Resection Followed by Involved-Field Fractionated Radiotherapy in the Management of Single Brain Metastasis.
We expanded upon our previous experience using involved-field fractionated radiotherapy (IFRT) as an alternative to whole brain radiotherapy or stereotactic radiosurgery for patients with surgically resected brain metastases (BM). All patients with single BM who underwent surgical resection followed by IFRT at our institution from 2006 to 2013 were evaluated. Local recurrence (LR)-free survival, distant failure (DF)-free survival, and overall survival (OS) were determined. Analyses were performed associating clinical variables with LR and DF. Salvage approaches and toxicity of treatment for each patient were also assessed. Median follow-up was 19.1 months. Fifty-six patients were treated with a median dose of 40.05 Gy/15 fractions with IFRT to the resection cavity. LR-free survival was 91.4%, DF-free survival was 68.4%, and OS was 77.7% at 12 months. No variables were associated with increased LR; however, melanoma histopathology and infratentorial location were associated with DF on multivariate analysis. LRs were salvaged in 5/8 patients, and DFs were salvaged in 24/29 patients. Two patients developed radionecrosis. Adjuvant IFRT is feasible and safe for well-selected patients with surgically resected single BM. Acceptable rates of local control and salvage of distal intracranial recurrences continue to be achieved with continued follow-up.


Safe and efficient ecotropic and amphotropic packaging lines for use in gene transfer experiments.
The construction of a retrovirus packaging cell line which produces high-titer, helper-free retrovirus is an essential prerequisite for experiments whose goal is gene therapy. We have constructed an ecotropic packaging cell line, GP + E-86, and an amphotropic packaging cell line, GP + envAm12, in which the viral gag and pol genes are on one plasmid and the viral env gene is on another plasmid. Both plasmids contain deletions of the psi packaging sequence and the 3' LTR. The fragmented helper virus genomes, when introduced into 3T3 cells, produce titers of delta neo or N2 retrovirus which are comparable to titers produced from packaging cells containing the helper virus genome on a single plasmid. We have found no evidence for the generation of wild-type retrovirus using the GP + E-86 and GP + envAm12 packaging lines, either alone or in combination with the N2 retroviral vector. These results indicate that these packaging lines are safe and efficient for use in experiments designed for murine (using GP + E-86) and human (using GP + envAm12) gene therapy.


[Sonographic appearance of the canine kidney compared with pathologic-histologic morphology].
Aim of the present study was to evaluate the possibility whether the ultrasonographic appearance of the canine kidney can be attached to a specific histopathologic diagnosis. The sonographic examination was performed in 117 dogs that were presented in the Small Animal Clinic of Hannover Veterinary School, Germany, for euthanasia. After the euthanasia the kidneys were exenterated and evaluated pathohistologically in the Department of Pathology of Hannover Veterinary School. According to the sonographic changes the patients were classified into seven different groups and compared with the histopathologic findings. The results of this study demonstrate that it is currently not feasible to relate a gray-scale sonography image of a diffuse renal parenchymal alteration to a specific histopathologic diagnosis. It remains to be seen if it is possible to improve the renal ultrasonography with new diagnostic methods, e.g. color-doppler ultrasonography.


6'"-p-Coumaroylspinosin protects PC12 neuronal cells from acrylamide-induced oxidative stress and apoptosis.
6'"-p-coumaroylspinosin (P-CS) is a flavonoid isolated from Ziziphi Spinosae Semen (ZSS), whereas, the antioxidative activity has not been reported. Oxidative stress is believed to be one of the main causes of neurodegenerative disorders. In this study, the antioxidative effect of P-CS on PC12 cells was determined. The cells were treated with acrylamide (AA) in the absence or presence of P-CS, and cell apoptosis was analyzed. Interestingly, P-CS pretreatment of the cells could significantly prevent AA-induced cell death, glutathione (GSH) contents decrease, and reactive oxygen species (ROS) overproduction. Further investigation of the molecular mechanism underlying the effect of P-CS on cell apoptosis revealed that P-CS was able to suppress the expression of Bax and Bim induced by AA and inhibit the JNKs pathway. Our findings support a role of P-CS in preventing neuronal cell apoptosis induced by AA, suggesting its therapeutic potential for the treatment of neurodegenerative disorders as a medicinal supplement. PRACTICAL APPLICATIONS: Oxidative stress is believed to cause damage in subcellular organelles, nucleic acids, and alteration in protein aggregation as well as disruption of the signaling cascades associated with aging and apoptosis. A small molecule, non-poisonous natural antioxidant is needed to protect the brain from oxidative stress. Compared with western medicine, natural products carry less risk of adverse effects and are not too expensive, especially for the third-world countries. Furthermore, ZSS could be used to produce or prepare antioxidants, such as P-CS, which has been reported significant anti-oxidative activity in this study.


Effect of colostrum intake on metabolic rate and plasma glucose in the neonatal pig in relation to environmental temperature.
The effects of feeding sow colostrum on oxygen consumption (VO2), heat production (HP), respiratory quotient (RQ) and rectal temperature (RT) were examined in 26 newborn piglets in a thermoneutral (32 degrees C) and in a cold (18 degrees C) environment. Colostrum (32 g/kg body weight) was given by gavage at 3 h of age. A control group received a similar amount of saline. VO2, HP, RQ and RT were measured for approximately 1 h prior to force-feeding and 2 h after feeding. The response of plasma glucose to ingestion of colostrum or saline was recorded in 18 additional piglets kept at 32 or 18 degrees C. The effects of feeding saline on all parameters studied were not significant (p greater than 0.10). Ingestion of colostrum was followed at both temperatures by a marked rise (p less than 0.05) in VO2 and RT. The responses of VO2 were curvilinear (p less than 0.05) with the maximum rise occurring in both treatments within 30 min after colostrum administration and amounting (% of prefeeding values) to 45 +/- 7 and 16 +/- 2% at 32 and 18 degrees C, respectively. The rises in VO2 persisted for more than 1 h postfeeding. The heat increment associated with feeding colostrum was lower (p less than 0.05) at 18 than at 32 degrees C. Nonsignificant transient increases in RQ were observed. Prefeeding plasma glucose was higher (p less than 0.05) at 18 than at 32 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)


Plasmonic Scattering Microscopy for Label-Free Imaging of Molecular Binding Kinetics: From Single Molecules to Single Cells.
Measuring molecular binding kinetics represents one of the most important tasks in molecular interaction analysis. Surface plasmon resonance (SPR) is a popular tool for analyzing molecular binding. Plasmonic scattering microscopy (PSM) is a newly developed SPR imaging technology, which detects the out-of-plane scattering of surface plasmons by analytes and has pushed the detection limit of label-free SPR imaging down to a single-protein level. In addition, PSM also allows SPR imaging with high spatiotemporal resolution, making it possible to analyze cellular response to the molecular bindings. In this Mini Review, we present PSM as a method of choice for chemical and biological imaging, introduce its theoretical mechanism, present its experimental schemes, summarize its exciting applications, and discuss its challenges as well as the promising future.


First-Line Alectinib vs. Brigatinib in Advanced NSCLC with ALK Rearrangement: Real-World Data.
Alectinib and brigatinib are second-generation anaplastic lymphoma receptor tyrosine kinases (ALKs) that are widely used as first-line therapy for treating ALK-positive advanced non-small cell lung cancer (NSCLC). Given the lack of a head-to-head comparison of these drugs as first-line therapies, this retrospective observational study aimed to compare the real-world efficacy and safety of alectinib and brigatinib. Patients who received alectinib or brigatinib as the first-line treatment for ALK-positive advanced NSCLC were evaluated for clinical outcomes of objective response rate (ORR), intracranial ORR, time to next treatment (TTNT), progression-free survival (PFS), overall survival (OS), and safety profiles. Of 208 patients who received either alectinib or brigatinib as a first-line treatment, 176 received alectinib and 32 received brigatinib. At the data cutoff point, the median follow-up duration was 16.5 months (95% CI; 14.7-18.3) in the brigatinib group and 27.5 months (95% CI; 24.6-30.4) in the alectinib group. The ORR was 92.5% with alectinib and 93.8% for brigatinib. The intracranial ORR rates were 92.7% (38/41) and 100% (10/10), respectively. The rate of PFS at 12 months was comparable between the alectinib group and the brigatinib groups (84.4% vs. 84.1%, p-value: 0.64), and the median TTNT, PFS, and OS were not reached in either group. Treatment-related adverse events were usually mild, and treatment discontinuation due to adverse events was rare (alectinib 4.5% vs. brigatinib 6.25%). Alectinib and brigatinib had similar clinical benefits when used as the first-line treatment of NSCLC patients with ALK rearrangement in the real world.


Morphological evidence for an apparent lysosomotropic activity by unsaturated putrescine analogues.
Treatment of cultured L1210 cells with the putrescine analogue, 2,5-diamino-3-hexyne, at 0.5 nM resulted in the rapid (1-2 h) appearance of numerous cytoplasmic vacuoles which were highly visible by light microscopy. Ultrastructural examination revealed that the vacuoles contained numerous membrane vesicles and electron-dense structures resembling endosomal elements. Other cellular organelles were unaffected by the drug. The overall morphological effect by 2,5-diamino-3-hexyne was nearly identical to that produced in the same cells by the known lysosomotropic agent, chloroquine. Since the putrescine analogue, 1,4-diamino-2-butyne at 1.2 mM, also produced comparable cytoplasmic vacuolation, and putrescine itself failed to do so at concentrations as high as 5 mM, it was concluded that the apparent lysosomotropic activity of the putrescine analogues was probably due to their weaker basicity related to the presence of an internal triple bond. Although it is uncertain whether the effect of the analogues on the endosomal system is related to the natural function of polyamines, the finding points out the previously unrecognized potential for certain polyamine analogues to act in this manner.


Structure of the type V-C CRISPR-Cas effector enzyme.
RNA-guided CRISPR-Cas nucleases are widely used as versatile genome-engineering tools. Recent studies identified functionally divergent type V Cas12 family enzymes. Among them, Cas12c2 binds a CRISPR RNA (crRNA) and a trans-activating crRNA (tracrRNA) and recognizes double-stranded DNA targets with a short TN PAM. Here, we report the cryo-electron microscopy structures of the Cas12c2-guide RNA binary complex and the Cas12c2-guide RNA-target DNA ternary complex. The structures revealed that the crRNA and tracrRNA form an unexpected X-junction architecture, and that Cas12c2 recognizes a single T nucleotide in the PAM through specific hydrogen-bonding interactions with two arginine residues. Furthermore, our biochemical analyses indicated that Cas12c2 processes its precursor crRNA to a mature crRNA using the RuvC catalytic site through a unique mechanism. Collectively, our findings improve the mechanistic understanding of diverse type V CRISPR-Cas effectors.


Severe hypoglycemia as a short-term side-effect of the somatostatin analog SMS 201-995 in insulin-dependent diabetes mellitus.
We report on a case of severe hypoglycemia observed after injection of the somatostatin analog SMS 201-995 in an insulin-dependent diabetic patient connected to an artificial pancreas (Biostator GCIIS). Hypoglycemia occurred in a sudden and unexpected way 23 min after the first SMS injection (50 ug). Details on patient's characteristics and on the peculiar clinical situation in which this complication appeared are given. Furthermore, the possible mechanism(s) responsible for the hypoglycemia are thoroughly discussed. Finally we express a call for caution when administering this drug in insulin-dependent diabetes mellitus.


Effectiveness of Helicobacter pylori eradication in preventing metachronous gastric cancer and preneoplastic lesions. A systematic review and meta-analysis.
Helicobacter pylori is a significant risk factor for gastric cancer. Recent trials show eradication decreases the incidence of gastric cancer in patients with early-stage gastric cancer. However, data on gastric cancer prevention are inconsistent for patients with precancerous lesions such as atrophic gastritis and intestinal metaplasia. The aim of the study is to assess the efficacy of H. pylori eradication in gastric cancer prevention in patients with varying risk factors for gastric cancer at baseline. A systematic review and meta-analysis were performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. PubMed, Medline, and Google Scholar were searched from inception through March 2019 for randomized controlled trials (RCTs) studying H. pylori eradication on gastric cancer prevention. We estimated the odds ratio (OR) with 95% confidence interval (CI) for each outcome using a random-effects model. P values of less than 0.05 were considered significant. Nine RCTs with total of 6967 patient were included in the analysis. There was significant reduction in gastric cancer incidence in the H. pylori group for patients with early gastric cancer status post endoscopic mucosal resection OR, 0.47; 95% CI, 0.33-0.67; P < 0.0001; I = 0%. There was no difference in gastric cancer incidence in patients with atrophic gastritis and intestinal metaplasia at baseline for H. pylori arm OR, 0.67; 95% CI, 0.42-1.07; P = 0.09; I = 0%). Atrophic gastritis and intestinal metaplasia improved from baseline in the H. pylori arm compared to placebo OR, 2.61; 95% CI, 1.41-4.81; P = 0.002; I = 88 and OR, 2.61; 95% CI, 1.66-4.11; P ≤ 0.0001; I = 0%, respectively. H. pylori eradication is associated with reduced gastric cancer incidence in patients with early-stage gastric cancer and improvement in atrophic gastritis and intestinal metaplasia. There was no difference in gastric cancer incidence in patients with atrophic gastritis and intestinal metaplasia at baseline.


Brain White Matter Impairment in Patients with Spinal Cord Injury.
It remains unknown whether spinal cord injury (SCI) could indirectly impair or reshape the white matter (WM) of human brain and whether these changes are correlated with injury severity, duration, or clinical performance. We choose tract-based spatial statistics (TBSS) to investigate the possible changes in whole-brain white matter integrity and their associations with clinical variables in fifteen patients with SCI. Compared with the healthy controls, the patients exhibited significant decreases in WM fractional anisotropy (FA) in the left angular gyrus (AG), right cerebellum (CB), left precentral gyrus (PreCG), left lateral occipital region (LOC), left superior longitudinal fasciculus (SLF), left supramarginal gyrus (SMG), and left postcentral gyrus (PostCG) (p < 0.01, TFCE corrected). No significant differences were found in all diffusion indices between the complete and incomplete SCI. However, significantly negative correlation was shown between the increased radial diffusivity (RD) of left AG and total motor scores (uncorrected p < 0.05). Our findings provide evidence that SCI can cause not only direct degeneration but also transneuronal degeneration of brain WM, and these changes may be irrespective of the injury severity. The affection of left AG on rehabilitation therapies need to be further researched in the future.


Vascular surgery: An essential hospital resource in modern health care.
In modern health care, vascular surgeons frequently serve as a unique resource to other surgical specialties for vascular exposure, repair, reconstruction, or control. These services occur both in planned and unplanned clinical settings. We analyzed the frequency, outcomes, and value of vascular services in this setting to other surgical specialties and the hospital. Intraoperative planned and unplanned vascular surgery operative consultations were reviewed over a 3-year period (2013-2016). Patient demographics, requesting surgical specialty, indication and type of vascular intervention, and work relative value units generated were recorded. Univariate and multivariate analysis of factors affecting a composite outcome of in-hospital and 30-day mortality or morbidity, or both, was performed. Seventy-six vascular surgery intraoperative consultations were performed, of which 56% of the consultations were unplanned. The most common unplanned consultation was for bleeding (33%). The aorta and lower extremity were the most common vascular beds requiring vascular services. The mean work relative value units generated per vascular surgery intervention was 23.8. In-hospital and 30-day mortality was 9.2%. No difference in mortality and morbidity was found between planned and unplanned consultations. Factors associated with the composite mortality/morbidity outcome were coronary artery disease (P = .002), heart failure (P = .02), total operative blood loss (P = .009), consultation for limb ischemia (P = .013), and vascular consultation for the lower extremity (P = .01). On multivariate analysis, high operative blood loss (>5000 mL) remained significant (P = .04), and coronary artery disease approached significance (P = .06). The need for vascular surgery services is frequent, involves diverse vascular beds, and occurs commonly in an unplanned setting. When requested, vascular surgery services effectively facilitate the completion of the nonvascular procedure, even those associated with significant intraoperative blood loss. Vascular surgery services are essential to other surgical specialties and the hospital in today's modern health care environment.


Technical note: assessment of recovery site of mobile nylon bags for measuring ileal digestibility of starch in dairy cows.
The objective of this study was to evaluate recovery site of mobile nylon bags for measuring ileal digestibility of ruminally undegraded starch in dairy cows. Eight feed samples of untreated and treated concentrates were examined. Three lactating cows equipped with rumen fistula and duodenal and ileal cannulas were used in the experiment. The mobile nylon bags containing intact feeds or residues after a 12-h ruminal incubation were pretreated using a 2-step procedure to simulate abomasal digestion before insertion through the duodenal cannula. To assess the effect of hindgut fermentation on starch digestibility, approximately half of the bags were collected from the ileum and half from the feces. The results indicate that feed samples should be preincubated in rumen before insertion into duodenum, and that samples with relatively high fractions of rumen-undigestible starch should be collected from the ileum instead of from feces.


The confusion of indexing aspirin crystals.
Much of the existing literature dealing with crystalline aspirin is vague or ambiguous with regard to indexing of the crystal faces. The inconsistency with which the indices of the dominant faces have been assigned leads to confusion in analysis of surface properties. To clarify this, we have conducted crystal growth experiments on aspirin, and indexed the crystal faces with X-ray diffraction (XRD), paying special attention to the placement of symmetry elements. The space group was confirmed as P2(1)/c, and the dominant face was (100). Contact angle measurements made on the two major faces of aspirin indicate the (100) face to be more hydrophobic than the (001) face, likely due to the acetyloxy moiety, not the carboxyl, exposed on the (100).


Oral histoplasmosis.
Histoplasmosis is a systemic fungal disease that takes various clinical forms, among which oral lesions are rare. The disseminated form of the disease that usually occurs in association with Human Immunodeficiency Virus (HIV) is one of the AIDS-defining diseases. Isolated oral histoplasmosis, without systemic involvement, with underlying immunosuppression due to AIDS is very rare. We report one such case of isolated oral histoplasmosis in a HIV-infected patient.


CRISPulator: a discrete simulation tool for pooled genetic screens.
The rapid adoption of CRISPR technology has enabled biomedical researchers to conduct CRISPR-based genetic screens in a pooled format. The quality of results from such screens is heavily dependent on the selection of optimal screen design parameters, which also affects cost and scalability. However, the cost and effort of implementing pooled screens prohibits experimental testing of a large number of parameters. We present CRISPulator, a Monte Carlo method-based computational tool that simulates the impact of screen parameters on the robustness of screen results, thereby enabling users to build intuition and insights that will inform their experimental strategy. CRISPulator enables the simulation of screens relying on either CRISPR interference (CRISPRi) or CRISPR nuclease (CRISPRn). Pooled screens based on cell growth/survival, as well as fluorescence-activated cell sorting according to fluorescent reporter phenotypes are supported. CRISPulator is freely available online ( http://crispulator.ucsf.edu ). CRISPulator facilitates the design of pooled genetic screens by enabling the exploration of a large space of experimental parameters in silico, rather than through costly experimental trial and error. We illustrate its power by deriving non-obvious rules for optimal screen design.


Do report cards influence hospital choice? The case of kidney transplantation.
The national program to report hospital-level outcomes for transplantation has been in place since 1991, yet it has not been addressed in the existing literature on hospital report cards. We study the impact of reported outcomes on demand at kidney transplant centers. Using a negative binomial regression with hospital fixed effects, we estimate the number of patients choosing each center as a function of reported outcomes. Parameters are identified by the within-hospital variation in outcomes over five successive report cards. We find some evidence that report cards influence younger and college-educated patients, but, overall, report cards do not affect demand.


Effect of partial hepatectomy on lactic dehydrogenase-5 clearance in mice.
The capacity of lactic dehydrogenase-5 (LDH-5) clearance of the liver following partial hepatectomy was investigated in ICR mice. Compared with sham-operated mice, the LDH-5 clearance rate was decreased slightly after the removal of 30 or 50%. Removal of approximately 65% of the liver induced a statistically significant decrease in the clearance rate. LDH activity in the blood was increased by the removal of about 50 and 65%, but not 30% of the liver. These results suggest that increase in LDH activity after hepatectomy may be due to decreased catabolic activity of the liver and the liver may play a significant role in the catabolism of LDH-5. The LDH-5 clearance capacity of the liver will be discussed.


Long-term use of left ventricular assist devices: a report on clinical outcomes.
The literature examining clinical outcomes and readmissions during extended (> 1 yr) left ventricular assist device (LVAD) support is scarce, particularly in the era of continuous-flow LVADs. We completed a retrospective cohort study on consecutive LVAD patients from June 2006 to March 2015, focusing on those who received more than 1 year of total LVAD support time. Demographic characteristics, clinical outcomes and readmissions were analyzed using standard statistical methods. All readmissions were categorized as per the Interagency Registry for Mechanically Assisted Circulatory Support 2015 guidelines. Of the 103 patients who received LVADs during the study period, 37 received LVAD support for more than 1 year, with 18 receiving support for more than 2 years. Average support time was 786 ± 381 days, with total support time reaching 80 patient-years. During a median follow-up of 2 years, 27 patients died, with 1-year conditional survival of 74%. Median freedom from first readmission was 106 days (range 1-603 d), with an average length of stay of 6 days. Readmissions resulted in an average of 41 ± 76 days in hospital per patient. Reasons for readmission were major infection (24%), major bleeding (19%) and device malfunction/thrombus (13%). There were a total of 112 procedures completed during the readmissions, with 60% of procedures being done in 13% (n = 5) of patients. Continuous-flow LVADs provide excellent long-term survival. The present study describes marked differences in reasons for readmissions between the general LVAD population and those supported for more than 1 year. Prolonged LVAD support resulted in decreased susceptibility to major bleeds and increased susceptibility to infection.


Associative and semantic priming effects occur at very short stimulus-onset asynchronies in lexical decision and naming.
Prior research has found significant associative/semantic priming effects at very short stimulus-onset asynchronies (SOAs) in experimental tasks such as lexical decision, but not in naming tasks (however, see Lukatela and Turvey, 1994). In this paper, the time course of associative priming effects was analyzed a several very short SOAs (33, 50, and 67 ms), using the masked priming paradigm (Forster and Davis, 1984), both in lexical decision (Experiment 1) and naming (Experiment 2). The results show small--but significant--associative priming effects in both tasks. Additionally, using the masked priming procedure at the 67 ms SOA. Experiments 3 and 4, shows facilitatory priming effects for both associatively and semantically (unassociated) related pairs in lexical decision and naming tasks. That is, automatic priming can be semantic. Taken together our data appear to support interactive models of word recognition in which semantic activation may influence the early stages of word processing.


A fast estimate of electrostatic group contributions to the free energy of protein-inhibitor binding.
Dissecting ligand-protein binding free energies in individual contributions of protein residues (which are referred to here as 'group contributions') is of significant importance. For example, such contributions could help in estimating the corresponding mutational effects and in studies of drug resistance problems. However, the meaning of group contributions is not always uniquely defined and the approximations for rapid estimates of such contributions are not well developed. In this paper, the nature of group contributions to binding free energy is examined, focusing particularly on electrostatic contributions which are expected to be well behaved. This analysis examines different definitions of group contributions; the 'relaxed' group contributions that represent the change in binding energy upon mutation of the given residue to glycine, and the 'non-relaxed' group contributions that represent the scaled Coulomb interaction between the given residue and the ligand. Both contributions are defined and evaluated by the linear response approximation (LRA) of the PDLD/ S method. The present analysis considers the binding of pepstatin to endothiapepsin and 23 of its mutants as a test case for a neutral ligand. The 'non-relaxed' group contributions of 15 endothiapepsin residues show significant peaks in the 'electrostatic fingerprint'. The residues that contribute to the electrostatic fingerprint are located in the binding site of endothiapepsin. They include the aspartic dyad (Asp32, Asp215) with adjacent residues and the flap region. Twelve of these 15 residues have a heavy atom distance of <3.75 A to pepstatin. The contributions of 8 (10) of these 12 residues can be reconciled with the calculated 'relaxed' group contributions where one allows the protein and solvent (solvent only) to relax upon mutation of the given residue to glycine. On the other hand, it was found that residues at the second 'solvation shell' can have relaxed contributions that are not captured by the non-relaxed approach. Hence, whereas residues with significant non-relaxed electrostatic contributions are likely to contribute to binding, residues with small non-relaxed contributions may still affect the binding energy. At any rate, it is established here that even in the case of uncharged inhibitors it is possible to use the non-relaxed electrostatic fingerprint to detect 'hot' residues that are responsible for binding. This is significant since some versions of the non-relaxed approximation are faster by several orders of magnitude than more rigorous approaches. The general applicability of this approach is outlined, emphasizing its potential in studies of drug resistance where it is crucial to have a rapid way of anticipating the effect of mutation on both drug binding and catalysis.


Quantitative Analysis of Soil Total Nitrogen Using Hyperspectral Imaging Technology with Extreme Learning Machine.
Soil nutrient detection is important for precise fertilization. A total of 150 soil samples were picked from Lishui City. In this work, the total nitrogen (TN) content in soil samples was detected in the spectral range of 900-1700 nm using a hyperspectral imaging (HSI) system. Characteristic wavelengths were extracted using uninformative variable elimination (UVE) and the successive projections algorithm (SPA), separately. Partial least squares (PLS) and extreme learning machine (ELM) were used to establish the calibration models with full spectra and characteristic wavelengths, respectively. The results indicated that the prediction effect of the nonlinear ELM model was superior to the linear PLS model. In addition, the models using the characteristic wavelengths could also achieve good results, and the UVE-ELM model performed better, having a correlation coefficient of prediction (rp), root-mean-square error of prediction (RMSEP), and residual prediction deviation (RPD) of 0.9408, 0.0075, and 2.97, respectively. The UVE-ELM model was then used to estimate the TN content in the soil sample and obtain a distribution map. The research results indicate that HSI can be used for the detection and visualization of the distribution of TN content in soil, providing a basis for future large-scale monitoring of soil nutrient distribution and rational fertilization.


Hydrogen-bond network distortion of water in the soft confinement of Nafion membrane.
A Compton spectroscopy investigation is carried out in hydrated Nafion membranes, enabling identification of distortions in the hydrogen-bond distribution of the polymer hydrating water by means of the subtle changes reflected by the Compton profiles. Indeed, deformations of the Compton profiles are observed when varying hydration, and two different bonding kinds are associated with the water molecules: at low hydration, water surrounds the sulfonic groups, while on increasing hydration, water molecules occupy the interstitial cavities formed upon swelling of the membrane. The analysis is proposed in terms of averaged OH bond length variation. A sizable contraction of the OH distance is observed at low hydration (∼0.09 Å), while at higher hydration levels, the contraction is smaller (∼0.02 Å) and the OH bond length is closer to bulk water. An evaluation of the electron kinetic energy indicates that the spatial changes associated with the water distribution correspond to a consistent binding energy increase. Distinct temperature dependences of each water population are observed, which can be straightly related to water desorption into ice on cooling below the freezing point.


Diagnostic Modalities for Invasive Mould Infections among Hematopoietic Stem Cell Transplant and Solid Organ Recipients: Performance Characteristics and Practical Roles in the Clinic.
The morbidity and mortality of hematopoietic stem cell and solid organ transplant patients with invasive fungal infections (IFIs) remain high despite an increase in the number of effective antifungal agents. Early diagnosis leading to timely administration of antifungal therapy has been linked to better outcomes. Unfortunately, the diagnosis of IFIs remains challenging. The current gold standard for diagnosis is a combination of histopathology and culture, for which the sensitivity is <50%. Over the past two decades, a plethora of non-culture-based antigen and molecular assays have been developed and clinically validated. In this article, we will review the performance of the current commercially available non-cultural diagnostics and discuss their practical roles in the clinic.


Safety of regional citrate anticoagulation for continuous sustained low efficiency dialysis (C-SLED) in critically ill patients.
Sustained low efficiency dialysis (SLED) is a hybrid therapy that uses a conventional hemodialysis machine to deliver lower solute clearance over prolonged periods of time, typically 8 to 12 hours per treatment, and utilizes the same sodium and bicarbonate concentrations as intermittent hemodialysis. The therapy has been shown to be an effective dialysis mode for the critically ill patient with acute renal failure and hemodynamic instability. At our institution, critically ill patients requiring renal replacement therapy receive SLED on a continuous, 24-hour schedule (C-SLED). The higher dialysis dose with C-SLED compared to continuous venovenous hemodiafiltration (CVVHDF) or traditional SLED would likely alter the prescription needed to provide regional citrate anticoagulation and the incidence of hypernatremia and metabolic alkalosis. To evaluate the safety of utilizing regional citrate anticoagulation with continuous SLED in critically ill patients who frequently clot the hemofilter and have contraindications to systemic anticoagulation with heparin. We hypothesized that the higher dialysis dose with C-SLED would affect the prescription of citrate anticoagulation and the development of hypernatremia and metabolic alkalosis. We prospectively followed the first 20 patients who received regional citrate anticoagulation on C-SLED for acute renal failure in the intensive care unit. Important outcomes measured included serum sodium, bicarbonate, ionized calcium concentration, serum pH, and PCO2. The number of clotting episodes for each patient while on regional citrate anticoagulation was recorded. Setting. Surgical and medical intensive care units at The University of Texas MD Anderson Cancer Center. In over 2200 hours of continuous dialysis with citrate anticoagulation none of the 20 patients had derangements in the serum sodium or acid base status requiring cessation of regional citrate anticoagulation. In 14 patients, no clotting occurred during 1500 hours of SLED with the citrate infusion. There were eight episodes of hemofilter clotting in six patients during 750 hours of C-SLED. Regional citrate anticoagulation is a safe method of anticoagulation in critically ill patients on continuous SLED.


Blastomeres and cells with mesendodermal fates of carp embryos express cth1, a member of the TIS11 family of primary response genes.
The carp cth1 gene, related to the mammalian TIS11 family of primary response genes, encodes a novel fish protein with two putative CCCH zinc fingers. This report describes the RNA expression of this gene during cleavage, blastula and gastrula stages of carp embryos. Cth1 mRNA is present in all cleavage stage blastomeres as a maternal message. After the late blastula stage, the maternal expression decreases, revealing a spot of higher expression at the margin of the blastoderm of the dome stage embryo. Further decrease of the maternal message reveals a ring of cth1 expressing cells at the blastoderm margin from the stage of 40% epiboly onwards. By alpha-amanitin treatment we established that this local cth1 expression is of zygotic origin. At the onset of gastrulation the cells of the cth1 ring involute, starting with those in the shield region, and at approximately 60% epiboly the ring is fully involuted and occupies the hypoblast layer. All cth1 transcripts have disappeared at completion of epiboly. We discuss a possible role for the putative cth1 protein during cleavage and gastrulation.


Effect of pH and polypropylene beads in hybrid water treatment process of alumina ceramic microfiltration and PP beads with air back-flushing and UV irradiation.
For advanced water treatment, effects of pH and pure polypropylene (PP) beads packing concentration on membrane fouling and treatment efficiency were observed in a hybrid process of alumina ceramic microfiltration (MF; pore size 0.1 μm) and pure PP beads. Instead of natural organic matters and fine inorganic particles in natural water source, a quantity of humic acid (HA) and kaolin was dissolved in distilled water. The synthetic feed flowed inside the MF membrane, and the permeated water contacted the PP beads fluidized in the gap of the membrane and the acryl module case with outside UV irradiation. Periodic air back-flushing was performed to control membrane fouling during 10 s per 10 min. The membrane fouling resistance (Rf) was the maximum at 30 g/L of PP bead concentration. Finally, the maximum total permeated volume (VT) was acquired at 5 g/L of PP beads, because flux maintained higher all through the operation. The treatment efficiency of turbidity was almost constant, independent of PP bead concentration; however, that of dissolved organic materials (DOM) showed the maximal at 50 g/L of PP beads. The Rf increased as increasing feed pH from 5 to 9; however, the maximum VT was acquired at pH 6. It means that the membrane fouling could be inhibited at low acid condition. The treatment efficiency of turbidity increased a little, and that of DOM increased from 73.6 to 75.7% as increasing pH from 5 to 9.


Correlation between clinical features and total maturation score by magnetic resonance imaging in very low birth weight premature infants with brain injury.
Brain injury in premature infants (BIPI) seriously affects the growth and development of preterm infants. Magnetic resonance imaging (MRI) has become an important method of assessing brain development. The aim of this study was to explore the correlation between clinical features and total maturation score (TMS) by MRI in very low birth weight (VLBW) preterm infants with brain injury at term postmenstrual age (PMA). A retrospective cohort of 65 cases of BIPI with VLBW and 40 normal control cases were included, and all cases underwent MRI examination. The 2 groups were assessed in terms of TMS and sub-parameters (myelination, cortical infolding, germinal matrix, bands of migrating glial cells), and the correlation between TMS and term PMA was also analyzed. The TMS of the BIPI group was lower than that of the control group (P<0.01). The differences in myelination and cortical infolding were statistically significant (P<0.01). No significant differences in the germinal matrix and bands of migrating glial cells were found. The linear regression equation showing a positive correlation between TMS and term PMA in normal preterm infants was y=1.164x-28.888 (t=9.478, P=0.000). TMS by conventional cranial MRI can objectively reflect the brain maturity and brain damage of premature infants, and is related to the term PMA.


A proof-of-principle study of epigenetic therapy added to neoadjuvant doxorubicin cyclophosphamide for locally advanced breast cancer.
Aberrant DNA methylation and histone deacetylation participate in cancer development and progression; hence, their reversal by inhibitors of DNA methylation and histone deacetylases (HDACs) is at present undergoing clinical testing in cancer therapy. As epigenetic alterations are common to breast cancer, in this proof-of-concept study demethylating hydralazine, plus the HDAC inhibitor magnesium valproate, were added to neoadjuvant doxorubicin and cyclophosphamide in locally advanced breast cancer to assess their safety and biological efficacy. This was a single-arm interventional trial on breast cancer patients (ClinicalTrials.gov Identifier: NCT00395655). After signing informed consent, patients were typed for acetylator phenotype and then treated with hydralazine at 182 mg for rapid-, or 83 mg for slow-acetylators, and magnesium valproate at 30 mg/kg, starting from day -7 until chemotherapy ended, the latter consisting of four cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 21 days. Core-needle biopsies were taken from primary breast tumors at diagnosis and at day 8 of treatment with hydralazine and valproate. 16 patients were included and received treatment as planned. All were evaluated for clinical response and toxicity and 15 for pathological response. Treatment was well-tolerated. The most common toxicity was drowsiness grades 1-2. Five (31%) patients had clinical CR and eight (50%) PR for an ORR of 81%. No patient progressed. One of 15 operated patients (6.6%) had pathological CR and 70% had residual disease <3 cm. There was a statistically significant decrease in global 5mC content and HDAC activity. Hydralazine and magnesium valproate up- and down-regulated at least 3-fold, 1,091 and 89 genes, respectively. Hydralazine and magnesium valproate produce DNA demethylation, HDAC inhibition, and gene reactivation in primary tumors. Doxorubicin and cyclophosphamide treatment is safe, well-tolerated, and appears to increase the efficacy of chemotherapy. A randomized phase III study is ongoing to support the efficacy of so-called epigenetic or transcriptional cancer therapy.


Apolipoprotein A-I gene transfer exerts immunomodulatory effects and reduces vascular inflammation and fibrosis in ob/ob mice.
Obesity is associated with vascular inflammation, fibrosis and reduced high-density lipoproteins (HDL)-cholesterol. We aimed to investigate whether adenoviral gene transfer with human apolipoprotein (apo) A-I (Ad.A-I), the main apo of HDL, could exert immunomodulatory effects and counteract vascular inflammation and fibrosis in ob/ob mice. Ad.A-I transfer was performed in 8 weeks (w) old ob/ob mice, which were sacrificed 7 w later. The aorta was excised for mRNA analysis and the spleen for splenocyte isolation for subsequent flow cytometry and co-culture with murine fibroblasts. HDL was added to mononuclear cells (MNC) and fibroblasts to assess their impact on adhesion capacity and collagen deposition, respectively. Ad.A-I led to a 1.8-fold (p < 0.05) increase in HDL-cholesterol versus control ob/ob mice at the day of sacrifice, which was paralleled by a decrease in aortic TNF-α and VCAM-1 mRNA expression. Pre-culture of MNC with HDL decreased their adhesion to TNF-α-activated HAEC. Ad.A-I exerted immunomodulatory effects as evidenced by a downregulation of aortic NOD2 and NLRP3 mRNA expression and by a 12 %, 6.9 %, and 15 % decrease of the induced proliferation/activity of total splenic MNC, CD4+, and CD8+ cells in ob/ob Ad.A-I versus control ob/ob mice, respectively (p < 0.05). Ad.A-I further reduced aortic collagen I and III mRNA expression by 62 % and 66 %, respectively (p < 0.0005), and abrogated the potential of ob/ob splenocytes to induce the collagen content in murine fibroblasts upon co-culture. Finally, HDL decreased the TGF-ß1-induced collagen deposition of murine fibroblasts in vitro. Apo A-I transfer counteracts vascular inflammation and fibrosis in ob/ob mice.


tRNAMetf2 gene in the leader region of the nusA operon in Escherichia coli.
The promoter-proximal portion of the operon containing the Escherichia coli nusA gene has been cloned. Its nucleotide sequence shows that genes for tRNAMetf2 and a 15-kilodalton protein of unknown function precede the nusA protein gene. The sequence suggests that the three genes form a single transcription unit. Consistent with this hypothesis, purified RNA polymerase formed full-length transcripts on the cloned DNA in vitro, although transcription was frequently arrested at the intercistronic site(s) between the gene for tRNAMetf2 and the 15-kilodalton protein.


3-dimensional composite scaffolds consisting of apatite-PLGA-atelocollagen for bone tissue engineering.
We fabricated 3-dimensional scaffolds consisting of biodegradable poly(D, L-lactide-co-glycolic acid)(PLGA)(75/25) with hydroxyapatite particles containing atelocollagen (aAC). The aim of this study was to evaluate this new type of scaffold in regard to its basic properties and biocompatibility. Characterization of the obtained scaffolds was performed to know the porosity, shrinkage, diametral tensile strength, and biocompatibility. Composite scaffolds made of PLGA with hydroxyapatite particles containing atelocollagen (PL-aAC) showed a greater strength and stability than PLGA scaffolds. PL-aAC also exhibited superior performance in terms of cell attachment and proliferation as compared to PLGA, while histological findings showed that PL-aAC had an excellent response toward soft tissues. Our results strongly suggest that PL-aAC is more useful for cell transplantation as compared to PLGA for bone tissue engineering.


Prevalence of Enterococcus faecalis and Porphyromonas gingivalis in infected root canals and their susceptibility to endodontic treatment procedures: a molecular study.
Because apical periodontitis is recognizably an infectious disease, elimination or reduction of intracanal bacteria is of utmost importance for optimum treatment outcome. The prevalence of Enterococcus faecalis and Porphyromonas gingivalis in infected root canals was studied Also, the effect of endodontic therapy by using intracanal medicaments, calcium hydroxide paste (CH) or gutta-percha points containing calcium hydroxide (CH-GP) or chlorhexidine (CHX-GP) on these microorganisms was assessed by polymerase chain reaction (PCR) assay. Fifty-one patients with chronic apical periodontitis were randomly allocated in one of the fol- lowing groups according to the intracanal medicament used: CH, CH-GP and CHX-GP group. Bacterial samples were taken upon access (S1), after chemomechanical instrumentation (S2) and after 15-day medication (S3). PCR assay was used to detect the presence of selected bacteria. E. faecalis was detected in 49% (25/51) and P. gingivalis in 17.6% (9/51) of the samples. Samples which showed no bacterial presence at S1 were excluded from further analysis. Overall analysis of all 29 samples revealed significant differences between S1 and S2 (p < 0.001), S2 and S3 (p < 0.05), and S1 and S3 (p < 0.001). When distinction was made between the intracanal medications, there was a significant difference in the number of PCR positive samples between S1 and 52, S1 and S3, but not between S2 and S3 samples. E. faecalis is more prevalent than P. gingivalis in primary endodontic infection. Intracanal medication in conduction with instrumentation and irrigation efficiently eliminates E. faecalis and P. gingivalis from infected root canals.


Symptomatic polyostotic fibrous dysplasia of the thoracic spine.
We present a case of polyostotic fibrous dysplasia with limited involvement in thoracic spine and adjacent ribs. The patient underwent posterior instrumentation performed between Th3 and Th11 with pedicle screw system, followed by costotransversectomy of 7th and 8th costovertebral junctions and posterior spinal fusion for costal lesions. In the same operation, curettage was done for the lesion in Th6 vertebra and bone grafting and anterior total corpectomy were performed for Th7 and Th8 vertebrae. 360 degrees spinal fusion was done using titanium mesh as strut graft and autogenous rib grafts. Fibrous dysplasia occurs rarely in axial bones than peripheral bones. The cystic lesions in segments of the whole spine should be evaluated for the possibility of fibrous dysplasia with detailed radiographical examination and biopsy.


Intracranial tuberculoma in children: a new look at an old problem.
Intracranial tuberculoma has become a rare cause of space-occupying intracranial lesions in childhood, but it must still be considered in the differential diagnosis. Tuberculosis remains a significant disease in developing countries and in the United States, and tuberculoma is a well known presentation of childhood tuberculosis. This diagnosis must be considered especially in persons traveling or living in developing countries and in immigrants from third-world areas. We report three cases of tuberculoma in children seen during one year at our institutions to illustrate the need for continued suspicion. We summarize the clinical presentation and current treatment recommendations and review the available literature.


[Examination of the abdomen, let's train again ?]
This article describes the main clinical gestures to perform when a patient complains of acute abdominal pain. It summarizes the knowledge in general medicine by integrating whenever possible clinical reasoning with likelihood ratios. This chapter does not address complex situations.


Species-dependent effects of seawater acidification on alkaline phosphatase activity in dinoflagellates.
Increases of atmospheric CO2 cause ocean acidification (OA) and global warming, the latter of which can stratify the water column and impede nutrient supply from deep water. Phosphorus (P) is an essential nutrient for phytoplankton to grow. While dissolved inorganic phosphorus (DIP) is the preferred form of P, phytoplankton have evolved alkaline phosphatase (AP) to utilize dissolved organic phosphorus (DOP) when DIP is deficient. Although the function of AP is known to require pH > 7, how OA affects AP activity and hence the capacity of phytoplankton to utilize DOP is poorly understood. Here, we examined the effects of pH conditions (5.5-11) on AP activity from six species of dinoflagellates, an important group of marine phytoplankton. We observed a general pattern that AP activity declined sharply at pH 5.5, peaked between pH 7 and 8, and dropped at pH > 8. However, our data revealed remarkable interspecific variations in optimal pH and niche breadth of pH. Among the species examined, Fugacium kawagutii and Prorocentrum cordatum had an optimal pH at 8, and Alexandrium pacificum, Amphidinium carterae, Effrenium voratum, and Karenia mikimotoi showed an optimal pH of 7. However, whereas A. pacificum and K. mikimotoi had the broadest pH niche for AP (7-10) and F. kawagutii the second (8-10), Am. carterae, E. voratum, and P. cordatum exhibited a narrow pH range. The response of Am. carterae AP to pH changes was verified using purified AP heterologously expressed in Escherichia coli. These results in concert suggest OA will likely differentially impact the capacity of different phytoplankton species to utilize DOP in the projected more acidified and nutrient-limited future ocean.


Confluent laser photocoagulation for the treatment of retinopathy of prematurity.
To describe the efficacy, outcomes, and complications of confluent laser technique in a cohort of premature infants with threshold retinopathy of prematurity. Laser photocoagulation has a good treatment outcome in the management of retinopathy of prematurity; however, the number and density of laser spots remains debatable. Laser treatment can be done in a scattered pattern, a near-confluent pattern, or a confluent treatment pattern. A retrospective chart review of patients with threshold retinopathy of prematurity treated between 2003 and 2006 was conducted. Confluent laser treatment was applied anterior to the ridge extending to the ora serrata 360 degrees . Rate of progression, frequency of retreatment, postoperative complications, structural outcomes, and refractive error were evaluated. A total of 100 eyes from 51 patients were included. Mean gestational age was 28 weeks (range: 23 to 32 weeks) and mean birth weight was 1,065 g (range: 477 to 1,905 g). Patients had a mean follow-up of 13 months (range: 6 to 50 months). Progression to stage 4 or 5 occurred only in a total of 6 eyes (6%). Postoperative complications included cataract, vitreous hemorrhage, corneal edema, and macular dragging. Mean spherical equivalent at the last follow-up visit was -3.80 diopters (range: -19.00 to+4.00 diopters). Patients treated with confluent laser photocoagulation had a low rate of progression to stage 4 or 5 retinopathy of prematurity. Also, the need for additional laser treatment was small, with rates of complications and structural outcomes comparable to previous reports using a nonconfluent laser pattern.


The effects of UV irradiation on collagen D-band revealed by atomic force microscopy.
The objective of this paper was to investigate the influence of UV irradiation on collagen D-band periodicity by using the AFM imaging and nanoindentation methods. It is well known than UV irradiation is one of the main factors inducing destabilization of collagen molecules. Due to the human's skin chronic exposure to sun light, the research concerning the influence of UV radiation on collagen is of great interest. The impact of UV irradiation on collagen can be studied in nanoscale using Atomic Force Microscopy (AFM). AFM is a powerful tool as far as surface characterization is concerned, due to its ability to relate high resolution imaging with mechanical properties. Hence, high resolution images of individual collagen fibrils and load-displacement curves on the overlapping and gap regions, under various time intervals of UV exposure, were obtained. The results demonstrated that the UV rays affect the height level differences between the overlapping and gap regions. Under various time intervals of UV exposure, the height difference between overlaps and gaps reduced from ~3.7 nm to ~0.8 nm and the fibril diameters showed an average of 8-10% reduction. In addition, the irradiation influenced the mechanical properties of collagen fibrils. The Young's modulus values were reduced per 66% (overlaps) and 61% (gaps) compared to their initial values. The observed alterations on the structural and the mechanical properties of collagen fibrils are probably a consequence of the polypeptide chain scission due to the impact of the UV irradiation.


Monte Carlo Calculation of Beam Quality and Phantom Scatter Corrections for Lithium Formate Electron Paramagnetic Resonance Dosimeter for High-energy Brachytherapy Dosimetry.
To investigate beam quality correction, KQQ0 (r) and phantom scatter correction, Kphan (r) for lithium formate dosimeter as a function of distance r along the transverse axis of the high-energy brachytherapy sources 60Co, 137Cs, 192Ir and 169Yb using the Monte Carlo-based EGSnrc code system. The brachytherapy sources investigated in this study are BEBIG High Dose Rate (HDR) 60Co (model Co0.A86), 137Cs (model RTR), HDR 192Ir (model Microselectron) and HDR 169Yb (model 4140). The solid phantom materials investigated are PMMA, polystyrene, solid water, virtual water, plastic water, RW1, RW3, A150 and WE210. KQQ0 (r) is about unity and distance independent fo 60Co, 137Cs and 192Ir brachytherapy sources, whereas for the 169Yb source, KQQ0 (r) increases gradually to about 4 % larger than unity at a distance of 15 cm along the transverse axis of the source. For 60Co source, phantoms such as polystyrene, plastic water, solid water, virtual water, RW1, RW3 and WE210 are water-equivalent but PMMA and A150 phantoms show distance-dependent Kphan (r) values. For 137Cs and 192Ir sources, phantoms such as solid water, virtual water, RW1, RW3 and WE210 are water-equivalent. However, phantoms such as PMMA, plastic water, polystyrene and A150 showed distance-dependent Kphan (r) values, for these sources. For 169Yb source, all the investigated phantoms show distance-dependent Kphan (r) values. KQQ0 (r) is about unity and distance independent for 60Co, 137Cs and 192Ir brachytherapy sources. Phantoms such as solid water, virtual water, RW1, RW3 and WE210 are water-equivalent for 60Co, 137Cs and 192Ir brachytherapy sources. For 169Yb source, all the investigated phantoms show distance-dependent Kphan (r) values.


Declining p53 function in the aging process: a possible mechanism for the increased tumor incidence in older populations.
Cancer is a disease of aging. The accumulation of mutations in individual cells over a lifetime is thought to be the reason. In this work, we explored an additional hypothesis: could p53 function decline with age, which would contribute to an enhanced mutation frequency and tumorigenesis in the aging process? The efficiency of the p53 response to gamma-irradiation was found to decline significantly in various tissues of aging mice from several inbred strains, including lower p53 transcriptional activity and p53-dependent apoptosis. This decline resulted from a decreased stabilization of the p53 protein after stress. The function of the Ataxia-telangiectasia mutated (ATM) kinase declined significantly with age, which may then be responsible for the decline of the p53 response to radiation. Declining p53 responses to other stresses were also observed in the cultured splenocytes from aging mice. Interestingly, the time of onset of this decreased p53 response correlated with the life span of mice; mice that live longer delay their onset of decreased p53 activity with time. These results suggest an enhanced fixation of mutations in older individuals because of the declining fidelity of p53-mediated apoptosis or senescence in response to stress, and they suggest a plausible explanation for the correlation between tumorigenesis and the aging process.


Clustered negative charges on the lipid membrane surface induce beta-sheet formation of prion protein fragment 106-126.
The conformational conversion of prion protein (PrP) from an alpha-helix-rich normal cellular isoform (PrPC) to a beta-sheet-rich pathogenic isoform (PrPSc) is a key event in the development of prion diseases, and it takes place in caveolae, cavelike invaginations of the plasma membrane. A peptide homologous to residues 106-126 of human PrP (PrP106-126) is known to share several properties with PrPSc, e.g., the capability to form a beta-sheet and toxicity against PrPC-expressing cells. PrP106-126 is thus expected to represent a segment of PrP that is involved in the formation of PrPSc. We have examined the effect of lipid membranes containing negatively charged ganglioside, an important component of caveolae, on the secondary structure of PrP106-126 by circular dichroism. The peptide forms an alpha-helical or a beta-sheet structure on the ganglioside-containing membranes. The beta-sheet content increases with an increase of the peptide:lipid ratio, indicating that the beta-sheet formation is linked with self-association of the positively charged peptide on the negatively charged membrane surface. Analogous beta-sheet formation is also induced by membranes composed of negatively charged and neutral glycerophospholipids with high and low melting temperatures, respectively, in which lateral phase separation and clustering of negatively charged lipids occur as shown by Raman spectroscopy. Since ganglioside-containing membranes also exhibit lateral phase separation, clustered negative charges are concluded to be responsible for the beta-sheet formation of PrP106-126. In caveolae, clustered ganglioside molecules are likely to interact with the residue 106-126 region of PrPC to promote the PrPC-to-PrPSc conversion.


Pore-Structure Determinations of Silica Aerogels by 129Xe NMR Spectroscopy and Imaging
Silica aerogels represent a new class of open-pore materials with pore dimensions on a scale of tens of nanometers, and are thus classified as mesoporous materials. In this work, we show that the combination of NMR spectroscopy and chemical-shift selective magnetic resonance imaging (MRI) can resolve some of the important aspects of the structure of silica aerogels. The use of xenon as a gaseous probe in combination with spatially resolved NMR techniques is demonstrated to be a powerful, new approach for characterizing the average pore structure and steady-state spatial distributions of xenon atoms in different physicochemical environments. Furthermore, dynamic NMR magnetization transfer experiments and pulsed-field gradient (PFG) measurements have been used to characterize exchange processes and diffusive motion of xenon in samples at equilibrium. In particular, this new NMR approach offers unique information and insights into the nanoscopic pore structure and microscopic morphology of aerogels and the dynamical behavior of occluded adsorbates. MRI provides spatially resolved information on the nature of the flaw regions found in these materials. Pseudo-first-order rate constants for magnetization transfer among the bulk and occluded xenon phases indicate xenon-exchange rate constants on the order of 1 s-1 for specimens having volumes of 0.03 cm3. PFG diffusion measurements show evidence of anisotropic diffusion for xenon occluded within aerogels, with nominal self-diffusivity coefficients on the order of D = 10(-3) cm2/s. Copyright 1998 Academic Press.


Capability of airline jets as an observation platform for noctilucent clouds at middle latitudes.
The exact occurrence frequency of noctilucent clouds (NLCs) in middle latitudes is significant information because it is thought to be sensitive to long-term atmospheric change. We conducted NLC observation from airline jets in the Northern Hemisphere during the summer 2019 to evaluate the effectiveness of NLC observation from airborne platforms. By cooperating with the Japanese airline All Nippon Airways (ANA), imaging observations of NLCs were conducted on 13 flights from Jun 8 to Jul 12. As a result of careful analysis, 8 of these 13 flights were found to successfully detect NLCs from middle latitudes (lower than 55° N) during their cruising phase. Based on the results of these test observations, it is shown that an airline jet is a powerful tool to continuously monitor the occurrence frequency of NLCs at midlatitudes which is generally difficult with a polar orbiting satellite due to sparse sampling in both temporal and spatial domain. The advantages and merits of NLC observation from jets over satellite observation from a point of view of imaging geometry are also presented.


[Expression of bone marrow macrophages antigen activation and its clinical significance in pancytopenia patients with positive bone marrow mononuclear cells-Coombs test.].
To explore the expression of antigen activated of macrophages (MPhi) of bone marrow and its clinical significance in pancytopenia patients with positive bone marrow mononuclear cells (BMMNC)-Coombs test (immunorelated pancytopenia, IRP). Sixty-one IRP patients, 10 severe aplastic anemia (SAA) patients and 13 healthy controls were enrolled in this study. The categories of auto-antibodies (IgG, IgM) on BMMNC (CD(34)(+)/CD(15)(+)/GlycoA(+) hematocytes), the quantity (CD(68)(+)/CD(45)(+))% and expression of antigen activated (CD(69)) of MPhi (CD(68)(+)CD(69)(+)/CD(+)(68))% in bone marrow of all cases and controls were measured by fluorescence activated cell sorting (FACS). The quantity and expression ratio of activated antigen of bone marrow (BM) MPhi in IRP patients [(0.57 +/- 0.30)% and (40.30 +/- 18.49)%] were respectively significantly higher than those in SAA [(0.46 +/- 0.08)% and (32.44 +/- 19.37)%] and healthy controls [(0.44 +/- 0.69)% and (29.71 +/- 11.67)%] (both P < 0.05). The quantity presented high-positive correlation with the expression ratio of activated antigen of BM MPhi (r = 0.89, P < 0.01). Patients with IRP were classified into two subgroups according to the quantity of MPhi: Group A (MPhi >/= 0.5%, 34 cases) and Group B (MPhi < 0.5%, 27 cases). Thirty-two cases (94.12%) were with auto antibody (IgG) in Group A, while only 2 (7.41%) with auto antibody (IgG) in Group B. There was significant difference in expression ratio of activated antigen of BM MPhi between Group A (49.19 +/- 16.63)% and Group B (29.11 +/- 14.30)% (P < 0.05), but no difference was found between Group B and the control group (P > 0.05). Total curative rates at 3 and 6 month (47.06% and 79.41%) of Group A were better than those of Group B (22.22% and 51.85%). Thirty-four IRP patients with autoantibody (IgG)(+) were divided into two subgroups according to the quantity of MPhi: high level group (>/= 0.75%, 9 cases) and low level group (< 0.75%, 25 cases), 24 cases (96%) in MPhi low level group were found auto-antibody (IgG) on one hemotopoietic cell lineage, 1 on two lineages, while 8 (88.89%) in MPhi high level group were detected auto-antibody (IgG) on two cell lineages, and 1 on three cell lineages. Expression ratio of activated antigen (56.12 +/- 15.11)% was much higher in MPhi high level group than that in MPhi low level group (44.58 +/- 18.16)% (P < 0.05). The count of red blood cell concentration of hemoglobin and platelet in peripheral blood in MPhi high level group were respectively lower than those in MPhi low level group, while the percentage of Ret, the level of total bilirubin and indirect bilirubin, the ratio of erythroid of sternal bone marrow in MPhi high level group were higher than those in MPhi low level group. The expression of activated antigen of BM MPhi was enhanced in IRP especially with auto-antibody (IgG), which might be involved in damage process of hemotopoietic cell.


Allergic contact dermatitis from dicyclohexylmethane-4,4'-diisocyanate.
From August 1999 to April 2001, there was an outbreak of severe eczema at a factory manufacturing medical equipment. A glue, mainly based on the isocyanate dicyclohexylmethane-4,4'-diisocyanate (DMDI), was suspected as being the cause of the problem. 16 workers with recent episodes of eczema were patch tested with a standard series, an isocyanate series and work material. The latter consisted of, among other things, the glue, DMDI, and an amine, dicyclohexylmethane-4,4'-diamine (DMDA), which is formed when DMDI reacts with water. 13 patients reacted to DMDI, 9 to 1,6-hexamethylenediisocyanate (HDI) and 4 to isophoronediisocyanate (IPDI), all of which are aliphatic isocyanates. None reacted to the aromatic isocyanates, diphenylmethane-4,4'-diisocyanate (MDI) or toluenediisocyanate (TDI). One explanation for this pattern could be that aromatic diisocyanates are more reactive than the aliphatic ones and that, therefore, they are inactivated before penetrating the skin. 5 patients reacted to DMDA and 5 to 4,4'-diaminodiphenylmethane (MDA). Concurrent reactions to DMDA and or MDA with DMDI could be due to cross-reactivity. The positive reactions to MDA could also be a marker of MDI exposure. Yet another patient, investigated in 1997 with suspected work-related contact dermatitis from the glue, is described. She, however, showed no positive reactions to any isocyanates.


Transvaginal ultrasonographic evaluation of the endometrium related to the histological findings in pre- and perimenopausal women.
To evaluate the clinical usefulness of high-resolution transvaginal ultrasonography in pre- and perimenopausal women suspected to have endometrial pathology. 196 women, aged between 32 and 57 years, were referred to the outpatient clinic for a dilatation and curettage (D&C). In 81% the clinical indication was irregular vaginal bleedings. Before the D&C an examination with transvaginal ultrasonography was performed, and the endometrial thickness and texture were determined. The ultrasonographic results were later compared with the histological diagnosis obtained from the D&C specimen. Ultrasonographically both normal and pathological endometrial changes could be detected, and 82% of the women had an endometrium characterized as normal. The endometrial phase determination correlated with the histological findings in approximately 50% of the women. Histologically 83% of the women had a normal endometrium. Endometrial hyperplasia was found in 12% and endometrial polyps in 4%. There were no malignancies found in this study. The hormone users (33% of the women) had no higher incidence of hyperplasias than non-users. Our data indicate that transvaginal ultrasonography is as effective as the D&C for depicting the endometrium in pre- and perimenopausal women with irregular bleedings.


Relationship between textural properties and sensory qualities of cookies made from medium- and long-chain triacylglycerol-enriched margarines.
This study aims to investigate the textural properties and sensory qualities of cookies made from medium- and long-chain triacylglycerol (MLCT)-enriched margarines. Margarine with formulations of MLCT:palm olein:palm stearin, 60:30:10 and 70:20:10, were selected to produce cookies. The textural properties of cookies were determined using a texture analyser. Quantitative descriptive analysis (QDA) and acceptance test were carried out to describe the attributes and to evaluate the degree of liking of cookies, respectively. Cookies made from MLCT-enriched margarines showed high values for hardness, fracturability, but also for cohesiveness and adhesiveness. Trained panelists rated the cookies made from MLCT-enriched margarines to be lower as compared to those made from commercial margarine for most of QDA attributes. However, cookies made from MOS 603010 and commercial margarines were scored similarly (P > 0.05) for all acceptance test attributes. Overall acceptability was found to be highly and negatively correlated for hardness, fracturability and cohesiveness (R(2) > 0.90). Principal component analysis showed that the taste attribute of cookies and the % solid fat content of margarine at 35 degrees C highly influenced the overall quality of the cookies. Cookies made from MLCT-enriched margarines were not successfully produced. However, the findings obtained provide new perspectives in the production of low-calorie bakery fat.


Optical lymph node detection system: A practical device to assist lymph node location in neck resection specimens.
The status of lymph node (LN) metastasis, including the number and location of positive LNs, is a significant prognostic factor for oral squamous cell carcinoma (OSCC). Therefore, knowing the number and location of positive LNs is essential for prognosis. However, surgeons often have difficulty locating LNs. In the present study a practical device to improve the location of LNs in neck resection specimens was intoduced: the optical lymph nodes detection system (OLNDS). With the assistance of the OLNDS LNs were easier to locate and a significantly higher number of LNs were identified (P=0.006). The false detection rate was also significantly reduced compared with the traditional method (P=0.0034). The OLNDS was observed to be a valuable adjunct to the traditional method and may be useful for studying the value of LN metastasis in OSCC prognosis.


Identification of prosaposin as a neurotrophic factor.
Prosaposin was identified as a neurotrophic factor stimulating neurite outgrowth in murine neuroblastoma (NS20Y) cells and choline acetyltransferase (ChAT) activity in human neuroblastoma (SK-N-MC) cells. The four naturally occurring saposins, which are derived by proteolytic processing of prosaposin, were tested for activity. Saposin C was found to be active, whereas saposins A, B, and D were inactive as neurotrophic factors. Dose-response curves demonstrated that nanomolar concentrations of prosaposin and saposin C stimulated neurite outgrowth and increased ChAT activity. Prosaposin and saposin C exerted activity by a mechanism independent of nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3. Binding assays utilizing saposin C as a ligand gave two saturable binding constants, a high-affinity (Kd = 19 pM) and a low-affinity (Kd = 1 nM) constant, with 2000 and 15,000 sites per NS20Y cell, respectively. Phosphorylation stimulation experiments demonstrated that brief treatment with prosaposin or saposin C enhanced phosphorylation of a variety of proteins, some of which contained phosphorylated tyrosine(s). Since both cell lines were also stimulated by ciliary neurotrophic factor (CNTF) as well as prosaposin, inhibition was tested by utilizing an anti-gp130 monoclonal antibody, which specifically inhibited CNTF stimulation; this antibody did not inhibit prosaposin or saposin C stimulation. These results indicate that prosaposin and saposin C are neurotrophic factors which initiate signal transduction by binding to a high-affinity receptor that induces protein phosphorylation.


Pediatric palliative and hospice care: Pennsylvania's model of collaboration.
In the state of Pennsylvania, a collaborative model has been developed for improving pediatric palliative care and end-of-life care services to children with life-limiting conditions and their families. The inspiration and efforts of several bereaved parents provided the initial impetus for this encouraging model. Pennsylvania's model involves cooperation and collaboration among several groups and initiatives across the state, as well as the integration of parent-professional collaboration at all levels and in each initiative. The collaborating groups include 1) a volunteer grassroots resource and education initiative, Helping Hands-Healing Hearts; 2) the Pittsburgh Pediatric Palliative Care Coalition, a coalition of concerned parents and experienced palliative and hospice care providers working together to improve service availability; and 3) the Pennsylvania Children's Hospice and Palliative Care Coalition, which developed as an outcome of a state-level Pennsylvania Pediatric Hospice Care Task Force, and which, among other activities, works with the Pennsylvania Department of Public Welfare and several Pennsylvania legislators on pertinent policy and legislative initiatives.


Extracellular matrix dynamics during mesenchymal stem cells differentiation.
Mesenchymal stem cells (MSCs) are stromal cells that display self-renewal and multipotent differentiation capacity. The repertoire of mature cells generated ranges but is not restricted to: fat, bone and cartilage. Their potential importance for both cell therapy and maintenance of in vivo homeostasis is indisputable. Nonetheless, both their in vivo identity and use in cell therapy remain elusive. A drawback generated by this fact is that little is known about the MSC niche and how it impacts differentiation and homeostasis maintenance. Hence, the roles played by the extracellular matrix (ECM) and its main regulators namely: the Matrix Metalloproteinases (MMPs) and their counteracting inhibitors (TIMPs and RECK) upon stem cells differentiation are only now beginning to be unveiled. Here, we will focus on mesenchymal stem cells and review the main mechanisms involved in adipo, chondro and osteogenesis, discussing how the extracellular matrix can impact not only lineage commitment, but, also, their survival and potentiality. This review critically analyzes recent work in the field in an effort towards a better understanding of the roles of Matrix Metalloproteinases and their inhibitors in the above-cited events.


Void coalescence in core/alloy nanoparticles with stainless interfaces.
The oxidation properties of nanoparticles with core/alloy microstructure and stainless steel like interfaces is described. In particular, 15-nm Fe/FeCr nanoparticles with a stainless steel like interface are prepared. These particles show a unique morphological transformation that is induced by surface oxidation, oxide passivation, and vacancy coalescence. This Kirkendall diffusion results in a tailorable oxide layer thickness, Fe-core size, as well as void size and symmetry. Much like the interface of bulk stainless steel, the interfacial FeCr oxide passivates oxidation, resulting in self-limited diffusion. Because of this, a highly uniform and stable core-void-shell morphology is observed.


Can nonstandardized bitewing radiographs be used to assess the presence of alveolar bone loss in epidemiologic studies?
To compare periodontitis-associated alveolar bone loss assessment by standardized and nonstandardized radiographs in clinical and epidemiologic studies. Participants included 37 patients aged 21-66 years with prior nonstandardized bitewing radiographs scheduled to receive bitewing radiographs as part of their next routine dental care visit. Standardized bitewing radiographs were taken with a Rinn film holder to position the film in the mouth and align the X-rays so that they were at 90 degrees to the film. Before taking the radiograph the bite was registered in centric relation using a polyether impression material. One registered dental hygienist took and processed all the standardized radiographs. One dentist read all radiographs using a viewing box, magnifying lens, and periodontal probe with William's markings. Radiographic bone loss was measured to the closest millimeter at mesial and distal sites of the posterior teeth excluding third molars. The examining dentist was blinded to the participant's name, age, gender, or if the radiograph was standardized or nonstandardized. Mean bone loss (+/- SD) was similar in the standardized and nonstandardized groups (1.60 +/- 0.72 mm versus 1.64 +/- 0.85 mm), and the correlation was high (r = 0.95). Periodontitis was defined as present if the participant had at least one site with 3, 4 and 5 mm bone loss. The Kappa statistics for concordance using these three cutoffs were good and ranged from 0.60 to 0.65. The sensitivity ranged from 72.7 to 80.8% and specificity from 88.5 to 90.9%. Periodontitis assessed as mean alveolar bone loss or the prevalence of disease based on alveolar bone loss can be accurately and reliably evaluated from nonstandardized radiographs.


Feasibility of ablative fractional laser-assisted drug delivery with optical coherence tomography.
Fractional resurfacing creates hundreds of microscopic wounds in the skin without injuring surrounding tissue. This technique allows rapid wound healing owing to small injury regions, and has been proven as an effective method for repairing photodamaged skin. Recently, ablative fractional laser (AFL) treatment has been demonstrated to facilitate topical drug delivery into skin. However, induced fractional photothermolysis depends on several parameters, such as incident angle, exposure energy, and spot size of the fractional laser. In this study, we used fractional CO2 laser to induce microscopic ablation array on the nail for facilitating drug delivery through the nail. To ensure proper energy delivery without damaging tissue structures beneath the nail plate, optical coherence tomography (OCT) was implemented for quantitative evaluation of induced microscopic ablation zone (MAZ). Moreover, to further study the feasibility of drug delivery, normal saline was dripped on the exposure area of fingernail and the speckle variance in OCT signal was used to observe water diffusion through the ablative channels into the nail plate. In conclusion, this study establishes OCT as an effective tool for the investigation of fractional photothermolysis and water/drug delivery through microscopic ablation channels after nail fractional laser treatment.


Endoplasmic reticulum stress as a novel mechanism in amiodarone-induced destructive thyroiditis.
Amiodarone (AMIO) is one of the most effective antiarrhythmic drugs available; however, its use is limited by a serious side effect profile, including thyroiditis. The mechanisms underlying AMIO thyroid toxicity have been elusive; thus, identification of novel approaches in order to prevent thyroiditis is essential in patients treated with AMIO. Our aim was to evaluate whether AMIO treatment could induce endoplasmic reticulum (ER) stress in human thyroid cells and the possible implications of this effect in AMIO-induced destructive thyroiditis. Here we report that AMIO, but not iodine, significantly induced the expression of ER stress markers including Ig heavy chain-binding protein (BiP), phosphoeukaryotic translation initiation factor 2α (eIF2α), CCAAT/enhancer-binding protein homologous protein (CHOP) and spliced X-box binding protein-1 (XBP-1) in human thyroid ML-1 cells and human primary thyrocytes. In both experimental systems AMIO down-regulated thyroglobulin (Tg) protein but had little effect on Tg mRNA levels, suggesting a mechanism involving Tg protein degradation. Indeed, pretreatment with the specific proteasome inhibitor MG132 reversed AMIO-induced down-regulation of Tg protein levels, confirming a proteasome-dependent degradation of Tg protein. Corroborating our findings, pretreatment of ML-1 cells and human primary thyrocytes with the chemical chaperone 4-phenylbutyric acid completely prevented the effect of AMIO on both ER stress induction and Tg down-regulation. We identified ER stress as a novel mechanism contributing to AMIO-induced destructive thyroiditis. Our data establish that AMIO-induced ER stress impairs Tg expression via proteasome activation, providing a valuable therapeutic avenue for the treatment of AMIO-induced destructive thyroiditis.


A Single-Molecule Bioelectronic Portable Array for Early Diagnosis of Pancreatic Cancer Precursors.
A cohort of 47 patients is screened for pancreatic cancer precursors with a portable 96-well bioelectronic sensing-array for single-molecule assay in cysts fluid and blood plasma, deployable at point-of-care (POC). Pancreatic cancer precursors are mucinous cysts diagnosed with a sensitivity of at most 80% by state-of-the-art cytopathological molecular analyses (e.g., KRASmut DNA). Adding the simultaneous assay of proteins related to malignant transformation (e.g., MUC1 and CD55) is deemed essential to enhance diagnostic accuracy. The bioelectronic array proposed here, based on single-molecule-with-a-large-transistor (SiMoT) technology, can assay both nucleic acids and proteins at the single-molecule limit-of-identification (LOI) (1% of false-positives and false-negatives). It comprises an enzyme-linked immunosorbent assay (ELISA)-like 8 × 12-array organic-electronics disposable cartridge with an electrolyte-gated organic transistor sensor array, and a reusable reader, integrating a custom Si-IC chip, operating via software installed on a USB-connected smart device. The cartridge is complemented by a 3D-printed sensing gate cover plate. KRASmut , MUC1, and CD55 biomarkers either in plasma or cysts-fluid from 5 to 6 patients at a time, are multiplexed at single-molecule LOI in 1.5 h. The pancreatic cancer precursors are classified via a machine-learning analysis resulting in at least 96% diagnostic-sensitivity and 100% diagnostic-specificity. This preliminary study opens the way to POC liquid-biopsy-based early diagnosis of pancreatic-cancer precursors in plasma.


Progress in the blood supply of Afghanistan.
The blood supply system in Afghanistan was badly damaged by years of conflict. In 2009, the Afghanistan National Blood Safety and Transfusion Service (ANBSTS) was established. For 6 years, we collaborated to assist with policy and infrastructure development; blood bank operations; blood collection, testing, and component production; transfusion practices; and training of technicians, nurses, midwives, and physicians. Policies were established, infrastructure was strengthened, and capable staff was acquired and trained. Standard operating procedures were developed, testing was improved, and quality systems were established. Thirty trainings were held for blood center staff. Four additional formal trainings were held for 39 physicians, 36 nurses and/or midwives, and 38 laboratory technicians. During 5 years of this project, blood collection increased by 40%. The ANBSTS has made impressive progress developing infrastructure, personnel, procedures, quality systems, and training programs and increasing blood collection. Knowledge of transfusion medicine was improved through structured training.


Triangular Alignment (TAME): A Tensor-Based Approach for Higher-Order Network Alignment.
Network alignment has extensive applications in comparative interactomics. Traditional approaches aim to simultaneously maximize the number of conserved edges and the underlying similarity of aligned entities. We propose a novel formulation of the network alignment problem that extends topological similarity to higher-order structures and provides a new objective function that maximizes the number of aligned substructures. This objective function corresponds to an integer programming problem, which is NP-hard. Consequently, we identify a closely related surrogate function whose maximization results in a tensor eigenvector problem. Based on this formulation, we present an algorithm called Triangular AlignMEnt (TAME), which attempts to maximize the number of aligned triangles across networks. Using a case study on the NAPAbench dataset, we show that triangular alignment is capable of producing mappings with high node correctness. We further evaluate our method by aligning yeast and human interactomes. Our results indicate that TAME outperforms the state-of-art alignment methods in terms of conserved triangles. In addition, we show that the number of conserved triangles is more significantly correlated, compared to the conserved edge, with node correctness and co-expression of edges. Our formulation and resulting algorithms can be easily extended to arbitrary motifs.


Plasma triglycerides and type III hyperlipidemia are independently associated with premature familial coronary artery disease.
This study was designed to explore contributions of plasma total triglycerides (TGs) and type III hyperlipidemia to the risk of premature familial coronary artery disease (CAD). Although plasma TGs are recognized as a risk factor for CAD, the independence of this association from related risk factors remains controversial. Also, the degree of CAD risk conferred by excess remnants of TG-rich lipoproteins in type III hyperlipidemia remains unclear. We analyzed lipids by ultracentrifugation in a series of 653 cases with premature familial CAD (myocardial infarction or revascularization by age 55 years in men or age 65 years in women, with similar onset in at least one other first-degree relative) and in 1,029 control subjects. The relationship of CAD risk to various strata of plasma TGs, high-density lipoprotein (HDL) cholesterol, and type III hyperlipidemia, and interactions among these variables were examined by multiple logistic regression, adjusting for other CAD risk factors. The odds ratio for CAD with elevated plasma TG rose progressively to 11.4 in those with TGs 500 to 799 mg/dl (95% confidence interval 3.4 to 38.0, p < 0.0001) compared with <100 mg/dl, even after correction for HDL cholesterol, other elements of the metabolic syndrome, and other CAD risk factors. Risk of CAD associated with type III hyperlipidemia (found in 3.4% of cases) was also markedly increased independent of other risk factors (odds ratios of 5 to 10 depending on the model, all with p < 0.002). The association between the plasma TG level and premature familial CAD is strong, graded, and independent. Risk of CAD is also strikingly elevated with type III hyperlipidemia.


[Relations between quality and nursing care: integrative literature review].
This article aims at presenting the strategies that can be used by the nurse to accomplish compromised actions for the promotion of the nursing assistance with quality through an integrative literature review. The conclusions of previous studies are summarized in order to formulate inferences about a specific topic. The research was proceeded using the LILACS and BEDENF databases, using indexed articles published up to 2006. Four studies composed the sample. It was used an instrument of data collection made by the researcher. Only one study pointed strategies with potential to promote the nursing assistance. Such strategies require action and persistence from the Nursing professionals to activate this potential, thus, provoking the necessary changes to the promotion of the assistance.


177Lu-EB-PSMA Radioligand Therapy with Escalating Doses in Patients with Metastatic Castration-Resistant Prostate Cancer.
This study was designed to assess the safety and therapeutic response to 177Lu-labeled Evans blue-modified prostate-specific membrane antigen (PSMA) 617 (EB-PSMA-617) treatment with escalating doses in patients with metastatic castration-resistant prostate cancer. Methods: With institutional review board approval and informed consent, patients were randomly divided into 3 groups: group A (n = 10) was treated with a 1.18 ± 0.09 GBq dose of 177Lu-EB-PSMA. Group B (n = 10) was treated with a 2.12 ± 0.19 GBq dose of 177Lu-EB-PSMA. Group C (n = 8) was treated with a 3.52 ± 0.58 GBq dose of 177Lu-EB-PSMA. Eligible patients received up to 3 cycles of 177Lu-EB-PSMA therapy, at 8-wk intervals. Results: Because of disease progression or bone marrow suppression, 4 of 10, 5 of 10, and 5 of 8 patients completed 3 cycles of therapy as planned in groups A, B, and C, respectively. The prostate-specific antigen response was correlated with treatment dose, and the prostate-specific antigen disease control rates were higher in groups B (70%) and C (75%) than in group A (10%) (P = 0.007), but no correlation between groups B and C was found. 68Ga-PSMA PET/CT showed a response in all treatment groups; however, there was no significant difference among the 3 groups. A hematologic toxicity study found that platelets decreased more in groups B and C than in group A and that grade 4 thrombocytopenia occurred in 2 (25.0%) patients in group C. No serious nephritic or hepatic side effects were observed. Conclusion: This study demonstrated that a 2.12-GBq dose of 177Lu-EB-PSMA seems to be safe and adequate in tumor treatment. Further investigations with an increased number of patients are warranted.


Medical underwriting gets an electronic makeover.
Taditional new business underwriting, especially in small group and individual markets, is limited by the amount of information that carriers obtain. The current method of medical underwriting driven by questionnaire responses is labor-intensive and time-consuming for the prospective insured, the broker, and the insurance carrier.


The relationship between ionic structure and viscosity in room-temperature ionic liquids.
We investigate the relationship between ionic structure and viscosity in room-temperature ionic liquids. We build on an earlier theoretical work and derive an ionic property we call the charge lever moment (CLM) that provides insight on ionic liquid dynamics. We use electronic structure calculations to determine the CLM for ions in typical ionic liquids and demonstrate a correlation between this property and the experimental viscosities of ionic liquids. The relationship provides insight into the role of librational motion in ionic liquids in general, and the interpretation of Kerr effect experiments is discussed.


Asymbiotic seed germination and in vitro seedling development of Orchis militaris, an endangered orchid in Siberia.
Terrestrial orchids belonging to the Orchis genus are difficult to propagate and are under great pressure in their natural habitats. Studies regarding the influence of photoperiod and temperature regimes on Orchis militaris germination and morphological changes during immature seed development in vitro are scarce. Our aim was to identify photoperiod, temperature, and different nutrient media requirements for optimization of O. militaris seed germination and vigorous seedling production. Post-germination morphological changes were recorded with O. militaris seeds collected from 32-day-old fruits, where the percentage of O. militaris seeds without embryo was 38.4%. The highest rate of O. militaris seed germination (82.6%) was obtained on Malmgren modified terrestrial orchid medium (mM), enriched by 5% coconut water, 5% birch sap, and 0.1% AC. Nine percent of seedlings were able to reach the advanced seedling stage (stage 6) after 12 months of maintenance on this medium. In all 3 modified media (Harvais, Knudson С and Malmgren), regeneration was via the production of protocorms and seedlings without callus formation. It was proved that more abundantly vigorous protocorms were formed on the modified Harvais 2 under continuous darkness, while the subculture in Knudson C medium with AC addition could be necessary to stimulate their further development. The regeneration success of the species for in vitro conditions was increased by following its natural seasonal cycle. This study demonstrated an efficient micropropagation system for O. militaris using immature seeds and thus widely opened the perspectives for its conservation in nature. The favorable conditions of seed germination periods for in vitro culture, identified as the definite shift of temperatures and photoperiod regimes intrinsic to the species in nature, could improve seedling survival of this medicinally important orchid.


4-Guanidino-2-pyrimidinone nucleobases: synthesis and hybridization properties.
N-Alkylated 4-guanidino-2-pyrimidinone-containing nucleosides, in which the guanidine group mimics the double hydrogen bond donor pattern of protonated cytosine, were introduced in polypyrimidine sequences to explore their triple-helix forming capabilites. UV and CD melting experiments showed that strands containing these base analogues did not form triplex complexes.


[Cholangitis revealing an intrahepatic Osler's disease].
Osler Weber Rendu Disease is an hereditary haemorrhagic télangectasia habitually revealed by reccurent bleeding (epistaxis). Hepatic involvement in Osler disease is found in 8 to 31%, manifested by cholestasis. We report an original observation of a cholangitis revealing Osler disease.


[Coping with anger by cardiovascular patients].
Patients with essential hypertension and coronary heart disease were compared to a healthy and clinical control group an the recently developed Müller-Anger-Coping Questionnaire (MAQ). The inventory measures the factors "Spontaneous Behavior" (f1), "Controlled Affect" (f2), "Guilt" (f3) and "Social Inhibition" (f4) as a trait. The patients, suffering from essential hypertension, in comparison to the healthy control group, showed significant differences on factors 2 to 4, indicating, that they are expressing anger to a lesser degree and that they are more likely to exhibit an anger-in/guilt coping style. The same was true for patients suffering from coronary heart disease with respect to factors 2 and 4. With respect to "Guilt" coronary heart disease patients showed a clear trend for more feelings of guilt after anger expression, as compared to the healthy control group. None of the groups showed significant differences on expressing anger-in an aggressive manner (factor 1). These results provide further evidence, that patients with cardiovascular disorders have a clear tendency to show anger to a lesser degree in an socially assertive manner and to suppress anger. If anger is expressed by these patients, they tend to feel guilty. Implications of the findings are discussed.


Survey of Korean dentists on the awareness on bisphosphonate-related osteonecrosis of the jaws.
This survey evaluates the awareness of bisphosphonate-related osteonecrosis of the jaws among Korean dentists. We prepared a questionnaire based on bisphosphonate-related osteonecrosis of the jaw guidelines, suggested by The American Association of Oral Maxillofacial Surgeons. Among 13,405 dentists, we randomly selected 264 (2%) practitioners. A total of 56.5% of respondents had heard of bisphosphonates as medication related to osteonecrosis, but only 31.4% routinely recorded bisphosphonate medication history. The cross-sectional analysis demonstrated that most dentists were unaware of The American Association of Oral Maxillofacial Surgeons' guidelines. Dentists with <5 years' clinical experience were significantly more aware than those with >5 years' experience. Experience with treating osteonecrosis of the jaw patients and recording medication histories were significantly greater in dental hospitals with >300 beds or university hospitals. Awareness of the severity of bisphosphonate-related osteonecrosis of the jaws was greatest among oral surgeons. Dentists should thoroughly check patients' medical histories, including bisphosphonate intake. With the exception of oral surgeons, most Korean dentists were not adequately aware of bisphosphonate-related osteonecrosis of the jaws and its seriousness, making it a potential risk in Korean dentistry. Therefore, it is important to educate clinicians regarding the potential risk of bisphosphonate medication in dentistry through education programs.


[Biodegradation of surface-active substances of Acinetobacter calcoaceticus K-4].
A capacity of microorganisms of different taxonomic groups to assimilate surface-active substances (surfactants) of Acinetobacter calcoaceticus K-4 as a single source of carbon and energy has been established. It was shown that A. calcoaceticus K-4 cannot use its own surfactants as a source of carbon nutrition. The use of biocide formalin in concentration of 0.1% permits to prolong the term of preservation of A. calcoaceticus K-4 surfactants to 3.5 months without a loss of their surfactant and emulsiying properties.