Incorporating reversible and irreversible transverse relaxation effects into Steady State Free Precession (SSFP) signal intensity expressions for fMRI considerations.
Among the multiple sequences available for functional magnetic resonance imaging (fMRI), the Steady State Free Precession (SSFP) sequence offers the highest signal-to-noise ratio (SNR) per unit time as well as distortion free images not feasible with the more commonly employed single-shot echo planar imaging (EPI) approaches. Signal changes occurring with activation in SSFP sequences reflect underlying changes in both irreversible and reversible transverse relaxation processes. The latter are characterized by changes in the central frequencies and widths of the inherent frequency distribution present within a voxel. In this work, the well-known frequency response of the SSFP signal intensity is generalized to include the widths and central frequencies of some common frequency distributions on SSFP signal intensities. The approach, using a previously unnoted series expansion, allows for a separation of reversible from irreversible transverse relaxation effects on SSFP signal intensity changes. The formalism described here should prove useful for identifying and modeling mechanisms associated with SSFP signal changes accompanying neural activation.


Nitric oxide differentially affects ERK and Akt in type 1 and type 2 diabetic rats.
We have shown that nitric oxide (NO) is more effective at inhibiting neointimal hyperplasia in type 2 diabetic rats than in nondiabetic rats, but is not effective in type 1 diabetic rats. Insulin signaling is mediated by the ERK and Akt pathways, and thus we hypothesized that NO differentially affects ERK and Akt activity in type 1 versus type 2 diabetic rats. To investigate this hypothesis, we induced type 2 diabetes in Zucker diabetic fatty (ZDF) rats by feeding them Purina 5008 chow. To induce type 1 diabetes, lean Zucker (LZ) rats were injected with streptozotocin (STZ; 60 mg/kg). The carotid artery injury model was performed. Groups included injury and injury + PROLI/NO (20 mg/kg) (n = 6/group). Three days following injury, all animal models exhibited an increase in pERK levels. Whereas NO reduced pERK levels in LZ and STZ rats, NO had no effect on pERK levels in ZDF rats. Following a similar pattern, NO reduced pAkt levels in LZ and STZ rats but increased pAkt levels in ZDF rats. Fourteen days following injury, NO increased total pERK levels throughout the arterial wall in both the STZ and ZDF rats. These changes were greatest in the adventitia. Interestingly, whereas NO decreased total pAkt levels in LZ and STZ rats, NO increased pAkt levels in ZDF rats. Evaluation of the pERK:pAkt ratio revealed that NO increased this ratio in LZ and STZ rats but decreased the ratio in ZDF rats. We report that NO differentially affects the expression of pERK and pAkt in type 1 versus type 2 diabetic rats. Given that NO is more effective at inhibiting neointimal hyperplasia in type 2 diabetic animals, the pERK:pAkt ratio may be the best surrogate to predict efficacy.


The near-peer tutoring programme: embracing the 'doctors-to-teach' philosophy--a comparison of the effects of participation between the senior and junior near-peer tutors.
While there is an increasing pool of literature documenting the benefits of near-peer tutoring programme, little is known about the benefits for junior and senior peer tutors. Knowledge of the peer tutors' perceived benefits at different levels of seniority will aid in the development of a near-peer tutoring programme that will better fulfil both curricula and personal aspirations of near-peer tutors. We, therefore, investigated the perceived benefits of participation in a near-peer tutoring programme for junior as well as senior near-peer tutors. Pre- and post-participation questionnaires were distributed to near-peer tutors after their clinical skills teaching sessions with Phase I undergraduate medical students. The Peer Tutor Assessment Instrument questionnaires were distributed to the 1) students, and to the 2) near-peer tutors (junior and senior) after each teaching and learning session for self-evaluation. The senior near-peer tutors felt that their participation in the programme had enhanced their skills (p=0.03). As a whole, the near-peer tutors were more motivated (Pre 5.32±0.46; Post 5.47±0.50; p=0.210) to participate in future teaching sessions but did not expect that having teaching experiences would make teaching as their major career path in the future (Pre 4.63±1.07; Post 4.54±0.98; p=0.701). The senior near-peer tutors were evaluated significantly higher by the students (p=0.0001). Students' evaluations of near-peer tutors on the domain of critical analysis was higher than self-evaluations (p=0.003). Generally, the near-peer tutors perceived that they have benefited most in their skills enhancement and these near-peer tutors were scored highly by the students. However, senior near-peer tutors do not perceive that the programme has a lasting impact on their choice of career path.


Bikini Line Sleeve Gastrectomy: Initial Report.
Several reports have discussed the potential for reducing port access in laparoscopic sleeve gastrectomy (LSG); however, each approach had its innate setbacks. Aiming at improving the aesthetic outcome, we report a novel approach to the LSG where we place the trocars at the bikini line in what we described as bikini line sleeve gastrectomy (BLSG). The present work is a prospective, pilot study on the use of BLSG in patients, during the period between April and October 2016. Exclusion criteria included the following: large hiatal hernia, upper abdominal surgery, and xiphi-umbilical, xiphi-symphysis pubis, and xiphi-anterior superior iliac spine distances of > 25,36 and 33 cm, respectively. Four trocars were used: one at the umbilicus and three at the bikini line. All laparoscopic graspers were bariatric length instruments (43 cm). However, camera telescope, endoscopic stapler, and bipolar dissectors were standard length. Twenty eight patients underwent BLSG. The mean age was 34.6 ± 3.7 years with a mean BMI of 42.46 kg/m2 ± 3. There were no major intra- or postoperative complications and no conversion to conventional port site placement. Patient's scar satisfaction was favorable. The mean postoperative BMI and weight at 6 m were 28.5 ± 1 kg/m2 and 79.8 kg ± 2, respectively. The mean percentage excess weight loss at 3, 6, and 12 months were 39.5 ± 4.6, 64.5 ± 5, and 69.8 ± 6%, respectively. BLSG was found to be potentially safe, feasible, and effective with a favorable aesthetic outcome; it could possibly be offered to a select group of patients that are conscious about their scar appearance.


Quantitation of the immunodominant 33-mer peptide from α-gliadin in wheat flours by liquid chromatography tandem mass spectrometry.
Coeliac disease (CD) is triggered by the ingestion of gluten proteins from wheat, rye, and barley. The 33-mer peptide from α2-gliadin has frequently been described as the most important CD-immunogenic sequence within gluten. However, from more than 890 published amino acid sequences of α-gliadins, only 19 sequences contain the 33-mer. In order to make a precise assessment of the importance of the 33-mer, it is necessary to elucidate which wheat species and cultivars contain the peptide and at which concentrations. This paper presents the development of a stable isotope dilution assay followed by liquid chromatography tandem mass spectrometry to quantitate the 33-mer in flours of 23 hexaploid modern and 15 old common (bread) wheat as well as two spelt cultivars. All flours contained the 33-mer peptide at levels ranging from 91-603 μg/g flour. In contrast, the 33-mer was absent (<limit of detection) from tetra- and diploid species (durum wheat, emmer, einkorn), most likely because of the absence of the D-genome, which encodes α2-gliadins. Due to the presence of the 33-mer in all common wheat and spelt flours analysed here, the special focus in the literature on this most immunodominant peptide seems to be justified.


Hematological studies in induction of abortion by extra-amniotic administration of sulproston.
The prostaglandin E2 derivative, Sulproston, was administered extra-amniotically for the induction of abortion in an average dosage of 200 microgram, in ten patients. With a success rate of 50%, the subjective side effects were very slight. Temperature, pulse rate, blood pressure and frequently of breathing did not change markedly. The ADP- and collagen-induced platelet aggregation showed a tendency to increase but disaggregation remained the same. Spontaneous platelet aggregation according to Breddin did not change. The parameters examined of the coagulation and fibrinolytic system showed only a slight increase in fibrinolytic activity during and after induction of abortion. The remaining hematological parameters showed no changes.


Is sleep disturbance linked to short- and long-term outcomes following treatments for recurrent depression?
Pre-treatment sleep disturbance has been shown to predict antidepressant treatment outcomes. How changes in sleep disturbance during acute treatment affect longitudinal outcomes, or whether continuation-phase treatment further improves sleep disturbance, is unclear. We assessed sleep disturbance repeatedly in: a) 523 adults with recurrent MDD who consented to 12-14 weeks of acute-phase cognitive therapy (A-CT) and b) 241 A-CT responders at elevated risk for depression relapse/recurrence who were randomized to 8 months of continuation-phase treatment (CCT vs. fluoxetine vs. matched pill placebo) and followed protocol-treatment-free for 24 months. Trajectories of change in sleep and depression during and after A-CT were evaluated with multilevel models; individual intercepts and slopes were retained and input into Cox regression models to predict remission, recovery, relapse, and recurrence of MDD. Sleep disturbance improved over the course of A-CT, but most patients continued to report clinically significant sleep complaints. Response and remission were more likely in patients with less overall sleep disturbance and those with greater reduction in sleep disturbance during A-CT; these patients also achieved post-A-CT remission and recovery sooner. Sleep improvements endured throughout follow-up but were not enhanced by continuation-phase treatment. Sleep disturbance did not predict relapse or recurrence consistently. Objective sleep disturbance was not assessed. Analyses were not specifically powered to use sleep changes to predict outcomes. Improvements in sleep disturbance during A-CT are linked to shorter times to remission and recovery, supporting consideration of monitoring and targeting sleep disturbance in adults with depression.


Measurements in Mandibular Pantomographic X-rays and Relation to Skeletal Mineral Densitometric Values.
The gold standard diagnostic modality for osteoporosis is dual-energy X-ray absorptiometry (DXA). But it is expensive and often unavailable. Studies have demonstrated that decreased bone mineral density (BMD) may affect mandibular bone morphometrically on radiographs. Such studies are rare in the Indian population. This study was conducted to evaluate correlation between radiomorphometric markers on digital orthopantomograms (OPGs) and BMD measurements done by DXA in an Indian population. A total of 344 subjects aged 45 years or above, who visited a dental outpatient department over a period of 6 years were included in the study after obtaining ethical committee approval and informed consent. Digital OPG and DXA BMD measurements were obtained. Subjects' T-scores were obtained, on the basis of which they were divided into osteoporotic, osteopenic, and normal. OPGs were evaluated to obtain the mandibular cortical index (MCI) and the panoramic mandibular index (PMI). Correlations of MCI and PMI with BMD were analyzed statistically with SPSS (version 16.0; SPSS, Chicago, IL). In the osteoporotic group, there was no subject with MCI finding of C1, and 77.42% prevalence of C3 finding was found. C2 finding was in highest proportion in the osteopenic group (p<0.05). Normal BMD group was associated with the C1 finding of 76.47%. Almost 48% of the osteoporotic group had a PMI score of <0.40, whereas 50% of osteopenic subjects had a PMI score of 0.4-0.44. Normal subjects having a PMI score of >0.44 constituted 49.1% of the population. Mean BMD scores decreased significantly with increasing MCI stage and increased significantly with increasing PMI (p<0.05). Significant correlations between PMI and MCI were obtained with DXA BMD. Digital OPGs may provide an economical and reliable diagnostic tool to rule out osteoporosis or osteopenia in undiagnosed patients, where DXA screening may not be available or is financially nonviable.


Cryo-EM structure of the activated NAIP2-NLRC4 inflammasome reveals nucleated polymerization.
The NLR family apoptosis inhibitory proteins (NAIPs) bind conserved bacterial ligands, such as the bacterial rod protein PrgJ, and recruit NLR family CARD-containing protein 4 (NLRC4) as the inflammasome adapter to activate innate immunity. We found that the PrgJ-NAIP2-NLRC4 inflammasome is assembled into multisubunit disk-like structures through a unidirectional adenosine triphosphatase polymerization, primed with a single PrgJ-activated NAIP2 per disk. Cryo-electron microscopy (cryo-EM) reconstruction at subnanometer resolution revealed a ~90° hinge rotation accompanying NLRC4 activation. Unlike in the related heptameric Apaf-1 apoptosome, in which each subunit needs to be conformationally activated by its ligand before assembly, a single PrgJ-activated NAIP2 initiates NLRC4 polymerization in a domino-like reaction to promote the disk assembly. These insights reveal the mechanism of signal amplification in NAIP-NLRC4 inflammasomes.


[RNA polymerase of a rifampicin-resistant mutant of Escherichia coli has an altered selectivity to phage T7 DNA promoters].
The formation of complexes of RNA polymerases from E. coli W12 and its rpoB409 rifampicin resistant mutant with A1 and D promoters of T7 delta D111 DNA was studied by an abortive RNA synthesis technique. The mutation was shown to affect RNA synthesis initiation at these two promotors differentially so that the efficiency of D promotor utilization is enhanced but the use of A1 promotor is unchanged. The mutation does not interfere with the affinity of the enzyme for both initiating substrates. The results show that the change in RNA polymerase beta-subunit structure has a differential effect on the enzyme interaction with different promotors. The necessity of a classificatory approach to structure-functional analysis of promotors was proposed.


Evidence of a Causal Effect of Estradiol on Fracture Risk in Men.
Observational studies indicate that serum estradiol (E2) is more strongly associated with bone mineral density (BMD) than serum testosterone (T) is, whereas both E2 and T associate with fracture risk in men. To evaluate the possible causal effect of serum E2 and T on fracture risk in men. A Mendelian randomization (MR) approach was undertaken using individual-level data on genotypes, BMD as estimated by quantitative ultrasound of the heel (eBMD), fractures (n = 17,650), and relevant covariates of 175,583 unrelated men of European origin from the UK Biobank. The genetic instruments for serum E2 and T were taken from the most recent large-scale genome-wide association study meta-analyses on these hormones in men. MR analyses demonstrated a causal effect of serum E2 on eBMD and fracture risk. A 1 SD (or 9.6 pg/mL) genetically instrumented decrease in serum E2 levels was associated with a 0.38 SD decrease in eBMD (P value: 9.7 × 10-74) and an increased risk of any fracture (OR: 1.35; 95% CI: 1.18, 1.55), nonvertebral major osteoporotic fractures (OR: 1.75; 95% CI: 1.35, 2.27), and wrist fractures (OR: 2.27; 95% CI: 1.62, 3.16). These causal effects of serum E2 levels on fracture risk were robust in sensitivity analyses and remained unchanged in stratified analyses for age, body mass index, eBMD, smoking status, and physical activity. MR analyses revealed no evidence of a causal effect of T levels on fracture risk. Our findings provide evidence of a robust causal effect of serum E2, but not T, on fracture risk in men.


Measurement of endogenous Na+,K+-ATPase inhibitors in human plasma and urine using high-performance liquid chromatography.
This study was undertaken to assess endogenous Na+,K+-ATPase inhibitors in both plasma and urine in the same subjects. Samples were chromatographed on reverse-phase HPLC using an acetonitrile gradient and the eluent screened using Na+,K+-ATPase inhibition and cross-reaction with anti-digoxin antibodies. The donors were divided into inhibiting and non-inhibiting subjects using a previously described method, plasma action on ouabain binding and on Na+,K+-ATPase activity. Three Na+,K+-ATPase inhibitors (1P, 2P and 3P) were detectable in plasma; the antibodies cross-reaction of the peaks 2P and 3P were larger than that of peak 1P. The peaks 2P and 3P were significantly higher in inhibiting subjects as compared to non-inhibiting subjects. The 24-h urine is resolved into two peaks inhibiting Na+,K+-ATPase activity (1U and 2U). Peak 2U cross-reacted with anti-digoxin antibodies to a greater extent than peak 1U and is significantly larger in inhibiting subjects in terms of Na+,K+-ATPase inhibition. These data support the heterogeneity of human Na+,K+-ATPase inhibitor in both plasma and urine.


Protective effects of crocin and zinc sulfate on hepatic ischemia-reperfusion injury in rats: a comparative experimental model study.
The aim of this study was to investigate the comparative protective effects of separate and combined pretreatment with Cr and ZnSO4 on serum levels of miR-122, miR-34a, liver function tests, protein expression of Nrf2 and p53, and histopathological changes following IR-induced hepatic injury. Fifty-six male Wistar rats randomly assigned into seven groups (n=8). Sham (S), IR, crocin pretreatment (Cr), and crocin pretreatment+IR (Cr+IR), ZnSO4 pretreatment (ZnSO4), ZnSO4 pretreatment+IR (ZnSO4+IR) and their combination (Cr+ZnSO4+IR) groups. In sham, ZnSO4 and Cr groups, animals received normal saline (N/S, 2ml/day), Cr (200mg/kg) and ZnSO4 (5mg/kg) for 7 consecutive days (intraperitoneally; i.p), then only laparotomy was performed. In IR, Cr+IR, ZnSO4+IR and Cr+ZnSO4+IR groups, rats received N/S, Cr and ZnSO4 with same dose and time, then underwent a partial (70%) ischemia for 45min that followed by reperfusion for 60min. Blood sample was taken for biochemical and microRNAs assay, tissue specimens were obtained for antioxidants, protein expression, histopathological and immunohistochemical evaluations. The results showed that Cr and ZnSO4 increased antioxidants activity and expression of Nrf2, decreased serum levels of liver enzymes, miR-122, miR-34a, p53 expression and also ameliorated histopathological abnormality. However, their combination caused more improvement on IR-induced liver injury. This study demonstrated that Cr, ZnSO4 and their combination through increasing antioxidant activity and Nrf2 expression, decreasing the serum levels of liver enzymes, miR-122, 34a, p53 expression, and amelioration of histopathological changes, protected liver against IR-induced injury.


Hajj vaccinations-facts, challenges, and hope.
Vaccination is an effective preventive measure that has been used in the unique Hajj pilgrimage setting to control the transmission of infectious diseases. The current vaccination policy applied during Hajj is reviewed herein, highlighting the effectiveness of the approaches applied and identifying research gaps that need to be filled in order to improve the development and dissemination of Hajj vaccination strategies.


Cardiovascular risk factors and body composition in adults with achondroplasia.
An increased cardiovascular mortality has been reported in achondroplasia. This population-based, case-control study investigated cardiovascular risk factors and body composition in Norwegian adults with achondroplasia. We conducted anthropometric, clinical, and laboratory assessments in 49 participants with achondroplasia, of whom 40 completed magnetic resonance imaging (MRI) for body composition analysis. Controls consisted of 98 UK Biobank participants, matched for body mass index (BMI), sex, and age. Participants were well matched for BMI (33.3 versus 32.5 kg/m2) and sex, but achondroplasia participants were younger than controls (mean age 41.1 versus 54.3 years). Individuals with achondroplasia had lower age-adjusted mean blood pressure, total and low-density lipoprotein (LDL) cholesterol, and triglycerides compared with controls, but similar fasting glucose and HbA1c values. Age-adjusted mean visceral fat store was 1.9 versus 5.3 L (difference -2.7, 95% confidence interval [CI] -3.6 to -1.9; P < 0.001), abdominal subcutaneous fat was 6.0 versus 11.2 L (-4.7, 95% CI -5.9 to -3.4; P < 0.001), and liver fat was 2.2 versus 6.9% (-2.8, 95% CI -5.2 to -0.4; P = 0.02). Despite a high BMI, the cardiovascular risks appeared similar or lower in achondroplasia compared with controls, indicating that other factors might contribute to the increased mortality observed in this condition.


Knowledge domain and hotspot trends in coal and gas outburst: a scientometric review based on CiteSpace analysis.
Coal and gas outburst is one of the main dynamic disasters in coal mine production. In order to deeply understand the overall research progress in the field of coal and gas outburst, the Web of Science (WOS) database is used as the sample source, and the bibliometric analysis of the literature in the field of coal and gas outburst from 2000 to 2021 is carried out by CiteSpace software. The knowledge maps of the publication quantity, country, institution, and keyword cluster are drawn. The results show that the time distribution has gone through three stages of germination period, development period, and growth period. In terms of the cooperation network, China, Australia, and the USA are the main core research countries, while China University of Mining and Technology, Chongqing University, and Henan Polytechnic University are the main core research institutions, and the main core journals are IGCG, IGRMM, and Fuel. By drawing the knowledge map of keywords timeline, the evolution law of keywords in the field of coal and gas outburst with time is obtained. Taking keywords as the object, cluster labels with gas outburst, gas extraction, gas control, and pore structure as the core are presented. On this basis, from a new perspective, this paper outlines the "scientific research landscape map" in the field of coal and gas outburst, in order to provide a scientific reference for coal and gas outburst research.


iRGD-conjugated DSPE-PEG2000 nanomicelles for targeted delivery of salinomycin for treatment of both liver cancer cells and cancer stem cells.
To develop novel iRGD (internalizing Arg-Gly-Asp peptide)-conjugated DSPE-PEG2000 nanomicelles (M-SAL-iRGD) for delivery of salinomycin to both liver cancer cells and cancer stem cells (CSCs). The characterization, antitumor activity and mechanism of action of M-SAL-iRGD were evaluated. M-SAL-iRGD possessed a small size of around 10 nm, and drug encapsulation efficacy higher than 90%. M-SAL-iRGD showed significantly increased cytotoxic effect toward both nontargeted M-SAL (salinomycin-loaded DSPE-PEG2000 nanomicelles) and salinomycin in both liver cancer cells and CSCs. The tissue distribution and antitumor assays in mice bearing liver cancer xenograft confirmed the superior penetration tumor efficacy and antitumor activity of M-SAL-iRGD. M-SAL-iRGD represent a potential effective nanomedicine against liver cancer.


Hypothalamic afferents to the dorsal dentate gyrus contain acetylcholinesterase.
Retrograde transport of Evans blue dye from the rat dentate gyrus was used to identify afferent hypothalamic cells. Photography of the fluorescent hypothalamic cells was followed by incubation in an acetylthiocholine medium. Slides were re-photographed for acetylcholinesterase-induced reaction product. Nearly all posterior hypothalamic cell afferents to the dentate gyrus could be positively identified as containing acetylcholinesterase.


Using synthetic biology to study gene regulatory evolution.
Transcriptional enhancers specify the precise time, level, and location of gene expression. Disentangling and characterizing the components of enhancer activity in multicellular eukaryotic development has proven challenging because enhancers contain activator and repressor binding sites for multiple factors that each exert nuanced, context-dependent control of enhancer activity. Recent advances in synthetic biology provide an almost unlimited ability to create and modify regulatory elements and networks, offering unprecedented power to study gene regulation. Here we review several studies demonstrating the utility of synthetic biology for studying enhancer function during development and evolution. These studies clearly show that synthetic biology can provide a way to reverse-engineer and reengineer transcriptional regulation in animal genomes with enormous potential for understanding evolution.


Australia's overseas development aid commitment to health through the sustainable development goals: a multi-stakeholder perspective.
In 2018, the Australian Government, through a Senate-led Parliamentary Inquiry, sought the views of diverse stakeholders on Sustainable Development Goal (SDG) implementation both domestically and as part of Australia's Overseas Development Assistance (ODA) program. One hundred and sixty-four written submissions were received. The submissions offered perspective and guidance from a rich cross-section of those involved, and with keen interest in, Australia's ODA-SDG commitment. This article identifies and explores the submissions to that Inquiry which placed impetus on Australia's ODA-SDG and health and development nexus. It then compares how the synthesized views, concerns and priorities of selected Inquiry stakeholders align with and reflect the Australian Government's treatment of SDG 3 in its SDG Voluntary National Review (VNR), as well as with the final Inquiry report summarizing submission content. Four key themes were synthesized and drawn from the thirty-one stakeholder submissions included in our analysis. Disconnect was then found to exist between the selected stakeholder views and the Australian Government's SDG-VNR's treatment of SDG 3, as well as with the content of the Parliamentary Inquiry's final report with respect to the ODA-SDG and health and development nexus. We situate the findings of our analysis within the wider strategic context of the Australian Government's policy commitment to "step up" in the Pacific region. This research provides an insight into both multi-stakeholder and Federal Government views on ODA in the Indo-Pacific region, especially at a time when Australia's Pacific engagement has come to the forefront of both foreign and security policy. We conclude that the SDG agenda, including the SDG health and development agenda, could offer a unique vehicle for enabling a paradigm shift in the Australian Government's development approach toward the Pacific region and its diverse peoples. This potential is strongly reflected in stakeholder perspectives included in our analysis. However, study findings remind that the political determinants of health, and overlapping political determinants of SDG achievement, will be instrumental in the coming decade, and that stakeholders from different sectors need to be genuinely engaged in SDG-ODA policy-related decision-making and planning by governments in both developed and developing countries alike.


Quantitation of Cyclosporin A in Cell Culture Media by Differential Mobility Mass Spectrometry (DMS-MS/MS).
Cell permeability is an important factor in determining the bioavailability of therapeutics that is usually measured by cell culture testing. The concentration of pharmaceutical in a medium such as Hank's Balanced Salt Solution with HEPES organic buffer (HBSS-HEPES) is measured at a series of time points, making simplicity and high throughput of the analytical method important characteristics. We report an electrospray differential mobility spectrometry mass spectrometry method (nanoESI-DMS-MS) for the rapid determination of cyclosporin A (CsA, cyclosporine) concentration in such a buffer. DMS technology provides gas phase atmospheric pressure ion filtration for small-molecule bioanalytical methods that suppresses interfering ions and reduces chemical noise, without the use of chromatography. This allows simplified sample preparation, fast calibration curve development, and shortened analysis times. It has also been noted that the DMS prefilter can reduce contamination of the mass spectrometer by salts, thereby extending mass spectrometer system uptime.In the application described here, DMS-MS/MS is applied to cyclosporine A (CsA) in cell medium. Sample preparation is limited to dilution with an ammonium acetate-methanol-water mobile phase and the addition of CsA-d4 internal standard. The isotope ratio data are obtained in DMS-MS MRM mode observing NH3 loss from the ammonium adduct of the two species. A calibration curve with high linearity (R2 = 0.998) is rapidly obtained with nearly zero intercept, while it was found that a liquid chromatography LC-MS method required a preliminary SPE step to obtain a linear calibration curve. The time for data acquisition in the DMS-MS MRM method with flow injection (FIA) or infusion introduction at ESI flow of 400 nL/min is typically 30 s leading to a cycle time of less than 1 min.


Reversal of sexual impotence in male patients with chronic obstructive pulmonary disease and hypoxemia with long-term oxygen therapy.
Erectile impotence is commonly encountered in male patients with respiratory failure and hypoxia. In this study, 42% of the patients experienced reversal of sexual impotence during long-term oxygen therapy (LTOT). We examine the association between sexual impotence, gonadal axis hormones, hypoxia, and oxygen therapy. Nineteen sexually impotent male patients eligible for LTOT (pO2 < 7.3 kPa during stable disease) and with sexual impotence received oxygen therapy for 1 month (n = 12) or 24 h (n = 7). pO2, LH, FSH, testosterone, and SHBG (sex hormone binding globulin) were monitored. Five of 12 patients receiving oxygen for 1 month regained sexual potency. The responders showed a significant increase in arterial pO2 and serum testosterone, and a decline in SHBG compared to non-responders. None of the patients receiving oxygen for 24 h experienced reversal of sexual impotence, despite a significant increase in pO2. In these patients, serum testosterone did not increase significantly. Reversal of sexual impotence may be achieved in some patients with respiratory failure. The oxygen therapy must, however be administered for an adequate length of time.


Changes in Racial and Ethnic Disparities in Estimated Diagnosis Rates of Heterosexually Acquired HIV Infection Among Heterosexual Males in the United States, 2014-2018.
Diagnoses of HIV infection among male adults and adolescents ≥13 years with infection attributed to heterosexual contact decreased from 2014 through 2018. Racial disparities exist; HIV diagnoses are higher among Black/African American men compared with men of other races/ethnicities. In 2018, Black/African American males accounted for 61% of diagnosed HIV infections attributed to heterosexual contact among males. We used national HIV surveillance data from Atlas Plus to obtain the annual case counts of new HIV diagnoses in males with infection attributed to heterosexual contact and population size for years 2014 through 2018 for males (United States excluding territories) by the racial/ethnic group. We used an adjusted population denominator to calculate rates of diagnoses of HIV infection acquired through heterosexual contact per 100,000 males and 12 absolute and relative measures of disparity to calculate racial/ethnic disparity changes from 2014 to 2018. Results from all disparity measures indicate that disparities decreased in 2018, compared with 2014. The decreases ranged from 18.8% to 34.6% among the 4 absolute disparity measures and from 5.3% to 22.7% among the 8 relative disparity measures. Despite the decrease, disparities remain. Tailored, effective strategies and interventions are needed to address the social and structural factors associated with HIV risk among heterosexual Black men and to promote continued progress toward reducing disparities.


Precision and predictive medicine in urothelial cancer: are we making progress?
Therapy for urothelial carcinoma appears poised for a breakthrough on the basis of information regarding molecular subtypes and promising activity of PD-1/PD-L1 inhibitors. Precision medicine may be possible using rational marker-driven trial designs with enriched information from tumor genotyping and extreme responders.


Changing patterns of hepatitis B infection in Italy and NAT testing for improving the safety of blood supply.
In Italy, as in most industrialized countries, the burden of hepatitis B has progressively declined in recent decades as a consequence of general improvements in hygiene and standard of living, the introduction of several public health measures, refinement in blood screening and the implementation of specific vaccination programmes. Universal hepatitis B vaccination for all infants and adolescents as well as individuals at increased risk has resulted in considerable progress towards prevention and control of HBV infection. The residual risk of transmitting blood-borne viruses through transfusion is currently very low. Nucleic acid testing can shorten the window period and, consequently, further reduce the risk of viral transmission. Blood donor screening for HCV by NAT was initiated in Italy in 2001 and became mandatory in June 2002. NAT for HIV is currently mandatory in four regions, not mandatory but almost universally performed in another thirteen regions, and not yet introduced in the remaining four regions. NAT for HBV is currently mandatory in four regions and under evaluation in the remaining. NAT for HBV may be a useful tool in detecting acute viral infections in the window phase as well as the occult infections. Its efficacy in improving the safety of blood supply is expected to be higher in countries with intermediate/high endemicity, where anti-HBc antibody screening cannot be routinely performed. There is agreement that, at present, the implementation of HBV DNA testing will not allow for discontinuation of screening for HBsAg.


Bone morphogenetic protein signalling in NGF-stimulated PC12 cells.
Bone morphogenetic proteins (BMPs) are shown to potentiate NGF-induced neuronal differentiation in PC12 phaeochromocytoma cells grown on collagen under low-serum conditions. Whereas, cell bodies remained rounded in control medium or with only BMPs present, addition of BMP4 or BMP6 robustly increased the neuritogenic effect of NGF within 2 days. NGF-increased phosphorylation of p44(Erk1) and p42(Erk2) between 2 and 24h was unaffected by addition of BMP6. PC12 cells transfected with the SBE(4x)-luc reporter showed that BMP4 significantly increased receptor-activated Smad activity. Expression of constitutively active BMP receptor ALK2 activating Smad1 and Smad5 resulted in a strong increase in the SBE(4x)-luc reporter response. Adding the inhibitory Smad7 drastically reduced this signal. In contrast to wild-type (wt) Smad5, a Smad5 variant lacking five Erk phosphorylation sites in the linker region (designated Smad5/5SA) showed a strong background transcriptional activity. A fusion construct (Gal4-Smad5/5SA) was also highly transcriptionally active. Addition of the MEK inhibitor U0126 to PC12 cells expressing Gal4-Smad5/wt did not increase background transcriptional activity. However, upon activation by constitutively active ALK2 both Gal4-Smad5/wt and Gal4-Smad5/5SA strongly stimulated transcription. The data show that serine residues of the linker region of Smad5 reduce spontaneous transcriptional activity and that NGF-activated Erk does not antagonise BMP signalling at this site. Hence, NGF and BMP signals are likely to interact further downstream at the transcriptional level in neuronal differentiation of the PC12 cells.


Antibiotic Exposure, Not Alloreactivity, Is the Major Driver of Microbiome Changes in Hematopoietic Cell Transplantation.
Both autologous hematopoietic cell transplantation (auto-HCT) and allogeneic hematopoietic cell transplantation (allo-HCT) are associated with significant alterations in the intestinal microbiome. The relative contributions of antibiotic use and alloreactivity to microbiome dynamics have not yet been elucidated, however. There is a lack of data on the kinetics of microbiome changes beyond 30 days post-transplantation and how they might differ between different transplantation modalities. A direct comparison of the differential effects of auto-HCT and allo-HCT on the microbiome may shed light on these dynamics. This study was conducted to compare intestinal microbial diversity between auto-HCT recipients and allo-HCT recipients from pre-transplantation to 100 days post-transplantation, and to examine the effect of antibiotics, transplant type (auto versus allo), and conditioning regimens on the dynamics of microbiome recovery. We conducted a longitudinal analysis of changes in the intestinal microbiome in 35 patients undergoing HCT (17 auto-HCT, 18 allo-HCT) at 4 time points: pre-conditioning and 14, 28, and 100 days post-transplantation. Granular data on antibiotic exposure from day -30 pre-transplantation to day +100 post-transplantation were collected. Pre-transplantation, allo-HCT recipients had lower α-diversity in the intestinal microbiome compared with auto-HCT recipients, which correlated with greater pre-transplantation antibiotic use in allo-HCT recipients. The microbiome diversity declined at days +14 and +28 post-transplantation in both cohorts but generally returned to baseline by day +100. Conditioning regimen intensity did not significantly affect post-transplantation α-diversity. Through differential abundance analysis, we show that commensal bacterial taxa involved with maintenance of gut epithelial integrity and production of short-chain fatty acids were depleted after both auto-HCT and allo-HCT. In our dataset, antibiotic exposure was the major driver of post-transplantation microbiome changes rather than alloreactivity, conditioning intensity, or immunosuppression. Our findings also suggest that interventions to limit microbiome injury, such as limiting the use of broad-spectrum antibiotics, should target the pre-transplantation period and not only the peri-transplantation period.


Serum lipids in long-lactating African mothers habituated to a low-fat intake.
African women, accustomed to a low fat intake, have relatively low blood lipid levels, and are virtually free from coronary heart disease. Among lactating mothers, the amount of fat voided daily in their breast milk is of the same order as that ingested in their habitual diet. However, investigations showed that long-lactating mothers, compared with appropriate control groups, did not exhibit significant hypolipidaemia.


Miniaturized electromechanical devices with multi-vibration modes achieved by orderly stacked structure with piezoelectric strain units.
Piezoelectric devices based on a variety of vibration modes are widely utilized in high-tech fields to make a conversion between mechanical and electrical energies. The excitation of single or coupled vibration modes of piezoelectric devices is mainly related to the structure and property of piezoelectric materials. However, for the generally used piezoelectric materials, e.g., lead zirconate titanate ceramics, most of piezoelectric coefficients in the piezoelectric matrix are equal to zero, resulting in many piezoelectric vibration modes cannot be excited, which hinders the design of piezoelectric devices. In this work, an orderly stacked structure with piezoelectric strain units is proposed to achieve all nonzero piezoelectric coefficients, and consequently generate artificially coupled multi-vibration modes with ultrahigh strains. As an example, an orderly stacked structure with two piezoelectric strain units stator, corresponding to 31-36 coupled vibration mode, was designed and fabricated. Based on this orderly stacked structure with two piezoelectric strain units stator, we made a miniature ultrasonic motor (5 mmLength × 1.3 mmHeight × 1.06 mmWidth). Due to the ultrahigh strain of the 31-36 coupled vibration mode, the velocity per volume of the motor reached 4.66 s-1 mm-2. Furthermore, its moving resolution is around 3 nm, which is two orders higher than that of other piezoelectric motors. This work sheds a light on optimizing the performance of state-of-the-art electromechanical devices and may inspire new devices based on multi-vibration modes.


[The water-cress pools in connection with cases of human fasciolasis in Limousin, France. Experimental studies of Trematode snails and their biological control (author's transl)].
Experimental studies on 16 water-cress pools with cases of human fasciolasis in Limousin were undertaken. Two species of snails, Lymnaea glabra and L. truncatula are here trematode hosts. L. glabra alone lives in 5 pools. The introduction of Zonitoides nitidus -- predatory snail -- without vegetation modification produces a progressive elimination of Lymnaea in 3 years. The author insists on the use of determine the trematode host-aptitude of L. glabra and its limits when the two species -- L. glabra and L. truncatula -- live in the same habitats.


Clones of cells from a human embryo lung: their growth and susceptibility to respiratory viruses.
Colonies of cells were obtained from human fetal lung tissue and exposed to recently isolated respiratory viruses. There was a considerable variation in the number of rounded cells found in different colonies exposed to rhinovirus types 2 and 9 (RV2 and 9), human coronavirus 229E (HCV), adenovirus type 3 (Ad3) and respiratory syncytial virus (RSV). Smaller colonies had more rounded cells than larger colonies. Clones were established from 9 out of 11 colonies. They varied in their rate of growth and the pattern formed on a plastic surface. They varied also in their virus susceptibility particularly to "difficult" rhinoviruses such as RV9 and SF1340. One cell clone (HL1/77 Clone 8), was highly susceptible to all these viruses. All cultures were more sensitive to RSV when maintained in F12K medium than in MEM, whereas there was no difference for rhinoviruses. Influenza A and B and parainfluenza 3 viruses sometimes produced cytopathic effect, and always produced haemadsorption, but unlike the previous strains could not be passed serially and presumably produced little infectious virus. All clones were rather insusceptible to Ad3; but the virus could be passed, whereas coxsackie virus B3 produced no CPE. Substantial yields of coronavirus and rhinovirus were obtained in gelatin sponge cultures. Two "very difficult" respiratory viruses which had just been adapted to tissue culture; namely, HS rhinovirus and JK coronavirus grew in 7 of 9 and in 6 of 9 clones respectively.


Competitive binding of gangliosides and glycophorin to wheat germ agglutinin.
Gangliosides and glycophorin are receptors for wheat germ agglutinin. The competitive binding of these molecules to wheat germ agglutinin is studied by electron spin resonance spectroscopy with spin labels attached to the oligosaccharide chains of gangliosides. Evidence shows that glycophorin is more accessible to wheat germ agglutinin binding than gangliosides. The interactions of gangliosides and glycophorin in liposomes is disrupted on low level binding of WGA.


Coherent singlet-triplet oscillations in a silicon-based double quantum dot.
Silicon is more than the dominant material in the conventional microelectronics industry: it also has potential as a host material for emerging quantum information technologies. Standard fabrication techniques already allow the isolation of single electron spins in silicon transistor-like devices. Although this is also possible in other materials, silicon-based systems have the advantage of interacting more weakly with nuclear spins. Reducing such interactions is important for the control of spin quantum bits because nuclear fluctuations limit quantum phase coherence, as seen in recent experiments in GaAs-based quantum dots. Advances in reducing nuclear decoherence effects by means of complex control still result in coherence times much shorter than those seen in experiments on large ensembles of impurity-bound electrons in bulk silicon crystals. Here we report coherent control of electron spins in two coupled quantum dots in an undoped Si/SiGe heterostructure and show that this system has a nuclei-induced dephasing time of 360 nanoseconds, which is an increase by nearly two orders of magnitude over similar measurements in GaAs-based quantum dots. The degree of phase coherence observed, combined with fast, gated electrical initialization, read-out and control, should motivate future development of silicon-based quantum information processors.


Aortic graft sepsis caused by Pasteurella multocida.
A case detailing the successful management of aortic graft sepsis resulting from Pasteurella multocida is reported. The infection was the result of a bite from the patient's dog.


Hepatic peroxisome proliferation in rodents and its significance for humans.
Peroxisomes are subcellular organelles found in all eukaryotic cells. In the liver they are usually round and measure about 0.5-1.0 microns; in rodents they contain a prominent crystalloid core, but this may be absent in newly formed rodent peroxisomes as well as in human peroxisomes. A major role of the peroxisomes is the breakdown of long-chain fatty acids, thereby complementing mitochondrial fatty-acid metabolism. Many chemicals are known to increase the number of peroxisomes in rat and mouse hepatocytes. This peroxisome proliferation is accompanied by replicative DNA synthesis and liver growth. No clear structure-activity relationships are apparent. Many of these peroxisome proliferators contain acid functions that can modulate fatty acid metabolism. Two mechanisms have been proposed for the induction of peroxisome proliferation. One is based on the existence of one or several specific cytosolic receptors that bind the peroxisome proliferator, facilitating its translocation to the cell nucleus and the activation of the expression of specific genes. The second, perhaps more general, hypothesis involves chemically mediated perturbation of lipid metabolism. These two hypotheses are not mutually exclusive. Many peroxisome proliferators have been shown to induce hepatocellular tumours, despite being uniformly non-genotoxic, when administered at high dose levels to rats and mice for long periods. Three mechanisms have been proposed to explain the induction of tumours. One is based on increased production of active oxygen species due to imbalanced production of peroxisomal enzymes; it has been proposed that these reactive oxygen species cause indirect DNA damage with subsequent tumour formation. In rodents, an alternative mechanism is the promotion of endogenous lesions by sustained DNA synthesis and hyperplasia. Thirdly, it is conceivable that sustained growth stimulation may be sufficient for tumour formation. Marked species differences are apparent in response to peroxisome proliferations. Rats and mice are extremely sensitive, and hamsters show an intermediate response while guinea pigs, monkeys and humans appear to be relatively insensitive or non-responsive at dose levels that produce a marked response in rodents. These species differences may be reproduced in vitro using primary culture hepatocytes isolated from a variety of species including humans. The available experimental evidence suggests a strong association and a probable casual link between peroxisome-proliferator-elicited liver growth and the subsequent development of liver tumours in rats and mice. Since humans are insensitive or unresponsive, at therapeutic dose levels, to peroxisome-proliferator-induced hepatic effects, it is reasonable to conclude that the encountered levels of exposure to these non-genotoxic agents do not present a hepatocarcinogenic hazard to humans.(ABSTRACT TRUNCATED AT 400 WORDS)


Obesity and psychotropic medication: a prospective register linkage study among midlife women and men.
Both obesity and mental health are major public health issues. This study aimed to examine whether overweight and obesity among midlife employees are associated with subsequent psychotropic medication. A further aim was to examine the potential effect of key covariates on the association. The Helsinki Health Study baseline survey was conducted in 2000-2002 among 40-60-year-old employees of the City of Helsinki, Finland (n = 8960). The participants were classified as of normal weight (18.5-24.9 kg/m(2)), overweight (25-29.9 kg/m(2)), obese (30-34.9 kg/m(2)) or severely obese (≥35 kg/m(2)) based on self-reported body mass index. Data on psychotropic medication purchases from baseline to 2009 were derived from registers of the Social Insurance Institution of Finland. The final analysis included 4760 women and 1338 men. Antidepressants and sedatives were examined separately. Covariates included socio-demographic factors, workload, health behaviours, physical functioning, somatic ill-health and psychotropic medication prior to baseline. Hazard ratios (HR) for the first psychotropic medication purchase were calculated using Cox regression analysis. Third of women and quarter of men made at least one psychotropic medication purchase during the follow-up. Adjusting for age, obese (HR = 1.57; 95 % CI = 1.10-2.24) and severely obese (HR = 2.15; 95 % CI = 1.29-3.56) men were at risk of having psychotropic medication compared to men of normal weight. These associations disappeared after further adjustment. Severe obesity remained associated with subsequent sedative medication among the men even after full adjustment (HR = 2.12; 95 % CI = 1.17-3.84). No associations were found among the women. Obese and severely obese men, but not women, were at risk of psychotropic medication. Further studies are needed to deepen understanding of the relationship between obesity and mental ill-health, and the possible protecting effects of age, employment, and living environment.


Functional analysis of tomato rhamnogalacturonan lyase gene Solyc11g011300 during fruit development and ripening.
Rhamnogalacturonan I (RG-I) is a domain of plant cell wall pectin. The rhamnogalacturonan lyase (RGL) enzyme (EC 220.127.116.11) degrades RG-I by cleaving the α-1,4 glycosidic bonds located between the l-rhamnose and d-galacturonic residues of the main chain. While RGL's biochemical mode of action is well known, its effects on plant physiology remain unclear. To investigate the role of the RGL enzyme in plants, we have expressed the Solyc11g011300 gene under a constitutive promoter (CaMV35S) in tomato cv. 'Ohio 8245' and evaluated the expression of this and other RGL genes, enzymatic activity and alterations in vegetative tissue, and tomato physiology in transformed lines compared to the positive control (plants harboring the pCAMBIA2301 vector) and the isogenic line. The highest expression levels of the Solyc11g011300, Solyc04g076630, and Solyc04g076660 genes were observed in leaves and roots and at 10 and 20 days after anthesis (DAA). Transgenic lines exhibited lower RGL activity in leaves and roots and during fruit ripening, whereas higher activity was observed at 10, 20, and 30 DAA than in the isogenic line and positive control. Both transgenic lines showed a lower number of seeds and fruits, higher root length, and less pollen germination percentage and viability. In red ripe tomatoes, transgenic fruits showed greater firmness, longer shelf life, and reduced shriveling than did the isogenic line. Additionally, a delay of one week in fruit ripening in transgenic fruits was also recorded. Altogether, our data demonstrate that the Solyc11g011300 gene participates in pollen tube germination, fruit firmness, and the fruit senescence phenomena that impact postharvest shelf life.


Effects of short-term supplementation of clinoptilolite in colostrum and milk on hematology, serum proteins, performance, and health in neonatal dairy calves.
In recent years, the use of both natural and synthetic zeolites in animal nutrition has increased, mainly to improve their performance, health, and to protect against mycotoxins intoxication. Thirty calves were used in the present study for the determination of the effects of clinoptilolite supplementation on hematology, serum proteins, performance, and health. The animals were divided equally into three groups (control, test 1 and test 2). The three groups of calves were homogeneous for parity of dams, sex, and month of birth. For test 1 group, clinoptilolite in the concentration of 2% of each colostrum meal was added for 48h and for test 2 group, clinoptilolite in the concentration of 2% was added to each colostrum and milk meal for 14 days. Blood samples were taken from all calves 12h after birth and at the end of the first, second, third, forth, fifth and sixth weeks of life (end of the experiment: 42 days of life) and analyzed for hematology, plasma fibrinogen and for total protein, albumin, beta and gamma globulin measurement. Performance and health of calves were also recorded during the experiment. For statistical analysis of data a repeated measures approach using ANOVA with Mixed linear models, and chi-test was used. Clinoptilolite supplementation had significant effect on the values of hematocrit (HCT), red cell count (RBC), hemoglobin (Hb), mean corpuscular volume (MCV), monocyte (Mono), and albumin (Alb). The values of most above parameters were significantly higher in test group 2, except MCV that was significantly lower in test group 1 than other trial groups (p<0.05). No significant difference was seen for other measured parameters, performance, and health between trial groups.


Exploratory, multicenter, open-label study to evaluate the effects of linaclotide in patients with chronic constipation with an insufficient response to magnesium oxide: A study protocol.
Chronic constipation leads to poor quality of life, and treatment remains unsatisfactory for patients. In Japan, magnesium oxide has been commonly used as the first choice of treatment for constipation; however, there are some cases of low satisfaction with magnesium oxide treatment. Linaclotide has recently been used to treat chronic constipation. In this study, we will examine whether linaclotide improves symptoms and quality of life in patients showing insufficient response to magnesium oxide. This is an exploratory multicenter open-label study. The target number of patients is 64: 32 patients with and 32 without abdominal symptoms. Patients with chronic idiopathic constipation or irritate bowel syndrome with constipation diagnosed according to the Rome-IV criteria are eligible. Patients prescribed 0.99-2 g/day of magnesium oxide for at least 4 weeks will be included. Those who consent to the study will continue taking magnesium oxide for 2-4 weeks, and defecation will be documented. Patients who meet the criteria will be prescribed linaclotide (0.5 mg) daily for 12 weeks. The primary endpoint is a change in the Japanese version of the Patient Assessment of Constipation Quality of Life (JPAC-QOL) score after 12 weeks of treatment. This is the first study to investigate the usefulness of linaclotide as a second-line treatment for chronic constipation. We will test the efficacy of treatment of constipation in patients with inadequate response to magnesium oxide. This study is registered with the Japan Registry of Clinical Trials (jRCT, jRCTs031200048).


Subpallidal-pedunculopontine projections but not subpallidal-mediodorsal thalamus projections contribute to spontaneous exploratory locomotor activity.
The contribution of the pedunculopontine nucleus to exploratory locomotion was investigated in rats. Locomotor activity recorded in a standard open-field apparatus was increased more than two-fold when wooden panels were inserted. This novelty-elicited locomotion was reduced significantly when procaine was injected bilaterally into the pedunculopontine nucleus but not when procaine was injected bilaterally into the mediodorsal thalamus, a second major projection site of the subpallidal area. These results support observations from earlier studies implicating hippocampal-accumbens-subpallidal-pedunculopontine projections in exploratory locomotion.


Neural networks based linear (PCA) and nonlinear (ISOMAP) feature extraction for soil swelling pressure prediction (North East Algeria).
The swelling pressure (SP) of expansive soils is crucial for both geotechnical studies as well as practitioners. Multiple attempts have been made to correlate the SP with the properties of soil due to the difficulty of determining it in the laboratory. However, the large number of environmental and physical governing parameters makes accurate SP predictions difficult. In this paper, Artificial Neural Networks (ANNs) are used to assess accurate prediction of SP of soil. Dimension reduction techniques are intensely required for ANNs inputs. Feature extraction (FE) based dimension reduction (DR) methods map original multidimensional space into a space of reduced dimensionality. This paper presents a comparative study of linear FE using Principal Component Analysis (PCA) and nonlinear FE using ISOmetric MAPping (ISOMAP) for feed forward neural models to predict SP. Results showed that FE technique improves ANNs models compared to multiple linear regression (MLR) and ANNs model without DR. Moreover, nonlinear ISOMAP based DR technique has proven its effectiveness regarding performance metrics for five dimensions inputs (Dims), Determination coefficient (R2 = 0.923), Mean absolute percentage error (MAPE = 0.072), and Root mean square error (RMSE = 54.937) and Root relative squared error (RRSE = 0.383). Therefore, ISOMAP-ANN models can be adopted to solve geotechnical problems specially those of expansive soils which have a very complex and nonlinear structure.


Fabrication of PNIPAM-chitosan/decatungstoeuropate/silica nanocomposite for thermo/pH dual-stimuli-responsive and luminescent drug delivery system.
A luminescent and dual-stimuli-responsive nanocomposite based on mesoporous silica, poly (N-isopropylacrylamide)-chitosan and decatungstoeuropate was prepared. To fabricate the nanocomposite, the mesoporous silica nanoparticles were coated with thermo/pH dual-responsive poly (N-isopropylacrylamide)-chitosan and the luminescent decatungstoeuropate particles were grafted onto copolymers. The designed nanocarrier could show exhibit good red luminescence as well as obvious thermo/pH stimuli-responsive properties, which could be employed as a drug storage reservoir for the loading and release of anticancer drug doxorubicin (DOX). The research indicated that the releases of DOX were thermo/pH dependent and high temperatures/acidic conditions were favorable for the fast release of drug. In vitro cytotoxicity tests revealed that the drug delivery carrier displayed excellent biocompatible and the composites loaded with DOX showed significant suppression effect on HeLa cells. Luminescence spectra showed that the composite containing decatungstoeuropate displayed fine red luminescence at various temperatures and pH values, which could be utilized as a potential labeling material in field of medicine.


MicroRNA-17 family as novel biomarkers for cancer diagnosis: a meta-analysis based on 19 articles.
Cancer remains as the leading cause of death all over the world due to the lack of efficient diagnostic techniques and therapeutic methods. Many studies have reported the potential diagnostic value of microRNA-17 (miRNA-17, miR-17) family members as biomarkers for cancer detection. However, inconsistent results were revealed from a wide range of studies. As a result of this, a meta-analysis based on 19 studies was conducted to assess the diagnostic performance of miR-17 family for cancer detection. A total of 1772 patients with certain types of cancer and 1320 healthy controls were involved in these studies. The overall diagnostic accuracy was measured by the following: sensitivity, 0.67 (95 % confidence interval (CI) 0.60-0.74); specificity, 0.83 (95 % CI 0.74-0.85); positive likelihood ratio (PLR), 3.9 (95 % CI 2.6-5.9); negative likelihood ratio (NLR), 0.40 (95 % CI 0.34-0.48); and diagnostic odds ratio (DOR), 10 (95 % CI 6-16), respectively. Additionally, the pooled area under the summary receiver operator characteristic (SROC) curve (area under the curve (AUC)) was 0.79 (95 % CI 0.75-0.82), indicating a relatively low accuracy of miR-17 family as biomarkers for cancer detection. Subgroup analysis further showed that miR-17 family had more reliable performance in cancer diagnosis for Asian than that for Caucasian. Moreover, multiple miRNAs containing miR-17, -20a/b, and -93 reflected higher diagnostic accuracy than both miR-106a/b (single miRNA) and the overall miR-17 family assay. Therefore, appropriate combinations of miR-17 family may be used as non-invasive screening biomarkers for cancer, and it is necessary to carry out a large-scale population-based study to further assess the potential diagnostic value of miR-17 family.


Characterization of unstable hemoglobin A1c complexes by dynamic capillary isoelectric focusing.
Glucose spontaneously reacts with hemoglobin amino groups to produce unstable Schiff base complexes that can dissociate or rearrange to form stable Amadori products. We used dynamic capillary isoelectric focusing and boronate affinity chromatography to assess the formation and dissociation of unstable hemoglobin complexes in vitro. Formation was studied by incubating erythrocytes at 37°C for up to 24h in phosphate-buffered saline (PBS) supplemented with 0 to 55.6 mmol/L glucose. Dissociation was studied by incubating glucose-loaded erythrocytes in PBS without glucose. Dynamic capillary isoelectric focusing separated hemoglobin A1c into two subfractions identified as A1c1 and A1c2. The A1c1 subfraction contained both stable and unstable hemoglobin complexes. The A1c2 subfraction contained only unstable hemoglobin complexes. Both subfractions quantitatively increased in the presence of glucose and decreased in its absence. Rates of increase and decrease were faster and time to equilibrium was shorter for A1c2 (~4 h) compared with A1c1 (~20 h). Unstable hemoglobin complexes did not bind to boronate affinity columns but instead eluted intact in A1c1 and A1c2 subfractions from nonglycated affinity fractions. Cyanoborohydride reduction confirmed the presence of Schiff base complexes. Evidence of multiple unstable hemoglobin complexes with different rates of glycation suggests that new models are needed to describe nonenzymatic hemoglobin glycation.


Testicular and spermatotoxic effects of quinalphos in rats.
Testicular and spermatotoxic effects were investigated in rats exposed to technical-grade quinalphos (70%) at dose levels of 0.52 mg kg(-1) (1/50th ld(50)) or 1.04 mg kg(-1) body weight (1/25th ld(50)) for 5 days a week for 60 days. The activities of marker testicular enzymes such as sorbitol dehydrogenase (SDH) and acid phosphatase were significantly decreased but those of lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (gamma-GT) and beta-glucuronidase were significantly increased in a dose-dependent manner. This particular pattern in the activity of testicular-cell-specific enzymes, a decrease in sperm motility and total epididymal sperm count and an increase in abnormal sperm suggest damage to germ cells and Sertoli cells. The testicular and spermatotoxic effects observed in rats may be due to the pesticide quinalphos or its metabolites.


Anxiety disorders are associated with reduced bone mineral density in men: Findings from the Geelong Osteoporosis Study.
Certain psychiatric disorders, including depression, appear to impact adversely on bone health. Anxiety disorders are highly prevalent but few studies have examined their effects on bone tissue. This study investigated the effect of anxiety disorders on bone mineral density (BMD). This prospective cohort study used data from the Geelong Osteoporosis Study. Participants were women and men aged ≥20 years randomly selected from the electoral roll and followed up for a mean of 14.7 and 11.0 years, respectively. Participants were assessed for a lifetime history of an anxiety disorder using the Structured Clinical Interview for DSM-IV-TR. BMD in the lumbar spine and femoral neck was measured using dual-energy x-ray absorptiometry. Eight hundred and ninety women and 785 men participated in the study. Adjusting for sociodemographic, biometric and lifestyle factors, medical comorbidities and medication use, anxiety disorders were associated with reduced BMD at the lumbar spine (partial η2 = 0.006; p = 0.018) and femoral neck (partial η2 = 0.006; p = 0.003) in men. These associations became non-significant when men with a history of comorbid mood disorders were excluded from the analysis. There was no significant association between anxiety disorders and BMD in women (p ≥ 0.168). Anxiety disorders are associated with reduced BMD in men. This effect may be mediated by comorbid depression.


Poly(ADP-ribose) polymerase: a new therapeutic target?
To overview the emerging data in the literature showing the role of poly(ADP-ribose) polymerase (PARP) in the pathogenesis of critical illness. PARP, an abundant nuclear enzyme involved in DNA repair and transcriptional regulation, is now recognized as a key regulator of cell survival and cell death in response to noxious stimuli in various forms of cardiovascular collapse. PARP becomes activated in response to oxidative DNA damage and depletes cellular energy pools, thus leading to cellular dysfunction in various tissues. The activation of PARP may also induce various cell death processes, and promotes an inflammatory response. In circulatory shock PARP plays a crucial role both in the development of early cardiovascular dysfunction and in the delayed systemic inflammatory response syndrome with associated multiple organ failure. Inhibition of PARP activity is protective in various models of circulatory shock. A solid body of literature supports the view that PARP is an important target for therapeutic intervention in critical illness.


Novel foods in the European Union: Scientific requirements and challenges of the risk assessment process by the European Food Safety Authority.
The European Food Safety Authority (EFSA) has been involved in the risk assessment of novel foods since 2003. The implementation of the current novel food regulation in 2018 rendered EFSA the sole entity of the European Union responsible for such safety evaluations. The risk assessment is based on the data submitted by applicants in line with the scientific requirements described in the respective EFSA guidance document. The present work aims to elaborate on the rationale behind the scientific questions raised during the risk assessment of novel foods, with a focus on complex mixtures and whole foods. Novel foods received by EFSA in 2003-2019 were screened and clustered by nature and complexity. The requests for additional or supplementary information raised by EFSA during all risk assessments were analyzed for identifying reoccurring issues. In brief, it is shown that applications concern mainly novel foods derived from plants, microorganisms, fungi, algae, and animals. A plethora of requests relates to the production process, the compositional characterization of the novel food, and the evaluation of the product's toxicological profile. Recurring issues related to specific novel food categories were noted. The heterogeneous nature and the variable complexity of novel foods emphasize the challenge to tailor aspects of the evaluation approach to the characteristics of each individual product. Importantly, the scientific requirements for novel food applications set by EFSA are interrelated, and only a rigorous and cross-cutting approach adopted by the applicants when preparing the respective application dossiers can lead to scientifically sound dossiers. This is the first time that an in-depth analysis of the experience gained by EFSA in the risk assessment of novel foods and of the reasoning behind the most frequent scientific requests by EFSA to applicants is made.


An ocular fixation device for freehand pars plana vitrectomy.
An adaptation of the stereotaxic micromanipulator is described which provides ocular support and stabilization during freehand vitrectomy. It consists of a baseplate for immobilization of the patient's head and an ocular fixation arm assembly which connects to the eye by grasping a special Flieringa ring sewed to the postlimbal sclera. The ocular fixation arm can be made alternately flexible or rigid, thereby providing needed ocular mobility or stability during the operation as is desired by the surgeon.


Sodium butyrate reduces insulin-resistance, fat accumulation and dyslipidemia in type-2 diabetic rat: A comparative study with metformin.
Recent evidences highlighted that histone deacetylases (HDACs) can deacetylate the histone, various transcription factors and regulatory proteins, which directly or indirectly affect glucose metabolism. The present study aimed to evaluate the comparative effects of sodium butyrate (NaB) and metformin on the glucose homeostasis, insulin-resistance, fat accumulation and dyslipidemia in type-2 diabetic rat. Diabetes was developed in Sprague-Dawley rats by the combination of high-fat diet (HFD) and low dose streptozotocin (STZ, 35 mg/kg). NaB at the doses of 200 and 400 mg/kg twice daily as well as metformin (as a positive control) 150 mg/kg twice daily for 10 consecutive weeks were administered by i.p. and oral route, respectively. NaB treatment significantly reduced the plasma glucose, HbA1c, insulin-resistance, dyslipidemia and gluconeogenesis, which are comparable to metformin treatment. Further, NaB treatment ameliorated the micro- and macro-vesicular steatosis in liver and fat deposition in brown adipose tissue, white adipose tissue (adipocytes hypertrophy) as well as pancreatic beta-cell damage. In the present study, both NaB and metformin inhibited the diabetes-associated increased HDACs activity, thereby increased the acetylation of histone H3 in liver. The present findings demonstrated that NaB and metformin reduced insulin-resistance, dyslipidemia, fat accumulation and gluconeogenesis thereby improved the glucose homeostasis in rat. Thus, NaB might be a promising molecule for the prevention and treatment of type-2 diabetes and dyslipidemia.


Granular cell tumour in the third ventricle. Case report with histological, electron-microscopic, immunohistochemical and necropsy findings.
A rare granular cell tumour was found in the third ventricle of a 56-year-old woman. Histological and electron-microscopic features obtained from the biopsy material were identical to those of previously recorded cases. Immunohistochemical study demonstrated vimentin but not S-100 protein in the tumour cells. The possibility should be re-considered that granular cell tumours may have more than one cell of origin.


Dantrolene and lymphocytic lymphoma.
A patient is reported who was on prolonged treatment with dantrolene for spastic paraplegia; he developed a malignant lymphoma which led to his death.


Ethanol protects cultured neurons against amyloid-β and α-synuclein-induced synapse damage.
The loss of synapses and a corresponding reduction in synaptic proteins are histopathological features of Alzheimer's disease that correlate strongly with dementia. Here we report that stable Aβ oligomers secreted by 7PA2 cells reduced the amount of synaptophysin, a protein used as an indicator of synapse density, in cultured cortical and hippocampal neurons. Pre-treatment with physiologically relevant concentrations of ethanol (0.02-0.08%) protected neurons against Aβ-induced synapse damage. Ethanol also protected neurons against synapse damage induced by α-synuclein (αSN), pre-synaptic aggregates of which are characteristic of Parkinson's disease and dementia with Lewy bodies. Exposure of neurons to ethanol did not affect the accumulation of Aβ at synapses, rather it reduced the Aβ and αSN-induced activation of cytoplasmic phospholipase A(2) (cPLA(2)) within synapses. Ethanol did not affect synapse damage caused by platelet-activating factor or prostaglandin E(2), bioactive lipids that are formed following the activation of cPLA(2). These results may help explain epidemiological reports that moderate alcohol consumption protects against the development of dementia in Alzheimer's and Parkinson's diseases.


Robotic Surgery for Male Infertility.
The robotic platform offers theoretical and practical advantages to microsurgical male infertility surgery. These include reduction or elimination of tremor, 3-dimensional visualization, and decreased need for skilled surgical assistance. This article reviews the application of robotic surgery to each of the 4 primary male infertility procedures: vasectomy reversal, varicocelectomy, testicular sperm extraction, and spermatic cord denervation. Historical perspective is presented alongside the available outcomes data, which are limited in most cases. Before the robotic approach can be widely adopted, further clinical trials are needed to compare outcomes and costs with those of other validated surgical techniques.


Burden of serious fungal infections in Ukraine.
Ukraine has high rates of TB, AIDS and cancer. We estimated the burden of fungal disease from epidemiology papers and specific populations at risk and fungal infection frequencies. HIV/AIDS cases and deaths (2012) and tuberculosis statistics were obtained from the State Service of Ukraine, while chronic obstructive pulmonary disease (COPD) cases were from M. Miravitlles et al., Thorax 64, 863-868 (2009). Annual estimates are 893,579 Ukrainian women get recurrent vaginal thrush (≥4× per year), 50,847 cases of oral candidiasis and 13,727 cases of oesophageal candidiasis in HIV, and 101 (1%) of 10,085 new AIDS cases develop cryptococcal meningitis, 6152 cases of Pneumocystis pneumonia (13.5 cases per 100,000). Of the 29,265 cases of active respiratory TB in 2012, it is estimated that 2881 new cases of chronic pulmonary aspergillosis (CPA) occurred and that the 5-year period prevalence is 7724 cases with a total CPA burden of 10,054 cases. Assuming adult asthma prevalence is ~2.9%, 28,447 patients with allergic bronchopulmonary aspergillosis (ABPA) are likely and 37,491 with severe asthma with fungal sensitisation. We estimate 2278 cases and 376 postsurgical intra-abdominal Candida infections. Invasive aspergillosis in immunocompromised patients is estimated at 303 patients annually; 930 cases in COPD patients. Ninety cases of mucormycosis (2 per 1,000,000) are estimated. In total, ~1,000,000 (2.2%) people in Ukraine develop serious fungal infections annually.


Current therapy of infants with congenital diaphragmatic hernia.
Congenital diaphragmatic hernia (CDH) is a life-threatening anomaly with a significant mortality rate. Despite widespread prenatal diagnosis, few parameters have been well defined to aid in prediction of outcome of these infants. Antenatal maternal steroid administration and foetal surgery are not proven interventions. Postnatal treatment has changed over the last 10 years, with avoidance of hyperventilation and ventilator-induced lung injury resulting in improved survival. Therapies such as inhaled nitric oxide, exogenous surfactant administration and extracorporeal membrane oxygenation (ECMO) have undergone limited study, but show no clear benefit in this population. With improved outcome, principally due to avoidance of barotrauma, greater opportunity exists for long-term evaluation of survivors. To date, continuing problems with pulmonary function, nutrition and growth, effects of right ventricular hypertension and developmental issues have been identified. Through co-ordinated, multidisciplinary evaluation of CDH survivors, improved long-term outcome for these challenging patients can be attained.


Surgical repair of rhegmatogenous retinal detachment in immunosuppressed patients with cytomegalovirus retinitis.
The authors performed retinal reattachment surgery in 29 eyes of 24 patients with acquired immune deficiency syndrome virus with retinal detachment associated with cytomegalovirus (CMV) retinitis and documented the course of eight additional untreated eyes. Retinal detachment repair using vitrectomy, posterior hyaloid removal, and intraocular tamponade with silicone oil or SF-6 gas resulted in a total retinal reattachment rate of 76% and a macular attachment rate of 90% in one operation. The mean postoperative visual acuity (best corrected) was 20/60, but, in some patients, the visual acuity decreased because of progressive retinitis. Prophylactic laser photocoagulation of fellow eyes to surround CMV lesions did not appear to prevent retinal detachment. The mean postoperative survival was 37 weeks (range, 8 to 127 weeks). The surgical techniques used and pathophysiology of these retinal detachments are discussed.


SOCS1 methylation level is associated with prognosis in patients with acute-on-chronic hepatitis B liver failure.
Glucocorticoids could greatly improve the prognosis of patients with acute-on-chronic hepatitis B liver failure (ACHBLF). Suppressor of cytokine signaling (SOCS) 1 methylation has been shown to be associated with mortality in ACHBLF. Eighty patients with ACHBLF were divided into group glucocorticoid (GC) and group conservative medical (CM). Sixty patients with chronic hepatitis B (CHB), and Thirty healthy controls (HCs) served as control group. SOCS1 methylation levels in peripheral mononuclear cells (PBMCs) was detected by MethyLight. SOCS1 methylation levels were significantly higher in patients with ACHBLF than those with CHB and HCs (P < 0.01, respectively). Nonsurvivors showed significantly higher SOCS1 methylation levels (P < 0.05) than survivors in both GC and CM groups in ACHBLF patients. Furthermore, the survival rates of the SOCS1 methylation-negative group were significantly higher than that of the methylation-positive group at 1 month (P = 0.014) and 3 months (P = 0.003) follow-up. Meanwhile, GC group and CM group had significantly lower mortality at 3 months, which may be related to application of glucocorticoid. In the SOCS1 methylation-positive group, the 1-month survival rate was significantly improved, which may be related to GC treatment (P = 0.020). However, no significant difference could be observed between the GC group and CM group in the methylation-negative group (P = 0.190). GC treatment could decrease the mortality of ACHBLF and SOCS1 methylation levels might serve as prognostic marker for favorable response to glucocorticoid treatment.


A simple and rapid determination of Al(III) in natural water samples using dispersive liquid-liquid microextraction after complexation with a novel antipyrine-based Schiff base reagent.
The purpose of this study is the development of a novel strategy for the determination of Al3+ ions using the combination of dispersive liquid-liquid microextraction (DLLME) and UV-Vis spectrophotometry. The method is grounded in the complexation between a novel antipyrine-based Schiff base reagent (EHMP) and Al3+ ions. Aluminum concentrations were detected using UV-Vis spectrophotometry at 260 nm and this technique was optimized using the absorbance value of EHMP-Al complex. pH, mixing period, type and volume of organic solvent, etc. were optimized stepwise in order to find out optimum experimental conditions. The limit of detection and the limit of quantification values for the improved analytical method were to be estimated 0.31 and 1.03 μmol.L-1, respectively. The new strategy was successfully performed to define Al3+ ions in natural water samples with RSD values (84.01-107.71%) and recovery values (0.01-0.09%).


Mapping LGBTQ+ Youth Resource Density Across Four High HIV Prevalence Corridors in the US.
Studies using geospatial data to understand LGBTQ+-friendly sexual health and wellness resource availability have often focused on services catered to adults. While HIV rates have increased in adolescents in recent years, few studies have explored disparities in resource access for adolescent gay and bisexual men (AGBMSM). We used geospatial data of resources (collected and verified 2017-2018) from the iReach app to understand disparities in resource access for AGBMSM within and between 4 high HIV prevalence corridors in the US. AGBMSM in non-metro areas had access to fewer resources and some rural counties had no LGBTQ+ -friendly resources. Corridors comprising states with legacies of punitive laws targeting sexual and gender minorities demonstrate stark geographic disparities across the US. Policy-makers must understand the granularity of disparities within regions. Online resources may be able to surmount LGBTQ+ resource deserts. However, physical access to LGBTQ+ -friendly services must be improved as a fundamental strategy for reducing HIV among AGBMSM. The online version contains supplementary material available at 10.1007/s13178-021-00660-0.


Calcite growth under controlled diffusion.
The growth of calcite was studied in a gelatin-gel medium under variable environmental conditions by 2 different methods. The results suggest that the organic matrix, the temperature, the diffusion fluctuation depending on ionic concentrations, and the presence of additives exert a fine control on the evolution of single crystals, polycrystalline aggregates, and highly structured concretions of calcite.


Optimal growth temperature of prokaryotes correlates with class II amino acid composition.
Partitioning of aminoacyl-tRNA synthetases and their associated amino acids into two classes allows us to distinguish between thermophilic and mesophilic species based only on amino acids composition. The CLASSDB program has been developed for amino acid content analysis in organisms treated individually or pooled together to form a pattern of characteristic properties. A strong correlation has been observed between optimal growth temperature (OGT) of organisms and class II amino acids content. Amino acid composition in organisms closely related phylogenetically but dissimilar in their OGT testifies that thermo-adaptation happens rather rapidly on the time scale of evolution.


Synthesis and Biological Evaluation of Cyclobutane-Based β3 Integrin Antagonists: A Novel Approach to Targeting Integrins for Cancer Therapy.
The Arg-Gly-Asp (RGD)-binding family of integrin receptors, and notably the β3 subfamily, are key to multiple physiological processes involved in tissue development, cancer proliferation, and metastatic dissemination. While there is compelling preclinical evidence that both αvβ3 and αIIbβ3 are important anticancer targets, most integrin antagonists developed to target the β3 integrins are highly selective for αvβ3 or αIIbβ3. We report the design, synthesis, and biological evaluation of a new structural class of ligand-mimetic β3 integrin antagonist. These new antagonists combine a high activity against αvβ3 with a moderate affinity for αIIbβ3, providing the first evidence for a new approach to integrin targeting in cancer.


Proposing Problem-Based Learning for teaching future forensic speech scientists.
In the last 10-15 years, Masters programmes and undergraduate modules have emerged in the UK that teach forensic speech science. Forensic speech science is the forensic subdiscipline concerned with analysing speech recordings, such as telephone calls of unknown speakers, when they arise as evidence. In order to answer questions surrounding the identity of the speakers in these recordings, forensic speech analysts draw on their expertise in phonetics and acoustics. Even though existing UK forensic speech science programmes do not claim to train students to a level where they are in a position to carry out real-life forensic casework, a proportion of the graduates from these programmes do go on to fill discipline-specific roles in security organisations or for private providers of forensic speech analysis. It is therefore surely in the community's interests to review educational approaches to capitalise on the current training opportunities. This paper specifically proposes to explore the potential of a Problem-Based Learning (PBL) approach to forensic speech science teaching. PBL is a student-centred learning approach that heavily relies on the students' independence in the solving of ill-structured problems. PBL has shown to be beneficial to programmes that directly lead on to discipline-specific professional roles, and has even become the standardised teaching approach in some of those areas (medicine being the flagship example). Given its reported success in other disciplines, the question arises as to whether PBL could bring similar benefits to prospective forensic speech practitioners and to forensic speech science as a whole.


Urolithiasis in patients with inflammatory bowel disease: A systematic review and meta-analysis of 13,339,065 individuals.
This study aimed to summarize the current literature regarding the prevalence of renal stones in patients with inflammatory bowel disease (IBD). Moreover, we aimed to evaluate the risk factors of urolithiasis in patients with IBD and the difference between patients with IBD and healthy controls in terms of urinary profile. On February 23, 2022, a computerized search was conducted on PubMed, OVID via MEDLINE, Web of Science, and Scopus using relevant keywords. Three independent reviewers performed 2-stage screening and data extraction. The National Institutes of Health tools were employed for quality assessment. Review Manager 5.4 software was used to calculate the mean difference (MD) between IBD patients and non-IBD in terms of urine profile using the Inverse-variance model and to estimate the odds ratio of reported risk factors for renal stones with the Generic Inverse-Variance model. Thirty-two articles (n = 13,339,065 patients) were included. The overall prevalence of renal stones in patients with IBD was 6.3%, 95% Confidence interval (4.8%-8.3%). The prevalence of urolithiasis was more common in Chron's disease vs Ulcerative colitis (7.9% vs 5.6%) and in old studies (1964-2009) than in more recent studies (2010-2022) (7.3% vs 5.2%), respectively. Compared to non-IBD patients, patients with IBD were associated with significantly lower urine volume (MD = -518.84 mL/day, P < .00001), calcium 24-hour urine (MD = -28.46 mg/day, P < .0001), citrate 24-hour urine (MD = -144.35 mg/day, P < .00001), sodium 24-hour urine (MD = -23.72 mg/day, P = .04), and magnesium 24-hour urine (MD = -33.25 mg/day, P < .00001). The overall prevalence of renal stones in patients with IBD was comparable to the general population. Patients with Chron's disease were associated with a higher prevalence of urolithiasis compared to Ulcerative colitis. Drugs that induce renal calculi should be stopped in high-risk patients.


Novel players in inflammatory bowel disease pathogenesis.
Technological and conceptual advances in inflammatory bowel disease research have uncovered new mechanisms that contribute to the pathogenesis of these disorders. It is becoming increasingly clear that the microbiota of the gut and the response of intestinal cells to that microbiota can initiate or contribute to intestinal inflammation. Evidence from genetic studies have identified IBD-associated genes implicated in autophagy and innate sensing of microbes. These genes also play key roles in the homeostasis of a cell type that stands at the interface of host-microbial interaction - the Paneth cell. Here we discuss recent findings that underscore the importance of the microbiome, Paneth cells and autophagy in inflammatory bowel disease.


Occurrence of Stiretrus decastigmus (Herrich-Schaeffer) (Hemiptera: Pentatomidae) preying on Microtheca semilaevis Stal (Coleoptera: Chrysomelidae).
Microtheca semilaevis Stal is a phythophagous insect associated to Brassicaceae, and frequently occurs with other species of beetles, such as Microtheca ochroloma Stal. Despite its importance to organic farmers, there is no information in the Brazilian literature about its natural enemies. Stiretrus decastigmus (Herrich-Schaeffer) was first found and here reported preying an adult of M. semilaevis in Chinese cabbage in Santa Maria, RS, Brazil (29°43'28″S, 53°43'19″W).


Induction of transforming growth factor alpha in irradiated mouse jejunum.
To determine the involvement of the mitogenic growth factors transforming growth factor alpha (TGF alpha), epidermal growth factor (EGF), and the EGF receptor (EGF-R) in the proliferative response after irradiation of the mouse jejunum. C3Hf/Kam mice were whole-body irradiated with 5 and 11 Gy 250 kV X rays. Mice were killed 1-10 days after irradiation, and immunohistochemistry, in situ hybridization (ISH), and RNase protection assays were performed. Damage to the jejunal crypts caused by irradiation resulted in a strong proliferative response 1-5 days after 5 Gy and 3-6 days after 11 Gy. Expression of TGF alpha, EGF, and EGF-R increased at 1-2 days and decreased at 4-8 days after 5- or 11-Gy irradiation. Also, TGF alpha mRNA increased during the early phase of the proliferative response (1-2 days after 5 or 11 Gy) followed by a decrease at 4 days after 5 Gy and 8 days after 11 Gy. These data indicate that, at the beginning of the proliferative response after irradiation, the transcription of TGF alpha mRNA is increased, and that it is inhibited just before compensatory proliferation decreases. Thus, active regulation of TGF alpha expression takes place at least at the transcriptional level, resulting in upregulation of TGF alpha production and increased TGF alpha levels in the crypts during the proliferative response.


Sonographic diagnosis of Fournier's gangrene: a rare surgical emergency.
Early diagnosis of life-threatening Fournier's gangrene, a rare surgical emergency, is essential. Detection of gas within the swollen scrotal skin by ultrasonography (US) is of great help in patients with equivocal physical examination findings.


Insights into the respiratory chain and oxidative stress.
Reactive oxygen species (ROS) are highly reactive reduced oxygen molecules that result from aerobic metabolism. The common forms are the superoxide anion (O2∙-) and hydrogen peroxide (H2O2) and their derived forms, hydroxyl radical (HO∙) and hydroperoxyl radical (HOO∙). Their production sites in mitochondria are reviewed. Even though being highly toxic products, ROS seem important in transducing information from dysfunctional mitochondria. Evidences of signal transduction mediated by ROS in mitochondrial deficiency contexts are then presented in different organisms such as yeast, mammals or photosynthetic organisms.


Supramolecular structure, phase behavior and thermo-rheological properties of a poly (L-lactide-co-ε-caprolactone) statistical copolymer.
PLAcoCL samples, both unaged, termed PLAcoCLu, and aged over time, PLAcoCLa, were prepared and analyzed to study the phase structure, morphology, and their evolution under non-quiescent conditions. X- ray diffraction, Differential Scanning Calorimetry and Atomic Force Microscopy were complemented with thermo-rheological measurements to reveal that PLAcoCL evolves over time from a single amorphous metastable state to a 3 phase system, made up of two compositionally different amorphous phases and a crystalline phase. The supramolecular arrangements developed during aging lead to a rheological complex behavior in the PLAcoCLa copolymer: Around Tt=131 °C thermo-rheological complexity and a peculiar chain mobility reduction were observed, but at T>Tt the thermo-rheological response of a homogeneous system was recorded. In comparison with the latter, the PLLA/PCL 70:30 physical blend counterpart showed double amorphous phase behavior at all temperatures, supporting the hypothesis that phase separation in the PLAcoCLa copolymer is caused by the crystallization of polylactide segment blocks during aging.


Production of glutinous rice flour from broken rice via ultrasonic assisted extraction of amylose.
In this study, a modified aqueous leaching method by complex formation of amylose with glycerol was employed for reducing the amylose content of starch in broken white rice to less than 2%, so that the resulting starch can be classified to that of glutinous rice flour. By employing ultrasonication in alkaline condition, extraction of amylose could be performed by washing at lower temperature in shorter time compared to the existing aqueous leaching method. The effects of glycerol concentration, alkali concentration, ultrasonication and treatment time on the amylose content of the treated starch were systematically investigated. Under optimum condition, amylose content of broken white rice starch can be reduced from 27.27% to 1.43% with a yield of 80.42%. The changes in the physicochemical properties of the rice flour before and after treatment were studied.


Early experience with intraluminal reinforcement of stapled gastrojejunostomy during laparoscopic Roux-en-Y gastric bypass.
The use of extraluminal staple-line buttressing material during laparoscopic Roux-en-y gastric bypass has shown the potential to reduce staple-line leak and bleeding. We herein present our early experience with intraluminal reinforcement of linear-cutting stapled gastrojejunal anastomosis with the use of bioabsorbable glycolide copolymer staple-line reinforcement. Laparoscopic Roux-en-Y gastric bypass was performed in 80 consecutive non-randomized morbidly obese patients. Gastrojejunal anastomosis was performed using a linear-cutting stapler without staple-line reinforcement in 40 patients (group A), while in the other 40 patients (group B), gastrojejunostomy was performed using a linear cutting stapler with intraluminal reinforcement material (bioabsorbable glycolide copolymer). Demographic data were collected. The rate of gastrojejunal anastomotic leak, bleeding, and stricture was determined. There was a statistically significant reduction in bleeding complications between the two groups (15% bleeding in group A vs. no bleeding in group B, P value=0.0255). Stricture rate was higher in-group A (10% group A vs. 2.5% in group B); however, the difference was not statistically significant (P value=0.2007). None of our patients developed a gastrojejunal leak. Intraluminal reinforcement of gastrojejunal anastomosis during laparoscopic gastric bypass is safe and feasible. The use of intraluminal bioabsorbable glycolide copolymer staple-line reinforcement significantly reduces the incidence of gastrojejunal bleeding.


Laparoscopic treatment of endometriosis in teenagers.
To determine the frequency and severity of endometriosis in adolescent and teenager girls with chronic pelvic pain (CPP) who fail to respond to medical treatment and to evaluate the outcome of radical laparoscopic surgery for severe endometriosis. Retrospective review of case records of all girls under the age of 21 years who underwent diagnostic and/or operative laparoscopy for CPP unresponsive to medical treatment between January 2001 and December 2003. The operative findings and the response to surgery were retrospectively reviewed. Thirty-one girls were referred. No pelvic abnormalities were detected in 11 patients (35.5%). Endometriosis was detected in 11 (35.5%). Six had severe endometriosis. Other diagnoses included: non-functional non-endometriotic ovarian cyst (4 patients), functional ovarian cyst (1 patient), hydrosalpinx (bilateral, 1 patient; unilateral, 1 patient) and obstructed uterine horn (2 patients). Of those with severe disease all six were treated laparoscopically without complications. Five were rendered pain free and one had an improvement in symptoms. Endometriosis can occur in adolescent and teenager girls. Laparoscopy should be carried out in all adolescents and teenagers with CPP unresponsive to medical treatment. This the first study reporting the outcome of radical excision treatment for severe endometriosis in this age group and early results are encouraging.


Hepatitis C virus core proteins derived from different quasispecies of genotype 1b inhibit the growth of Chang liver cells.
To investigate the influence of different quasispecies of hepatitis C virus (HCV) genotype 1b core protein on growth of Chang liver cells. Three eukaryotic expression plasmids (pEGFP-N1/core) that contained different quasispecies truncated core proteins of HCV genotype 1b were constructed. These were derived from tumor (T) and non-tumor (NT) tissues of a patient infected with HCV and C191 (HCV-J6). The core protein expression plasmids were transiently transfected into Chang liver cells. At different times, the cell cycle and apoptosis was assayed by flow cytometry, and cell proliferation was assayed by methyl thiazolyl tetrazolium (MTT) assay. The proportion of S-phase Chang liver cells transfected with pEGFP-N1/core was significantly lower than that of cells transfected with blank plasmid at three different times after transfection (all P < 0.05). The proliferation ratio of cells transfected with pEGFP-N1/core was significantly lower than that of cells transfected with blank plasmid. Among three different quasispecies, T, NT and C191 core expression cells, there was no significant difference in the proportion of S- and G0/G1-phase cells. The percentage of apoptotic cells was highest for T (T > NT > C191), and apoptosis was increased in cells transfected with pEGFP-N1/core as the transfection time increased (72 h > 48 h > 24 h). These results suggest that HCV genotype 1b core protein induces apoptosis, and inhibits cell-cycle progression and proliferation of Chang liver cells. Different quasispecies core proteins of HCV genotype 1b might have some differences in the pathogenesis of HCV persistent infection and hepatocellular carcinoma.