Advanced CT techniques for hepatic microwave ablation zone monitoring and follow-up.
To evaluate utility of advanced CT techniques including HighlY constrained back-projection and dual-energy CT for intra- and post-procedure hepatic microwave ablation zone monitoring. 8 hepatic microwave ablations were performed in 4 adult swine (5 min/65 W). Low-dose routine CECT and dual-energy CT images were obtained every 1 min during ablation. Images were reconstructed ± HYPR. Image quality and dose metrics were collected. 21 MWA were performed in 4 adult swine. Immediate post-procedure CECT was performed in the arterial, portal venous, and delayed phases using both routine and DECT imaging with full-dose weight-based IV contrast dosing. An additional 16 MWA were subsequently performed in 2 adult swine. Immediate post-procedure CT was performed with half-dose IV contrast using routine and DECT. 12 patients (10 M/2F, mean age 62.4 yrs) with 14 hepatic tumors (4 HCC, 10 metastatic lesions) treated with MWA were prospectively imaged with DECT 1 month post-procedure. 120 kV equivalent images were compared to DECT [51 keV, iodine material density]. Image quality and dose metrics were collected. Gas created during MWA led to high CNR in all intraprocedural CT datasets. Optimal CNRs were noted at 4 min with CNR 6.7, 15.5,15.9, and 21.5 on LD-CECT, LD-CECT + HYPR, DECT, and DECT + HYPR, respectively (p < 0.001). Image quality scores at 4 min were 1.8, 2.8, 2.4, and 3, respectively (p < 0.001). Mean radiation dose (CTDIvol) was eightfold higher for the DECT series. For swine, post-procedural DECT images (IMD/51 keV) showed improved CNR compared to routine CT at all time points with full and with reduced dose contrast (CNR 4.6, 3.2, and 1.5, respectively, at half-contrast dose, p < 0.001). For human subjects, the 51 keV and IMD images showed higher CNRs (5.8, 4.8 vs 4.0, p < 0.001) and SNRs (3.7, 5.9 vs 2.8). Ablation zone sharpness was improved with DECT (routine 3.0 ± 0.7, DECT 3.5 ± 0.5). Diagnostic confidence was higher with DECT (routine 2.3 ± 0.9, DECT 2.6 ± 0.8). Mean DLP for DECT was 905.7 ± 606 mGy-cm, CTDIvol 37.5 ± 21.2 mGy, and effective dose 13.6 ± 9.1 mSv, slightly higher than conventional CT series. Advanced CT techniques can improve CT image quality in peri-procedural hepatic microwave ablation zone evaluation.


Electrocaloric effect in ferroelectric nanowires from atomistic simulations.
Electrocaloric effect is presently under active investigation owing to both the recent discoveries of giant electrocaloric effects and its potential for solid state cooling applications. We use first-principles-based direct simulations to predict the electrocaloric temperature change in ferroelectric ultrathin nanowires. Our findings suggest that in nanowires with axial polarization direction the maximum electrocaloric response is reduced when compared to bulk, while the room temperature electrocaloric properties can be enhanced by tuning the ferroelectric transition temperature. The potential of ferroelectric nanowires for electrocaloric cooling applications is discussed.


Soluble ST2 in Ventricular Dysfunction.
Heart failure is a commonly encountered condition associated with increased morbidity, mortality, and healthcare cost. For years, its management has been strongly influenced by the use of B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide biomarkers. In some cases, this approach does not always identify patients with heart failure accurately and may not provide the best prognostic assessment, particularly in the presence of comorbidities. Biomarkers that help refine diagnosis and risk stratification are needed. Soluble ST2, a peptide belonging to the interleukin-1 receptor family, is secreted when cardiomyocytes and cardiac fibroblasts are subjected to mechanical strain. Although preliminary results on this novel biomarker are encouraging, additional and more comprehensive studies are clearly needed to establish its role in the management of patients with heart failure. The purpose of this chapter is to provide an overview of data currently available.


A homologue of the human STRIPAK complex controls sexual development in fungi.
Sexual development in fungi is a complex process involving the generation of new cell types and tissues - an essential step for all eukaryotic life. The characterization of sterile mutants in the ascomycete Sordaria macrospora has led to a number of proteins involved in sexual development, but a link between these proteins is still missing. Using a combined tandem-affinity purification/mass spectrometry approach, we showed in vivo association of developmental protein PRO22 with PRO11, homologue of mammalian striatin, and SmPP2AA, scaffolding subunit of protein phosphatase 2A. Further experiments extended the protein network to the putative kinase activator SmMOB3, known to be involved in sexual development. Extensive yeast two-hybrid studies allowed us to pinpoint functional domains involved in protein-protein interaction. We show for the first time that a number of already known factors together with new components associate in vivo to form a highly conserved multi-subunit complex. Strikingly, a similar complex has been described in humans, but the function of this so-called striatin interacting phosphatase and kinase (STRIPAK) complex is largely unknown. In S. macrospora, truncation of PRO11 and PRO22 leads to distinct defects in sexual development and cell fusion, indicating a role for the fungal STRIPAK complex in both processes.


Spongy Myelinopathy in Newborn Beef Calves Associated with Consumption of Corn Infected with Stenocarpella maydis.
Stillbirth and perinatal mortality with neurological signs and lesions were diagnosed in two calves following ingestion by their dams of corn infected with Stenocarpella maydis during the third trimester of gestation. Grossly, the brain and spinal cord were unremarkable. Microscopically, diffuse severe status spongiosis of the white matter was detected in the cerebral hemispheres, brainstem, spinal cord and cerebellum. To the best of our knowledge this is the first pathological description of congenital disease in calves associated with the consumption of S. maydis-infected corn; the findings resemble those reported for the naturally occurring and experimentally induced disease in lambs.


The bigger the better: determining nephron size in kidney.
The main functions of the kidney are to excrete metabolic waste products and actively reabsorb essential molecules such as amino acids, ions, glucose and water. In humans, a wide range of genetic disorders exist characterized by wasting of metabolically important compounds. At the cellular level, more than 20 highly specialized renal epithelial cell types located in different segments of the nephron contribute to the reabsorption process. In particular, proximal tubular cells play a crucial role and are uniquely adapted to maximize reabsorption efficiency. They accommodate high numbers of transporters and channels by increasing the apical surface area in contact with the primary filtrate by forming a brush border as well as undergoing hypertrophy and hyperplasia. This adaptation is evolutionarily conserved and is detected in the primitive pronephric kidney of fish and amphibians as well as the metanephric kidney of higher vertebrates. Surprisingly, signaling pathways regulating these three processes have remained largely unknown. Here we summarize recent studies that highlight the early phases of kidney development as a critical juncture in establishing proximal tubule size.


Dual-modal imaging-guided theranostic nanocarriers based on 2-methoxyestradiol and indocyanine green.
Drug toxicity and insufficient drug dosing place a limit on the effect of chemotherapy. Optimal efficacy is achieved by exposing tumor cells to the maximum tolerated dose of a chemotherapeutic drug. In this study, we developed a strategy (graphic summary) for enhancing the therapeutic and diagnostic capabilities of known chemotherapeutics. We used a dual-mode near-infrared (NIR) fluorescence/photoacoustic imaging technology to achieve actively guided tumor targeting of the photothermal therapeutic agent indocyanine green (ICG) and the chemotherapeutic drug 2-methoxyestradiol (2-ME), which were loaded into thermosensitive liposomes (TSLs) with surface-grafted tumor-targeting peptide cRGDyk (cRGDyk-2-ME@ICG-TSLs). In vitro studies demonstrated that cRGDyk-2-ME@ICG-TSLs effectively induced drug accumulation and cytotoxicity in NIR laser-irradiated B16-F10 melanoma cells using dual targeting based on the cRGDyk peptide and temperature sensitivity. An in vivo study showed that 24 h after intravenously injecting cRGDyk-2-ME@ICG-TSLs into melanoma tumor-bearing mice, the dual-mode NIR fluorescence/photoacoustic imaging could accurately identify tumors and normal tissues. In addition, the combination of cRGDyk-2-ME@ICG-TSLs and NIR radiation suppressed tumor growth in tumor-bearing nude mice and was associated with a low risk of side effects on normal organs. Our results indicate that TSLs are a suitable drug delivery system for diagnostic and chemotherapeutic agents guided by dual-mode imaging.


Stopped flow kinetic-spectrophotometric determination of Diquat in waters.
Using the measures of initial reaction rate, a kinetic-photometric method is developed that uses the reaction of Diquat with H2O2 in basic medium. The reaction rate is very high and therefore the stopped-flow mixing technique is required in order to make kinetic measurements. The reaction rate is obtained in 20 s after the reactants are mixed and it allows the simple application of the method proposed to the routine analyses. The sensitivity of the method is very high being the detection limit 0.44 microgmL(-1) and the application range between 1 and 16 microgmL(-1). The time of measure per sample is 90s. The proposed kinetic-photometric method has been applied to the direct determination of this compound in river water, in the water of laundry of the olives, and in a commercial product. The results are very acceptable.


Comparison of cardiac pacing modes in patients with chronic obstructive pulmonary disease.
This study compares the relative benefits of dual chamber adaptive rate pacing (DDDR) with ventricular adaptive rate pacing (VVIR) in patients with chronic obstructive pulmonary disease (COPD). Cardiac hemodynamics were evaluated with serial exercise tests. A minimum of 2 h was allowed between studies. Pulmonary gas exchange was measured and cardiac output (CO) was determined at rest and immediately after maximum exercise by Doppler echocardiography. Sixteen patients with DDDR pacemakers were studied. Eight patients had COPD and eight patients had normal lung function (NLF). Baseline lung function was documented with spirometry. The patients with NLF functioned as a control group. Prior to entry into the study, the rate-modulated parameters of the pacemaker were programmed to a clinically determined optimal set of parameters for each individual patient. These were not changed for the duration of the study. Both groups showed a statistically significant improvement in exercise duration, CO at maximum exercise, and cardiac output difference (CODiff) with the dual chamber adaptive rate pacing mode (DDDR). (COdiff is the change in CO from rest to maximum exercise.) Patients with NLF also showed a significant improvement in anaerobic threshold (AT) and VCO2 max with DDDR. Patients with lung disease showed a statistically significant improvement at all levels of exercise in the ventilatory equivalent for oxygen. In this study, those patients with chronic lung disease who required cardiac pacing performed significantly better in the DDDR mode as compared with the VVIR mode. Therefore, the DDDR pacing mode should provide an improved quality of life for the patient with COPD who also requires cardiac pacing.


Inhibition of flower pigmentation by antisense CHS genes: promoter and minimal sequence requirements for the antisense effect.
Introduction of a constitutive antisense full-length chalcone synthase (CHS) cDNA gene in petunia can result in an inhibition of flower pigmentation. We have evaluated some of the factors which may be important for the effectiveness of an antisense CHS gene. Antisense CHS genes encoding half-length or quarter-length RNA complementary to the 3' half of CHS mRNA are able to affect flower pigmentation, while a gene encoding RNA complementary to the 5' half of CHS mRNA did not show phenotypic effects in transgenic petunia plants. We demonstrate that the RNA encoded by the latter gene has a much lower average steady-state level in leaf tissue than the RNAs encoded by the other antisense gene constructs. We have compared the CaMV 35S and endogenous CHS promoter strengths and intrinsic stabilities of sense and antisense CHS RNAs. From the data we conclude that the constitutive antisense CHS genes are not likely to provide an excess of antisense RNA compared to the CHS mRNA derived from the endogenous genes. Effective inhibition of flower pigmentation is also observed when the antisense CHS gene is under control of the homologous CHS promoter. The results indicate that the mechanism of antisense inhibition cannot solely operate via RNA duplex formation between sense and antisense RNA.


Improved cerebrospinal fluid suppression for intracranial vessel wall MRI.
To develop and assess a three-dimensional (3D) high resolution black blood MRI (BBMRI) method for evaluation of intracranial vessels with improved cerebrospinal fluid (CSF) suppression. The anti-driven-equilibrium (ADE) pulse was incorporated into a variable flip-angle TSE-based 3D BBMRI to improve CSF suppression. ADE-BBMRI was optimized in 8 participants and compared with BBMRI, with acquired 0.5 mm isotropic resolution and scan time of 5.4 min at 3 Tesla. Contrast-enhanced ADE-BBMRI protocol was implemented in nine patients with intracranial atherosclerosis. Signal and morphological measurements were compared between ADE-BBMRI and BBMRI, as well as pre- and postcontrast ADE-BBMRI. Reliability was assessed by intraclass correlations (ICC). ADE-BBMRI effectively suppressed the surrounding CSF signal of intracranial vessels, with a 36-44% reduction compared with BBMRI. ADE-BBMRI also reduced the overall wall signal by 8-8.5%, but provided a significant improvement in wall-to-CSF contrast-to-noise ratio over BBMRI (middle cerebral artery, 5.93 ± 0.59 versus 3.95 ± 1.67, P < 0.01; basilar artery, 3.8 ± 1.76 versus 1.34 ± 0.54, P = 0.01, respectively). No differences were noted in morphological measurements between ADE-BBMRI and BBMRI (lumen area, 6.35 ± 2.87 versus 6.32 ± 2.84 mm(2) ; wall area, 1.28 ± 0.52 versus 1.27 ± 0.53 mm(2) ; mean wall thickness, 0.93 ± 0.30 versus 0.93 ± 0.32 mm; maximum wall thickness, 1.27 ± 0.33 versus 1.28 ± 0.36 mm, all P > 0.05). Contrast enhanced ADE-BBMRI improved the plaque delineation by the increased wall signal, wall-to-CSF and wall-to-blood contrast-to-noise ratio. ICC ranged from 0.54 to 0.95. The 3D ADE-BBMRI provides excellent blood and CSF suppression, and accurate measurements of intracranial vessels at 0.5 mm isotropic resolution in 5 min. Its clinical application may provide insight into stroke risk. J. Magn. Reson. Imaging 2016;44:665-672.


A serologically assessed neo-epitope biomarker of cellular fibronectin degradation is related to pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is characterized by excessive extracellular matrix (ECM) remodeling, herein ECM degradation. Fibronectin (FN) is an important component of the ECM that is produced by multiple cell types, including fibroblasts. Extra domain B (EDB) is specific for a cellular FN isoform which is found in the ECM. We sought to develop a non-invasive test to investigate whether matrix metalloproteinase 8 (MMP-8) degradation of EDB in cellular FN results in a specific protein fragment that can be assessed serologically and if levels relate to pulmonary fibrosis. Cellular FN was cleaved in vitro by MMP-8 and a protein fragment was identified by mass spectrometry. A monoclonal antibody (mAb) was generated, targeting a neo-epitope originating from EDB in cellular FN. Utilizing this mAb, a neo-epitope specific enzyme-linked immunosorbent assay (FN-EDB) was developed and technically validated. Serum FN-EDB was assessed in an IPF cohort (n = 98), registered at clinicaltrials.gov (NCT02818712), and in healthy controls (n = 35). The FN-EDB assay had high specificity for the MMP-8 degraded neo-epitope and was technically robust. FN-EDB serum levels were not influenced by age, sex, ethnicity, or BMI. Moreover, FN-EDB serum levels were significantly higher in IPF patients (median 31.38 [IQR 25.79-46.84] ng/mL) as compared to healthy controls (median 28.05 [IQR 21.58-33.88] ng/mL, p = 0.023). We developed the neo-epitope specific FN-EDB assay, a competitive ELISA, as a tool for serological assessment of MMP-8 mediated degradation of EDB in cellular FN. This study indicates that degradation of EDB in cellular FN is elevated in IPF and warrants further investigation.


Radiologic diagnosis and pathology of the spondyloarthropathies.
Five different subtypes of spondyloarthropathy (SpA) are now recognized. Clinical and radiologic involvement of the sacroiliac joint is an outstanding feature of the SpA, especially ankylosing spondylitis (AS). In this partly debilitating form of SpA a unique type of inflammatory axial involvement is observed which is characterized by inflammation and new bone formation at different spinal sites. In longstanding disease sacroiliitis, spondylitis and spondylodiscitis are easily recognized by conventional radiography and even better by computed tomography--especially when bony changes have already taken place. The advantage of dynamic magnetic resonance imaging (MRI) is to visualize morphologic changes and inflammation at the same time. This facilitates detection of sacroiliitis and spondylitis/spondylodiscitis at early time points. Hopefully, this will lead to other forms of therapy to prevent ankylosis of the spine. The origin of the granulation tissue infiltrating cartilage and bone in AS might be the synovium, the subchondrium or the bone marrow itself. T cells and macrophages seem to play an important role in this inflammatory process in which TNF-alpha is present in severe cases. The mechanisms responsible for the increased bone formation observed in the course of AS are unknown.


An increase in sensitivity of rat cingulate cortical neurones to substance P occurs following withdrawal of chronic administration of antidepressant drugs.
The sensitivity of neurones in the cingulate cortex of the rat to iontophoretically applied substance P (SP) was tested one hour after a single dose of various antidepressant drugs and also 1 day following the termination of a chronic dosing schedule (14 once daily injections) of the same agents. One hour after a single injection of desipramine (DMI), chlorimipramine (CMI), trimipramine (TMI) or zimelidine ( ZIM ) (all at 10 mg kg-1 i.p.) there was no change in the mean size of excitatory responses to SP compared to those before the injection. There was a tendency towards a decrease in the TMI group. One day following the last of 14 consecutive daily injections (10 mg kg-1 i.p.) of the above agents there was a significant increase in the size of excitatory responses to SP compared to those in rats receiving daily saline injections. However, 14 days of treatment with DMI did not alter the responses to L-glutamate. Similar chronic dosing schedules with either diazepam (5 mg kg-1) or fluphenazine (5 mg kg-1) did not affect the responses to SP. Thus chronic but not acute administration of antidepressant drugs results in an increase in the sensitivity of neurones, in the cingulate cortex of the rat, to SP.


Incidence and outcomes of long QTc in acute medical admissions.
Prolonged QT interval on electrocardiogram (ECG) increases the risk of ventricular arrhythmia. Patients admitted to acute medical units (AMU) may be at risk of QT prolongation from multiple, recognised risk factors. Few data exist regarding incidence or outcomes of QT prolongation in acute general medical admissions. The aims were to determine the incidence of Bazett's-corrected QT (QTc) prolongation upon admission to AMU; the relationship between QTc and inpatient mortality, length of stay and readmission; proportion with prolonged QTc subsequently administered QT interval-prolonging drugs. Retrospective, observational study of 1000 consecutive patients admitted to an AMU in a large urban hospital. age <18 years, ventricular pacing, poor quality/absent ECG. QTc determined manually from ECG obtained within 4-hours of admission. QTc prolongation considered ≥470 milliseconds (males) and ≥480 milliseconds (females). In both genders, >500 milliseconds was considered severe. Study end-points, (a) incidence of QTc prolongation at admission; (b) inpatient mortality, length of stay and readmission rates; (c) proportion with QTc prolongation subsequently administered QT interval-prolonging drugs. Of 1000 patients, 288 patients were excluded, therefore final sample was n = 712. Patient age (mean ± SD) was 63.1 ± 19.4 years; females 49%. QTc prolongation was present in n = 50 (7%) at admission; 1.7% had QTc interval >500 ms. Of the 50 patients admitted with prolonged QTc, 6 (12%) were subsequently administered QT interval-prolonging drugs. QTc prolongation was not associated with worse inpatient mortality or readmission rate. Length of stay was greater in those with prolonged QTc, 7.2 (IQR 2.4-13.2) days vs 3.3 (IQR 1.3-10.0; P = 0.004), however, in a regression model, presence of QTc did not independently affect length of stay. QTc interval prolongation is frequent among patients admitted to AMU. QT interval-prolonging drugs are commonly prescribed to patients presenting with prolonged QTc but whether this affects clinical outcomes is uncertain.


Up-regulated CCL18, CCL28 and CXCL13 Expression is Associated with the Risk of Gastritis and Peptic Ulcer Disease in Helicobacter Pylori infection.
Helicobacter pylori (H. pylori) infection causes inflammation and increases the risk of developing peptic ulcer disease (PUD); however, the exact molecular mechanisms of PUD development remain unclear. The aim of this study was to investigate the expression of CCL18, CCL28, and CXCL13 in H. pylori-positive subjects in comparison with H. pylori-negative subjects, and to determine its association with different clinical outcomes and virulence factors. In total, 55 H. pylori-positive subjects with gastritis, 47 H. pylori-positive subjects with PUD, and 48 H. pylori-negative subjects were enrolled in this study. CCL18, CCL28, and CXCL13 expression were determined using real time polymerase chain reaction (PCR). The virulence factors of H. pylori such as cytotoxin-associated gene A (cagA), outer inflammatory protein A (oipA), blood group antigen-binding adhesin (babA), and vacuolating cytotoxin A (VacA) genes were evaluated using PCR. CCL18, CCL28, and CXCL13 expression in H. pylori-positive subjects were significantly higher than H. pylori-negative subjects. CCL18 and CXCL13 expression in H. pylori-positive subjects with oipA+ and babA2+were significantly higher than H. pylori-positive subjects with oipA¯ and babA2¯. CCL18 and CXCL13 expression were found to be significantly elevated in H. pylori-positive subjects with gastritis compared with H. pylori-positive subjects with PUD. CCL28 expression was significantly higher in H. pylori-positive subjects with PUD compared with H. pylori-positive subjects with gastritis. The increased of CCL18 and CXCL13 may be involved in the pathogenesis of H. pylori-associated gastritis, while the increased of CCL28 may be involved in the pathogenesis of H. pylori-associated PUD.


Supporting racial, ethnic minority, and disadvantaged undergraduate nursing students with honors projects.
Underrepresented racial and ethnic minority (UREM) and disadvantaged background (DB) students often feel a lack of belonging and community in higher education. Participation in Honors Programs has been shown to build a sense of belonging and community associated with short and long-term benefits for both students and their academic institutions. To describe the program we implemented (the MM program) to increase UREM and DB student representation in a SON Honors Program. A prospective, descriptive study of SON UREM and DB honors students with a May graduation date of 2017-2020. A total of 129 students completed honors with 23 MM UREM and DB students completing honors. Seven received highest honors award distinction that exemplifies exceptional work at a level beyond usually high expectations. A supportive environment for UREM and DB students with resources are essential for students to consider and also complete an honors project.


Detection and genetic characterization of a putative novel Borrelia genospecies in Ixodes apronophorus / Ixodes persulcatus / Ixodes trianguliceps sympatric areas in Western Siberia.
Four genospecies from the Borrelia burgdorferi sensu lato complex were detected in Ixodes persulcatus and Ixodes pavlovskyi ticks from Siberia and genetically characterized. The presence of Borrelia spp. in Ixodes apronophorus and Ixodes trianguliceps ticks found in Asia has never been studied. In this study, genetic diversity of B. burgdorferi s.l. was investigated in three I. persulcatus / I. trianguliceps / I. apronophorus sympatric habitats in Western Siberia. Three groups of samples were examined: (i) ticks that were taken from rodents and molted in a laboratory; (ii) non-molted ticks collected from rodents; (iii) specimens from small mammals. Expectedly, Borrelia afzelii and Borrelia bavariensis were detected in I. persulcatus and in small mammals from the studied locations. Borrelia bavariensis was first found in molted I. apronophorus and I. trianguliceps. Identical genovariants of B. bavariensis were found in I. apronophorus, I. trianguliceps, and I. persulcatus. In addition, a new Borrelia genovariant was discovered in non-molted and molted I. apronophorus and non-molted I. persulcatus and I. trianguliceps, as well as in small mammals. This new genovariant was genetically characterized using MLST and single locus sequence analysis, which indicated that the new Borrelia genovariant significantly differs from all known Borrelia species. We propose the name "Candidatus Borrelia sibirica" for this putative new species.


Insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 in women with premenstrual syndrome.
To determine whether women with premenstrual syndrome (PMS) have aberrations of the GH axis as has been demonstrated in individuals with depression. Prospective trial. Department of Obstetrics and Gynecology, University of California, Los Angeles. After prospective screening, 32 healthy women with PMS and 32 asymptomatic controls completed the study. Subjects completed a daily PMS symptom diary and a Beck Depression Inventory. They underwent phlebotomy 5 days and 12 days after the LH midcycle surge, which was identified with the use of a urinary LH detection kit. Serum levels of insulin-like growth factor-1 (IGF-1), insulin-like growth factor-binding protein-3 (IGFBP-3), E2, and progesterone. Levels of IGF-1, IGFBP-3, E2, and progesterone did not differ between women with prospectively documented PMS and control subjects. Premenstrual syndrome and affective disorder share common symptoms and possibly a common cause. Biochemical markers such as alterations in the somatotropic system often are associated with major depression. Levels of IGF-1 and IGFBP-3 did not differ between women with PMS and control subjects, supporting the concept that PMS and endogenous depression are biologically distinct entities.


Adverse Effect of Mobile Phone on Hearing in Healthy Individuals: A Clinical Study.
The mobile phone is a ubiquitous piece in this modern world. An estimated 85% of Americans, 80% of the British, and perhaps 75% of Indians use it, as of today. Mobile phones communicate by transmitting radio waves through a network of fixed antennas called base stations. Radio frequency waves are electromagnetic fields, and unlike ionizing radiation such as X-rays or gamma rays, can neither break chemical bonds nor cause ionization in the human body. 1000 participants from outpatient department of a tertiary care center over a period of one and a half years, were included in the study and were divided equally into case (> 1 year use) and control (< 1 year use) groups. Out of 500 cases, maximum 233(46.6%) subjects were using mobile since last 4-6 year and 134(26.8%) were using mobile since last 7-9 year and maximum 344(68.8%) subjects were using mobile 1-3 h/day and 145(29.0%) were using mobile 4-6 h/day.


Characterization of Ground State Electron Configurations of High-Spin Quintet Ferrous Heme Iron in Deoxy Myoglobin Reconstituted with Trifluoromethyl Group-Substituted Heme Cofactors.
We introduced trifluoromethyl (CF3) group(s) as heme side chain(s) of sperm whale myoglobin (Mb) in order to characterize the electronic nature of heme Fe(II) in deoxy Mb using 19F NMR spectroscopy. On the basis of the anti-Curie behavior of CF3 signals, we found that the deoxy Mb is in thermal equilibrium between the 5B2, (dxy)2(dxz)(dyz)(dz2)(dx2-y2), and 5E, (dxy)(dxz)2(dyz)(dz2)(dx2-y2), states of the heme Fe(II), i.e., 5B2 ⇆ 5E. Analysis of the curvature in Curie plots has yielded for the first time ΔH and ΔS values of ∼-20 kJ mol-1 and ∼-60 J K-1 mol-1, respectively, for the thermal equilibrium. Thus, the 5E state is slightly dominant over the 5B2 one at 25 °C. These findings provide not only valuable information about the ground state electronic structure of the high-spin heme Fe(II) in deoxy native Mb but also an important clue for elucidating the mechanism responsible for acceleration of the spin-forbidden oxygenation of the protein.


Self-replenishment cycles generate a threshold response.
Many metabolic cycles, including the tricarboxylic acid cycle, glyoxylate cycle, Calvin cycle, urea cycle, coenzyme recycling, and substrate cycles, are well known to catabolize and anabolize different metabolites for efficient energy and mass conversion. In terms of stoichiometric structure, this study explicitly identifies two types of metabolic cycles. One is the well-known, elementary cycle that converts multiple substrates into different products and recycles one of the products as a substrate, where the recycled substrate is supplied from the outside to run the cycle. The other is the self-replenishment cycle that merges multiple substrates into two or multiple identical products and reuses one of the products as a substrate. The substrates are autonomously supplied within the cycle. This study first defines the self-replenishment cycles that many scientists have overlooked despite its functional importance. Theoretical analysis has revealed the design principle of the self-replenishment cycle that presents a threshold response without any bistability nor cooperativity. To verify the principle, three detailed kinetic models of self-replenishment cycles embedded in an E. coli metabolic system were simulated. They presented the threshold response or digital switch-like function that steeply shift metabolic status.


How we do it: adjunctive intravenous midazolam: diagnosis and treatment of therapy-resistant muscle tension dysphonia.
Dysphonic patients with muscle tension are common at voice clinics. The majority respond to intensive vocal therapy. A small number of cases remain resistant to intensive vocal therapy. We have used intravenous midazolam to enhance therapy-resistant dysphonic patients' self-monitoring, their self-awareness and to change fixed patterns. Six of seven patients were discharged with restoration of normal voice 1 month after treatment.


Depressive symptoms and self-reported occupational injury in small and medium-sized companies.
This survey was designed to determine whether depressive symptoms had an effect on the risk of self-reported occupational injury in South Korea. We conducted a prospective follow-up survey of workers at 44 small- to medium-sized companies classified into manufacturing or service businesses; 1,350 questionnaires were used in the final analysis. The first survey requested information regarding personal characteristics, work characteristics, and depressive symptoms (CES-D); the second survey queried participants in the first survey about self-reported occupational injuries (including minor scratches or cuts) experienced in the previous 4 months. Risk ratios (RRs) were calculated through Poisson regression analysis. The number of occupational injuries during the previous 4 months served as the dependent variable, and depressive symptoms served as the independent variable. After adjustment for demographic factors, the RRs were 1.75 (95% CI: 1.41-2.18) and 2.68 (95% CI: 1.98-3.64) in male and female, respectively. Additional adjustment for work-related variables did not alter the RR considerably in females (2.65; 95% CI: 1.95-3.59). Among the male workers, however, the RR was not significant (1.21; 95% CI: 0.95-1.55). On the other hand, when the analysis was limited to blue-collar workers, after adjustment for demographic and work-related factors, the RRs remained significant in both genders (male: 1.34; 95% CI: 1.03-1.74; female: 2.04; 95% CI: 1.41-2.95). We found that the risk of self-reported occupational injury experience was higher in workers who reported depressive symptoms. Additional study using objective data is required to confirm our results.


Choosing between two semi-finalists: On academic performance gap, sex category, and decision question.
We use an application-files experimental design to investigate a new topic in the assessment of candidates for junior-engineering jobs. Our focus is on two semi-finalists, a man and a woman, who show clearly different but still good levels of academic record. We keep the gap between those levels constant, but vary the sex category of the better performer. We also include control conditions in which the two have similar records. Each assessor's task was to choose either one applicant or neither, and to rate both in competence and suitability. The control-group competence ratings indicate no gender bias by either men or women; the experimental-conditions competence data are consistent with the candidates' records as predicted, but also show women minimizing the record of the better-performing male candidate. Choice and suitability, on the other hand, reveal a preference for the female applicant across respondents and conditions, as anticipated given the more open nature of those two questions, while still reflecting the academic records. Findings and their interpretation are presented in detail.


From chemical structure to environmental biosynthetic pathways: navigating marine invertebrate-bacteria associations.
Many natural products from marine invertebrates are promising drugs or drug leads but the problem of supply has delayed the development of these agents. Bacteria living in complex associations with animals are often proposed to be the real producers of "invertebrate" metabolites. Recent advances in biosynthetic pathway discovery from these symbiotic bacteria herald a new era in which biosynthetic genes will be cloned rapidly to provide promising molecules from marine invertebrates.


Roles of dorsal column pathway and transient receptor potential vanilloid type 1 in augmentation of cerebral blood flow by upper cervical spinal cord stimulation in rats.
Clinical and basic studies have indicated that upper cervical spinal cord stimulation (cSCS) significantly increases cerebral blood flow (CBF), but the mechanisms are incompletely understood. This investigation was conducted to differentiate between stimulation of dorsal column fibers and upper cervical spinal cord cell bodies in cSCS-induced increases in CBF and decreases in cerebrovascular resistance (CVR). cSCS (50 Hz, 0.2 ms, 1 min) was applied on the left C1-C2 dorsal column of pentobarbital anesthetized, ventilated and paralyzed male rats. Laser Doppler flowmetry probes were placed bilaterally over the parietal cortex, and arterial pressure was monitored. cSCS at 30%, 60%, and 90% of motor threshold (MT) produced vasodilation bilaterally in cerebral cortices. Subsequently, cSCS was applied at 90% MT, and ipsilateral responses were recorded. Ibotenic acid (0.3 mg/ml, 0.1 ml) placed on dorsal surface of C1-C2 (n=7) to suppress cell body activity, did not affect cSCS-induced %DeltaCBF (42.5+/-8.1% vs. 36.8+/-7.1%, P>0.05) and %DeltaCVR (-19.4+/-4.2% vs. -15.2+/-5.6%, P>0.05). However, bilateral transection of the dorsal column at rostral C1 (n=8) abolished cSCS-induced changes in CBF and CVR. Also, rostral C1 transection (n=7) abolished cSCS-induced changes in CBF and CVR. Resinferatoxin (RTX), an ultrapotent transient receptor potential vanilloid type 1 (TRPV1) agonist, was used to inactivate TRPV1 containing nerve fibers/cell bodies. RTX (2 microg/ml, 0.1 ml) placed on the C1-C2 spinal cord (n=7) did not affect cSCS-induced %DeltaCBF (60.2+/-8.1% vs. 46.3+/-7.7%, P>0.05) and %DeltaCVR (-25.5+/-3.5% vs. -21.4+/-8.9%, P>0.05). However, i.v. RTX (2 microg/kg, n=9) decreased cSCS-induced %DeltaCBF from 65.0+/-9.5% to 27.4+/-7.2% (P<0.05) and %DeltaCVR from -28.0+/-7.6% to -14.8+/-4.2% (P<0.05). These results indicated that cSCS-increases in CBF and decreases in CVR occurred via rostral spinal dorsal column fibers and did not depend upon C1-C2 cell bodies. Also, our results suggested that cerebral but not spinal TRPV1 was involved in cSCS-induced cerebral vasodilation.


Effect of chronic hypoxia on contents of urotensin II and its functional receptors in rat myocardium.
The cyclic peptide urotensin II (UII) has recently been cloned in mammals and reported to constrict rat pulmonary arteries potently. An enhanced maximal response was shown in rats exposed to chronic hypoxia. The aim of this study was to investigate changes in plasma and myocardial UII levels and its receptor sites in crude sarcolemma of ventricles from chronic hypoxic rats. We observed that rats exposed to chronic hypoxia for 4 weeks developed pulmonary hypertension and right ventricular hypertrophy. Compared with controls, the UII content in hypoxic rats was increased by 97.5% (45.24 +/- 7.1 vs. 22.9 +/- 3.24pg/mg protein, P < 0.01) in the right ventricle and 33.2% (24.89 +/- 0.99 vs. 18.68 +/- 2.04pg/mg protein, P < 0.01) in the left ventricle, respectively. However, there was no significant difference in plasma (27.44 +/- 3.11 vs. 27.82 +/- 5.57pg/ml, P > 0.05) and lung tissue levels (34.03 +/- 4.63 vs. 33.74 +/- 4.06 pg/ mg protein, P > 0.05) between the control and hypoxic groups. The time course of the binding of [125I]UII to crude ventricular sarcolemma was specific and time dependent. Scatchard plot analysis of the data demonstrated that the maximal number of specific binding sites (Bmax) in both the right and left ventricles was upregulated in the hypoxic group. Moreover, Bmax in the right ventricular specimens was upregulated to a greater extent than in the left ventricle (increased by 114% and 25% in the right and left ventricles, respectively, compared with control group, P < 0.01). In contrast, the UII binding affinity in right and left ventricular membranes from hypoxic rats was decreased (the dissociation constant Kd) increased by 20% and 33%, respectively compared with controls, P < 0.01). These results indicate that UII may act as an autocrine and/or paracrine hormone rather than as a circulating hormone, playing important roles in the development of ventricular hypertrophy induced by chronic hypoxia, and that the pathophysiological significance of UII in pulmonary and cardiovascular alteration induced by chronic hypoxia deserves further investigation.


Morphometric analysis of patient-specific 3D-printed acetabular cups: a comparative study of commercially available implants from 6 manufacturers.
3D printed patient-specific titanium acetabular cups are used to treat patients with massive acetabular defects. These have highly porous surfaces, with the design intent of enhancing bony fixation. Our aim was to characterise these porous structures in commercially available designs. We obtained 12 final-production, patient-specific 3D printed acetabular cups that had been produced by 6 manufacturers. High resolution micro-CT imaging was used to characterise morphometric features of their porous structures: (1) strut thickness, 2) the depth of the porous layer, (3) pore size and (4) the level of porosity. Additionally, we computed the surface area of each component to quantify how much titanium may be in contact with patient tissue. Statistical comparisons were made between the designs. We found a variability between designs in relation to the thickness of the struts (0.28 to 0.65 mm), how deep the porous layers are (0.57 to 11.51 mm), the pore size (0.74 to 1.87 mm) and the level of porosity (34 to 85%). One manufacturer printed structures with different porosities between the body and flange; another manufacturer had two differing porous regions within the body of the cups. The cups had a median (range) surface area of 756.5 mm2 (348 - 1724). There is a wide variability between manufacturers in the porous titanium structures they 3D print. We do not currently know whether there is an optimal porosity and how this variability will impact clinically on the integrity of bony fixation; this will become clearer as post market surveillance data is generated.


Vedolizumab does not increase risk of clostridium difficile infection in patients with inflammatory bowel disease using vedolizumab: A retrospective cohort study.
Several studies have shown increased incidence, recurrence, and severity of Clostridium difficile infection (CDI) over the last decade. Patients with inflammatory bowel disease (IBD) who develop CDI are more prone to morbidity and mortality than CDI in patients without IBD. This study seeks to evaluate whether IBD patients who use vedolizumab are at increased risk of CDI compared to IBD patients using other therapies. This was a retrospective cohort study, and 684 patients with confirmed IBD (228 on vedolizumab, 228 on anti-TNF, and 228 on 5- Aminosalicylates acid therapy) were enrolled from January 2009 to August 2019 at a tertiary referral IBD center at McMaster University Medical Centre (MUMC) in Hamilton, Ontario, Canada. The primary outcome was time to the development of CDI in IBD patients using different therapies. Secondary outcomes included rates of CDI and the association between baseline variables and risk of CDI. A Cox proportional hazards (PH) model was used to evaluate baseline factors and development of CDI. There was no difference in time to CDI between the three treatment groups (log rank p-value 0.37). CDI occurred in 16 patients (2.3%), specifically four patients (1.75%) in the vedolizumab group, four patients (1.75%) in the anti-TNF group, and eight patients (3.5%) in the 5-ASA group. The Cox PH model found current smoking, older age, and concomitant immunomodulator use as risk factors for CDI, after adjustment for other covariates. Vedolizumab was not associated with increased risk of CDI in the model. Biologic therapy with vedolizumab or anti-TNF did not impact risk of CDI. Risk factors for CDI in IBD patients included smoking, older age at the onset of medication, and immunomodulator therapy. Clinicians should have high degree of suspicion for CDI in IBD patients presenting with diarrhea, particularly in those with risk factors identified in this study.


Landmark lipid-lowering trials in the primary prevention of cardiovascular disease.
Although atherosclerotic cardiovascular disease (CVD) is the most common cause of morbidity and mortality in the world, the long disease latency affords ample opportunity for preventive care. Indeed, lifelong exposure to atherogenic apoliprotein B-containing lipoproteins has consistently been shown to increase the cumulative risk of suffering a CVD event, including myocardial infarction, stroke, and symptomatic peripheral arterial disease. Over the past 25 years, lipid-lowering therapies have been developed that are proven to not only lower cholesterol, but also to decrease adverse CVD events and CVD mortality. This review will highlight several key clinical trials encompassing several classes of lipid-lowering medications that have provided clinicians with an evidence-based framework for managing their patients' cardiovascular risk.


Impact of time of day on radiology image interpretations.
To examine the impact of the time of day on radiologists' mammography reading performance. Retrospective mammographic reading assessment data were collected from the BreastScreen Reader Assessment Strategy database and included timestamps of the readings and reader-specific demographic data of 197 radiologists. The radiologists performed the readings in a workshop setting with test case sets enriched with malignancies (one-third of cases were malignant). The collected data were evaluated with an analysis of covariance to determine whether time of day influenced radiologists' specificity, lesion sensitivity or the jackknife alternative free-response receiver operating characteristic (JAFROC). After adjusting for radiologist experience and fellowship, specificity varied significantly by time of day (p=0.027), but there was no evidence of any significant impact on lesion sensitivity (p=0.441) or JAFROC (p=0.120). The collected data demonstrated that specificity during the late morning (10.00-12.00) was 71.7%; this was significantly lower than in the early morning (08.00-10.00) and mid-afternoon (14.00-16.00), which were 82.74% (p=0.003) and 81.39% (p=0.031), respectively. Specificity during the late afternoon (16.00-18.00) was 73.95%; this was significantly lower than in the early morning (08.00-10.00) and mid-afternoon (14.00-16.00), which were 82.74% (p=0.003) and 81.39% (p=0.031), respectively. The results indicated that the time of day may influence radiologists' performance, specifically their ability to identify normal images correctly.


A shorter hospital stay after cardiac pacemaker implantation.
In an effort to shorten the hospital stay after implantation of a permanent cardiac pacemaker, some physicians have begun performing pacemaker implantation on an ambulatory basis. To assess the potential safety of shortening the duration of hospitalization after pacemaker implantation, we reviewed the complications that occurred in 100 consecutive patients after pacemaker implantation and noted the time after the implantation when the complications occurred. In our study group, all complications that necessitated invasive intervention occurred within 24 hours after the pacemaker implantation. Complications that necessitated noninvasive programming occurred as long as 72 hours after implantation, and all could have been safely corrected at the time of follow-up had the patient been dismissed at the 24-hour period. Although we do not believe that ambulatory pacemaker implantation should be routinely implemented at this time, the practice of dismissing patients at 24 hours after pacemaker implantation and scheduling subsequent outpatient follow-up seems to be safe and effective.


A theoretical study of Zn++ interacting with models of ligands present at the thermolysin active site.
The binding energy and the geometrical arrangements of the complexes formed by the zinc dication with OH-, one, four, five or six water molecules, SH-, H2S, formic acid, the formate anion, imidazole, its anion and formamide are calculated using the MNDO method. The comparison of the results obtained with those of ab initio computations on the same complexes induced us to propose for Zn++ a set of parameters different from the one determined by Dewar for the neutral metal atom. Using the two MNDO parametrizations, similar calculations are carried out for Zn++ interacting with two molecules of 2-aminoethanethiol and with models of the four ligands which are present at the thermolysin active site, in order to evaluate the possibilities and limitations of this semiempirical method for theoretical studies concerning zinc metalloenzymes. In the last case, the results obtained suggest that, in the crystal state, the water molecule could be deprotonated. This finding is discussed in relation with the mechanism of action of the enzyme which has been proposed.


Influence of increased catecholamine levels in blood plasma during cold-adaptation and intramuscular infusion on thresholds of thermoregulatory reactions in guinea-pigs.
Catecholamines and some of their metabolites were determined in urine and blood plasma of guinea-pigs before, during and after acclimation to a cold or warm environment. During adaptation to 5 degrees C the amounts of noradrenaline in plasma and 24-h urine samples continuously increased up to 600% compared with values obtained at an ambient temperature of 22 degrees C. Higher levels of dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol further indicated an increased turnover of noradrenaline during cold adaptation. Acclimation to an ambient temperature of 28 degrees C reduced the peripheral release of noradrenaline in comparison to the release observed at 22 degrees C. Cold-induced increases in metabolic rate and electrical muscle activity both occur at a considerably lower mean body temperature in cold-than in warm-adapted guinea-pigs. The shift of thermoregulatory cold defence reactions to a lower mean body temperature could also be observed in warm-adapted animals after intramuscular infusion of noradrenaline in amounts comparable to those released during cold adaptation. It is concluded that high peripheral sympathetic activity directly or indirectly inhibits noradrenergic neurons in the lower brain stem that modulate the thermoregulatory control system by means of their afferents to the hypothalamus. As a consequence of this peripheral influence the thermoregulatory set point is shifted to a lower mean body temperature.


Voxelwise Prediction of Recurrent High-Grade Glioma via Proximity Estimation-Coupled Multidimensional Support Vector Machine.
To provide early and localized glioblastoma (GBM) recurrence prediction, we introduce a novel postsurgery multiparametric magnetic resonance-based support vector machine (SVM) method coupling with stem cell niche (SCN) proximity estimation. This study used postsurgery magnetic resonance imaging (MRI) scans from 50 patients with recurrent GBM, obtained approximately 2 months before clinically diagnosed recurrence. The main prediction pipeline consisted of a proximity-based estimator to identify regions with high risk of recurrence (HRRs) and an SVM classifier to provide voxelwise prediction in HRRs. The HRRs were estimated using the weighted sum of inverse distances to 2 possible origins of recurrence-the SCN and the tumor cavity. Subsequently, multiparametric voxels (from T1, T1 contrast-enhanced, fluid-attenuated inversion recovery, T2, and apparent diffusion coefficient) within the HRR were grouped into recurrent (warped from the clinical diagnosis) and nonrecurrent subregions and fed into the proximity estimation-coupled SVM classifier (SVMPE). The cohort was randomly divided into 40% and 60% for training and testing, respectively. The trained SVMPE was then extrapolated to an earlier time point for earlier recurrence prediction. As an exploratory analysis, the SVMPE predictive cluster sizes and the image intensities from the 5 magnetic resonance sequences were compared across time to assess the progressive subclinical traces. On 2-month prerecurrence MRI scans from 30 test cohort patients, the SVMPE classifier achieved a recall of 0.80, a precision of 0.69, an F1-score of 0.73, and a mean boundary distance of 7.49 mm. Exploratory analysis at early time points showed spatially consistent but significantly smaller subclinical clusters and significantly increased T1 contrast-enhanced and apparent diffusion coefficient values over time. We demonstrated a novel voxelwise early prediction method, SVMPE, for GBM recurrence based on clinical follow-up MR scans. The SVMPE is promising in localizing subclinical traces of recurrence 2 months ahead of clinical diagnosis and may be used to guide more effective personalized early salvage therapy.


Interferon augments the cytotoxicity of hydroxyurea without enhancing its activity against the M2 subunit of ribonucleotide reductase: effects in wild-type and resistant human colon cancer cells.
The effects of prolonged exposure to the ribonucleotide reductase (RR) inhibitor, hydroxyurea (HU), were assessed in the presence or absence of recombinant interferon alfa-2a (IFN) in wild-type human colon cancer cells (HT-29) and variants expressing low-level resistance to HU (R200). IFN at nontoxic concentrations decreased the IC50 of HU from 368 microM to 215 microM (P < 0.01) in wild-type cells, but not in the resistant variants. Potential cellular targets for the HU/IFN interaction were examined. In wild-type, but not resistant cells, treatment with HU at clinically achievable concentrations (1000 microM) resulted in rapid early inhibition of RR activity between 4 and 24 h after treatment with a maximal decrease of 65% at 12 h, decreases in cellular levels of dATP, dCTP and dGTP by 50-90% over the same time course, and a two- to fourfold increase in the level of mRNA for both the M1 and M2 subunits of RR, at 24, but not between 1 and 4 h, which probably represents a response to the earlier decrease in RR activity. IFN at a clinically achievable concentration (500 U/ml) failed to augment the effects of HU on RR protein, RR mRNA levels or RR enzyme activity in either the wild-type or resistant cells, suggesting that the mechanism by which IFN augments the effects of HU in the wild-type cells is independent of the effects of HU on M2.


Characteristics and local risk factors of community-acquired and health-care-associated Staphylococcus aureus pneumonia.
This study aims at identifying characteristics, risk factors and mortality of community-acquired (CAP) and health-care-associated pneumonia (HCAP) by Staphylococcus aureus (S. aureus). We retrieved adults with S. aureus CAP or HCAP diagnosed by blood or pleural effusion culture in 2.6 years, and compared with those of Streptococcus pneumoniae (S. pneumoniae) CAP or HCAP diagnosed by blood or respiratory culture, or urine antigen. We found 18 patients with CAP and 9 HCAP due to S. aureus (female 33%, 66.6 ± 12.4 years-old), and 48 patients with CAP and 15 HCAP due to S pneumoniae (female 41%, 69.5 ± 17.5 years). Diabetes mellitus (52% vs. 24%, p = 0.019), hemodialysis (11% vs. 0%, p = 0.046), skin lesions (44% vs. 0%, p < 0.001), cavitary nodules (37% vs. 1.6%, p < 0.001) and pleural effusions (48% vs. 18%, p = 0.007) were more common in staphylococcal than pneumococcal group. Three patients with staphylococcal pneumonia had acute myocardial infarction. Pneumonia severity index (139 ± 52 vs. 109 ± 43, p = 0.005) and 30-day mortality (41% vs. 9.5%, p = 0.001) were higher in staphylococcal group. Multivariate analysis showed underlying disease (especially cancer and cirrhosis), risk class 4/5, altered mentality, shock and bilateral pneumonia were risk factors for 30-day mortality.


Predictive non-linear modeling of complex data by artificial neural networks.
An artificial neural network (ANN) is an artificial intelligence tool that identifies arbitrary nonlinear multiparametric discriminant functions directly from experimental data. The use of ANNs has gained increasing popularity for applications where a mechanistic description of the dependency between dependent and independent variables is either unknown or very complex. This machine learning technique can be roughly described as a universal algebraic function that will distinguish signal from noise directly from experimental data. The application of ANNs to complex relationships makes them highly attractive for the study of biological systems. Recent applications include the analysis of expression profiles and genomic and proteomic sequences.


Production of recombinant h-AT III with mammalian cell cultures using capillary electrophoresis for product monitoring.
The importance of mammalian cell cultures for biotechnological production processes is steadily increasing, despite the high demands of these organisms on their culture conditions. Efforts towards a more efficient bioprocess generally concentrate on maximizing the culture's life time, the cell number, and the product concentration. Here recombinant BHK 21 c13 cells are used to produce rh-AT III, an anticoagulant of high therapeutic value. The influence of the process mode (batch, repeated batch, continuous perfusion) and the process temperature (30°C vs. 37°C) on the above mentioned parameters is investigated. It is possible to increase the length of the culture from 140 h (batch) to more than 500 h (continuous perfusion culture), while concomitantly increasing the cell density from 0.72 10(6)/ml (batch) to 2.27 10(6)/ml (repeated batch) and 2.87 10(6)/ml (continuous perfusion culture). The accumulation of toxic metabolites, such as lactate, can be curtailed by reducing the bioreactor temperature from 37°C to 30°C during the later part of the exponential growth phase. Fast and reliable product monitoring became essential during process optimization. Capillary zone electrophoresis (CZE) in uncoated fused silica capillaries was studied for that purpose and compared to the standard ELISA. Under optimized conditions an AT III quantification could be done within 2 min with CZE. The detection limit was 5 μg/ml. A relative standard deviation of less than 0.9% was calculated. The detection limit could be lowered by one order of magnitude by using a two dimensional system, where an liquid chromatographic (LC) system is coupled to the CZE. Concomitantly the resolution is improved. The two-dimensional analysis required 5 min. Membrane adsorbers (MA) were used as stationary phase in the LC-system, to allow the application of high flow rates (5-10 ml/min). The correlation between the LC-CZE analysis and the standard AT III-ELISA was excellent, with r(2): 0.965. Using the assay for at line product monitoring, it is shown, that the process temperature is of no consequence for the productivity whereas the process mode strongly influences this parameter.


A novel cDNA restores reduced folate carrier activity and methotrexate sensitivity to transport deficient cells.
Mammalian cells accumulate reduced folates and methotrexate, a folate antagonist, through the reduced-folate carrier (RFC) (Goldman, I.D., Lichtenstein, N.S., and Oliverio, V.T. (1968) J. Biol. Chem. 243, 5007-5017). This study describes the isolation and expression of a cDNA clone that restores RFC activity to human breast cancer cells defective in this transporter. The cDNA cancer cells defective in this transporter. The cDNA codes for a peptide (mRFC1) of 58 kDa, whose hydropathy plot, resembling those of mammalian sugar transporters, predicts that it may be a member of a superfamily of transporter genes. Transfection of methotrexate-resistant (MTXR) ZR-75-1 cells with an expression vector, pRFC1, that codes for this peptide restores their ability to accumulate methotrexate. Furthermore, transport of methotrexate into pRFC1-transfected cells is blocked by a 10-fold molar excess of the reduced folate, 5-formyltetrahydrofolic acid, but is unaffected by folic acid. The increase in methotrexate uptake that is observed in pRFC1-transfected MTXR ZR-75-1 cells reverses their resistance to this antitumor agent.


A pregnant woman with severe dyspnoea.
Preterm delivery is a feasible option in the third trimester of pregnancy in the treatment of pregnant women with acute respiratory distress syndrome due to miliary tuberculosis with respiratory failure https://bit.ly/3stKOzj.


Longitudinal bioimpedance vector plots add little value to fluid management of peritoneal dialysis patients.
Bioimpedance (BI) has the potential to enable better management of fluid balance, which can worsen over time on peritoneal dialysis (PD) due to loss of residual kidney function and progressive muscle wasting. We undertook a prospective, randomized, open-label, blinded end-point controlled trial to determine whether availability of longitudinal BI measures as vector plots helped clinicians maintain stable fluid status over 12 months in 308 peritoneal dialysis patients from the United Kingdom and Shanghai, China. Patients were recruited into 4 groups nested within a single trial design according to country and residual kidney function. Nonanuric subjects from both countries demonstrated stable fluid volumes irrespective of randomization. Hydration worsened in control anuric patients in Shanghai with increased extracellular/total body water (ECW/TBW) ratio (0.04; 95% CI: 0.01, 0.06) and reduced TBW (-1.76 L 95% CI: -2.70, -0.82), but was stable in the BI intervention group whose dialysate glucose prescription was increased. However, multilevel analysis incorporating data from both countries showed worsening ECW/TBW in active and control anuric patients. Clinicians in the United Kingdom reduced target weight in the nonanuric BI intervention group causing a reduction in TBW without beneficial effects on ECW or blood pressure. Thus, routine use of longitudinal BI vector plots to improve clinical management of fluid status is not supported.


Gene expression profile in streptozotocin rat model for sporadic Alzheimer's disease.
Sporadic Alzheimer's disease (SAD), a progressive neurodegenerative disease, is the most common cause of dementia. The etiology of the disease is still unknown, but it is suspected to be a concert of genetic and environmental factors. Intracerebroventricular injection of streptozotocin (STZ), which inhibits insulin receptor function, develops long-term and progressive deficits in learning, memory and cognitive behavior as well as biochemical changes and neuronal degeneration in rats similar to SAD. Micro-array analysis provides a genome-wide, non-biased study of gene expression patterns. The aim of this study was to investigate the gene expression pattern in the STZ animal model for SAD. RNA from rat cortex, striatum and cerebellum were analyzed for gene expression pattern via Affymetrix neurobiology chip-array and confirmed by real-time RT-PCR. Genes such as potassium channels, GABA receptors and glutamate transporter were up regulated, while insulin-like growth factor receptor was down regulated in STZ rats. These pathways may reveal molecular events causing the neuronal death in SAD.


Studies on antidiabetic agents. IX. A new aldose reductase inhibitor, AD-5467, and related 1,4-benzoxazine and 1,4-benzothiazine derivatives: synthesis and biological activity.
N-Acetic acid derivatives (I) of 2-substituted 1,4-benzoxazines and benzothiazines were designed and synthesized for evaluation as new aldose reductase inhibitors. In general, 3-thioxo derivatives were more potent inhibitors of aldose reductase from human palcenta in vitro than the corresponding 3-oxo derivatives. While many compounds (I) were not very effective in inhibiting sorbitol accumulation in the rat sciatic nerve in vivo, the 3-thioxo compounds bearing an isopropyl group at the 2-position showed highly potent activity in the in vivo assay. Compound 46 (AD-5467) was selected from this series as a candidate for further development.


[Robot-assisted (da Vinci) laparoscopy: the beginning of a new era in operative urology?].
The da Vinci Surgical System represents a new technology in advanced laparoscopy: Sitting at a console that allows three-dimensional vision of the operating field, the robotic surgeon is enabled to perform complex laparoscopic procedures. The movements of telemanipulators ("masters") are transferred to EndoWrist instruments with all degrees of freedom. Compared with conventional laproscopy, the technology allows more dexterity, a shorter learning curve, improved vision, reduced operating time with reduced staff requirements, and an ergonomically designed work station with minimal burden on the back and joints. The following article describes the principles of this technology and the challenges of the capital investment and the running costs.


Reverse Koebner's phenomenon in a case of Lymphohemangioma circumscriptum: A diagnostic clue representative of the Whimster hypothesis.
Lymphangioma circumscriptum are benign hamartomatous lymphatic growths, diagnosed clinically by the morphology of groups of clear fluid filled to serosanguinous fluid vesicles. MRI is an essential investigation to assess the depth of the lesions. To report an interesting hitherto unreported observation of Reverse Koebner's phenomenon, which can be used as a new diagnostic technique in Lymphohemagioma. Biopsy was taken for the confirmation of the lesion which is an inflicted iatrogenic trauma which showed Reverse koebner's phenomenon in the lesion. Irregular shaped reddish blue painless plaque with rough lobulated surface with discrete firm reddish-blue painless papules, of varying sizes were biopsied. Post biopsy, significant reduction in size and redness of the lesions noticed. Disappearance of the lesions on biopsy indicates reminiscensce of the reverse koebner's phenonmenon.


Delayed lung expansion after decortication in a case of trapped lung resulting from catamenial haemothorax.
Herein, we report the case of a 35-year-old female with a trapped right lung secondary to catamenial haemothorax. Following surgical decortication, re-expansion of the lung was not observed until postoperative day 81. This delay represents a heretofore unencountered complication that should be considered in the surgical management of catamenial haemothorax due to thoracic endometriosis syndrome.


Breast Cancer Epidemiology and Survival Analysis of Shenyang in Northeast China: A Population-Based Study from 2008 to 2017.
To investigate the status of breast cancer incidence, trends, and survival in women in urban Shenyang from 2008-2017 using large Cancer Registry data. Breast cancer incidence and mortality data were abstracted from the Shenyang Cancer Registry between 2008 and 2017. The crude and age-standardized incidence and mortality rates were calculated for each year. Average annual percentage changes (AAPC) were used to describe the change over time. A total of 14,255 out of 18,782,956 women were diagnosed with breast cancer between 2008 and 2017 in urban Shenyang. The overall crude and age-standardized incidences were 75.89 and 43.42 per 100,000, respectively. The crude incidence increased from 61.93 per 100,000 in 2008 to 90.07 per 100,000 in 2017, with an AAPC of 5.10%. The crude mortality increased from 11.41 per 100,000 in 2008 to 17.29 per 100,000 in 2017, with an AAPC of 4.60. The highest age-specific incidence occurs in the 55-59 year age group at a rate of 140.67 per 100,000. During the study period, 2,710 women died from breast cancer. The overall crude and age-standardized mortality rates were 14.43 and 7.43 per 100,000, respectively. The highest age-specific mortality occurs at 80-84 years old at a rate of 57.57 per 100,000. The 3-year and 5-year survival rates for female breast cancer in urban Shenyang from 2008 to 2013 were 85.61% and 77.39%, respectively, and both declined with age. The incidence and mortality rates of breast cancer in Shenyang increased over time. Screening and control strategies should be enhanced, especially for perimenopausal females.


A novel nomogram for predicting respiratory adverse events during transport after interventional cardiac catheterization in children.
The rate and predictors of respiratory adverse events (RAEs) during transport discharged from operating room after interventional cardiac catheterization in children remain unclear. This study aimed to investigate the incidence and predictors, and to construct a nomogram for predicting RAEs during transport in this pediatric surgical treatment. This prospective cohort study enrolled 290 consecutive pediatric patients who underwent ventricular septal defects (VSD), atrial septal defects (ASD), and patent ductus arteriosus (PDA) between February 2019 and December 2020. Independent predictors were used to develop a nomogram, and a bootstrap resampling approach was used to conduct internal validation. Composite RAEs were defined as the occurrence of at least 1 complication regarding laryngospasm, bronchospasm, apnea, severe cough, airway secretions, airway obstruction, and oxygen desaturation. The rate of RAEs during transport was 23.1% (67 out of 290). Multivariate analysis identified age (vs. ≤3 years, adjusted odds ratio (aOR) = 0.507, 95% confidence interval (CI), 0.268-0.958, P = 0.036), preoperative upper respiratory tract infections (URI, aOR = 2.335, 95% CI, 1.223-4.460, P = 0.01), type of surgery (vs. VSD, for ASD, aOR = 2.856, 95% CI, 1.272-6.411, P = 0.011; for PDA, aOR = 5.518, 95% CI, 2.425-12.553, P < 0.001), morphine equivalent (vs. ≤0.153 mg/kg, aOR = 2.904, 95% CI, 1.371-6.150, P = 0.005), atropine usage (aOR = 0.463, 95% CI, 0.244-0.879, P = 0.019), and RAEs during extubation to transport (aOR = 5.004, 95% CI, 2.633-9.511, P < 0.001) as independent predictors of RAEs during transport. These six candidate predictors were used to develop a nomogram, which showed a C-statistic value of 0.809 and good calibration (P = 0.844). Internal validation revealed similarly good discrimination (C-statistic, 0.782; 95% CI, 0.726-0.837) and calibration. Decision curve analysis (DCA) also demonstrated the clinical usefulness of the nomogram. The high rate of RAEs during transport reminds us of the need for more medical care and attention. The proposed nomogram can reliably identify pediatric patients at high risk of RAEs during transport and guide clinicians to make proper transport plans. Our findings have important and meaningful implications for RAEs risk prediction, clinical intervention and healthcare quality control.


Gram-Negative Bacteria Are Internalized Into Osteocyte-Like Cells.
While Gram-positive organisms are the most common causative agent of initial bone infections, the percentage of Gram-negative species increases in reoccurring bone infections. As bacterial internalization has been suggested as one cause of reoccurring bone infection, we tested the hypothesis that Gram-negative species of bacteria can be internalized into bone cells. Using the MLO-A5 and the MLO-Y4 cell lines as our cell models, we demonstrated that the Gram-negative species, Proteus mirabilis and Serratia marcescens, can be internalized in these cells using an internalization assay. This rate at which these two species were internalized was both time- and initial concentration-dependent. Confocal analysis demonstrated the presence of internalized bacteria within both cell types. Inhibition of the cellular uptake with methyl-β-cyclodextrin and chloroquine both reduced internalized bacteria, indicating that this process is, at least in part, cell mediated. Finally, we demonstrated that the presence of internalized P. mirabilis did not impact cell viability, measured either by lactate dehydrogenase (LDH) release or 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) activity, while the presence of S. marcescens, on the other hand, both increased LDH release and reduced MTT activity, indicating a loss of cell viability in response to the organism. These results indicated that both species of Gram-negative bacteria can be internalized by bone cells and that these internalized bacteria could potentially result in reoccurring bone infections. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:861-870, 2020.


Genomic organization and gene expression in a chromosomal region of Leishmania major.
Little is known about the relation between the genome organization and gene expression in Leishmania. Bioinformatic analysis can be used to predict genes and find homologies with known proteins. A model was proposed, in which genes are organized into large clusters and transcribed from only one strand, in the form of large polycistronic primary transcripts. To verify the validity of this model, we studied gene expression at the transcriptional, post-transcriptional and translational levels in a unique locus of 34kb located on chr27 and represented by cosmid L979. Sequence analysis revealed 115 ORFs on either DNA strand. Using computer programs developed for Leishmania genes, only nine of these ORFs, localized on the same strand, were predicted to code for proteins, some of which show homologies with known proteins. Additionally, one pseudogene, was identified. We verified the biological relevance of these predictions. mRNAs from nine predicted genes and proteins from seven were detected. Nuclear run-on analyses confirmed that the top strand is transcribed by RNA polymerase II and suggested that there is no polymerase entry site. Low levels of transcription were detected in regions of the bottom strand and stable transcripts were identified for four ORFs on this strand not predicted to be protein-coding. In conclusion, the transcriptional organization of the Leishmania genome is complex, raising the possibility that computer predictions may not be comprehensive.


Reduction of MTT by flavonoids in the absence of cells.
The tetrazolium salt 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) is used to determine cell viability in assays of cell proliferation and cytotoxicity. MTT is reduced in metabolically active cells to yield an insoluble purple formazan product. However, in this study, using a colorimetric method with MTT, we demonstrated that luteolin and quercetin (both are flavonoids) can reduce MTT in the absence of living cells. We also examined effects of some experimental conditions on the reaction, such as concentrations of flavonoids, incubation time, the structure and the existing form in solvents of flavonoids. The maximal absorbance values, which were 0.355 (luteolin) and 0.491 (quercetin), were observed when the concentrations of flavonoids were 200 microg/ml. Incubating MTT with flavonoids for 8 h, the absorbance values got the maximum, which were 0.320 (luteolin) and 0.398 (quercetin). The ability of flavonoids reducing MTT in RPMI-1640 with 10% fetal calf serum was higher than that in anhydrous ethanol. And the ability of quercetin reducing MTT was higher than that of luteolin both in RPMI-1640 with 10% fetal calf serum and anhydrous ethanol. Based on the results, this undescribed reaction can significantly influence the results of experiments using the MTT assay to measure the effects of flavonoids on cell growth.


The performance of intellectually normal and educable mentally retarded boys on tests of throwing accuracy.
Educable retarded (n =71) and intellectually normal (n =71) boys were measured for both vertical and horizontal errors on an overarm throwing task. The accuracy of throwing errors in terms of the total variance about the target of the intellectually normal boys was superior to that of the retarded boys. Variable errors and constant errors (absolute values) of the retarded boys were greater than those measures for the normals. The relative contributions of variable error to the total variance of the retarded boys were not substantially greater on either horizontal or vertical measures than were those for the normals. These findings did not support the variability hypothesis (Baumeister, 1968) which states that variable error contributes more to the performance levels of retarded than of normals.


Delhi urbanization footprint and its effect on the earth's subsurface state-of-stress through decadal seismicity modulation.
Urban land and its expansion have profoundly impacted the global environment, including the stress change in the earth's subsurface, even though urban land is a small fraction of the global land surface. Divulging such effects has never been more important, given the role of stress in determining the safety of the urban population against earthquakes. However, knowledge of this time-dependent non-linear effect of urbanization on the subsurface remains in the gray area. This study focuses on the area surrounding Delhi, the capital city of India, to understand the relative contribution of the building load created by rapid urbanization in exacerbating the subsurface state-of-stress. The results highlight that, since 2010, the modulation in the seismicity rate and the stability of basement thrust faults is linked not only to urbanization but also to decadal groundwater storage. Mounting evidence suggests that the rapid urbanization, and the resulting non-tectonic horizontal compression, stabilize faults in the Aravalli Delhi belt, which are destabilized due to the extensive groundwater extraction. This affects the decadal seismicity trend around the Aravalli Delhi fold belt. Nonetheless, the magnitude of this time-dependent deformation influence on the seismicity modulation remains uncertain. The findings from this study quantify the geomechanical impacts of urbanization in the Delhi area for the first time.


'Disk shedding' in the cone outer segments of the teleost, Poecilia reticulata P.
Electron microscopical observations show that the cones in the retina of the diurnal Poecilia reticulata shed their membranous outer segment disks. This occurs at the side of the disk which is open to the extracellular space. Shedding is observed in single and twin cones and occurs at any level of the outer segment. The disks are not discarded in packages or as single disks, but are shed in small vesicular portions. This mode of 'disk shedding' may explain why in cone outer segments radioactively labelled replacement protein is diffusely distributed.


Differential X-ray diagnosis of renal dystopias and ectopias in children.
A survey was made of the types of renal allotopia in children based on 5250 urographic examinations. The X-ray anatomy of allotopic kidney and the clinical symptoms of the conditions were discussed. The diagnostic value of individual X-ray techniques was critically appraised and the merits of renal angiography were stressed in terms of both diagnostics and the selection of appropriate surgical procedure. The inadequate terminology of allotopically displaced kidney was discussed.


Effectiveness of Strategies to Decrease Animal-Sourced Protein and/or Increase Plant-Sourced Protein in Foodservice Settings: A Systematic Literature Review.
Effective population-based strategies are required to move toward healthy sustainable diets that replace a proportion of animal- with plant-based protein. Food service can support this using a variety of strategies across the food supply chain. This systematic review aimed to evaluate the effectiveness of strategies to decrease animal protein and/or increase plant protein in foodservice settings on uptake, satisfaction, financial, environmental, and dietary intake outcomes. Seven databases were searched in November 2020 with no restriction on study dates to identify peer-reviewed study designs conducted in commercial and institutional food services using any strategy to decrease beef, lamb, pork, poultry, eggs, fish, or seafood and/or increase legumes/pulses and legume/pulse-based meat substitutes or nuts and reported this review's primary outcome, uptake by consumers, either quantitatively or qualitatively. Secondary outcomes were satisfaction and financial, environmental, and dietary intake outcomes. Titles/abstracts then full texts were screened independently by 2 authors. The Mixed Methods Appraisal Tool was used for quality appraisal. Results were described using a narrative synthesis by strategy type. The protocol is registered with PROSPERO (CRD42021235015). From 20,002 records identified, 38 studies met eligibility criteria, of which 16% were high quality. Strategies included forced restriction (n = 4), menu redesign (n = 6), recipe redesign (n = 6), service redesign (n = 4), menu labeling (n = 7), prompt at point of sale (n = 7), and multipronged strategies (n = 4). Menu labeling, prompting at the point of sale, and redesigning menus, recipes, and service increased uptake of target foods in most studies with the largest consistent changes in menu redesign. Few studies explored secondary outcomes. Recipe redesign, prompting at the point of sale, and menu labeling strategies that measured satisfaction found a positive or neutral effect. The most promising strategies are likely in menu redesign, followed by menu labeling and service redesign. Satisfaction appears to not be negatively impacted by recipe redesign, prompting at the point of sale and menu labeling. More studies are needed to evaluate financial, environmental, and dietary outcomes.


The knit stitch. An improved method of laparoscopic knot tying.
Intracorporeal suturing is essential to advanced laparoscopy and is a rate-limiting step in many procedures. We have outlined an improved method of intracorporeal knot tying which is easier to learn, faster, and more consistently performed than current methods. Conventional intracorporeal knot-tying technique was compared to the knit-stitch method by ten volunteer surgeons. Each participant tied ten conventional-style knots in a video trainer. Surgeons were then taught the knit-stitch method and tied an additional ten knots. Knot-tying times were recorded and compared. Participants were asked to choose the method they preferred. The knit-stitch method was demonstrated to be faster than the conventional method for all participants, regardless of level of training or laparoscopic expertise (mean 63 +/- 19 vs 97 +/- 48 s; P < 0.001). The difference was most marked in participants with the least laparoscopic suturing experience. The knit-stitch was preferred by 90% of the surgeons. Reasons cited for this preference were ease of learning, conservation of instrument motion, better utilization of the nondominant hand, and ability to work with shorter suture. Knit stitching is a faster, more consistent method of intracorporeal suturing. It is preferred because of its simplicity, efficiency, and potential to further reduce tissue trauma during the course of laparoscopic suturing.


DNA analogues: from supramolecular principles to biological properties.
Mainly driven by the needs of antisense research, a large number of oligonucleotide analogues have been prepared and evaluated over the last 15 years. Besides minor structural modifications of the building blocks of DNA and RNA itself, a considerable effort has been devoted to the de novo design of nucleoside analogues with improved binding properties. A particularly successful concept turned out to be that of conformational restriction. This review focuses on recent advances in this area and tries to summarize scope and limitations of this design principle.


Protein mass analysis of histones.
Posttranslational modification of chromatin-associated proteins, including histones and high-mobility-group (HMG) proteins, provides an important mechanism to control gene expression, genome integrity, and epigenetic inheritance. Protein mass analysis provides a rapid and unbiased approach to monitor multiple chemical modifications on individual molecules. This review describes methods for acid extraction of histones and HMG proteins, followed by separation by reverse-phase chromatography coupled to electrospray ionization mass spectrometry (LC/ESI-MS). Posttranslational modifications are detected by analysis of full-length protein masses. Confirmation of protein identity and modification state is obtained through enzymatic digestion and peptide sequencing by MS/MS. For differentially modified forms of each protein, the measured intensities are semiquantitative and allow determination of relative abundance and stoichiometry. The method simultaneously detects covalent modifications on multiple proteins and provides a facile assay for comparing chromatin modification states between different cell types and/or cellular responses.


Persistent presence of postoperative circulating tumor cells is a poor prognostic factor for patients with stage I-III colorectal cancer after curative resection.
To detect pre- and postoperative circulating tumor cells (CTCs) in stage I-III colorectal cancer (CRC) patients undergoing curative resection and so identify a subgroup of patients who are at high risk for relapse. Four mRNA molecular markers including human telomerase reverse transcriptase, cytokeratin-19, cytokeratin-20, and carcinoembryonic antigen mRNA were used to detect CTCs in 438 CRC patients underwent curative resection. Out of 438 patients, 80 CRC patients were classified to preoperative (-)/postoperative (-), 221 patients were preoperative (+)/postoperative (-), while 137 patients were preoperative (+)/postoperative (+). Univariately, postoperative relapse was significantly correlated with depth of invasion (P = 0.032), lymph node metastasis (P < 0.001), vascular invasion (P = 0.001), perineural invasion (P = 0.013), and persistent presence of CTCs (P < 0.001). Using a multivariate proportional hazards regression analysis, the presence of lymph node metastasis (P = 0.012; HR, 7.652; 95% CI: 4.162-14.827), vascular invasion (P = 0.033; HR, 4.360; 95% CI: 2.793-10.847), and the persistent presence of CTCs (P < 0.001; HR, 29.486; 95% CI: 10.281-87.792) were demonstrated to be independent predictors for postoperative relapse. Combination of these three independent predictors showed that patients with any one positive predictor had a hazard ratio of sevenfold to develop postoperative relapse (P < 0.001; HR, 7.064; 95% CI: 4.354-11.464). Furthermore, the persistent presence of CTCs was strongly correlated with poorer relapse-free survival rates (all P < 0.001). The promising results of this study suggest that persistent presence of postoperative CTCs may be a crucial prognostic factor adjuvant to conventional tumor markers in CRC patients who have undergone curative resection. Identification of these high-risk patients of persistent CTCs positivity is important and thus could help to define patients for adjuvant therapy with this tumor entity.


Transpapillary biliary forceps biopsy to distinguish benign biliary stricture from malignancy: how many tissue samples should be obtained?
The sensitivity of transpapillary biliary forceps biopsy for malignancy has been reported as varying from 43-81%. Therefore, there are false negatives in more than 20% of patients, which makes it difficult to diagnose benign biliary stricture as benignancy in a clinical setting. To clarify the number of tissue samples that should be obtained during transpapillary forceps biopsy to distinguish benign biliary stricture from malignancy, patients undergoing transpapillary biliary forceps biopsy at our institute were examined retrospectively in this study. Seventy-two biliary forceps biopsy procedures were performed on 61 patients. The final diagnoses were malignant biliary stricture in 34 patients and benign stricture in 27 patients. The overall sensitivity and specificity for malignancy in this study were 76.5% and 100%, respectively. There were zero out of 10 (0%) false-negative patients when three or more tissue samples were obtained. In contrast, when four or more tissue samples were obtained, eight out of eight (100%) patients had negative diagnoses for malignancy and were finally diagnosed with benignancy. We suggest that three or more tissue samples are recommended for the diagnosis of biliary malignant stricture.


Evaluation of a novel hydrophilic derivatized capillary for protein analysis by capillary electrophoresis-electrospray mass spectrometry.
A new type of hydrophilic derivatized capillary has been used to enable the on-line capillary electrophoresis separation and electrospray mass spectrometric detection of a mixture of proteins containing bovine cytochrome c, tuna cytochrome c and horse heart myoglobin. Less than 40 fmol of each compound were loaded into the capillary. Baseline resolution of components was achieved, as were accurate assignments of molecular masses. The hydrophilic derivatized capillaries were taken through extensive testing procedures to characterize their performance and capabilities for protein analysis. A mixture of six proteins (cytochrome c, ribonuclease A, alpha-chymotrypsinogen, myoglobin, carbonic anhydrase II and alpha-lactalbumin) in acetic acid-sodium acetate buffer was used to delineate the relationships between migration time and pH, along with migration time and buffer concentration for each protein. The variations in capillary efficiency as a function of pH and as a function of buffer concentration were also characterized for the same six proteins in the acetic acid-sodium acetate system. A pH of 4.8 was found to offer an excellent compromise between separation efficiency (up to 500,000 theoretical plates) and analysis time. Capillary efficiencies were also found to be very good when employing a Tris.HCl electrolyte adjusted to pH 4.8. Lastly, electropherogram reproducibility and capillary durability were examined with the finding that little deterioration of the capillary occurred over the course of 400 injections (200 h run time). This represents a notable improvement over previously documented derivatization procedures designed to reduce protein adsorption to fused-silica capillary walls.


Specific detection and differentiation of classic goose parvovirus and novel goose parvovirus by TaqMan real-time PCR assay, coupled with host specificity.
Classic goose parvovirus (cGPV) causes high mortality and morbidity in goslings and Muscovy ducklings. Novel GPV (N-GPV) causes short beak and dwarfism syndrome (SBDS) in Cherry Valley ducks, Pekin ducks and Mule ducks. Both cGPV and N-GPV have relatively strict host specificity, with obvious differences in pathogenicity. Specific detection of cGPV and N-GPV may result in false positives due to high nucleotide similarity with Muscovy duck parvovirus (MDPV). The aim of this study was to develop a highly specific, sensitive, and reliable TaqMan real-time PCR (TaqMan qPCR) assay for facilitating the molecular detection of cGPV and N-GPV. After genetic comparison, the specific conserved region (located on the NS gene) of cGPV and N-GPV was selected for primer and probe design. The selected regions were significantly different from MDPV. Through a series of optimization experiments, the limit of detection was 50.2 copies/μl. The assay was highly specific for the detection of cGPV and N-GPV and no cross-reactivity was observed with E. coli., P.M., R.A., S.S., MDPV, N-MDPV, DAdV-A, DEV, GHPV, DHAV-1, DHAV-3, ATmV, AIV, MDRV and N-DRV. The assay was reproducible with an intra-assay and inter-assay variability of less than 2.37%. Combined with host specificity, the developed TaqMan qPCR can be used for cGPV and N-GPV in differential diagnoses. The frequency of cGPV in Muscovy duckling and goslings was determined to be 12 to 44%, while N-GPV frequency in Mule ducks and Cherry Valley ducks was 36 to 56%. Additionally, fluorescence-positive signals can be found in Mule duck embryos and newly hatched Mule ducklings. These findings provide evidence of possible vertical transmission of N-GPV from breeding Mule ducks to ducklings. We established a quantitative platform for epidemiological investigations and pathogenesis studies of cGPV and N-GPV DNA that was highly sensitive, specific, and reproducible. N-GPV and cGPV infections can be distinguished based on host specificity.


COVID-19 pandemic and adrenals: deep insights and implications in patients with glucocorticoid disorders.
Coronavirus disease-19 (COVID-19) has spread throughout the world. It was initially defined as a potentially severe syndrome affecting the respiratory tract, but it has since been shown to be a systemic disease with relevant extrapulmonary manifestations that increase mortality. The endocrine system has been found to be vulnerable to COVID-19 infection. The current review aims to evaluate the available data on the impact of COVID-19 infection and treatment, as well as COVID-19 vaccines, on adrenal gland function, particularly in patients with GC disorders. A thorough search of published peer-reviewed studies in PubMed was performed using proper keywords. Adrenal viral tropism and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in the adrenal glands have been demonstrated, and adrenal insufficiency (AI) is a rare, but potentially severe complication in COVID-19 disease, whose recognition can be difficult if only for the empirical treatments administered in the early stages. Glucocorticoid (GC) treatment have had a pivotal role in preventing clinical deterioration in patients with COVID-19, but long-term GC use may increase COVID-19-related mortality and the development of iatrogenic AI. Patients with GC disorders, especially AI and Cushing's syndrome, have been identified as being at high risk of COVID-19 infection and complications. Published evidence suggests that AI patient awareness and proper education may help adjust GC replacement therapy appropriately when necessary, thereby reducing COVID-19 severity. The COVID-19 pandemic has had an impact on AI management, particularly in terms of adherence to patients' care plans and self-perceived challenges. On the other hand, published evidence suggests that the clinical course of COVID-19 may be affected by the severity of hypercortisolism in patients with CS. Therefore, to ameliorate the risk profile in these patients, cortisol levels should be adequately controlled, along with careful monitoring of metabolic and cardiovascular comorbidities. To date, the COVID-19 vaccine remains the only available tool to face SARS-CoV-2, and it should not be treated differently in patients with AI and CS. SARS-CoV-2 infection has been linked to adrenal damage and AI is a rare complication in COVID-19 disease, requiring prompt recognition. Educational efforts and patient awareness may reduce COVID-19 severity in patients with AI. Control of cortisol levels and monitoring of complications may improve the clinical course of COVID-19 in patients with CS.


Influence of arbuscular mycorrhizal fungi on bioaccumulation and bioavailability of As and Cd: A meta-analysis.
Increasing industrial activity has led to a growing risk of arsenic (As) and cadmium (Cd) accumulations and biomagnifications in plants and humans. Arbuscular mycorrhizal fungi (AMF) have been extensively studied as a soil amendment owing to their capability to reduce the accumulation of As and Cd in plant tissues. However, a quantitative and data-based consensus has yet to be reached on the effect of AMF on As and Cd bioaccumulation and bioavailability. Here, a meta-analysis was conducted to quantitatively evaluate the impact of AMF using 1430 individual observations from 194 articles. The results showed that AMF inoculation caused a decrease in shoot and root As and Cd accumulation compared to control, and the reduction rates were affected by experimental duration, P fertilizer, AMF species, plant family, plant lifecycle, and soil properties. Intermediate experimental duration (lasting 56-112 days) and no P fertilizer favored AMF to reduce the shoot As and root Cd accumulation. Compared to other plant families, the reduction in As and Cd accumulation in legumes was the greatest, following AMF inoculation. The soils with alkaline, high organic carbon (OC), and low available phosphorus (AP) appeared to be more favorable for AMF to reduce As accumulation in plant tissues, while soils with low AP were more conducive to reducing the Cd accumulation in plant tissues. In addition, AMF inoculation increased pH (1.92%), OC (6.27%), easily-extractable glomalin-related soil protein (EE-GRSP) (29.36%), and total glomalin-related soil protein (T-GRSP) (29.99%), and reduced bioavailable As (0.52%) and Cd (2.35%) in soils compared to control. Overall, the meta-analysis provides valuable guidelines for the optimal use of AMF in different plant-soil systems.


Compositional Fluctuations Locked by Athermal Transformation Yielding High Thermoelectric Performance in GeTe.
Phase transition in thermoelectric (TE) material is a double-edged sword-it is undesired for device operation in applications, but the fluctuations near an electronic instability are favorable. Here, Sb doping is used to elicit a spontaneous composition fluctuation showing uphill diffusion in GeTe that is otherwise suspended by diffusionless athermal cubic-to-rhombohedral phase transition at around 700 K. The interplay between these two phase transitions yields exquisite composition fluctuations and a coexistence of cubic and rhombohedral phases in favor of exceptional figures-of-merit zT. Specifically, alloying GeTe by Sb2 Te3 significantly suppresses the thermal conductivity while retaining eligible carrier concentration over a wide composition range, resulting in high zT values of >2.6. These results not only attest to the efficacy of using phase transition in manipulating the microstructures of GeTe-based materials but also open up a new thermodynamic route to develop higher performance TE materials in general.


Sham versus transurethral microwave thermotherapy in patients with symptoms of benign prostatic bladder outflow obstruction.
Transurethral microwave thermotherapy (TUMT) is a single-session, minimally invasive outpatient treatment for patients with symptoms of benign prostatic bladder outflow obstruction. We designed a prospective randomised trial to identify any placebo response. Patients with a Madsen symptom score over 8 for at least 6 months were eligible for study. Two measurements of urinary flow less than 15 mL/s and a residual urine of under 350 mL were also required for entry. Patients with renal dysfunction, upper urinary tract disease, co-existing bladder disease, and malignant prostatic change were excluded. 43 patients were studied: 21 were randomised to receive a sham treatment and 22 to thermotherapy. Sham treatments were done with the urethral applicator in situ. 40 patients were available for evaluation at 3 months. 2 patients had delayed follow-up and 1 patient randomised to TUMT has undergone transurethral resection. The thermotherapy group showed a 70% decrease (from 14.5 to 4.3) in the mean Madsen score, a 53% increase in flow-rate (8.5 to 13.0 mL/s), and 92% decrease in residual urine volume (147 to 12 mL). No significant change was seen in these mean indices in the sham group. There was no difference in the main complication of transient haematuria between the two groups. However, there was a 22% frequency of acute retention in the TUMT group. The results show little significant placebo component to the subjective and objective improvement that occurs in patients who have received TUMT.