Impact of steaming pretreatment process on characteristics and antioxidant activities of black garlic (Allium sativum L.).
Impact of steaming pretreatment processes on physical properties, bioactive compounds and antioxidant activities, of black garlics (Allium sativum L.) was studied. Steaming pretreatment at different times (0, 4 and 6 min) was conducted before incubating in 60 °C-incubator at different incubation times (0, 9 and 18 days). Different steaming pretreatment processes affected the color and hardness of black garlic differently, while total polyphenol content (TPC) and total flavonoid content (TFC) were also determined by the steaming pretreatment time used. TPC and TFC increased with increasing of incubating time, where the highest those bioactive compounds was observed from 18-day incubation, especially with 4 min of steaming pretreatment (p ≤ 0.05). Increase of those bioactive compounds was in accordance with increasing of DPPH radical scavenging activity (DPPH) and ferric reducing antioxidant power (FRAP) of black garlic during incubation. In addition, black garlic obtained from 18-day incubation with steaming pretreated for 4 min revealed the optimum condition providing the black garlic with high in both DPPH and FRAP, compared with others (p ≤ 0.05). Therefore, steaming pretreatment could effectively improve the efficiency of black garlic production process by increase the generation rate of bioactive compounds as well as induce antioxidant properties of black garlic with shorten process time.


[Influence of atrial contraction on stroke volume in pacemaker stimulation].
The contribution of the atrial systole to the stroke volume was studied in 12 patients with implanted pacemakers by means of impedance-cardiography. P-ST-intervals between 70 and 200 msec. increased the stroke volume as compared with systoles without preceding P-waves. A maximal stroke volume was observed with a P-ST-interval of 130 msec. The increase of the stroke volume by 33% justifies the application of atrial triggered pacemakers in selected cases, mainly in younger patients despite of the technical limitations of these pacemaker systems.


The dnd operon for DNA phosphorothioation modification system in Escherichia coli is located in diverse genomic islands.
Strains of Escherichia coli that are non-typeable by pulsed-field gel electrophoresis (PFGE) due to in-gel degradation can influence their molecular epidemiological data. The DNA degradation phenotype (Dnd(+)) is mediated by the dnd operon that encode enzymes catalyzing the phosphorothioation of DNA, rendering the modified DNA susceptible to oxidative cleavage during a PFGE run. In this study, a PCR assay was developed to detect the presence of the dnd operon in Dnd(+) E. coli strains and to improve their typeability. Investigations into the genetic environments of the dnd operon in various E. coli strains led to the discovery that the dnd operon is harboured in various diverse genomic islands. The dndBCDE genes (dnd operon) were detected in all Dnd(+) E. coli strains by PCR. The addition of thiourea improved the typeability of Dnd(+) E. coli strains to 100% using PFGE and the Dnd(+) phenotype can be observed in both clonal and genetically diverse E. coli strains. Genomic analysis of 101 dnd operons from genome sequences of Enterobacteriaceae revealed that the dnd operons of the same bacterial species were generally clustered together in the phylogenetic tree. Further analysis of dnd operons of 52 E. coli genomes together with their respective immediate genetic environments revealed a total of 7 types of genetic organizations, all of which were found to be associated with genomic islands designated dnd-encoding GIs. The dnd-encoding GIs displayed mosaic structure and the genomic context of the 7 islands (with 1 representative genome from each type of genetic organization) were also highly variable, suggesting multiple recombination events. This is also the first report where two dnd operons were found within a strain although the biological implication is unknown. Surprisingly, dnd operons were frequently found in pathogenic E. coli although their link with virulence has not been explored. Genomic islands likely play an important role in facilitating the horizontal gene transfer of the dnd operons in E. coli with 7 different types of islands discovered so far.


Targeted stabilization of Munc18-1 function via pharmacological chaperones.
Heterozygous de novo mutations in the neuronal protein Munc18-1 cause syndromic neurological symptoms, including severe epilepsy, intellectual disability, developmental delay, ataxia, and tremor. No disease-modifying therapy exists to treat these disorders, and while chemical chaperones have been shown to alleviate neuronal dysfunction caused by missense mutations in Munc18-1, their required high concentrations and potential toxicity necessitate a Munc18-1-targeted therapy. Munc18-1 is essential for neurotransmitter release, and mutations in Munc18-1 have been shown to cause neuronal dysfunction via aggregation and co-aggregation of the wild-type protein, reducing functional Munc18-1 levels well below hemizygous levels. Here, we identify two pharmacological chaperones via structure-based drug design, that bind to wild-type and mutant Munc18-1, and revert Munc18-1 aggregation and neuronal dysfunction in vitro and in vivo, providing the first targeted treatment strategy for these severe pediatric encephalopathies.


Angiotensin-converting enzyme single nucleotide polymorphism is a genetic risk factor for cardiovascular disease: a cohort study of hypertensive patients.
The renin-angiotensin system (RAS) adversely affects stroke and cardiovascular disease; polymorphisms in genes involved in this system are associated with cardiovascular disease. The aim of the present study was to confirm the genetic risk of these polymorphisms for stroke and cardiovascular events in a cohort study of 515 hypertensive patients in Japan (follow-up period 90.6±30.2 months). The insertion/deletion (I/D) polymorphism of the gene encoding angiotensin-converting enzyme (ACE), the M235T amino acid change in angiotensinogen, and the A1166C polymorphism in angiotensin II type 1 receptor were determined by TaqMan PCR. In Kaplan-Meier analyses, the ACE I/D polymorphism was a risk factor for cerebro-cardiovascular events, especially cardiovascular events (P<0.0001), and the M235T mutation was a risk factor for cardiovascular events (P<0.0105). The cumulative rates of cerebro-cardiovascular end points for the ACE polymorphism were 10.6, 16.4 and 42.2% for the II (n=207), ID (n=244) and DD (n=64) genotype carriers, respectively (P<0.0001). Cox's proportional hazard models revealed that the ACE DD genotype was a risk factor for cerebro-cardiovascular and cardiovascular events (after adjusting for common risk factors), anti-hypertensive treatment and RAS inhibition (P<0.0001). Moreover, after adjustment for the common risk factors left ventricular hypertrophy and previous myocardial infarction/stroke, these phenomena were preserved. Thus, the DD genotype of ACE may be a genetic risk factor for cerebro-cardiovascular disease, especially cardiovascular events, in hypertensive patients in Japan.


Hypomania Checklist-32 - cross-validation of shorter versions screening for bipolar disorders in an epidemiological study.
Self-reports such as Hypomania Checklist (HCL-32) can be used to enhance recognition of bipolar disorders, but they are often too long and only validated in clinical samples. The objectives of this study are therefore to test whether (i) the HCL-32 can be used for screening in the community and (ii) whether two previously suggested shorter versions would do as well. Data stemmed from the CoLaus|PsyColaus, a prospective cohort study which included randomly selected residents aged 35-66 years from an urban area. Participants underwent semistructured interviews to assess DSM-IV disorders and 1712 of them completed the HCL-32. Forty individuals (2.3%) were diagnosed as having BD. Compared to others, participants with BD scored significantly higher on the HCL-32. The HCL-32 had a sensitivity of 0.78 and specificity of 0.68. Very similar figures were found for two previously proposed shorter versions with 16 and 20 items. The results of confirmatory factor analysis and item response theory (IRT) models supported the postulated two-factor structure for the three HCL versions. Despite the low base rate of BD in this sample, the screening properties of the HCL-32 remained almost as good. Importantly, two previously proposed shorter versions performed as well, suggesting that those could be used without losing essential information.


Effect of using Celosia argentea grown from seeds treated with a magnetic field to conduct Cd phytoremediation in drought stress conditions.
The mechanisms of the stimulatory effect of external magnetic fields on plant growth have been revealed; however, the role of magnetic fields in the efficiency of phytoremediation with Celosia argentea grown under drought stress which results in detrimental influences on food security has not been reported. Therefore, this study evaluated the physiological responses of C. argentea to the interactions between exposure to a magnetic field and drought stress. Compared with a control, a drought treatment negatively affected the dry weight, transpiration rate, and Cd extraction efficiency of the species and caused oxidative damage in plant cells, as manifested by the increase in malondialdehyde levels and antioxidant enzyme activities. The biomass production, pigment levels, Cd content, and phytoremediation efficiency of the plant were positively affected by all magnetic field treatments compared to the control. All magnetic treatments, except those at 30 mT, alleviated the detrimental effects induced by a 10-day irrigation regime by enhancing the dry weight, chlorophyll content, and activities of antioxidant enzymes in the leaves of the plant. In terms of the interaction between pre-sowing magnetic field seed treatment and drought stress, a 100 mT treatment increased most of the measured parameters, particularly under a 3-day irrigation regime; this corresponded to the optimal phytoremediation efficiency. The results suggest that magnetic field treatment is a novel, economical, and practicable strategy by which to increase the efficiency of phytoremediation using C. argentea under drought stress.


Cross-sectional internet survey exploring symptomatic urinary tract infection by type of urinary catheter in persons with spinal cord lesion in Japan.
Cross-sectional study by members of patient advocacy groups. To evaluate the incidence and frequency of symptomatic urinary tract infection (sUTI) in persons with spinal cord lesion (SCL) using different types of catheters based on an internet survey in Japan. An internet survey. We conducted an Internet survey of persons with SCL who were considered to be able to perform intermittent self-catheterization (ISC). We evaluated the incidence and frequency of sUTI over the last year in persons performing ISC and those managed by indwelling catheterization (IDC). We also compared the same parameters between persons in the ISC group using reusable silicone catheters and single-use catheters and those with and without a concomitant use of intermittent balloon catheters (i-IDC). Two-hundred and eighty-two persons were analyzed. In the ISC and IDC groups, sUTI occurred in 52.2% and 31.4% of persons (p = 0.021), respectively, in the last year, and the frequencies were 2.8 and 3.5 times a year (p = 0.127), respectively. There were no significant differences in the incidence or frequency of sUTI between persons using reusable catheters and single-use catheters or those with and without the concomitant use of i-IDC. sUTI occurred in about 1 in 2 persons with SCL performing ISC, which was significantly higher than in the IDC group, and the frequency of sUTI in persons performing ISC was about 3 times a year. The different types of catheters used for ISC were not associated with the incidence or frequency of sUTI. Sponsorship Coloplast Japan Inc.


Traumatic laryngotracheal stenosis--an alternative surgical technique.
Reconstruction of combined laryngotracheal stenosis requires complex techniques including resection and incorporation of grafts and stents that can be performed as single or multistaged procedure. A complicated case of traumatic laryngotracheal stenosis was managed by us, surgical technique is discussed. A 16-year-old male presented with Stage-3 laryngotracheal stenosis of grade-3 to 4 (>70% of the complete obstruction of tracheal lumen) of 5 cm segment of the larynx and trachea. Restoration of the critical functions of respiration and phonation was achieved in this patient by resection anastomosis of the trachea and with subglottic remodeling. Resection of 5 cm long segment of trachea and primary anastomosis in this case would have created tension at the site of anastomosis. So we did tracheal resection of 3 cm segment of trachea along with subglottic remodeling instead of removing the 5 cm segment of stenosed laryngotracheal region and doing thyrotracheal anastomosis. In complicated long segment, laryngotracheal stenosis, tracheal resection and subglottic remodeling with primary anastomosis can be an alternative approach. Fibrin glue can be used to support free bone/cartilage grafts in laryngotracheal reconstructions.


Comparative proteomics analysis of high n-butanol producing metabolically engineered Clostridium tyrobutyricum.
The acidogenic Clostridium tyrobutyricum has recently been metabolically engineered to produce n-butanol. The objective of this study was to obtain a comprehensive understanding as to how butanol production was regulated in C. tyrobutyricum to guide the engineering of next-generation strains. We performed a comparative proteomics analysis, covering 78.1% of open reading frames and 95% of core enzymes, using wild type, ACKKO mutant (Δack) producing 37.30 g/L of butyrate and ACKKO-adhE2 mutant (Δack-adhE2) producing 16.68 g/L of butanol. In ACKKO-adhE2, the expression of most glycolytic enzymes was decreased, the thiolase (thl), acetyl-CoA acetyltransferase (ato), 3-hydroxybutyryl-CoA dehydrogenase (hbd) and crotonase (crt) that convert acetyl-CoA to butyryl-CoA were increased, and the heterologous bifunctional acetaldehyde/alcohol dehydrogenase (adhE2) catalyzing butanol formation was highly expressed. The apparent imbalance of energy and redox was observed due to the downregulation of acids production and the addition of butanol synthesis pathway, which also resulted in increased expression of chaperone proteins and glycerol-3-phosphate dehydrogenase (glpA) and the silence of sporulation transcription factor Spo0A (spo0A) as the cellular responses to butanol production. This study revealed the mechanism of carbon redistribution, and limiting factors and rational metabolic cell and process engineering strategies to achieve high butanol production in C. tyrobutyricum.


Effects of a single dose of the cytochrome P450 inducer, beta-naphthoflavone, on hepatic and renal covalent DNA modifications (I-compounds).
I-compounds are age-dependent covalent DNA modifications, which occur in rodent tissues without known carcinogen exposure. A number of studies from our laboratory indicate that I-compounds may serve as biomarkers of carcinogenesis. Recently, we demonstrated significant lowering of liver I-compound levels in rats that were exposed to different cytochrome P450 inducers. In order to gain further mechanistic insights into the possible relationship between P450 induction and I-compound reduction, female Sprague-Dawley rats were administered a single dose of the CYP1A1 inducer, beta-naphthoflavone (BNF) (80 mg/kg), in corn oil (CO) (2 ml/kg) or CO only (2 ml/kg) as vehicle control. Liver and kidney microsomal P450 contents and P450-related enzyme activities and DNA I-compounds were determined at 4, 24, and 48 h after treatment. Liver and kidney I-compounds were analyzed by nuclease P1-enhanced 32P-postlabeling. DNA synthesis was determined by measuring [3H]methylthymidine incorporation. Liver and kidney microsomal P450 contents were elevated by BNF at 24 and 48 h. Ethoxyresorufin-O-deethylase (EROD) and methoxyresorufin-O-demethylase (MROD) were significantly elevated at all time points, with the former displaying a much higher extent of induction. BNF treatment resulted in significant diminution of the levels of several individual and total I-compounds in liver at 48 h, but few effects were seen at the earlier time-points. Kidney I-compounds were also markedly affected by BNF at 48 h, albeit to a lesser extent than in liver. In both tissues, P450 induction preceded I-compound reduction. Taken together, the results of this investigation demonstrate significant diminution of I-compound levels by a single dose of BNF, a CYP1A1 inducer, in a time-dependent manner, suggesting the participation of a specific biochemical process, possibly involving CYP1A1, in the metabolic regulation of these endogenous DNA adducts.


Baseline assessment of beach cast appearance in the South-Eastern Baltic by video monitoring at a pilot site in the Kaliningrad Oblast (Russia).
A webcam was installed on the shore of the South-Eastern Baltic (Kaliningrad Oblast, Russia) to monitor the beach dynamics and beach-cast (BC) daily from November 1, 2019, to October 31, 2020. The beach was formed not the whole year (77%). The most frequent BC residence time was one day (1-21, 4.1 on average, and 1-19, 4.3 on average days to the west and east of the groin, respectively). The BC consisted primarily of algae. Fresh BC occupied smaller area, and its layer was thicker than that of long-discarded and trampled BC. The specific amount of material (per m2) in a fresh BC was 3.7 times higher in volume and 2.6 times higher in weight than in long-discarded and trampled BC. For fresh and old BC, the specific volumes were 63 and 17 l per m2, respectively, and the specific masses were 48 and 18 kg per m2, respectively.


Free arterial graft as internal mammary artery-Y complex.
Because of excellent surgical results obtained with in situ internal mammary artery grafts, recent efforts have been made to extend the use of arterial conduits. In this study 2 cases of coronary revascularization using free internal mammary artery and gastroepiploic artery grafts as an internal mammary artery-Y complex are described. We believe that complete revascularization with only arterial conduit can be achieved more widely by using this technique.


Brief Report: HIV Testing and Risk Among Justice-Involved Youth.
Justice-involved youth have a number of risk factors for HIV infection, including high rates of substance use, psychiatric comorbidities, and risky sexual behaviors. Although detained youth are likely to receive health care-which may include HIV testing-court-involved, non-incarcerated (CINI) youth may be unlikely to receive HIV testing services either before or during their justice involvement. However, the relationship between risk factors and HIV testing among CINI youth is largely unknown. We explored the association between HIV testing and factors commonly associated with both HIV testing and HIV risk among 173 CINI youth with identified behaviors that put them at risk for HIV acquisition. Only 15.6% of participants reported a lifetime history of HIV testing, despite high rates of sexual and substance use risk behaviors. Age (older), gender (female), sexual orientation (non-heterosexual), recent marijuana use, lifetime use of other drugs, history of a sexually transmitted infection, pap smear in the past year and history of mental health/substance use treatment were all significantly associated with lifetime HIV testing. The extremely low testing rates in this sample emphasize that the juvenile justice system outside of detention is not adequately addressing youths' needs related to HIV testing or ensuring access to testing services for youth at risk of contracting HIV. Results suggest that additional efforts are needed to connect justice-involved youth to healthcare more broadly and HIV testing in particular.


What are the concerns of second-degree medical students entering specialty OMFS training?
Oral and maxillofacial surgery (OMFS) applicants are faced with numerous challenges. Previous research has demonstrated that financial burden, length of OMFS training, and impact on personal life are cited as major drawbacks to pursuing the specialty, with trainees having concerns about the Membership of the Royal College of Surgeons (MRCS) examinations. The current study aimed to explore second-degree medical students' concerns about obtaining a specialty training post in OMFS. An online survey was distributed via social media to second-degree students across the United Kingdom and 106 responses were received. A lack of publications and lack of involvement in research (54%) as well as attaining accreditation with the Royal College of Surgeons (27%) were cited as the primary and secondary concerns in relation to securing a higher training post. Seventy-five per cent of respondents had no first-author publications, 93% expressed concerns about passing the MRCS examination, and 73% had more than 40 OMFS procedures within their logbook. Second-degree medical students reported having ample clinical and operative experience in OMFS. Their main concerns were about research and MRCS examinations. To alleviate these concerns, BAOMS could provide educational initiatives and dedicated mentorship programmes for second-degree students, and could adopt a collaborative approach with discussion with major postgraduate training stakeholders.


Comparison of two once-daily regimens with a regimen consisting of nelfinavir, didanosine, and stavudine in antiretroviral therapy-naïve adults: 48-week results from the Antiretroviral Regimen Evaluation Study (ARES).
To improve the dosing frequency and pill burden of antiretroviral therapy, we compared two once-daily dosed regimens to a twice-daily dosed regimen. HIV-1-infected, antiretroviral drug-naïve adults were randomized to either twice-daily nelfinavir and stavudine and once-daily didanosine (regimen A) or simplified once-daily dosed antiretroviral regimens consisting of nevirapine, didanosine, and lamivudine (regimen B) or saquinavir, ritonavir, didanosine, and lamivudine (regimen C). At 48 weeks of therapy, the proportion of patients with a blood plasma HIV-1 RNA concentration (pVL) <50 copies/mL by intention-to treat analysis was 42.3%, 50.0%, and 56.5% for regimens A (n = 26), B (n = 22), and C (n = 23), respectively. The time to a pVL <50 copies/mL for the first time was significantly shorter in regimen C, and there was significantly more progression to CDC events in regimen B. These differences are possibly due to differences in baseline characteristics. Adverse events were lowest for regimen C; more signs associated with mitochondrial toxicity occurred in regimen A. Increase in CD4 count was comparable between arms. No statistically significant difference in efficacy was found between the two investigated once-daily dosed treatment regimens (B and C) and the reference (A). Regimen C possibly had a better virological response and less toxicity than regimens A and B.


Comparative analysis of two assays for genotyping hepatitis C virus based on genotype-specific primers or probes.
The importance of determining the hepatitis C virus genotype has increased since several authors have described a good correlation between hepatitis C virus genotype and response to interferon treatment or to disease severity. It is thus of particular importance to develop reliable assays for hepatitis C virus genotyping. We have comparatively analyzed hepatitis C virus genotypes of 208 French and Italian chronically infected patients using genotype-specific primers polymerase chain reaction in the capsid region and a genotype-specific probe-based assay in the 5' untranslated region (LiPA). We found a good concordance between the two assays for the prevalent genotypes in our regions (145/174). The nucleotide sequences in the 5'UTR and capsid domain were investigated to determine the molecular basis of some discordant results. This analysis showed that the genotype-specific probe-based assay gave more consistent results, probably because this technique is based on several probes distributed along the 5'UTR to reveal each genotype. In contrast, the low variability of 5'UTR did not always permit classification of the hepatitis C virus genotype 1 subtypes. We also found some problems, using genotype-specific primers polymerase chain reaction, for less represented genotypes; in particular, in the presence of type 2a/III we obtained more discordant results. This observation is of importance in view of the potential association of this genotype with mild liver disease and a good response to interferon-a treatment.


Reproducibility of Doppler echocardiographic quantification of aortic and mitral valve stenoses: comparison between two echocardiography centers.
Doppler echocardiography has been widely used as a noninvasive method to quantify valvular heart diseases. This study assessed the variability between 2 echocardiography centers concerning 2-dimensional and Doppler echocardiographic results in the quantification of mitral and aortic valve stenoses. Forty-two patients were studied by 2 different echocardiography centers in a blinded, independent fashion. In patients with aortic and mitral valve stenosis, mean and maximal flow velocities were measured. The aortic valve orifice area was calculated according to the continuity equation. Mitral valve orifice area was determined by direct planimetry and by pressure half-time. In patients with an aortic valve stenosis, a close relation between the 2 centers was found for the maximal and mean flow velocities (coefficient of correlation, r = 0.72 to 0.92; coefficient of variation, 3.7 to 7.7%). A close correlation and a small observer variability was found for the flow velocity ratio determined by flow velocities measured in the left ventricular outflow tract and over the stenotic valve (r = 0.88; coefficient of variation, 0.01 +/- 0.009). In contrast, there was a poor correlation between the diameter of the left ventricular outflow tract and the aortic orifice area (r = 0.36 and 0.59, respectively). In patients with a mitral valve stenosis, mean and maximal velocities were closely correlated (r = 0.85 and 0.77, respectively). Velocities were not found to be significantly different between the 2 centers. Variability between the 2 centers for the mitral valve orifice area was 9.8% (2-dimensional echocardiography) and 5.7% (pressure half-time).(ABSTRACT TRUNCATED AT 250 WORDS)


The sensitivity of cells from normal mouse bone marrow to gamma radiation in vitro and in vivo.
1. A survival curve for the colony-forming ability of mouse bone marrow cells irradiated in vivo with Co60 gamma-rays has been obtained. The curve may be characterized by D0 of 95 rads and an extrapolation number of 1.5. 2. Comparison with the survival curve obtained for irradiated in vitro indicated a statistically significant difference in extrapolation number. Possible explanations for this finding are considered.


Influence of the norepinephrine and medium acidification in the growth and adhesion of Salmonella Heidelberg isolated from poultry.
Salmonella spp. are among the leading pathogens responsible for foodborne illnesses worldwide. Bacterial communities use a quorum sensing (QS) system to control biofilm formation. QS is a cell-to-cell signaling mechanism involving compounds called auto-inducers (AI). Norepinephrine utilizes the same bacterial signaling of AI-3 and serves as a signal of QS. Acid stress is a challenge encountered by microorganisms in food processing environments and in the gastrointestinal tracts of hosts. Thus, adaptation to acidic environments may increase the pathogenicity of the strain. The aim of this study was to evaluate the influence of two concentrations of norepinephrine (100 μM and 250 μM) and acidification (pH 3.0) of the medium on the growth and adhesion of Salmonella Heidelberg strains isolated from poultry sources at 12 °C and 25 °C. Furthermore, three genes associated with the biofilm formation process were detected (adrA, csgD, and sidA). Norepinephrine stimulation did not influence the growth or adhesion of Salmonella Heidelberg strains, regardless of the catecholamine concentration and temperature. On the other hand, the use of acidified medium (pH 3.0) resulted in a significant reduction of growth and a significant increase of S. Heidelberg adhesion at both temperatures, indicating that the acidified medium favors the biofilm formation process. The adrA and sidA genes showed higher detection frequencies than csgD. Experiments analyzing the biofilm production process by S. Heidelberg strains are not common, and further studies are necessary to understand this complex process.


Prediction of lofepramine-response in depression based on response to partial sleep deprivation.
The improvement of depression after partial sleep deprivation in the second half of the night (sd) is tested for its predictory power for the therapeutical efficacy of pharmacotherapy with lofepramine. In a group of 15 patients with depression, we found that in contradiction to the findings of Wirz-Justice and collaborators (1976), the velocity of the antidepressive effect of sd has no predictive value. On the other hand, the amount of depression improvement after sd is of predictive value. This is independent of the time of occurrence of the improvement peak after sd. An improvement of more than 35% measured in the Bf-S or in the H.DRS on the first or the second day after sd is highly predictive for a good response to three weeks of 210 mg lofepramine per day (p = .05).


Cardiomyopathies in China: A 2018-2019 state-of-the-art review.
Cardiomyopathies are diseases of the cardiac muscle and are often characterized by ventricular dilation, hypertrophy, and cardiac arrhythmia. Patients with cardiomyopathies often experience sudden death and cardiac failure and require cardiac transplantation during the course of disease progression. Early diagnosis, differential diagnosis, and genetic consultation depend on imaging techniques, genetic testing, and new emerging diagnostic tools such as serum biomarkers. The molecular genetics of cardiomyopathies has been widely studied recently. The discovery of mechanisms underlying heterogeneity and overlapping of the phenotypes of cardiomyopathies has revealed the existence of disease modifiers, and this has led to the emergence of novel disease-modifying therapy. This 2018-2019 state-of-the-art review outlines the pathogenesis, diagnosis, and treatment of cardiomyopathies in China.


Evidence that glutathione is the unidentified amine (Unk 2.5) released by high potassium into cochlear fluids.
An unidentified substance, Unk 2.5, may be important in the function of the cochlea. The efflux of Unk 2.5 into cochlear fluids is increased by intense sound (Bobbin and Fallon, 1992) and by exposure of the cochlear tissue to high concentrations of K+ (Bobbin et al., 1990,1991; Bobbin and Fallon, 1992). The unidentified chemical eluted at 2.5 min in chromatograms obtained by HPLC utilizing fluorescence detection and precolumn o-phthalaldehyde (OPA) derivatization of samples of effluent from the cochlea (e.g., Bobbin et al., 1990). The purpose of this investigation was to provide evidence as to the identity of this unidentified chemical we call Unk 2.5. Therefore, we carried out additional HPLC assays on samples obtained during perfusion of the cochlear perilymph compartment. Glutathione (GSH) was found to elute at the same time (@ 2.5 min) as Unk 2.5 in HPLC chromatograms utilizing precolumn derivatization with OPA and mercaptoethanol. In addition, both Unk 2.5 and GSH reacted with OPA without mercaptoethanol present in the reaction mixture to give a peak at 2.5 min in the chromatogram, but failed to show this peak if stored in solutions with a pH > 7 for several days before the reaction. Results indicate that Unk 2.5 is GSH or a closely related compound. Given this probable identification GSH, aka Unk 2.5, has been demonstrated to be released from tissue in the cochlea by high concentrations of K+ (Bobbin et al., 1990,1991) and by intense sound (124 dB SPL; Bobbin and Fallon, 1992).


Alterations in forebrain catecholamine metabolism produced by cerebellar lesions in the rat.
Projections from the midline cerebellar nuclei to norepinephrine (NE) and dopamine (DA) cell groups in the brain stem have been demonstrated histologically. To determine if these connections are significant biochemically, unilateral electrolytic lesions were placed in either vermis or paravermis and levels of DA, NE and gamma-aminobutyric acid (GABA) were measured in each half of the forebrain at 1 1/2, 3 or 6 weeks. In the cerebral hemisphere ipsilateral to a vermis lesion, there was a decrease in NE levels at 3 and 6 weeks. Relative to the opposite side DA was also reduced at 3 and 6 weeks. Paravermal lesions caused a contralateral reduction in DA at 3 weeks but no change in NE. GABA was only slightly altered. These results suggest that the cerebellum can modify levels and turnover of catecholamines in the brain, possibly via direct anatomic connections as well as by functional interaction with catecholaminergic pathways.


Mohs' micrographic surgery and distal urethrectomy with immediate urethral reconstruction for glanular carcinoma in situ with significant urethral extension.
To report the use of conservative extirpative surgical techniques to manage glanular carcinoma in situ with significant urethral extension. Over a 5-year period, 2 patients with carcinoma in situ of the glans with significant distal urethral involvement, who refused penectomy, were managed with combined treatment modalities using Mohs' micrographic surgery and distal urethrectomy with immediate urethral reconstruction. At follow-up of 5 years and of 12 months, there has been no evidence of meatal or proximal urethral recurrence. Mohs' micrographic surgical excision and distal urethrectomy with immediate urethral reconstruction offers an acceptable alternative to partial penectomy in patients with perimeatal carcinoma in situ who fail conservative treatment or refuse penectomy.


Epicardial foci of atrial arrhythmias apparently originating in the left pulmonary veins.
Epicardial potential sources of atrial arrhythmias, such as the ligament of Marshall, are in close proximity with, and electrically connected to, the left superior pulmonary vein. Ectopic activity arising from these areas may be difficult to differentiate from ectopy that, according to endocardial only mapping, originates in the left superior pulmonary vein. We hypothesized that in patients with paroxysmal atrial fibrillation (AF) apparently originating in the left pulmonary veins, mapping through the distal coronary sinus might identify possible epicardial locations of the arrhythmogenic focus. Forty patients (age 48 +/- 12 years) who underwent catheter ablation for paroxysmal AF were studied by epicardial mapping through the distal, superoposterior coronary sinus. Catheterization of the distal coronary sinus in order to approach the ostium of the left superior pulmonary vein was feasible in 14 of 19 patients with AF originating in the left superior vein (11 patients) or inferior pulmonary vein (3 patients) according to endocardial mapping criteria. In 2 patients, the sole focus of atrial tachycardia/fibrillation was epicardial with earliest activation clearly preceding electrograms recorded at the os of the left superior pulmonary vein or any other endocardial mapping site. Epicardial potentials separated from atrial electrograms were present during sinus rhythm in both patients and during atrial tachycardia in one patient. Catheter ablation through the coronary sinus rendered the arrhythmia noninducible in both patients without abolishing epicardial potentials in one of them. In patients with paroxysmal AF apparently originating from the left superior or inferior pulmonary vein, detailed epicardial mapping through the distal coronary sinus might identify epicardial locations of the arrhythmogenic focus.


The value of multimodality imaging in diagnosis and treatment of cardiac lipoma.
Cardiac lipoma is a rare primary tumor in the heart and pericardium. Multimodality imaging methods, especially magnetic resonance imaging (MRI), are crucial in detecting and diagnosing cardiac lipomas. Besides, they are of significant importance in management of cardiac lipomas. The aim of this study was to evaluate the value of multimodality imaging methods in diagnosing and treatment of cardiac lipoma by describing a series of cases of cardiac lipoma. Data of patients with cardiac lipoma at a local institution were retrospectively collected. Their imaging findings on echocardiography, computed tomography (CT), and cardiac MRI and clinical management were described in detail. 12 patients with cardiac lipoma were retrospectively included with thirteen lipomas found within heart and pericardium. Two patients' lipoma were symptomatic, while lipomas in other 10 patients were found incidentally. Most lipomas were sensitively detected with echocardiography. Accurate diagnoses were achieved with CT and MRI in all cases. Surgical resection was performed in one symptomatic patient due to the obstruction of the left ventricular outflow tract, while the removal of pericardial lipoma in another symptomatic patient was not possible due to diffuse myocardial infiltration observed in MRI. Based on MRI findings, two patients without clinical symptoms also underwent surgery to prevent the risk of detachment of ventricular lipoma with a narrow pedicle in one patient and potential further thinning of the myocardium by pericardial lipoma growth in another patient. Cardiac lipoma could be sensitively detected and accurately diagnosed with multiple noninvasive imaging tools. Comprehensive evaluation with multimodality imaging methods should also be conducted for better management planning and follow-up in all patients.


Galectin-1 modulation of neutrophil reactive oxygen species production depends on the cell activation state.
Here we report the effects of exogenous and endogenous galectin-1 (Gal-1) in modulating the functional responses of human and murine neutrophils at different stages of activation, i.e. naive, primed, and activated. Exposure to Gal-1 did not induce ROS production in either naive or N-formyl-methionyl-leucyl-phenylalanine-primed (fMLP; 10-9 M) neutrophils. However, Gal-1 elicited a concentration-dependent ROS production in neutrophils activated with fMLP at concentrations ranging from 10-8 M to 10-6 M. Additional fMLP (10-7 M) stimulation of fMLP-activated neutrophils increased ROS production, whose intensity was inversely related to the fMLP concentration used in the first activation step (10-8 M to 10-6 M), and was not influenced by the presence of Gal-1. Naive neutrophils treated with Gal-1 and then exposed to fMLP (10-6 M) or phorbol-12-myristate-13-acetate (10-7 M) produced less ROS, as compared to naive neutrophils not treated with Gal-1. Interestingly, these in vitro Gal-1 effects were associated with Gal-1 carbohydrate-binding activity and the ability to decrease FPR-1 (formyl peptide receptor 1) expression in naive human neutrophils. Conversely, positive ROS modulation by Gal-1 in activated neutrophils was not associated with FPR-1 expression but it was related to its carbohydrate recognition. In vitro, fMLP stimulation of Gal-1-/- mouse neutrophils produced more ROS than fMLP stimulation of Gal-1+/+ neutrophils and this effect may be associated with increased FPR-1 expression. Exogenous Gal-1 induced ROS production in Gal-1-/- mouse neutrophils more effectively than in Gal-1+/+ mouse neutrophils. Compared to Gal-1+/+ mice, Gal-1-/- mice exhibited lower bacterial load in the peritoneal fluid and peripheral blood, thus indicating a greater bactericidal activity in vivo. These findings demonstrate that endogenous Gal-1 restricts ROS generation that correlates with bacterial killing capacity in inflammatory neutrophils. Thus, endogenous and exogenous Gal-1 may either positively or negatively modulate the effector functions of neutrophils according to the cell activation stage.


The fine structure of Walker 256 carcinoma cells.
Several ultrastructural features of Walker 256 rat tumor cells which have not been observed before are revealed. Nuclear bodies either singlely or in pairs were found in some cells. Cytofilaments were observed in the cytoplasm and cytoplasmic projections in a few cells. Desmosomes which are usually regarded as a feature of differentiated cells were also observed.


Posttreatment but not pretreatment with selective beta-adrenoreceptor 1 antagonists provides neuroprotection in the hippocampus in rats subjected to transient forebrain ischemia.
beta-Adrenoreceptor antagonists provide neuroprotection against focal cerebral ischemia, but the effects of these antagonists on experimental global cerebral ischemia are unknown. That is, the effect of beta-adrenoreceptor antagonism in vulnerable brain regions after ischemic insult has not been examined. Therefore, we investigated the neuroprotective effects of preischemic or postischemic administration of propranolol (a nonselective beta-adrenoreceptor antagonist), esmolol, and landiolol (selective beta-adrenoreceptor 1 antagonists) against forebrain ischemia in rats. IV administration of saline 10 microL . h(-1), propranolol 100 microg . kg(-1) . min(-1), esmolol 200 microg . kg(-1) . min(-1), or landiolol 50 microg . kg(-1) . min(-1) in male Sprague-Dawley rats was started 30 minutes before or 60 minutes after 8-minute bilateral carotid artery occlusion combined with hypotension (35 mm Hg) under isoflurane (1.5%) anesthesia. All drugs were administered continuously until 5 days after reperfusion, and the animals were evaluated neurologically and histologically after this 5-day period. Preischemic treatment with propranolol, esmolol, or landiolol failed to provide neuroprotection against forebrain ischemia in the hippocampus. Rats treated with propranolol tended to have a worse score for motor activity and a higher mortality rate (up to 64%), but the differences with other groups were not statistically significant. Postischemic treatment with esmolol and landiolol, but not with propranolol, reduced neuronal injury after forebrain ischemia. However, motor activity did not differ among rats treated postischemically with any of the beta-adrenoreceptor antagonists or saline. Postischemic treatment with esmolol and landiolol provided neuroprotection in the hippocampus in rats subjected to bilateral carotid artery occlusion combined with hemorrhagic shock, whereas treatment with propranolol failed to show neuroprotection. We suggest that concomitant beta-blockade and shock might work as a systemic depressant, rather than a neuroprotectant, resulting in exacerbation of cerebral ischemia.


Effects of trophic 2,2', 4,4'-tetrabromodiphenyl ether (BDE-47) exposure in Oreochromis niloticus: A multiple biomarkers analysis.
Polybrominated diphenyl esters are emerging environmental contaminants with few toxicological data, being a concern for the scientific community. This study evaluated the effects of BDE-47 on the health of Oreochromis niloticus fish. The animals were exposed to three doses of BDE-47 (0, 0.253, 2.53, 25.3 ng g-1) every 10 days, for 80 days. The BDE-47 affected the hepatosomatic and gonadosomatic index in female and the condition factor by intermediate dose in both sexes. The levels of estradiol decreased and the T4 are increased, but the vitellogenin production was not modulated in male individuals. Changes in AChE, GST, LPO and histopathology were observed while the integrated biomarker response index suggests that the lowest dose of BDE-47 compromised the activity of antioxidant enzymes. The oral exposure to BDE-47 in environmental concentrations is toxic to O. niloticus and the use of multiple biomarkers is an attribution in ecotoxicology studies and biomonitoring programs.


Isolation and cholinesterase-inhibition studies of sterols from Haloxylon recurvum.
Haloxysterols A-D (1-4), new C-24 alkylated sterols, have been isolated from the chloroform soluble fraction of Haloxylon recurvum, along with five known sterols 5-9, which are reported for the first time from this species. Their structures were determined by means of 1D- and 2D-NMR techniques. Compounds 1-9 inhibited cholinesterase enzymes in a concentration-dependent manner with K(i) values ranging between 0.85-25.5 and 1.0-19.0 microM against acetylcholinesterase (AChE; EC 188.8.131.52) and butyrylcholinesterase (BChE; EC 126.96.36.199) enzymes, respectively. Lineweaver-Burk, Dixon plots and their secondary replots indicated that compounds 1-9 are non-competitive inhibitors of both AChE and BChE enzymes.


Nucleoprotein-enriched diet enhances protein synthesis pathway and satellite cell activation via ERK1/2 phosphorylation in unloaded rat muscles.
What is the central question of this study? The purpose of this study was to determine whether the nucleotides in a nucleoprotein-enriched diet could ameliorate the unloading-associated decrease in soleus muscle mass and fibre size. What is the main finding and its importance? The results indicate that the nucleotides in the nucleoprotein-enriched diet could ameliorate the unloading-associated decrease in type I fibre size and muscle mass, most probably owing to the activation of protein synthesis pathways and satellite cell proliferation and differentiation via ERK1/2 phosphorylation. Thus, nucleotide supplementation appears to be an effective countermeasure for muscle atrophy. Hindlimb unloading decreases both the protein synthesis pathway and satellite cell activation and results in muscle atrophy. Nucleotides are included in nucleoprotein and provide the benefits of increasing extracellular signal-regulated kinase (ERK) 1/2 phosphorylation. ERK1/2 phosphorylation is also important in the activation of satellite cells, especially for myoblast proliferation and stimulating protein synthesis pathways. Therefore, we hypothesized that nucleotides in the nucleoproteins would ameliorate muscle atrophy by increasing the protein synthesis pathways and satellite cell activation during hindlimb unloading in rat soleus muscle. Twenty-four female Wistar rats were divided into four groups: control rats fed a basal diet without nucleoprotein (CON), control rats fed a nucleoprotein-enriched diet (CON+NP), hindlimb-unloaded rats fed a basal diet (HU) or hindlimb-unloaded rats fed a nucleoprotein-enriched diet (HU+NP). HU for 2 weeks resulted in reductions in phosphorylation of p70S6K and rpS6, the numbers of myoblast determination protein (MyoD)- and myogenin- positive nuclei, type I muscle fibre size and muscle mass. Both CON+NP and HU+NP rats showed an increase in ERK1/2, phosphorylation of p70S6K and rpS6, and the numbers of MyoD- and myogenin-positive nuclei compared with their basal diet groups. The NP diet also ameliorated the unloading-associated decrease in type I muscle fibre size and muscle mass. The results indicate that the nucleotides in the nucleoprotein-enriched diet could ameliorate the unloading-associated decrease in type I fibre size and muscle mass, most probably owing to the activation of protein synthesis pathways and satellite cell proliferation and differentiation via ERK1/2 phosphorylation. Thus, nucleotide supplementation appears to be an effective countermeasure for muscle atrophy.


Purification of the fusion protein of Sendai virus: analysis of the NH2-terminal sequence generated during precursor activation.
The two glycoproteins of Sendai virus, the hemagglutinin-neuraminidase and the fusion protein (F), were separated and purified by affinity chromatography on a Lens culinaris lectin-Sepharose column. F was shown to consist of two disulfide-bonded glycopolypeptide chains, F1 and F2, of molecular weights 51,000 and 11,000, each of which contained 15% carbohydrate by weight. Amino-terminal sequence analysis showed that F2 was blocked and that the hydrophobic sequence NH2-Phe-Phe-Gly-Ala-Val-Ile-Gly-Ile-Ile-Ala-Leu-Gly-Pro-Ala-Thr- was at the amino terminus of F1. This sequence shows identity at six positions with the hydrophobic amino-terminal sequence of the smaller glycopolypeptide chain, HA2, of the hemagglutinin of influenza virus. Both F1 and HA2 are formed by proteolytic cleavage of precursor glycoproteins (Fo, Sendai virus; HAo, influenza virus). Since these cleavages confer infectivity upon both Sendai and influenza viruses and the ability to induce cell-to-cell fusion upon Sendai virus, the hydrophobic NH2-terminal sequences on F1 and HA2 may play a role in fusion of viral and host-cell membranes.


Evidence of suboptimal management of cardiovascular risk in patients with type 2 diabetes mellitus and symptomatic atherosclerosis.
Given that most deaths among patients with diabetes mellitus are due to cardiovascular disease, we sought to determine the extent to which medications proven to reduce cardiovascular mortality are prescribed for patients with type 2 diabetes who have symptomatic atherosclerosis (i.e., coronary artery disease [CAD], cerebrovascular disease [CBVD] or peripheral arterial disease [PAD]). Administrative records from Saskatchewan Health were used to evaluate the use of antiplatelet agents, statins and angiotensin-converting enzyme (ACE) inhibitors by people with treated type 2 diabetes with and without symptomatic atherosclerosis. CAD and CBVD were defined by International Classification of Diseases (ninth revision) codes, and PAD was defined on the basis of pentoxifylline use or lower limb amputation. Multivariate logistic regression analysis was used to compare medication use in patients with and without PAD, with adjustments for differences in age, sex and comorbidity. In this cohort of 12,106 patients with type 2 diabetes (mean age 64 years, 55% male, mean follow-up 5 years), fewer than 25% received an antiplatelet agent or statin, and fewer than 50% received an ACE inhibitor. Although patients with CAD were more likely to receive antiplatelet agents, statins or ACE inhibitors than people without CAD (p < 0.001 for all), the overall use of these medications was suboptimal (37%, 29% and 60% respectively among patients with symptomatic CAD). Similar patterns of practice were found for patients with symptomatic CBVD and PAD. All 3 proven efficacious therapies were prescribed for only 11% of patients with CAD, 22% with CBVD and 12% with PAD. Patients with PAD who had undergone lower limb amputation were no more likely to subsequently receive antiplatelet agents or statins than those without an amputation. Diabetic patients with symptomatic atherosclerotic disease are undertreated with medications known to reduce cardiovascular morbidity and mortality, perhaps because of a "glucocentric" view of diabetes. Programs to improve the quality of cardiovascular risk reduction in these high-risk patients are needed.


Coamplification of the L-myc and N-myc oncogenes in a neuroblastoma cell line.
The L-myc, N-myc and c-myc genes are members of the myc oncogene family. In particular, L-myc is novel, and amplification of L-myc is still unknown except in small cell lung carcinoma. We examined L-myc amplification in 30 human neuroblastomas using Southern blot hybridization, and found that the L-myc gene was amplified approximately 5-fold in GOTO, a human neuroblastoma cell line. The N-myc gene was also amplified approximately 60-fold and furthermore, over-expression of L-myc and N-myc genes was observed in this cell line. In this report, we describe the coamplification of the myc gene family in the GOTO neuroblastoma cell line.


Copy number variation of microRNA genes in the human genome.
MicroRNAs (miRNAs) are important genetic elements that regulate the expression of thousands of human genes. Polymorphisms affecting miRNA biogenesis, dosage and target recognition may represent potentially functional variants. The functional consequences of single nucleotide polymorphisms (SNPs) within critical miRNA sequences and outside of miRNA genes were previously demonstrated using both experimental and computational methods. However, little is known about how copy number variations (CNVs) affect miRNA genes. In this study, we analyzed the co-localization of all miRNA loci with known CNV regions. Using bioinformatic tools we identified and validated 209 copy number variable miRNA genes (CNV-miRNAs) in CNV regions deposited in Database of Genomic Variations (DGV) and 11 CNV-miRNAs in two sets of CNVs defined as highly polymorphic. We propose potential mechanisms of CNV-mediated variation of functional copies of miRNAs (dosage) for different types of CNVs overlapping miRNA genes. We also showed that, consistent with their essential biological functions, miRNA loci are underrepresented in highly polymorphic and well-validated CNV regions. We postulate that CNV-miRNAs are potential functional variants and should be considered high priority candidate variants in genotype-phenotype association studies.


Turbulence hierarchy in a random fibre laser.
Turbulence is a challenging feature common to a wide range of complex phenomena. Random fibre lasers are a special class of lasers in which the feedback arises from multiple scattering in a one-dimensional disordered cavity-less medium. Here we report on statistical signatures of turbulence in the distribution of intensity fluctuations in a continuous-wave-pumped erbium-based random fibre laser, with random Bragg grating scatterers. The distribution of intensity fluctuations in an extensive data set exhibits three qualitatively distinct behaviours: a Gaussian regime below threshold, a mixture of two distributions with exponentially decaying tails near the threshold and a mixture of distributions with stretched-exponential tails above threshold. All distributions are well described by a hierarchical stochastic model that incorporates Kolmogorov's theory of turbulence, which includes energy cascade and the intermittence phenomenon. Our findings have implications for explaining the remarkably challenging turbulent behaviour in photonics, using a random fibre laser as the experimental platform.


Variable-field magnetic force microscopy.
A new variable external field magnetic force microscope is introduced here. The most outstanding feature of the system is its capability to perform stable images under a variable external magnetic field that can be applied both in in-plane and out-of-plane directions. The performances of the microscope are illustrated for four different suitable selected samples: highly oriented pyrolytic graphite, longitudinal magnetic storage media, FePt thin films with in-plane anisotropy and Ni nanowires with axial easy axis embedded on a ceramic matrix. The use of this variable-field magnetic force microscope as a magnetic writing-reading technique is also shown in this contribution.


From handmaiden to right hand--World War I--the mud and the blood.
By the beginning of World War I, modern innovations and advances in the field of medicine were common. Physicians knew about bacteria, how disease spread, and the importance of antisepsis. To prepare for the war, Great Britain developed elite corps of army nurses, fully-equipped military hospitals, and trained personnel who established field hospitals and base hospitals. Alice Fitzgerald, a nurse from Baltimore, was drawn into the conflict when she was asked to serve as the Edith Cavell Memorial Nurse with the British Army.


Toward a direct and scalable identification of reduced models for categorical processes.
The applicability of many computational approaches is dwelling on the identification of reduced models defined on a small set of collective variables (colvars). A methodology for scalable probability-preserving identification of reduced models and colvars directly from the data is derived-not relying on the availability of the full relation matrices at any stage of the resulting algorithm, allowing for a robust quantification of reduced model uncertainty and allowing us to impose a priori available physical information. We show two applications of the methodology: (i) to obtain a reduced dynamical model for a polypeptide dynamics in water and (ii) to identify diagnostic rules from a standard breast cancer dataset. For the first example, we show that the obtained reduced dynamical model can reproduce the full statistics of spatial molecular configurations-opening possibilities for a robust dimension and model reduction in molecular dynamics. For the breast cancer data, this methodology identifies a very simple diagnostics rule-free of any tuning parameters and exhibiting the same performance quality as the state of the art machine-learning applications with multiple tuning parameters reported for this problem.


The complete mitochondrial genome of Sargassum siliquastrum (Phaeophyceae) and its phylogenetic analysis.
The complete S. siliquastrum mitogenome length was 34,765 bp. The mitogenome contains 67 genes, including 37 protein-coding, three rRNA, 25 tRNA genes, and two conserved open reading frames (ORFs). The overall GC content of the genome is 36.59%. The complete mitogenome sequence provided herein would help understand Sargassum evolution.


Phosphorylation of Wat1, human Lst8 homolog is critical for the regulation of TORC2 -Gad8 dependent pathway in fission yeast Schizosacchromyces pombe.
Mammalian Lst8 interacts with the kinase domain of mTOR and stabilizes its interaction with Raptor regulating cell growth through the mTOR-S6K1 signalling pathway. Fission yeast Wat1, an ortholog of mammalian Lst8 is also an essential component of TOR complex 1 (TORC1) and TOR Complex 2 (TORC2) that control protein kinases essential for metabolic pathways. Here, we show that in response to osmotic stress, the Wat1 protein undergoes hyper-phosphorylation at S116 position. Wat1 interacts with the C-terminal region of Tor1 that also contain kinase domain. Co-immunoprecipitation and molecular modelling studies suggest that Wat1-Tor1 interaction is stabilized by FATC domain of Tor1 protein present at the C-terminal region. We have also demonstrated a physical interaction of Wat1 with Gad8, an AGC family protein kinase that is dependent on phosphorylation of Wat1 at S116 residue. Wat1 phosphorylation is required for the maintenance of vacuolar integrity and sexual differentiation. Collectively, our study reveals Wat1 phosphorylation regulates Gad8 function in a manner dependent on Tor1 interaction.


Accuracy of grading pancreatic neuroendocrine neoplasms with Ki-67 index in fine-needle aspiration cellblock material.
The aim of this study was to assess the preoperative tumour grade of pancreatic neuroendocrine neoplasms (panNENs) by determining the Ki-67 index in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) material and to correlate the preoperative tumour grade with the postoperative tumour grade in surgical specimens. We performed a retrospective review of the institutional pathology database over a 10-year period (2007-2017) to identify all cases of panNENs with corresponding preoperative EUS-FNA cytological material and surgical specimens. Fifteen cases with adequate EUS-FNA material (more than 400 tumour cells on cellblock) were identified. The cytological and histological samples were graded based on the mitotic rate and the Ki-67 index in accordance with the 2017 World Health Organisation grading system for panNENs. The tumour grades determined on EUS-FNA cellblock material were compared with the histological tumour grades. Mean age at diagnosis was 64.8 ± 12.7 years (range, 38-85 years). The grading scores assigned to the cytological and histological samples were concordant in all 15 (100%) cases. Of those, two (13%) cases were scored as grade 1, nine (60%) cases as grade 2 and four (27%) cases as grade 3 tumours. Our study shows that tumour grade in patients with PanNENs can be reliably determined by assessing the Ki-67 index in EUS-FNA specimens based on the 2017 World Health Organisation classification and grading system.


From "What" to "How": Experiential Learning in a Graduate Medicine for Ethicists Course.
Teaching healthcare ethics at the doctoral level presents a particular challenge. Ethics is often taught to medical students, but rarely is medicine taught to graduate students in health care ethics. In this paper, Medicine for Ethicists [MfE] - a course taught both didactically and experientially - is described. Eight former MfE students were independently interviewed in a semi-structured, open-ended format regarding their experience in the experiential component of the course. Themes included concrete elements about the course, elements related to the broader PhD student learning experience, and themes related to the students' past and future career experiences. Findings are related to the educational philosophy of John Dewey and David Kolb's experiential learning theory. Broader implications of this work are explored.


Subcritical and supercritical water oxidation for dye decomposition.
The total annual output of synthetic dyes exceeds 7 × 105 tons. About 1,000 tons of non-biodegradable synthetic dyes are released every year into the natural streams and water sources from textile wastes. The release of these colored wastewater exerts negative impact on aquatic ecology and human beings because of the poisonous and carcinogenic repercussions of dyes involved in coloration production. Therefore, with a growing interest in the environment, efficient technologies need to be developed to eliminate dyes from local and industrial wastewater. Supercritical water oxidation as a promising wastewater treatment technology has many advantages, such as a rapid reaction and pollution-free products. However, due to corrosion, salt precipitation and operational problems, supercritical water oxidation process did not gain expected industrial development. These technical difficulties can be overcome by application of non-corrosive subcritical water as a reaction medium. This work summarizes the negative impacts of dyes and role of subcritical and supercritical water and their efficiencies in dye oxidation processes.


Health of adolescents and young adults: trends in achieving the 21 Critical National Health Objectives by 2010.
The 21 Critical National Health Objectives (CNHOs) for Adolescents and Young Adults derived from Healthy People 2010 addressed the most significant threats to the health of individuals aged 10-24 years. This study assessed trends in the 21 CNHOs between 1991 and 2009, and from baseline years for which 2010 targets were established to 2009, and the extent to which targets were achieved. For one CNHO (new HIV diagnoses), national data were not available. For CNHOs measured by census systems, the percentage of change in each health outcome was calculated between 1991 and 2009 and between baseline years and 2009. Any change ≥5% was considered as an improvement or deterioration. For CNHOs measured by national probability-based surveillance surveys, multivariate logistic regression was conducted using Stata Version 10.0 (StataCorp, College Station, TX) to calculate odds ratios for each outcome from 1991, and from baseline years to 2009, controlling for gender, race/ethnicity, and age or school grade-level. To calculate the percentage of targets being achieved, the difference between baseline data and 2009 data was divided by that between baseline data and target. Adolescents and young adults achieved two targets (rode with a driver who had drunk alcohol, physical fighting), improved for 12 CNHOs, made mixed progress by sub-objective for two, showed no progress in four, and regressed in achieving two (Chlamydia infections; overweight). Progress varied by demographic variables. Although encouraging trends were seen in young people's health, the United States achieved only two CNHOs. Attention is needed to improve the health and reduce disparities among young people.


Impact of tight glucose control on circulating 3-hydroxybutyrate in critically ill patients.
Recent evidence suggests a potentially protective effect of increasing ketone body availability via accepting low macronutrient intake early after onset of critical illness. The impact of blood glucose control with insulin on circulating ketones is unclear. Whereas lowering blood glucose may activate ketogenesis, high insulin concentrations may have the opposite effect. We hypothesized that the previously reported protective effects of tight glucose control in critically ill patients receiving early parenteral nutrition may have been mediated in part by activation of ketogenesis. This is a secondary analysis of 3 randomized controlled trials on tight versus liberal blood glucose control in the intensive care unit, including 700 critically ill children and 2748 critically ill adults. All patients received early parenteral nutrition as part of the contemporary standard of care. Before studying a potential mediator role of circulating ketones in improving outcome, we performed a time course analysis to investigate whether tight glucose control significantly affected ketogenesis and to identify a day of maximal effect, if any. We quantified plasma/serum 3-hydroxybutyrate concentrations from intensive care unit admission until day 3 in 2 matched subsets of 100 critically ill children and 100 critically ill adults. Univariable differences between groups were investigated by Kruskal-Wallis test. Differences in 3-hydroxybutyrate concentrations between study days were investigated by Wilcoxon signed-rank test. In critically ill children and adults receiving early parenteral nutrition, tight glucose control, as compared with liberal glucose control, lowered mean morning blood glucose on days 1-3 (P < 0.0001) via infusing insulin at a higher dose (P < 0.0001). Throughout the study period, caloric intake was not different between groups. In both children and adults, tight glucose control did not affect 3-hydroxybutyrate concentrations, which were suppressed on ICU days 1-3 and significantly lower than the ICU admission values for both groups (P < 0.0001). Tight versus liberal glucose control in the context of early parenteral nutrition did not affect 3-hydroxybutyrate concentrations in critically ill patients. Hence, the protective effects of tight glucose control in this context cannot be attributed to increased ketone body availability.


Quantification of fatty acids as methyl esters and phospholipids in cheese samples after separation of triacylglycerides and phospholipids.
Determination of the individual fatty acid composition of neutral- and phospholipids as well as the phospholipid content of dairy food and other foodstuffs are important tasks in life sciences. For these purposes, a method was developed for the separation of lipids (standards of triolein and diacylphosphatidylcholines as well as three cheese samples) by solid-phase extraction using a self-packed column filled with partly deactivated silica. Non-halogenated solvents were used for the elution of the lipid classes. Cyclohexane/ethyl acetate (1:1, v/v) served for the elution of neutral lipids, while polar lipids were eluted with three solvents (ethyl acetate/methanol, methanol, and methanol/water) into one fraction. The separated lipid fractions were transesterified and the individual fatty acids were quantified by using gas chromatography coupled to electron ionization mass spectrometry (GC/EI-MS) in the selected ion monitoring (SIM) mode. The recovery rate for standard phosphatidylcholines was approximately 90% and cross-contamination from neutral lipids was negligible. The method was applied to cheese samples. Quantitative amounts of individual fatty acids in the phospholipid fraction were <0.002-0.29% of total lipids from camembert, <0.002-0.12% of total lipids from mozzarella, and <0.002-0.18% of total lipids in a goat cream cheese. Differences in the fatty acid pattern of neutral and polar lipids were detected. The quantity of the fatty acids determined in the phospholipid fraction was divided by the factor 0.7 in order to convert the fatty acid content into the phospholipid content of the cheese samples. This factor is based on the contribution of 16:0 to dipalmitoylphosphatidylcholine (DPPC). The resulting DPPC equivalents (DPPC(eq)) were found to be representative for the average contribution of fatty acids to all classes of phospholipids in dairy products. Using this approach, the phospholipid content of lipids from mozzarella, camembert, and goat cream cheese was 0.60%, 1.42% and 0.79%, respectively.


Seasonal distribution and ecological risk of phthalate esters in surface water and marine organisms of the Bohai Sea.
The spatiotemporal variability and ecological risks related to 16 phthalate esters (PAEs) were investigated in surface water and marine organisms of the Bohai Sea. The average PAE concentrations in the surface water were 8.02, 4.53, and 3.16 μg L-1 in spring, summer, and winter, respectively. Additionally, suspended particle matter was positive related to PAE content in seawater in spring and winter. The predominant PAEs in both water and biota were dimethyl phthalate (DMP), di-butyl phthalate (DBP), di-isobutyl phthalate (DIBP), and diethylhexyl-phthalate (DEHP). Because they do not exhibit long-distance migratory behavior, Chaeturichthys hexanema, Cynoglossus lighti, and Loligo japonica were good candidate indicator organisms for PAE pollution in Bohai Sea. The risk quotient method revealed that DIBP, DBP, and DEHP posed relatively greater risks to the aquatic system. This research establishes baseline data from which future management strategies to control PAEs in the Bohai Sea can be developed.


Patient-reported urinary incontinence following stereotactic body radiation therapy (SBRT) for clinically localized prostate cancer.
Urinary incontinence (UI) following prostate radiotherapy is a rare toxicity that adversely affects a patient's quality of life. This study sought to evaluate the incidence of UI following stereotactic body radiation therapy (SBRT) for prostate cancer. Between February, 2008 and October, 2010, 204 men with clinically localized prostate cancer were treated definitively with SBRT at Georgetown University Hospital. Patients were treated to 35-36.25 Gray (Gy) in 5 fractions delivered with the CyberKnife (Accuray). UI was assessed via the Expanded Prostate Index Composite (EPIC)-26. Baseline UI was common with 4.4%, 1.0% and 3.4% of patients reporting leaking > 1 time per day, frequent dribbling and pad usage, respectively. Three year post treatment, 5.7%, 6.4% and 10.8% of patients reported UI based on leaking > 1 time per day, frequent dribbling and pad usage, respectively. Average EPIC UI summary scores showed an acute transient decline at one month post-SBRT then a second a gradual decline over the next three years. The proportion of men feeling that their UI was a moderate to big problem increased from 1% at baseline to 6.4% at three years post-SBRT. Prostate SBRT was well tolerated with UI rates comparable to conventionally fractionated radiotherapy and brachytherapy. More than 90% of men who were pad-free prior to treatment remained pad-free three years following treatment. Less than 10% of men felt post-treatment UI was a moderate to big problem at any time point following treatment. Longer term follow-up is needed to confirm late effects.


Co-purification of A1 adenosine receptors and guanine nucleotide-binding proteins from bovine brain.
A1 adenosine receptors and guanine nucleotide-binding proteins (G proteins) solubilized with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate have been co-purified from bovine cerebral cortex. A portion of solubilized receptors which displays high affinity GTP-sensitive agonist binding (40-50%) adheres tightly to agonist affinity columns composed of N6-aminobenzyladenosine-agarose. A1 adenosine receptors and G proteins are rapidly and selectively coeluted from agonist columns by the addition of 8-p-sulfophenyltheophylline, but only in combination with Mg2+-GTP or N-ethylmaleimide, agents which lower the affinity of receptors for agonists. Purified receptors and G protein alpha-subunits can be detected with the potent A1-selective antagonist radioligand, [125I]3-(4-amino-3-iodo)phenethyl-1-propyl-8-cyclopentylxanthine (125I-BW-A844U) and [35S]guanosine 5'-3-O-(thio)triphosphate [( 35S]GTP gamma S), respectively. Pretreatment of solubilized receptors with 0.1 mM N-ethylmaleimide or 0.1 mM R-phenylisopropyladenosine abolishes adsorption of receptors and G proteins to affinity columns. Following removal of 8-p-sulfophenyltheophylline and GTP, purified receptors bind agonists (2 sites) and antagonists (1 site) with affinities similar to crude soluble receptors and typical of A1 receptors. Some receptors may be denatured as a result of purification since only 23% of the radioligand binding sites which adhere to the affinity column can be detected in the eluate. The Bmax of purified receptors, 820 +/- 100 pmol/mg protein (n = 3) is 1800-fold higher than crude soluble receptors. The specific activity of [35S]GTP gamma S binding sites in affinity column eluates is 4640 pmol/mg protein. Assuming a 1:1 stoichiometry, this specific activity indicates that receptor-G protein complexes are greater than 50% pure following affinity chromatography. The photoaffinity labeled purified receptor was identified by polyacrylamide gel electrophoresis as a single band with a molecular mass of 35 kDa which when deglycosylated undergoes a characteristic shift in molecular mass to a sharp band at 32 kDa. In addition to the receptor, silver staining revealed polypeptides with molecular masses of 39 and 41 kDa, which are ADP-ribosylated by pertussis toxin, and 36 kDa corresponding to G protein beta-subunits.


Effective sample selection for classification of pre-miRNAs.
To solve the class imbalance problem in the classification of pre-miRNAs with the ab initio method, we developed a novel sample selection method according to the characteristics of pre-miRNAs. Real/pseudo pre-miRNAs are clustered based on their stem similarity and their distribution in high dimensional sample space, respectively. The training samples are selected according to the sample density of each cluster. Experimental results are validated by the cross-validation and other testing datasets composed of human real/pseudo pre-miRNAs. When compared with the previous method, microPred, our classifier miRNAPred is nearly 12% more accurate. The selected training samples also could be used to train other SVM classifiers, such as triplet-SVM, MiPred, miPred, and microPred, to improve their classification performance. The sample selection algorithm is useful for constructing a more efficient classifier for the classification of real pre-miRNAs and pseudo hairpin sequences.


The effect of energy resources on economic growth and carbon emissions: A way forward to carbon neutrality in an emerging economy.
Globally, all countries have producing different levels of carbon emissions and also facing both the problems of climate change and global warming due high carbon emissions in the atmosphere. Therefore, it is important to cutting carbon emissions in the atmosphere. This is only possible by switching to cleaner fuels, use of innovation technologies and development of carbon capture storages. These can substantially help the nations to reaching carbon neutrality. Given this background, this paper examines the effect of disaggregated energy consumption, technological innovations, capital on economic output and CO2 emissions in India for the period of 1990-2018. Based on empirical analysis, our long-run elasticities indicate that disaggregated energy consumption and technological innovations have a positive impact on economic growth, while renewable energy consumption and technological innovations have a positive impact on CO2 emissions. It implies that more use of energy consumption producing significant amount of CO2 emissions and by using renewable energy consumption and technological innovations (i.e. carbon capture storages) can significantly lowering CO2 emissions, which is clearly indicating that India has moving towards carbon neutrality. The causality analysis further indicates a unidirectional causal relationship running from disaggregated energy usage to economic growth and carbon emissions. These empirical findings suggest that the increased consumption of renewable power does not lead to rise carbon emissions, which, in turn, ensures sustainable economic growth.


Function of pH-dependent transcription factor PacC in regulating development, pathogenicity, and mycotoxin biosynthesis of phytopathogenic fungi.
pH, as one of the most important environmental factors, affects various biological processes in pathogenic fungi. Sensing and responding to fluctuations in ambient pH are essential for these fungi to complete their life cycle. Fungi have evolved a complicated and conserved system, the so-called Pal-pH pathway, to regulate genes and adapt to alterations in ambient pH. PacC is the dominant transcription factor in the Pal-pH pathway and regulates various biological processes. The regulatory mode of PacC has been extensively studied in Aspergillus nidulans and is generally conserved in other fungal species, including numerous phytopathogenic fungi. However, species-specific alterations have been reported. This review summarizes recent advances in the regulatory mechanisms of PacC and its role in controlling development, pathogenicity, and mycotoxin biosynthesis in phytopathogenic fungi. Potential applications of these findings and some unresolved questions are also discussed.


Solitary necrotic nodules of the liver with "ring"-like calcification: A case report.
Solitary necrotic nodule of the liver (SNNL) is a rare benign lesion with a complete necrotic core and a clear fibrous capsule containing elastic fibers. We present the case of a patient with a radiographic computed tomography (CT) finding of "ring"-like annular calcification within the lesion and postoperative pathologic diagnosis of necrotic nodules wrapped by dense fibers in liver tissue, as well as the patient's subsequent management and outcome. A 38-year-old Chinese woman with a history of systemic lupus erythematosus treated with prednisone and hydroxychloroquine, without any symptoms, was found to have hepatic space-occupying lesions by imaging examination at a health examination. A subsequent CT scan suggested a space-occupying lesion of the liver with annular calcification, which was not defined to be benign or malignant. After that, a laparoscopic hepatic space-occupying resection was performed. The postoperative pathological diagnosis was necrotic nodules wrapped by dense fibers in the liver tissue, and the final diagnosis was SNNL. The patient had an uneventful postoperative recovery. There is a "ring"-like calcification in SNNL. This patient had a history of systemic lupus erythematosus, without a history of parasite infection, trauma, or tumor. Therefore, whether the etiology and pathological changes of SNNL are related to rheumatic immune diseases remains to be investigated.


Incomplete pseudo-Meigs' syndrome caused by endometrial ovarian cyst: A case report.
A 63-year-old female was admitted to our hospital with history of persistent dyspnea. Right pleural effusion and ovarian tumor were discovered, but here were no significant findings on thoracoscopy under local anesthesia. The pleural effusion was suspected to be secondary to Meigs' syndrome, and a diagnosis of endometriotic ovarian cyst was made. Since the pleural effusion resolved after surgery, the patient was diagnosed with incomplete pseudo-Meigs' syndrome. We consider this to be a valuable case, as there are no previously reported cases of pseudo-Meigs' syndrome derived from an endometriotic ovarian cyst, to the best of our knowledge.


Safety, efficacy and tolerability of exenatide in combination with insulin in the Association of British Clinical Diabetologists nationwide exenatide audit*.
To assess the extent, safety, efficacy and tolerability of reported off-licence exenatide use through a nationwide audit. The Association of British Clinical Diabetologists hosted a password-protected, online collection of anonymized data of exenatide use in real clinical practice. Three hundred and fifteen contributors from 126 centres across UK provided data on 6717 patients. HbA1c and weight changes, exenatide discontinuation, adverse events and treatment satisfaction were compared between non-insulin and insulin-treated patients. Four thousand eight hundred and fifty-seven patients had baseline and follow-up treatment status with mean (±s.d.) baseline HbA1c 9.45 ± 1.69% and BMI 40.0 ± 8.2 kg/m(2) . Of the 4857 patients, 1921 (39.6%) used exenatide with insulin. Comparing patients who continued insulin with exenatide with non-insulin-treated patients, mean (±s.e.) latest HbA1c and weight reduction (median 26 weeks) were 0.51 ± 0.06 versus 0.94 ± 0.04% (p < 0.001) and 5.8 ± 0.2 versus 5.5 ± 0.1 kg (p = 0.278). Insulin-treated patients had higher rates of exenatide discontinuation (31.0 vs. 13.9%, p < 0.001), hypoglycaemia (8.9 vs. 6.1%, p < 0.001), gastrointestinal side effects (28.4 vs. 25.0%, p = 0.008) and treatment dissatisfaction (20.8 vs. 5.7%, p < 0.001). However, 34.2% of the patients continuing insulin still achieved HbA1c reduction ≥1%. There was significant insulin discontinuation, dose reduction and greater sulphonylurea discontinuation among insulin-treated patients. Addition of exenatide to obese, insulin-treated patients can improve glycaemia and weight. Adverse events were statistically but probably not clinically significantly higher, but combination treatment was less well tolerated. Overall, exenatide was less effective in lowering HbA1c among insulin-treated patients, although significant number of insulin-treated patients still achieved significant HbA1c, weight and insulin reductions. Further research into identifying obese, insulin-treated patients who will tolerate and benefit from exenatide treatment is urgently needed.


A comparison of contaminant dynamics in arctic and temperate fish: A modeling approach.
In order to compare the abilities of arctic and temperate fish to accumulate PCBs we conduct a metabolic analysis to determine how process rates in a mathematical fish contaminant model change with temperature. We evaluate the model by applying the original and adapted models to estimate PCB concentrations in lake trout (Salvelinus namaycush) in Trout Lake, Ontario, Canada, and in arctic char (Salvelinus alphinus) in Lake Øyangen, in the Norwegian high arctic. Modeled concentrations are, for the most part, within 50% of mean measured values and are comparable to the error associated with the fish data. In order to evaluate differences in fish bioaccumulation processes, the model is applied to hypothetical arctic and temperate systems, assuming the same contaminant input values in water and diet. The model predicts that temperate salmonids are able to biomagnify PCBs 6-60% more than arctic salmonids. For all congeners, the lower BMF(MAX) of arctic fish contribute to their lower concentrations. For congeners with log K(ow) < 6.0, the lower concentrations in arctic fish are also attributed to faster loss due to gill ventilation. Faster growth rates for temperate fish reduce the difference in bioaccumulation for congeners with log K(ow) > 7.0. These processes are controlled by the influence of lipid in the fish and their diet as well as the dependence of growth on temperature. We suggest that fish models originally calibrated for temperate systems may be directly applied to arctic lakes after accounting for the lipid content of the fish and their diet as well as water temperature.


Extracellular Matrix Scaffold Using Decellularized Cartilage for Hyaline Cartilage Regeneration.
The repair of osteochondral defects is among the top ten medical needs of humans in the 21st centuries with many countries facing rapidly aging population involved with osteoarthritis as a major contributor to global disease burden. Tissue engineering methods have offered new windows of hope to treat such disorders and disabilities. Regenerative approaches to cartilage injuries require careful replication of the complex microenvironment of the native tissue. The decellularized hyaline cartilage derived from human allografts or xenografts is potentially an ideal scaffold, simulating the mechanical and biochemical properties, as well as biological microarchitecture of the hyaline cartilage. There have been many attempts to regenerate clinically viable hyaline cartilage tissue using decellularized cartilage-derived extracellular matrix with stem cell technology. This chapter describes the reproducible methods for hyaline cartilage decellularization and recellularization. In addition, quality control and characterization requirements of the product at each step, as well as the clinical applications of final product have been discussed.


A High Resolution MRI Study of the Relationship Between Plaque Enhancement and Perforator Stroke after Stenting for Symptomatic Vertebrobasilar Artery Stenosis.
Perforator stroke is one of the most common complications of vertebrobasilar arterial stenting. We investigated whether perforator stroke after vertebrobasilar arterial stenting is associated with plaque enhancement in patients with severe vertebrobasilar artery stenosis. We studied patients with symptomatic vertebrobasilar arterial stenosis who underwent stenting from January 2017 to July 2020. Patients who underwent high resolution magnetic resonance imaging were recruited among them. Demographic data, risk factors of atherosclerosis, procedure details, and characteristics of imaging were extracted from electronic health records and imaging data. Plaque features were investigated by high resolution magnetic resonance imaging. 136 patients were enrolled in this study, 39 of whom fulfilled the inclusion criteria. 18 patients (46.2%) had obvious plaque enhancement among the 39 patients, and 21 (53.8%) had plaque non-enhancement. 21 patients (53.8%) had diffuse distribution, and 22 patients (56.4%) had irregular plaques surface. Patients were divided into plaque enhanced and plaque non-enhanced groups according to the degree of plaque enhancement. Clinical characteristics and other plaque features were similar between two groups. Procedure-related perforator stroke was identified in 4 patients (10.3%). Patients with plaque enhancement were more likely to have perforator stroke after stenting compared with those with plaque non-enhancement (22.2% versus 0%, P = 0.037). Plaque enhancement in high resolution magnetic resonance imaging may be associated with perforator stroke after vertebrobasilar artery stenting.


A week-long diabetes simulation for pharmacy students.
To assess students' attitudes and confidence about type 2 diabetes mellitus and diabetes self-management education before and after participation in Living With Diabetes Week simulation. Third-year pharmacy students took part in diabetes lectures, interactive laboratory sessions, and a week-long simulation of life as a patient with diabetes in the Clinical Assessment course. Pre-/postintervention survey instruments and experimental and control group comparisons were completed assessing attitudes and confidence relating to knowledge about diabetes. The understanding that diabetes has a psychosocial impact, patient autonomy is necessary, and the seriousness of the disease increased. Students' confidence in their diabetes self-management education skills also increased. The Living With Diabetes Week simulation changed pharmacy students' attitudes toward patients with diabetes and increased confidence in diabetes education skills.


Accuracy rate of lie-detection in China: estimate the validity of CQT on field cases.
To explore the accuracy rate of the comparison question test (CQT) by Binomial Distribution way on field cases in Chengdu area of China. In detail, the study revealed the accuracy rate of detecting guilty and innocent examinees, and the rate of False Positive and False Negative. The study was built on the field cases with only two examinees that held the opposite opinions to the same single case. The original evaluators and four experienced polygraph specialists independently chose and scored 148 field criminal cases into the final study, among which 111 paired-records were concluded as indicative records and the rest, 37 ones, were ruled as non-indicative. Judging from all records, the accuracy rate of detecting guilty examinees was 0.836 with a 0.164 False Negative rate. In addition, the rate to detect innocents was 0.822 with a 0.178 False Positive rate. Judging from indicative cases only excluding the non-indicative, the accuracy rate rose to 0.958 for perceiving guilty examinees with a 0.042 False Negative rate. To innocents, the accuracy rate was 0.859 with a 0.141 False Positive rate. The study with non-standard methodology was not limited to mock cases and the final confessions. It was able to estimate validity of other lie-detection ways, GKT, POT, etc., with this method being applied. With high accuracy rate and validity, polygraph examinations were able to give better decisions to real-life investigations.


Bioelectrical impedance assay (BIA) of total body composition in alcohol-induced migraine patients. Preliminary report.
"Whole body composition" was investigated in 30 people subject to alcohol-induced migraine. The control group was 30 people matched for age, sex, height and weight, who were not subject to migraine and who consumed moderate amounts of alcohol. The following were evaluated: anthropometric data, alcohol intake in grams per day, total body water, fat-free mass, fat mass, and body mass index (kg/m2). Two methods of measurement were used: skin fold thickness evaluation, and bioelectric impedance assay (BIA). BIA is a non-invasive method based on the principle that lean tissues conduct a low frequency alternating current of electricity better than do fatty tissues. Body mass index was increased in the alcohol-induced migraine patients (p less than 0.04), as was fat mass, (p less than 0.03) as evaluated by skin fold measurements. Bioelectric impedance assay demonstrated a slight total body water increase in alcohol-induced migraine patients (p less than 0.07). Possibly, if this total body water increase was reflected at the neuronal level, the bioelectric properties of the migrainous brain may be altered, thus creating a hypothetical link with the phenomenon of spreading depression.


Ultrastructural identification of monoaminergic synaptosomes from one day old rat brain.
Synaptosomes from one day old and adult rat brain were studied. Specific cytochemical methods for demonstrating monoaminergic (MA) nerve endings were used. Permanganate fixation after preincubation with 5-OHDA or alpha-methyl-NA demonstrated MA synaptosomes. Their number was small in the adult (less than 1 %) and still smaller in the one day old rat brain. The MA synaptosomes from developing rats were different from the adult ones. The large amount of endoplasmic reticulum in developing synaptosomes suggests that granular vesicles are formed from endoplasmic reticulum in nerve endings.


Optimizing energy for a 'green' vaccine supply chain.
This paper describes an approach piloted in the Kasserine region of Tunisia to increase the energy efficiency of the distribution of vaccines and temperature sensitive drugs. The objectives of an approach, known as the 'net zero energy' (NZE) supply chain were demonstrated within the first year of operation. The existing distribution system was modified to store vaccines and medicines in the same buildings and to transport them according to pre-scheduled and optimized delivery circuits. Electric utility vehicles, dedicated to the integrated delivery of vaccines and medicines, improved the regularity and reliability of the supply chains. Solar energy, linked to the electricity grid at regional and district stores, supplied over 100% of consumption meeting all energy needs for storage, cooling and transportation. Significant benefits to the quality and costs of distribution were demonstrated. Supply trips were scheduled, integrated and reliable, energy consumption was reduced, the recurrent cost of electricity was eliminated and the release of carbon to the atmosphere was reduced. Although the initial capital cost of scaling up implementation of NZE remain high today, commercial forecasts predict cost reduction for solar energy and electric vehicles that may permit a step-wise implementation over the next 7-10 years. Efficiency in the use of energy and in the deployment of transport is already a critical component of distribution logistics in both private and public sectors of industrialized countries. The NZE approach has an intensified rationale in countries where energy costs threaten the maintenance of public health services in areas of low population density. In these countries where the mobility of health personnel and timely arrival of supplies is at risk, NZE has the potential to reduce energy costs and release recurrent budget to other needs of service delivery while also improving the supply chain.


Distinct sucrose isomerases catalyze trehalulose synthesis in whiteflies, Bemisia argentifolii, and Erwinia rhapontici.
Isomaltulose [alpha-D-glucopyranosyl-(1,6)-D-fructofuranose] and trehalulose [alpha-D-glucopyranosyl-(1,1)-D-fructofuranose] are commercially valuable sucrose-substitutes that are produced in several microorganisms by the palI gene product, a sucrose isomerase. Trehalulose also occurs in the silverleaf whitefly, Bemisia argentifoli, as the major carbohydrate in the insect's honeydew. To determine if the enzyme that synthesizes trehalulose in whiteflies was similar to the well-characterized sucrose isomerase from microbial sources, the properties of the enzymes from whiteflies and the bacterium, Erwinia rhapontici, were compared. Partial purification of both enzymes showed that the enzyme from whiteflies was a 116 kD membrane-associated polypeptide, in contrast to the enzyme from E. rhapontici, which was soluble and 66 kD. The enzyme from E. rhapontici converted sucrose to isomaltulose and trehalulose in a 5:1 ratio, whereas the enzyme from whiteflies produced only trehalulose. Unlike the E. rhapontici enzyme, the whitefly enzyme did not convert isomaltulose to trehalulose, but both enzymes catalyzed the transfer of fructose to trehalulose using sucrose as the glucosyl donor. The results indicate that trehalulose synthase from whiteflies is structurally and functionally distinct from the sucrose isomerases described in bacteria. The whitefly enzyme is the first reported case of an enzyme that converts sucrose to exclusively trehalulose.


Neurodevelopmental and psychological assessment of adolescents born to drug-addicted parents: effects of SES and adoption.
Prenatal exposure to heroin may have long-term consequences for development during early and middle childhood. The present research studied the cognitive, social, and emotional functioning of adolescents exposed to drugs prenatally, and investigated the extent to which the early adoption of children exposed prenatally to drugs would alleviate the possible effects of exposure. The study included 191 adolescents (12-16 years of age) and their parents in Israel, who had or had not been exposed prenatally to drugs and differing in socio-economic status (SES), and in adoptive status. They were administered five subtests of the Wechsler Intelligence Scale for Children (WISC-III), and the Youth Self-Report Form for assessing behavior problems that measures problems associated with attention deficit, self-esteem and risk-taking. Parents were administered the Child Behavior Checklist (CBCL) for assessing behavior problems, the Conners Rating Scale (CRS) for assessing attention deficit problems in their children and the Wender Utah Rating Scale (WURS), a self-report measure of ADHD-related problems. Adolescents exposed to at least one risk factor (exposure to drugs, low SES, or adoption) performed more poorly than those exposed to none of these risk factors on the WISC-III subtests, the CBCL and the CRS. The effects of risk factors did not cumulate. Contrary to our hypothesis, adoption did not mitigate the effects of prenatal exposure to drugs: for cognitive functioning exposure to drugs was associated with poorer performance among the exposed High SES Adopted versus non-exposed High SES non-adopted children on three of the WISC-III subtests. Exposed low SES children living with their parents performed at the same relatively low level as non-exposed low SES controls. Exposure to drugs was associated with adult ADHD-related problems assessed by the WURS. There were no direct or interaction effects of exposure on neurological functioning, self-competence, behavior problems on the CBCL or risk-taking. Children exposed to drugs of abuse prenatally, including those adopted away, and children who grow up in low SES backgrounds, may be at risk of relatively reduced cognitive functioning (though still within the normal range) in adolescence. Children exposed to drugs, who are from low SES backgrounds, or who are adopted, may be at risk for lower cognitive or social functioning than children who have not experienced such risks. There is a need for implementing early monitoring and long-term intervention programs featuring encouragement of cognitive and social skills for children prenatally exposed to drugs in order to alleviate the possible long-term effects of exposure to risk.