immune complex type crescentic glomerulonephritis and ANCA-positivity in a nine-year-old girl.
We report a nine-year-old girl who presented with the clinical and laboratory findings of rapidly progressive glomerulonephritis. She was found to be positive for both pANCA and cANCA. However, renal histopathology revealed immune complex type of crescentic glomerulonephritis. Thus, although testing for ANCA is an important tool in the prediction of the subtype of crescentic glomerulonephritis, a renal biopsy is still required to establish the diagnosis.


Time of maximum cycloplegia after instillation of cyclopentolate 1% in children with brown irises.
We aimed to 1) determine the time of maximum cycloplegia after instillation of cyclopentolate 1% in children with brown irises, 2) evaluate the correlation between the pupillary reaction and time of maximum cycloplegia, and 3) identify any side effects of the medication. This was a prospective analytical study involving children aged 5 to 14 years who were attending refraction clinic. Cyclopentolate 1% was instilled three times at 10-minute intervals. The spherical equivalent, pupillary reaction, and pupillary diameter were recorded before the first drop and nine times after the last drop at 10-minute intervals. Side effects were assessed. Time of maximum cycloplegia was determined from the time point at which the 95% confidence interval of the differences between the mean spherical equivalent at each point and its final value at 110 minutes was reached and remained within the equivalence limit (±0.25 D). Sixty children were enrolled in this study. Their mean age was 9.8 years (range: 5-4 years). Time of maximum cycloplegia was reached at 30 minutes after the first instillation of cyclopentolate. A poor correlation was observed between the pupillary reaction and the time of maximum cycloplegia (r=-0.07). The mean pupillary diameter at 30 minutes was 3.7±1.3 mm, and further dilation occurred thereafter. No side effects were observed. In most children, maximum cycloplegia was reached 30 minutes after the first instillation of cyclopentolate. The absence of a pupillary reaction should not be used as an indicator of maximum cycloplegia.


Hind wing variation in Leptura annularis complex among European and Asiatic populations (Coleoptera, Cerambycidae).
The ability to quantify morphological variation is essential for understanding the processes of species diversification. The geometric morphometrics approach allows reliable description of variation in animals, including insects. Here, this method was used to quantify the morphological variation among European and Asiatic populations of Leptura annularis Fabricius, 1801 and its closely related species L. mimica Bates, 1884, endemic for Japan and Sakhalin islands. Since the taxonomic status of these two taxa is differently interpreted by taxonomists, they are collectively called "Leptura annularis complex" in this paper. The analysis was based on the measurements of hind wings of 269 specimens from six populations from Europe and Asia. The level of morphological divergence between most of continental European and Asiatic populations was relatively small and proportional to the geographic distance between them. However, distinct morphotype was detected in Sakhalin Is. and Japan. These data confirm the morphological divergence of the endemic L. mimica species. Obtained results highlight the potential of the geometric morphometric method in studying morphological variation in beetles.


Attention to visual, but not tactile, properties of a stimulus results in activation of FOS protein in the visual thalamic reticular nucleus of rats.
Previous reports have suggested that the modality-specific sectors of the thalamic reticular nucleus (TRN) may become selectively activated as a result of attention being drawn to their respective sensory modalities. Here we used a task that required the discrimination of digging bowls on the basis of their visual (the colour of the bowl) or tactile (the external texture of the bowl) characteristics. We trained rats to perform both modality discriminations, ensuring the equity of exposure to both visual and tactile aspects of the stimuli. On the test day, animals had to perform only one of the modality discriminations for a 1-h period prior to being transcardially perfused and their brains removed and processed for Fos immunocytochemistry. We found that animals that performed the visual discrimination prior to sacrifice demonstrated a selective activation of cells in the visual TRN. On the other hand, animals that had performed the tactile discrimination, despite encountering the same stimuli and having received equal visual stimulation as the animals performing the visual discrimination, did not have activation of the visual TRN. This evidence suggests that activation of visual TRN is a function of visual selective attention, and not merely visual stimulation. Surprisingly, the same was not true for somatic TRN, which was not labeled in any animals. It is possible that this lack of a double dissociation is the result of modality-specific differences in the attentional demands of the two discrimination tasks.


Screening Prognosis-Related lncRNAs Based on WGCNA to Establish a New Risk Score for Predicting Prognosis in Patients with Hepatocellular Carcinoma.
Hepatocellular carcinoma (HCC) remains an important cause of cancer death. The molecular mechanism of hepatocarcinogenesis and prognostic factors of HCC have not been completely uncovered. In this study, we screened out differentially expressed lncRNAs (DE lncRNAs), miRNAs (DE miRNAs), and mRNAs (DE mRNAs) by comparing the gene expression of HCC and normal tissue in The Cancer Genome Atlas (TCGA) database. DE mRNAs were used to perform Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Then, the miRNA and lncRNA/mRNA modules that were most closely related to the survival time of patients with HCC were screened to construct a competitive endogenous RNA (ceRNA) network by weighted gene coexpression network analysis (WGCNA). Moreover, univariable Cox regression and Kaplan-Meier curve analyses of DE lncRNAs and DE mRNAs were conducted. Finally, the lasso-penalized Cox regression analysis and nomogram model were used to establish a new risk scoring system and predict the prognosis of patients with liver cancer. The expression of survival-related DE lncRNAs was verified by qRT-PCR. A total of 1896 DEmRNAs, 330 DElncRNAs, and 76 DEmiRNAs were identified in HCC and normal tissue samples. Then, the turquoise miRNA and turquoise lncRNA/mRNA modules that were most closely related to the survival time of patients with HCC were screened to construct a ceRNA network by WGCNA. In this ceRNA network, there were 566 lncRNA-miRNA-mRNA regulatory pairs, including 30 upregulated lncRNAs, 16 downregulated miRNAs, and 75 upregulated mRNAs. Moreover, we screened out 19 lncRNAs and 14 hub mRNAs related to prognosis from this ceRNA network by univariable Cox regression and Kaplan-Meier curve analyses. Finally, a new risk scoring system was established by selecting the optimal risk lncRNAs from the 19 prognosis-related lncRNAs through lasso-penalized Cox regression analysis. In addition, we established a nomogram model consisting of independent prognostic factors to predict the survival rate of HCC patients. Finally, the correlation between the risk score and immune cell infiltration and gene set enrichment analysis were determined. In conclusion, the results may provide potential biomarkers or therapeutic targets for HCC and the establishment of the new risk scoring system and nomogram model provides the new perspective for predicting the prognosis of HCC.


Evaluation of a novel poly(epsilon-caprolactone)-organosiloxane hybrid material for the potential application as a bioactive and degradable bone substitute.
A novel poly(epsilon-caprolactone)-organosiloxane hybrid material containing calcium salt (Si-O-PCL) was prepared and evaluated as a bioactive and degradable bone substitute material. The Si-O-PCL hybrid was synthesized by the end-capping of 3-isocyanatopropyl triethoxysilane with alpha,omega-hydroxyl PCL following sol-gel reaction with calcium nitrate tetrahydrate. Its tensile mechanical properties were evaluated, and additional specimens were exposed to simulated body fluid (SBF) for the time range from 3 h to 7 days. The SBF exposure led to the deposition of a layer of apatite crystals on the surface of the Si-O-PCL hybrid within 9 h of soaking. The tensile strength was around 18 MPa, Young's modulus was around 200 MPa, and the strain at break was around 290%. This material is likely to have a potential application as a bioactive and degradable bone substitute because of its apatite forming ability, biodegradability, and mechanical properties comparable to those of human cancellous bone.


Anticipatory interpretations: addressing "cautionary tales" and the problem of premature termination.
This article explores the use of anticipatory interpretations early in the therapeutic process as a means of addressing the problem of premature termination with some patients. The author argues that emerging transference references, detected through a close attention to "cautionary tales" or derivative communications, should be used in early interpretive interventions. It is suggested that such transference references form a "template of intention" that help determine future difficulties in the therapeutic alliance. Being able to communicate these observations in a future-orientated way lays the groundwork for "thinking about" actions that threaten the therapeutic alliance when they occur, in turn curtailing the possibility of acting out through termination. The author uses two case examples to illustrate his observations and goes on to suggest that anticipatory interpretations involve: (1) isolating derivatives and underlying anxieties, (2) future-orientated transference references, and (3) an affirmation of difficulty.


Associations between Genetically Proxied Inhibition of Lipid-Lowering Drug Targets and Serum Micronutrients among Individuals of European Descent: A Mendelian Randomization Study.
Limited and inconclusive data exist concerning the associations between lipid-lowering drugs and serum micronutrient concentrations. We conducted Mendelian randomization (MR) analyses to explore the associations between lipid-lowering drug targets and serum micronutrients. Single-nucleotide polymorphisms in genes encoding molecular targets of LDL cholesterol-lowering therapies were selected as instrumental variables for 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR; target of statins), proprotein convertase subtilisin/kexin type 9 (PCSK9; target of PCSK9 inhibitors), and Niemann-Pick C1-Like 1 (NPC1L1; target of ezetimibe). Exposure data were extracted from a published genome-wide association study (GWAS) of lipids in 188,577 European individuals, with outcome data obtained from the Integrative Epidemiology Unit (IEU) GWAS database (https://gwas.mrcieu.ac.uk). Overall, age and sex information were not calculable from the summary-level GWAS data. MR analyses were performed using the inverse-variance weighted method and MR sensitivity analysis methods. We found genetically proxied inhibition of HMGCR to lower iron (effect, -0.16; 95% CI: -0.27, -0.06; P value = 0.003), zinc (effect, -0.83; 95% CI: -1.36, -0.31; P value = 0.002), magnesium (effect, -0.17; 95% CI: -0.27, -0.06; P value = 0.003), potassium (effect, -0.17; 95% CI: -0.27, -0.06; P value = 0.002), genetically proxied inhibition of NPC1L1 to increase calcium (effect, 0.28; 95% CI: 0.10, 0.46; P value = 0.003), retinol (effect, 0.25; 95% CI: 0.07, 0.44; P value = 0.01), and genetically proxied inhibition of PCSK9 to increase vitamin D (effect, 0.10; 95% CI: 0.07, 0.12; P value = 1.8 × 10-19). These associations were robust in MR sensitivity analyses. However, the associations between genetically proxied inhibition of HMGCR and NPC1L1 and the micronutrients were not consistent in multiple comparisons. Our results provide evidence that statin use may lower serum concentrations of iron, zinc, magnesium, and potassium, PCSK9 inhibitors may increase serum vitamin D, and ezetimibe may increase serum calcium and retinol concentrations.


HMGA1 promotes hepatocellular carcinoma proliferation, migration, and regulates cell cycle via miR-195-5p.
HMGA1 has been reported to be aberrantly expressed and correlate with the poor prognosis of many carcinomas. This study aimed to investigate the clinical significance and molecular mechanism of HMGA1 as a tumor-suppressing gene in hepatocellular carcinoma (HCC). Analysis of TCGA dataset by TANRIC website and R2 platform, we found that HMGA1 expression was significantly higher in HCC tissues compared to that in normal liver tissues and was associated with Edmondson grade. Patients with highly expressed HMGA1 had worse overall survival. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes analysis showed the potential relationships between HMGA1 and other genes in HCC. We also demonstrated that the downregulation of HMGA1 dramatically suppressed the proliferation and migration of HCC cells. Furthermore, ectopic expression of HMGA1 blocked G0/G1 to S transition. Subsequent investigation characterized HMGA1 as a direct target of miR-195-5p, and miR-195-5p downregulation abrogated the effect of HMGA1 on HCC proliferation, migration, and cell cycle arrest. In addition, we also demonstrated that miR-195-5p downregulation abrogated the effect of HMGA1 on HCC growth in vivo. Taken together, our data provide strong evidence that HMGA1 promotes HCC and is negatively regulated by the tumor-suppressor, miR-195-5p.


[Study of erythrocyte deformability using visco-diffractometry (ektacytometry) in hereditary hemolytic anemias].
Deformability is a basic characteristic of red blood cells; its regulating factors are presently well known (surface volume ratio, internal viscosity, viscoelastic properties of the membrane). The contribution of each of these factors in the pathogeny of hemolytic anemias has not been fully established. We report 64 hereditary hemolytic anemias in which we studied the deformability, using a visco-diffractometric method (ektacytometer) on whole blood and various subpopulations separated by density. Comparison of the response of the cells submitted to isotonic and hypotonic media allows the determination of the respective contribution of viscosity and surface volume ratio. Deformability is always decreased in red blood cell membrane diseases and in homozygous or double heterozygous hemoglobinopathies; on the other hand, deformability is normal in all the enzymopathies studied. This decrease could be due either to one regulation factor (increase of internal viscosity easily demonstrated by this method in hereditary xerocytosis and hemoglobin CC) or to several parameters: increase of internal viscosity and decrease of surface volume ratio in hereditary spherocytosis.


[Uses and risks of hemodynamic monitoring by inflow catheter in acute myocardial infarct].
Using hemodynamic monitoring by flow-directed heart catheterization in acute myocardial infarction, left ventricular dysfunction can be analyzed and quantified. Differential therapy concerning substitution of volume and administration of drugs with influence on pre- and after-load is facilitated. Since the introduction of the Swan-Ganz flow-directed catheter the monitoring has been technically improved with the additional advantage of lower incidence of catheter-induced arrhythmias and the possibility to measure the pulmonary capillary wedge pressure. The Swan-Ganz thermodilution catheter further improved the technical assessment of cardiac output. Using hemodynamic monitoring during acute myocardial infarction different phases of cardiac failure can be discerned, e.g., backward failure with increased filling pressure, foreward failure with decreased cardiac output, and cardiogenic shock with the combination of both. In some cases a hyperkinetic hemodynamic status is observed. The differential diagnosis of pulmonary embolism, and cardiac and pulmonary shock can be clarified. Complications of myocardial infarction as acute mitral insufficiency due to papillary muscle rupture in inferior myocardial infarction, rupture of the septal myocardium in septal infarction, as well as myocardial rupture with pericardial tamponade show characteristic diagnostic findings. Drug therapy with influence on pre- and after-load and therapy with positive-inotropic agents can be adjusted to the individual hemodynamic status and to the monitored drug effects.(ABSTRACT TRUNCATED AT 250 WORDS)


Use of naloxone nasal spray 4 mg in the community setting: a survey of use by community organizations.
Naloxone hydrochloride, an opioid antagonist, has been approved as a concentrated 4 mg dose intranasal formulation for the emergency treatment of known or suspected opioid overdose. This new formulation is easier to use and contains a higher dose of naloxone compared with earlier, unapproved kits. A survey of first responders and community-based organizations was conducted to understand initial real-world experiences with this new formulation for opioid overdose reversal. In August 2016, 152 US organizations known to have received units of the approved 4 mg dose/unit naloxone nasal spray (Narcan®1 nasal spray 4 mg; NNS) were surveyed regarding experiences using this formulation and availability of recorded data on these cases. Descriptive statistics were calculated based on the number of responses received for each item. Eight first-responder or community-based organizations provided case report data on 261 attempted overdose reversals using NNS, with survival reported for 245 cases. Successful overdose reversals were reported in 98.8% (242/245) of cases; most cases (73.5%; 125/170) reported a time to response of ≤5 minutes after NNS administration. Heroin was the substance reportedly involved in a majority (95.4%; 165/173) of these cases; fentanyl was reported to be involved in 5.2% (9/173) of the cases. Many reversals (97.6%; 248/254) involved administration of ≤2 units of NNS. Three deaths were reported (NNS was reported to have been administered too late for two cases [the individuals were deceased prior to NNS administration]; details were not provided for the third case). The most commonly reported observed events were "withdrawal" (14.3%; 28/196); "nausea", "vomiting", or "gagging/retching" (10.2%; 20/196); and "irritability" or "anger" (8.7%; 17/196). This survey of data provided by first-responder and community-based organizations indicated that NNS was successful at reversing the effects of opioid overdose in most reported cases.


Differences in lymphocyte profile between BAL fluid and human lung tissue from patients with interstitial lung disease.
Bronchoalveolar lavage (BAL) is a technique that samples the inflammatory cells from distal airways and alveoli; however, it is unclear whether or not cellular profiles in the BAL fluid reflect the cellular components of the lung parenchyma in interstitial lung disease (ILD). The aim of this study is to compare immunophenotypes of lymphocytes between BAL fluid and human lung tissue from patients with ILD. Fourteen consecutive patients with ILD who underwent BAL and surgical lung biopsy were enrolled. The diagnosis of ILD was confirmed by the presence of clinical symptoms and impaired respiratory function and on high-resolution computed tomography (CT) of the chest. Mononuclear cells in BAL were immunophenotyped for the expression of CD3, CD4, CD8, CD19, CD45, and CD103 by flow cytometry. Lung tissue obtained by surgical biopsy was digested with collagenase and then centrifuged to extract parenchymal cells. Isolated cells were also immunophenotyped for the same CD expression. Frequencies of positive cells were compared statistically between BAL and different lobes. Seven out of 14 patients were diagnosed clinically as suffering idiopathic interstitial pneumonia. Frequency of CD19+ cells from BAL was significantly lower than that from the upper/middle lobes (P < 0.05). Frequency of CD103+ cells from BAL was significantly higher than that from the upper/middle lobes and the lower lobe (P = 0.01 and P < 0.05, respectively). Comparison between different lobes demonstrated that the frequency of CD4+ cells from the upper/middle lobes was significantly lower than that from the lower lobe (P < 0.05). The results suggest that lymphocyte immunophenotype profiles from BAL may not reflect those in the inflammatory tissue of ILD.


Clinical and biochemical heterogeneity in an Italian family with CPT II deficiency due to Ser 113 Leu mutation.
Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive disorder which presents with recurrent myoglobinuria. Heterozygotes are usually asymptomatic. We correlate the clinical, biochemical and molecular features of a family in which the proband is homozygous for CPT II deficiency, due to the common Ser 113 Leu mutation. The 20-year-old female proband presented at age three years with episodic myalgia and myoglobinuria, elevated creatine kinase (CK) of 3600 IU/L and had a 33% residual CPT II activity in cultured skin fibroblasts. Her 25-year-old dizygotic twin brothers presented with muscle stiffness following prolonged exercise but no overt pigmenturia and had interictal CKs up to 662 lU/L. Her parents and a 13-year-old brother are asymptomatic. An elder sister, not investigated, had recurrent pigmenturia and died at eight years with myoglobinuria. Molecular analysis revealed that the proband is homozygous for the Ser 113 Leu mutation. Her parents are heterozygotes with CPT II activities of 55% to 70%. Her younger brother is normal with 83% activity. The symptomatic twin brother are heterozygous but demonstrated unexpectedly low CPT II activities of 40%, which may explain their phenotype. We postulate that there may be genetic, environmental and sex hormonal factors accounting for this manifesting heterozygosity and biochemical heterogeneity in CPT II deficiency.


The crystal structure of mismatch-specific uracil-DNA glycosylase (MUG) from Deinococcus radiodurans reveals a novel catalytic residue and broad substrate specificity.
Deinococcus radiodurans is extremely resistant to the effects of ionizing radiation. The source of the radiation resistance is not known, but an expansion of specific protein families related to stress response and damage control has been observed. DNA repair enzymes are among the expanded protein families in D. radiodurans, and genes encoding five different uracil-DNA glycosylases are identified in the genome. Here we report the three-dimensional structure of the mismatch-specific uracil-DNA glycosylase (MUG) from D. radiodurans (drMUG) to a resolution of 1.75 angstroms. Structural analyses suggest that drMUG possesses a novel catalytic residue, Asp-93. Activity measurements show that drMUG has a modified and broadened substrate specificity compared with Escherichia coli MUG. The importance of Asp-93 for activity was confirmed by structural analysis and abolished activity for the mutant drMUGD93A. Two other microorganisms, Bradyrhizobium japonicum and Rhodopseudomonas palustris, possess genes that encode MUGs with the highest sequence identity to drMUG among all of the bacterial MUGs examined. A phylogenetic analysis indicates that these three MUGs form a new MUG/thymidine-DNA glycosylase subfamily, here called the MUG2 family. We suggest that the novel catalytic residue (Asp-93) has evolved to provide drMUG with broad substrate specificity to increase the DNA repair repertoire of D. radiodurans.


No association between catalase (CAT) gene polymorphisms and susceptibility to vitiligo in a Turkish population.
Vitiligo is an acquired hypomelanotic skin disorder resulting from the loss of functional melanocytes from the cutaneous epidermis. Low catalase (CAT) activity and Accumulation of hydrogen peroxide (H2O2) have been demonstrated in the epidermis of vitiligo patients. Some polymorphisms on catalase gene may have effect on the quantity and activity of catalase enzyme. The aim of this study was to investigate whether catalase (CAT) gene polymorphisms are associated with susceptibility to vitiligo in Turkish population. One hundred and three patients with vitiligo and one hundred and seven gender, age and ethnic matched controls were enrolled in the study. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The CAT gene -89A>T (rs7943316) and 389C>T (rs769217) genotypes and allele frequencies of vitiligo patients did not differ significantly from those of healthy controls. We found no association between CAT gene -89A>T and 389C>T polymorphism and vitiligo susceptibility in Turkish vitiligo patients. Further studies with greater sample size should be performed to verify these results.


Epoxide formation on the aromatic B ring of flavanone by biphenyl dioxygenase of Pseudomonas pseudoalcaligenes KF707.
Prokaryotic dioxygenase is known to catalyze aromatic compounds into their corresponding cis-dihydrodiols without the formation of an epoxide intermediate. Biphenyl dioxygenase from Pseudomonas pseudoalcaligenes KF707 showed novel monooxygenase activity by converting 2(R)- and 2(S)-flavanone to their corresponding epoxides (2-(7-oxabicyclo[4.1.0]hepta-2,4-dien-2-yl)-2, 3-dihydro-4H-chromen-4-one), whereby the epoxide bond was formed between C2' and C3' on the B ring of the flavanone. The enzyme also converted 6-hydroxyflavanone and 7-hydroxyflavanone, which do not contain a hydroxyl group on the B-ring, to their corresponding epoxides. In a previous report (S.-Y. Kim, J. Jung, Y. Lim, J.-H. Ahn, S.-I. Kim, and H.-G. Hur, Antonie Leeuwenhoek 84:261-268, 2003), however, we found that the same enzyme showed dioxygenase activity toward flavone, resulting in the production of flavone cis-2',3'-dihydrodiol. Extensive structural identification of the metabolites of flavanone by using high-pressure liquid chromatography, liquid chromatography/mass spectrometry, and nuclear magnetic resonance confirmed the presence of an epoxide functional group on the metabolites. Epoxide formation as the initial activation step of aromatic compounds by oxygenases has been reported to occur only by eukaryotic monooxygenases. To the best of our knowledge, biphenyl dioxygenase from P. pseudoalcaligenes KF707 is the first prokaryotic enzyme detected that can produce an epoxide derivative on the aromatic ring structure of flavanone.


[Progress in the treatment of gastrointestinal cancers due to introduction of neoadjuvant concept].
Formerly the treatment of gastrointestinal cancers was exclusively surgical. Though the results were improved by increased radicality, the real progress was achieved by the introduction of multimodal therapy, particularly by the neoadjuvant concept. The basic prerequisite for neoadjuvant treatment is precise staging and risk assessment. According to staging patients can be divided into three categories: (1) Early cancers, confined to the mucosal and submucosal layers, are approached with primary surgery. (2) Systemically metastasized tumors receive merely palliative treatment. (3) Locally advanced cancers are treated by neoadjuvant therapy. Due to neoadjuvant treatment the tumor can be downsized (or downstaged) in some patients. These are the responders benefiting from the therapy, because of the increased RO-resection rate, decreased recurrence rate and improved survival. The non-responders, by contrast have poor prognosis. Neoadjuvant treatment considerably improved the chance for cure for patients with gastrointestinal cancers, thus this method became an evidence based treatment for locally advanced gastrointestinal cancers.


Role of estrogen in postmenopausal depression.
Estrogen has been reported to improve the cognitive functioning of postmenopausal women. It is suggested that estrogen replacement therapy (ERT) might be beneficial for improvement of mood and cognition in menopausal women. We have shown that this improvement is selective and is probably more apparent in complex integrative functions. We have also shown that estrogen can augment serotonergic activity as well as some norepinephrine-related processes in postmenopausal women. Because of its effects on mood-related neurotransmitter processes, ERT might decrease vulnerability to depression and be effective as an adjunct therapy to prevent treatment nonresponse to conventional antidepressants.


Seizure-like spreading depression in immature rabbit hippocampus in vitro.
Study of immature rabbit hippocampus, using the in vitro slice preparation, has revealed seizure-like spreading depression (SD) episodes in tissue from 8-12-day-old animals. These SDs occur both spontaneously and in response to stimulation, and are seen in both extracellular and intracellular recordings. At the cellular level, SDs are similar to epileptiform ictal phenomena in their onset bursts of action potentials, prolonged membrane depolarizations, and afterdischarge bursts. Glial recordings indicate that a large rise in [K+]0 occurs during these SD episodes. Low chloride concentration in the bathing medium facilitates SD occurrence. The immature CA1 region, where inhibition is slow to develop, is more susceptible to SDs than the CA3 region, where inhibitory post-synaptic potentials are potent early in development. These observations suggest that the slice preparation of immature rabbit hippocampus may provide a useful model in which to study epileptiform mechanisms, such as inhibitory efficacy and extracellular potassium clearance, which might be responsible for ictal onset and control.


[Spinal stenosis].
Spinal stenosis is an abnormal narrowing of the spinal canal that mainly occurs in the cervical and lumbar regions. The number of the patients of spinal stenosis is increasing in the aging society like Japan because the major reason for the stenosis is the degeneration of the spinal components including the intervertebral disc, facet, and ligamentum flavum. The development of the disease-concept is historically different between cervical spinal stenosis and lumbar spinal stenosis. Therefore, some confusion is still present in the definition and diagnosing criteria of these conditions. In this report, we mainly describe about the degenerative lumbar spinal stenosis, which is most common in the outpatient clinic, concerning the diagnosis, various options of conservative therapy, and the surgical indication.


The mirror effect and mixture signal detection theory.
The mirror effect for word frequency refers to the finding that low-frequency words have higher hit rates and lower false alarm rates than high-frequency words. This result is typically interpreted in terms of conventional signal detection theory (SDT), in which case it indicates that the order of the underlying old item distributions mirrors the order of the new item distributions. However, when viewed in terms of a mixture version of SDT, the order of hits and false alarms does not necessarily imply the same order in the underlying distributions because of possible effects of mixing. A reversal in underlying distributions did not appear for fits of mixture SDT models to data from 4 experiments.


Morphological assessment of the mandibular canal trajectory in dentate subjects.
The mandibular canal is the most important vital structure within the mandibular body. The aim of the present study was to determine the course of mandibular canal in relation to external surfaces of the mandible (buccal, lingual) and to root apices of the lateral teeth, in order to minimize the risk of its content being injured during either conservative or radical treatment of the mandibular lateral teeth. Morphometric evaluations were performed on 11 dried dentate human mandibles and on cone-beam computed tomography (CBCT) cross-sectional images of the mandible, from 18 dentate patients. By means of both methods, the following parameters were assessed: (i) the distance between the mandibular canal and the buccal (lateral) surface of the mandible (MC-BS distance); (ii) the distance between the mandibular canal and the lingual (medial) surface of the mandible (MC-LS distance); (iii) the distance between the mandibular canal and the root apices of the second premolar, the first and second molars (MC-T distance). The results were statistically processed in Stata MP÷13 software package using analysis of variance (ANOVA). With respect to buccal-lingual location, the mandibular canal passed horizontally through the mandibular trabecular bone, from posterior to anterior, and from lingual to lateral (buccal), and so at premolar level it approached the lateral (buccal) cortical bone plate, main topographic pattern found in 26 (89.65%) of the cases. The mandibular canal had a descending trajectory from the second molar to the first molar, after which it ascended slightly towards the second premolar, main topographic pattern found in 24 (82.75%) of the cases. According to the results, the second mandibular molar is the most common tooth involved in the accidental damaging of the content of the mandibular canal, during various therapeutic procedures. Overlooking the location of the mandibular canal can lead to complications in endodontic therapy and in dentoalveolar surgical procedures in the posterior region of the mandible.


Natural paucity of anaplerotic enzymes: basis for dependence of Arthrobacter pyridinolis on L-malate for growth.
Previous work has shown that in Arthrobacter pyridinolis the transport systems for glucose and several amino acids are respiration coupled, with malate oxidation occurring concomitantly with transport. The requisite malate has to be supplied exogenously, so that growth on glucose or certain amino acids only occurs if malate is also present in the medium. These and other data suggested that A. pyridinolis might be deficient in anaplerotic enzymes, which maintain intracellular levels of dicarboxylic acids. A comparative study was undertaken of anaplerotic enzymes in A. pyridinolis and in a closely related species, A. crystallopoietes, which has respiration-coupled transport of glucose but can grow on glucose without added malate. The paucity of anaplerotic enzymes in A. pyridinolis and its probable relationship to the malate requirement for growth on glucose were documented as follows: (i) A. crystallopoietes, but not A. pyridinolis, possesses phosphoenolpyruvate carboxylase activity, and neither species contains pyruvate carboxylase; (ii) both A. pyridinolis and A. crystallopoietes possess glyoxylate pathways that are induced by acetate but not by hexoses; (iii) isocitrate lyase-deficient mutants of A. pyridinolis fail to grow on rhamnose and fructose as well as acetate; and (iv) mutants of A. crystallopoietes that require malate for growth on glucose are deficient in phosphoenolpyruvate carboxylase.


A Novel Triage Tool: Optic Nerve Sheath Diameter in Traumatic Brain Injury and its Correlation to Rotterdam Computed Tomography (CT) Scoring.
Optic nerve sheath diameter (ONSD) evaluated in CT imaging as well as Rotterdam CT Score (RCTS) are proven independent predictors of outcome in patients with traumatic brain injury (TBI). To date, no study has correlated ONSD on admission CT scan with RCTS. Retrospective cohort study comprised of consecutive patients undergoing CT imaging for traumatic brain injury recruited between January and October 2015. Bilateral ONSD was measured 3 mm behind the eyeball in axial and sagittal planes and mean value was calculated. RCTS was assessed on the same CT images, bias was eliminated by blinding RCTS to ONSD measurement. 150 patients were included; mean age in the group was 42.94±16.7 years. ONSD in mild TBI, RCTS 2 and 3 were 3.3 mm (SD 0.39 mm) and 4.1 mm (0.047 mm), respectively. Mean ONSD in moderate and severe TBI (RCTS score 4 and above) was 4.83 mm and above, SD 0.4 mm. Mean ONSD correlated with occurrence of diffuse cerebral oedema, presence of subdural and extradural hematoma; however in isolation there was no statistical significance. Higher ONSD was observed in patients with moderate and severe TBI, correlating with admission RCTS of 4 and above. Subsequent increase in ONSD was also found with increase in RCTS. ONSD could serve as an initial triage tool in the emergency department as well as a method of determining the need for sequential CT in patients with mild TBI.


[A delayed life-threatening complication after uneventful varicella infection: transient complete heart block].
A 9 year old boy presented with uncharacteristic gastroenteric complaints due to a complete heart block 9 days after an uneventful varicella infection. Echocardiographically there were no signs of gross myocardial involvement. Bradydysrhythmia necessitated isoproterenol application however without the need for temporary transvenous cardiac pacing. After a short period of second-degree atrioventricular block and transient left bundle branch block the rhythm recovered completely and sinus rhythm is maintained so far. Worrying is the delayed onset of this complication after an uneventful course of a typically undangerous children's disease. Presumably a remaining inflammatory reaction in different parts of the specific conducting system has to be assumed. The long lasting prognosis of the atrioventricular conduction properties remains to be seen.


Feline myocardial transcriptome in health and in hypertrophic cardiomyopathy-A translational animal model for human disease.
Hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats, characterized by primary left ventricular hypertrophy. Feline HCM closely resembles human HCM and is suggested as translational animal model for the human disease. A genetic cause is established in humans and suspected for cats, but little is known about the gene expression and pathways involved in the pathogenesis of HCM. To investigate the myocardial transcriptome changes in HCM, RNA sequencing was conducted on left ventricle (LV) and left atrium (LA) samples of healthy cats and cats with HCM (each n = 5; 20 samples). Ingenuity Pathway Analysis was used to determine functional pathways, regulators, and networks. Distinct gene expression profiles were identified in the LV and LA of the feline healthy and HCM myocardium. Analysis of differentially expressed mRNAs (>2 fold; FDR < 0.01) found chamber-specific (LV vs. LA) expression in both healthy and HCM groups, with higher transcriptional activity in the LA. Genes that contribute to the distinct structure and function of each chamber in health and HCM were identified in the regional comparison. The gene expression profiles of HCM compared to healthy hearts revealed disease related genes, including THBS4 and KLHL33 (LV), FAM177B and THRSP (LA), the latter 3 have not been reported for the myocardium so far, as the top differently expressed genes in the HCM heart. Differently expressed genes and functional pathways found in the HCM heart are associated with cardiac remodeling and fibrosis, inflammation, microvascular changes, calcium signaling and cardiac metabolism, with some regional differences. RhoGDI-RhoGTPase signaling, integrin and ILK signaling pathways, the LXR/RXR pathway in the LA, and the PPARα/RXRα, HIF1α and CXCR4 pathways in the LV might be of particular importance in the HCM disease process. This study identified region-specific myocardial gene transcription patterns as well as novel genes and pathways associated with HCM.


Adaptive Memory: The Evolutionary Significance of Survival Processing.
A few seconds of survival processing, during which people assess the relevance of information to a survival situation, produces particularly good retention. One interpretation of this benefit is that our memory systems are optimized to process and retain fitness-relevant information. Such a "tuning" may exist, in part, because our memory systems were shaped by natural selection, using a fitness-based criterion. However, recent research suggests that traditional mnemonic processes, such as elaborative processing, may play an important role in producing the empirical benefit. Boundary conditions have been demonstrated as well, leading some to dismiss evolutionary interpretations of the phenomenon. In this article, we discuss the current state of the evolutionary account and provide a general framework for evaluating evolutionary and purportedly nonevolutionary interpretations of mnemonic phenomena. We suggest that survival processing effects are best viewed within the context of a general survival optimization system, designed by nature to help organisms deal with survival challenges. An important component of survival optimization is the ability to simulate activities that help to prevent or escape from future threats which, in turn, depends in an important way on accurate retrospective remembering of survival-relevant information.


Intermediate-dose CY and G-CSF more efficiently mobilize adequate numbers of PBSC for tandem autologous PBSC transplantation compared with low-dose CY in patients with multiple myeloma.
Autologous PBSC transplantation is the standard care for patients with multiple myeloma. The most common regimen used to mobilize PBSC consists of CY and G-CSF. We retrospectively analyzed the efficacy and toxicity of two regimens of CY for PBSC mobilization: low-dose CY (1-2 g/m(2), LD-CY, n=61) plus G-CSF, and intermediate-dose CY (3-4 g/m(2), ID-CY, n=26) plus G-CSF. In the LD-CY group, 5.17 (0.23-17.3)x10(6) CD34(+) cells/kg, and in the ID-CY group 7.71 (0.08-26.4)x10(6) CD34(+) cells/kg (P=0.018), were collected. Although >/=2x10(6)/kg CD34(+) cells were collected in 89% of the LD-CY group and 92% of the ID-CY group, this was achieved after a single leukapheresis in 54% of the LD-CY group and 92% of the ID-CY group (P=0.0001). Patients who are to have tandem autologous PBSC transplants require >/=4x10(6)/kg CD34(+) cells. This was achieved in only 65% patients in the LD-CY group but 88% in the ID-CY group (P=0.05). Among patients who had not had prior melphalan and/or >12 months of prior treatment, 74% in the LD-CY group and 100% in ID-CY group mobilized >/=4x10(6)/kg CD34(+) cells. Febrile neutropenia was more frequent in the ID-CY group (38% vs. 13%). In conclusion, compared with LD-CY, patients receiving ID-CY were more likely to collect a total CD34(+) cell number adequate for tandem autologous PBSC transplantation. The increased toxicity was manageable and considered acceptable.


Association of Candidate Genes With Submergence Response in Perennial Ryegrass.
Perennial ryegrass is a popular cool-season grass species due to its high quality for forage and turf. The objective of this study was to identify associations of candidate genes with growth and physiological traits to submergence stress and recovery after de-submergence in a global collection of 94 perennial ryegrass accessions. Accessions varied largely in leaf color, plant height (HT), leaf fresh weight (LFW), leaf dry weight (LDW), and chlorophyll fluorescence (Fv/Fm) at 7 days of submergence and in HT, LFW and LDW at 7 days of recovery in two experiments. Among 26 candidate genes tested by various models, single nucleotide polymorphisms (SNPs) in 10 genes showed significant associations with traits including 16 associations for control, 10 for submergence, and 8 for recovery. Under submergence, Lp1-SST encoding sucrose:sucrose 1-fructosyltransferase and LpGA20ox encoding gibberellin 20-oxidase were associated with LFW and LDW, and LpACO1 encoding 1-aminocyclopropane-1-carboxylic acid oxidase was associated with LFW. Associations between Lp1-SST and HT, Lp6G-FFT encoding fructan:fructan 6G-fructosyltransferase and Fv/Fm, LpCAT encoding catalase and HT were also detected under submergence stress. Upon de-submergence, Lp1-SST, Lp6G-FFT, and LpPIP1 encoding plasma membrane intrinsic protein type 1 were associated with LFW or LDW, while LpCBF1b encoding C-repeat binding factor were associated with HT. Nine significant SNPs in Lp1-SST, Lp6G-FFT, LpCAT, and LpACO1 resulted in amino acid changes with five substitutions found in Lp1-SST under submergence or recovery. The results indicated that allelic diversity in genes involved in carbohydrate and antioxidant metabolism, ethylene and gibberellin biosynthesis, and transcript factor could contribute to growth variations in perennial ryegrass under submergence stress and recovery after de-submergence.


Evolution in the Acute Management of Open Fracture Treatment? Part 2.
In the first installment of this two-part series, we explored the history of open fracture treatment focusing primarily on bacteriology and antibiotic selection/stewardship. In this follow-up segment, we will analyze and summarize the other aspects of open fracture care such as time to debridement, pulsatile lavage, and open wound management (including time to closure)-finishing with summative statements and recommendations based on the current most up-to-date literature. Therapeutic Level V. See Instructions for Authors for a complete description of levels of evidence.


Sedative Plasma Concentrations and Delirium Risk in Critical Illness.
The relationship between plasma concentration of sedatives and delirium is unknown. We hypothesized that higher plasma concentrations of lorazepam are associated with increased delirium risk, whereas higher plasma concentrations of dexmedetomidine are associated with reduced delirium risk. This prospective cohort study was embedded in a double-blind randomized clinical trial, where ventilated patients received infusions of lorazepam and dexmedetomidine. Plasma concentrations of these drugs and delirium assessments were measured at least daily. A multivariable logistic regression model accounting for repeated measures was used to analyze associations between same-day plasma concentrations of lorazepam and dexmedetomidine (exposures) and the likelihood of next-day delirium (outcome), adjusting for same-day mental status (delirium, coma, or normal) and same-day fentanyl doses. This critically ill cohort (n = 103) had a median age of 60 years (IQR: 48-66) with APACHE II score of 28 (interquartile range [IQR] = 24-32), where randomization resulted in assignment to lorazepam (n = 51) or dexmedetomidine (n = 52). After adjusting for same-day fentanyl dose and mental status, higher plasma concentrations of lorazepam were associated with increased probability of next-day delirium (comparing 500 vs 0 ng/mL; odds ratio [OR] = 13.2; 95% CI = 1.4-120.1; P = 0.02). Plasma concentrations of dexmedetomidine were not associated with next-day delirium (comparing 1 vs 0 ng/mL; OR = 1.1; 95% CI = 0.9-1.3; P = 0.45). In critically ill patients, higher lorazepam plasma concentrations were associated with delirium, whereas dexmedetomidine plasma concentrations were not. This implies that the reduced delirium risk seen in patients sedated with dexmedetomidine may be a result of avoidance of benzodiazepines, rather than a dose-dependent protective effect of dexmedetomidine.


Left ventricular diverticulum and previous rhabdomyoma: an occasional detection.
A 35-year-old patient previously operated when a child for right ventricular (RV) rhabdomyoma was submitted to cardiac magnetic resonance (CMR) that showed a dilated RV and a small contractile cavity in the inferior left ventricular (LV) wall suggestive for diverticulum. This report shows the first description of a simultaneous evidence of LV diverticulum and previous rhabdomyoma, and furthermore highlights the important role of CMR for an easy detection of this congenital abnormality.


Toward an epidemiology of work disability.
The indirect cost of illness due to lost wages exceeds the cost of medical services by a large margin. Social characteristics of persons with physical impairment are more important than the characteristics of their medical condition in predicting whether disability will lead to work loss. Public policy toward disability currently emphasizes the "human capital" with which persons with impairments confront the labor market; this study suggests a new emphasis on social characteristics of the workplace.


Identification and verification of IGFBP3 and YTHDC1 as biomarkers associated with immune infiltration and mitophagy in hypertrophic cardiomyopathy.
Background: Hypertrophic cardiomyopathy (HCM) is the main cause of sudden cardiac death among young adults, yet its pathogenesis remains vague. N6-methyladenosine (m6A) methylation modification was involved in various cardiovascular diseases such as coronary heart disease and heart failure, although its influence on HCM remains unclear. This study aimed to explore the potential role of m6A in the diagnosis and pathogenesis of HCM. Methods: GSE36961 including 106 HCM and 39 controls was used in the study. The HCM-related m6A regulators were selected using support vector machine recursive feature elimination and random forest algorithm. A significant gene signature was then established using least absolute shrinkage and selection operator and then verified by GSE130036. Subgroup classification of HCM was performed based on the expression of m6A biomarkers. Gene set variation analysis was employed to explore the functional difference between distinct subgroups. Weighted gene co-expression network analysis was used to determine the m6A-related hub module. Single-sample gene set enrichment analysis was conducted to assess the immune and mitophagy features between subgroups. Besides, transfection of recombinant plasmids with targeted genes into H9c2 cells was performed to further verify the function of the significant biomarkers. Results: Significant difference existed in m6A landscape between HCM and control patients, among which IGFBP3 and YTHDC1 were identified as the independent biomarkers of HCM. Highly infiltrated immune cells (MDSC, macrophages, etc.), more enriched immune-related pathways (TNFα signaling via NFκB and IL6-JAK-STAT3 signaling) and cardiac remodeling-associated pathways (epithelial mesenchymal transition, angiogenesis, etc.) were identified in the subgroup with higher IGFBP3. Consistently, overexpression of IGFBP3 in H9c2 cells led to upregulation of extracellular-matrix-related genes (COL1A2, COL3A1 and MMP9) and inflammation-related genes (TNFα and IL6). Besides, higher YTHDC1 expression seemed to be consistent with less-activated mitophagy (PINK1-PRKN mediated mitophagy) and energy metabolism. Further experiments demonstrated that overexpression of YTHDC1 resulted in up-regulation of PINK and PRKN in cardiomyocytes, which are essential genes mediating mitophagy. Conclusion: Two m6A readers (IGFBP3 and YTHDC1) well distinguished HCM and may facilitate clinical diagnosis. IGFBP3 may play a role in the immune-microenvironments and remodeling of cardiac tissues, while YTHDC1 may influence mitophagy and energy metabolism in HCM.


Putative vaccine breakthrough event associated with heterotypic rotavirus infection in newborn calves, Turkey, 2015.
Group A rotaviruses (RVA) are regarded as major enteric pathogens of large ruminants, including cattle. Rotavirus vaccines administered to pregnant cows are commonly used to provide passive immunity that protects newborn calves from the clinical disease. In this study we report the detection of RVA from calves with severe diarrhea in a herd regularly vaccinated to prevent enteric infections including RVA. Diarrheic disease was observed in newborn calves aged 4-15days, with high morbidity and mortality rates, but no diarrhea was seen in adult animals. Rotavirus antigen was detected by enzyme-immunoassay in the intestinal content or the fecal samples of all examined animals. Besides RVA, bovine coronavirus and bovine enteric calicivirus were detected in some samples. Selected RVA strains were characterized by whole genome sequencing. Two strains, RVA/Cow-wt/TUR/Amasya-1/2015/G8P[5] and RVA/Cow-wt/TUR/Amasya-2/2015/G8P[5] were genotyped as G8-P[5]-I2-R2-C2-M2-A3-N2-T6-E2-H3 and showed >99% nucleotide sequence identity among themselves. This genomic constellation is fairly common among bovine RVA strains; however, phylogenetic analysis of the G8 VP7 gene showed close genetic relationship to some European human RVA strains (up to 98.4% nt identity). Our findings is the first indication regarding the circulation of G8 RVA strains in Turkey. Given that the administered RVA vaccines contained type G6 and G10 VP7 antigens some concerns raised with regard to the level of heterotypic protection elicited by the vaccine strains against circulating bovine G8 RVA strains. Enhancement of surveillance of circulating RVA strains in calves across Turkey is needed to support ongoing vaccination programs.


Screening for Y chromosome microdeletions in idiopathic and nonidiopathic infertile men with varicocele and cryptorchidism.
Cytogenetic and molecular studies of azoospermic and oligozoospermic males have suggested the presence of azoospermia factors (AZF) in the Y chromosome. Deletion in AZF regions has been reported to disrupt spermatogenesis and cause infertility. Several candidate genes responsible for spermatogenesis have been identified in this region and some of them are thought to be functional in human spermatogenesis. And we reported clinical and molecular studies of Y chromosome microdeletions in Chinese. This study aimed at assessing the frequency of microdeletions in Chinese men with idiopathic and nonidiopathic infertility problems and dicussing the clinical significance of the AZF region. In this study, we screened 143 infertile men (62 with idiopathic infertilitas and 81 with nonidiopathic infertilitas), in whom karyotype, sperm count, hormonal parameters and fine needle aspiration cytology were evaluated. Genomic DNA was extracted from the peripheral leukocytes. Molecular analysis was performed by two multiplex polymerase chain reactions (PCR) using a set of a sequence tagged sites (STS) from 3 different regions of the Y chromosome: AZFa (sY84, sY86), AZFb (sY127, sY134), AZFc (sY254, sY255). Nineteen point four percent of idiopathic males (12/62, 19.4%) had microdeletions of either the AZFa, AZFb, AZFc or AZFb + c region. Significantly, a high frequency of microdeletions (9/81, 11.1%) was found in nonidiopathic patients with varicocele and cryptorchidism. No deletions were found in healthy fertile men. There were no significant differences in the localization and extent of deletions between idiopathic and nonidiopathic patients. The knowledge of the presence of these deletions in idiopathic and nonidiopathic cases is important to understand the prognosis, better management and counsel these patients accordingly. Furthermore, a more extended screening for Y chromosome microdeletions in idiopathic and nonidiopathic men, particularly candidates for intracytoplasmic sperm injection, is recommended.


GW182 proteins cause PABP dissociation from silenced miRNA targets in the absence of deadenylation.
GW182 family proteins interact with Argonaute proteins and are required for the translational repression, deadenylation and decay of miRNA targets. To elicit these effects, GW182 proteins interact with poly(A)-binding protein (PABP) and the CCR4-NOT deadenylase complex. Although the mechanism of miRNA target deadenylation is relatively well understood, how GW182 proteins repress translation is not known. Here, we demonstrate that GW182 proteins decrease the association of eIF4E, eIF4G and PABP with miRNA targets. eIF4E association is restored in cells in which miRNA targets are deadenylated, but decapping is inhibited. In these cells, eIF4G binding is not restored, indicating that eIF4G dissociates as a consequence of deadenylation. In contrast, PABP dissociates from silenced targets in the absence of deadenylation. PABP dissociation requires the interaction of GW182 proteins with the CCR4-NOT complex. Accordingly, NOT1 and POP2 cause dissociation of PABP from bound mRNAs in the absence of deadenylation. Our findings indicate that the recruitment of the CCR4-NOT complex by GW182 proteins releases PABP from the mRNA poly(A) tail, thereby disrupting mRNA circularization and facilitating translational repression and deadenylation.


Nanopatterning of alkynes on hydrogen-terminated silicon surfaces by scanning probe-induced cathodic electrografting.
The electrochemical cathodic electrografting reaction, previously demonstrated on bulk silicon surfaces, can be patterned on the nanoscale utilizing conducting probe atomic force microscopy (CP-AFM). Alkyne electrografting is a particularly useful chemical technique since it leads to direct covalent attachment of conjugated alkynes to silicon. In addition, application of a forward bias during the reaction renders the surface less sensitive to oxidation and the resulting monolayers are very stable in air and basic aqueous solution. Alkyne monolayer lines can be drawn down to 40 nm resolution using a Pt-coated AFM tip, and the heights of the monolayers scale with the molecular length of the alkyne. The tip is biased (+) and the surface is biased (-) to drive the cathodic electrografting reaction under ambient conditions. The resistance of the monolayers to fluoride, as well as friction force microscopy, indicate that the alkynes are covalently bonded to the surface, not oxide-based, and hydrophobic. The reaction does not work with alkenes, and therefore hydrosilylation is not the primary mode of reaction. Wider lines (300 nm) can be produced using broadened Pt-coated AFM tips. This reaction could be important for the interfacing of conjugated molecules directly to silicon in a spatially controlled fashion.


Olanzapine induced DNA methylation changes support the dopamine hypothesis of psychosis.
The dopamine (DA) hypothesis of schizophrenia proposes the mental illness is caused by excessive transmission of dopamine in selected brain regions. Multiple lines of evidence, including blockage of dopamine receptors by antipsychotic drugs that are used to treat schizophrenia, support the hypothesis. However, the dopamine D2 receptor (DRD2) blockade cannot explain some important aspects of the therapeutic effect of antipsychotic drugs. In this study, we hypothesized that antipsychotic drugs could affect the transcription of genes in the DA pathway by altering their epigenetic profile. To test this hypothesis, we examined the effect of olanzapine, a commonly used atypical antipsychotic drug, on the DNA methylation status of genes from DA neurotransmission in the brain and liver of rats. Genomic DNA isolated from hippocampus, cerebellum, and liver of olanzapine treated (n = 2) and control (n = 2) rats were analyzed using rat specific methylation arrays. Our results show that olanzapine causes methylation changes in genes encoding for DA receptors (dopamine D1 receptor, dopamine D2 receptor and dopamine D5 receptor), a DA transporter (solute carrier family 18 member 2), a DA synthesis (differential display clone 8), and a DA metabolism (catechol-O-methyltransferase). We assessed a total of 40 genes in the DA pathway and found 19 to be differentially methylated between olanzapine treated and control rats. Most (17/19) genes showed an increase in methylation, in their promoter regions with in silico analysis strongly indicating a functional potential to suppress transcription in the brain. Our results suggest that chronic olanzapine may reduce DA activity by altering gene methylation. It may also explain the delayed therapeutic effect of antipsychotics, which occurs despite rapid dopamine blockade. Furthermore, given the common nature of epigenetic variation, this lends insight into the differential therapeutic response of psychotic patients who display adequate blockage of dopamine receptors.


Radiation dose in pelvic imaging.
To compare the radiation dose during pelvic x-ray examinations using computed radiography (CR) and film-screen (FS) radiography at various x-ray tube voltages (kV) and tube-current time product (mAs) values. A pelvic phantom was imaged using FS and CR systems. The entrance surface dose was measured using an ionization chamber, and the gonadal dose and effective dose were calculated using the XDOSE program. The diagnostic quality of the images was assessed using a 5-point subjective scoring system. At standard kV values, the image quality did not vary significantly between the CR and the FS system, but at higher kV values, the CR images werefound to be of better quality than FS images. In addition, the lower limit of entrance skin dose consistent with diagnostically acceptable CR images was 50% lower than that for FS images. The gonadal dose and effective dose for pelvic x-ray examinations can be reduced by 50% when CR systems are used and appropriate exposure factors are established.


A Cross-Cultural Investigation of Metamotivational Beliefs About Regulatory Focus Task-Motivation Fit.
Recent metamotivation research revealed that Westerners recognize that promotion versus prevention motivations benefit performance on eager versus vigilant tasks, respectively; that is, they know how to create task-motivation fit with respect to regulatory focus. Westerners also believe that, across tasks, promotion is more beneficial than prevention (i.e., a promotion bias). Adopting a cross-cultural approach, we examined whether beliefs about task-motivation fit generalize across cultures, whether Easterners exhibit a contrasting prevention bias, and the role of independence/interdependence in these beliefs. Results revealed cross-cultural similarities in metamotivational beliefs. Moreover, Easterners and Westerners alike often exhibited a promotion bias, suggesting that this effect may not be shaped by culture. One potential cultural difference did emerge: Easterners appeared to recognize how to create task-motivation fit for both independent and interdependent outcomes, whereas Westerners only recognized how to do so for independent outcomes. We discuss the role of culture in shaping metamotivation.


Endogenous retroviruses as potential hazards for vaccines.
Retroviruses are classified as exogenous or endogenous according to their mode of transmission. Generally, endogenous retroviruses (ERVs) are not pathogenic in their original hosts; however, some ERVs induce diseases. In humans, a novel gammaretrovirus was discovered in patients with prostate cancer or chronic fatigue syndrome. This virus was closely related to xenotropic murine leukemia virus (X-MLV) and designated as xenotropic murine leukemia virus-related virus (XMRV). The origin and transmission route of XMRV are still unknown at present; however, XMRV may be derived from ERVs of rodents because X-MLVs are ERVs of inbred and wild mice. Many live attenuated vaccines for animals are manufactured by using cell lines from animals, which are known to produce infectious ERVs; however, the risks of infection by ERVs from xenospecies through vaccination have been ignored. This brief review gives an overview of ERVs in cats, the potential risks of ERV infection by vaccination, the biological characteristics of RD-114 virus (a feline ERV), which possibly contaminates vaccines for companion animals, and the methods for detection of infectious RD-114 virus.


Inosine synthesis and phosphoribosylpyrophosphate availability in rat liver cells in the presence of allopurinol.
In the presence of allopurinol, apparent phosphoribosylpyrophosphate (PP-ribose-P) availability as measured by adenine incorporation into ribonucleotides was decreased in rat liver cells, hypoxanthine incorporation into ribonucleotides was increased, and there was a large synthesis of inosine from hypoxanthine. Inosine was formed directly by the reversal of the purine nucleoside phosphorylase reaction which was very rapid in liver cells. We tested the hypothesis that utilization of ribose 1-phosphate for inosine synthesis could decrease PP-ribose-P availability. Our results indicate that the apparent decrease of PP-ribose-P availability in the presence of allopurinol was due to competition between adenine and hypoxanthine salvage pathways into nucleotides, and not to the synthesis of inosine.


[Mutagenicity of 3 organic fractions of atmospheric dust and gas chromatographic analysis of the basic fraction].
Suspended particulate matter (PM) with a Dae less than 0.4 micron was collected from July 1981 till January 1982. The ether/benzene soluble extract (EEOM) and the acidic, basic and neutral fractions were determined and investigated for their mutagenic activities in the Ames bioassay. In addition particles (Dae) less than 10.2 micron derived in January were investigated. Five compounds of the basic fraction were determined by gaschromatography. The following results were obtained: Suspended particulate matter (Dae less than 0.4 micron) and the ether/benzene extract increase from July to January. The lowest rates occur in July (PM: 16.9 micron/m3) and August (EEOM: 3.0 micrograms/m3), the highest in January (PM: 48.9 micrograms/m3, EEOM: 10.5 micrograms/m3). The ether/benzene soluble portion of the suspended particulate matter increases from the average rate of 16.3% (July-September) to 22.7% (November-January). The neutral fraction amounts to 44.9%, the acidic fraction to 27.3% and the basic fraction to 3.5% of the organic matter (on an average). In experiments with metabolic activation 99% of the total mutagenicity during the period of July till September can be demonstrated by summing up the mutagenicity of the three fractions on the other hand only 59.7% from November till January. The EEOMs derived from winter exhibit without metabolic activation (250 micrograms/plate) distinctively higher numbers of revertants than the single fractions. Dose-response curves of extracts derived from back-up filters (Dae less than 0.4 micron) in January show that the acidic fraction has a slightly higher mutagenic activity than the neutral fraction (mean values of tests with and without S9-mix). The basic fraction shows no mutagenicity without S9-mix, with activation the mutagenic activity is lower than that of the other fractions. Mutagenicity expressed as rev./m3 air shows, that the neutral fraction is most efficient. The number of revertants per plate reveals-in relation to the particle size-different results concerning the three fractions (January).


[Cloning, soluble expression and mutant activity analysis of lactate dehydrogenase gene from Plasmodium falciparum].
To establish a platform for high throughput screening and in vitro evaluating novel metabolic enzyme-targeted inhibitors towards anti-malarial drugs, a lactate dehydrogenase gene of Plasmodium falciparum (PfLDH) was amplified from the Hainan isolate FCC1/HN. The fusion expression vectors, pGEX-2TK and pET-29a( + ), were utilized to introduce the PfLDH gene into strains of Escherichia coli, BL21 and BL21 (DE3), for over-expression. Consequently, the enzymatic activity of PfLDH was successfully detected in the suspension of lytic bacteria. The PfLDH gene cloned in pGEX-2TK was mainly expressed as inclusion bodies, while the same gene cloned in pET-29a( + ) was nearly expressed in a soluble form of PfLDH, demonstrating the latter vehicle might be more suitable for the large-scale preparation of recombinant PfLDH. Furthermore, according to the electrophoregram of SDS-PAGE and the sequencing data, a series of truncated PfLDH sequences generated randomly from gene amplification were screened and cloned, from which four pre-matured genes with a terminator mutation, PfLDH-delta271, -delta236, -delta167 and -delta53 coding for 45, 80, 149 and 263 amino acid residues, were individually recovered. Through the gene expression and enzymatic activity measurement, the effect of pre-matured terminator mutation on the activity of PfLDH was evaluated, which should pave the way for probing the relationship between structure and function of PfLDH.