Subdural Hemorrhage in Asymptomatic Neonates: Neurodevelopmental Outcomes and MRI Findings at 2 Years.
Background Subdural hemorrhage (SDH) is thought to have a benign course in asymptomatic neonates. However, effects on neurodevelopmental outcomes have not been established. Purpose To evaluate neurodevelopmental outcomes, gray matter volumes, and MRI findings in asymptomatic neonates with SDH compared with control neonates. Materials and Methods This retrospective analysis was conducted between 2003 and 2016 and was based on data from the University of North Carolina Early Brain Development Study. Neurodevelopmental outcomes were evaluated at 2 years of age by using the Mullen Scales of Early Learning (MSEL). All infants were imaged with 3.0-T MRI machines and were evaluated for SDH at baseline (neonates) and at ages 1 and 2 years. Volumetric MRI for brain segmentation was performed at ages 1 and 2 years. A secondary analysis was performed in neonates matched 1:1 with control neonates. Differences in categorical variables were measured by using the Fisher exact test, and the t test was used for continuous variables. Results A total of 311 neonates (mean gestational age ± standard deviation, 39.3 weeks ± 1.5), including 57 with SDH (mean gestational age, 39.5 weeks ± 1.2), were evaluated. The subgroup included 55 neonates with SDH (mean gestational age, 39.6 weeks ± 1.2) and 55 matched control neonates (mean gestational age, 39.7 weeks ± 1.2). Fifty-five of 57 neonates with SDH (97%; 95% CI: 92, 100) were delivered vaginally compared with 157 of 254 control neonates (62%, 95% CI: 56, 68; P < .001). Otherwise, there were no differences in perinatal, maternal, or obstetric parameters. There were no differences in composite MSEL scores (115 ± 15 and 109 ± 16 at 2 years, respectively; P = .05) or gray matter volumes between the neonatal SDH group and control neonates (730 cm3 ± 85 and 742 cm3 ± 76 at 2 years, respectively; P = .70). There was no evidence of rebleeding at follow-up MRI. Conclusion Neurodevelopmental scores and gray matter volumes at age 2 years did not differ between asymptomatic neonates with subdural hemorrhage and control neonates. © RSNA, 2020 Online supplemental material is available for this article.


Naphthalimide-Based AIEgens for Sensing Protein Disulfide Isomerase through Thiol-Disulfide Redox Exchange.
Aggregation-induced emission (AIE)-based fluorescent organic nanoparticles (FONPs) with distinctive characteristics are emerging as superior sensors due to their facile fabrication, high signal-to-noise ratio, and good biocompatibility. The present article delineates the detection and analysis of the redox behavior of the protein disulfide isomerase (PDI) enzyme by exploitation of the AIE of novel naphthalimide (NI) derivatives having thiol (-SH) and disulfide (-S-S-) moieties. Self-aggregated spherical-shaped organic nanoparticles were prepared by synthesized NI-based amphiphiles (NISH, NISS, NINSS, and TNINSH) through J-type aggregation in DMSO-water (fw = 99 vol %). Naphthyl residue containing NI-derived amphiphiles (NINSS and TNINSH) exhibited AIE (blue and yellow) at 470 and 550 nm, respectively, in DMSO-water (fw = 99 vol %). NINSS and TNINSH FONPs were suitably utilized in sensing PDI through their redox nature of thiol-disulfide exchange. Fluorescence quenching of NINSS FONPs was observed due to reduction of disulfide to thiol by PDI, whereas emission intensity was progressively red-shifted and enhanced ("Dual-AIE") for TNINSH (containing ER-targeting N-tosylethylenediamine), owing to oxidation of thiol to disulfide by PDI. NINSS and TNINSH FONPs were found to be highly efficient in sensing PDI through the AIE-based "fluorescence off/on" mechanism having limits of detection of ∼12.6-17.7 and ∼11.7-16.5 ng/mL, respectively. In vitro cell imaging for NIH3T3 (noncancer) and B16F10 (melanoma) cells with NINSS and TNINSH FONPs displayed excellent diagnosis of eukaryotic cells upon interaction with indigenous PDI. Notably, detection of cancer cells was more sensitive over the noncancerous cells by these FONPs due to overexpression of PDI within cancer cells.


Obesity among black women in food deserts: An "omnibus" test of differential risk.
The "omnibus" hypothesis, as forwarded by Ford and Dzewaltowski (2008), asserts that poor-quality food environments differentially affect low- and high-socioeconomic status (SES) populations. Accordingly, we examine, in a large sample of non-Hispanic (NH) black women, whether low access to healthy food corresponds with increased risk of obesity among residents of low- and high-poverty neighborhoods. In addition, we analyze whether any discovered association between low-food access and obesity appears stronger in neighborhoods with a high proportion of black residents. We retrieved body mass index (BMI) data for 97,366 NH black women residing in 6258 neighborhoods from the California Department of Public Health birth files for years 2007-2010. We linked BMI data with census tract-level data on neighborhood food access from the 2010 Food Access Research Atlas and neighborhood poverty and black composition from the 2006-2010 American Community Survey 5-year estimates. We applied generalized estimating equation methods that permit analysis of clustered data within neighborhoods. Methods also controlled for individual-level characteristics which might confound the relation between food access and obesity, including health insurance status, age, education, and parity. Results indicate that low-food access does not impact risk of obesity among NH black women residing in low-poverty neighborhoods. However, low-food access varies positively with risk of obesity in high-poverty neighborhoods. Moreover, the association between low-food access and obesity appears stronger in high-poverty, high-black composition neighborhoods, relative to high-poverty, low-black composition neighborhoods. Our findings support the omnibus hypothesis and indicate a potential interaction between factors in the local food and social environments on an individual's risk of obesity.


Ochratoxin A in sultanas from Turkey I: Survey of unprocessed sultanas from vineyards and packing-houses.
A method for the determination of ochratoxin A (OTA) in sultanas from Turkey using extraction with a sodium bicarbonate solution (2% NaHCO3) followed by immunoaffinity clean-up and liquid chromatography with fluorescence detection was used to assess the frequency of occurrence and level of OTA. In-house validation was carried out with spiked samples at levels of 0.15, 1.5, 5.0 and 10 microg kg-1 and average recoveries were 91, 93, 87 and 89%, respectively. The limits of detection and limit of quantification in Turkish sultanas were 0.026 and 0.09 microg kg-1, respectively. A survey for the presence of OTA was carried out on 264 unprocessed sultana samples during the production seasons between 1998 and 2000 collected annually from vineyards and from packing-houses. The analyses of unprocessed sultanas showed that 32.2% of the total number of samples contained no detectable OTA, whereas 9.8% of sultana samples had OTA concentrations above 10 microg kg-1, and the remaining 58% had levels within the range 0.026-10 microg kg-1. There were big differences in median concentrations between years. Considering the year of production, it appears that sultanas produced in 1998 and 2000 showed the lowest incidence of OTA contamination (median<0.02 microg kg-1), whereas 2002 showed the highest incidence (median=4.3 microg kg-1). The overall mean OTA concentration was calculated as 3.4 microg kg-1, and the overall median as 0.9 microg kg-1. Among the samples analysed, the highest detected level of OTA was 54 microg kg-1.


An International Marine-Atmospheric 222Rn Measurement Intercomparison in Bermuda Part I: NIST Calibration and Methodology for Standardized Sample Additions.
As part of an international 222Rn measurement intercomparison conducted at Bermuda in October 1991, NIST provided standardized sample additions of known, but undisclosed ("blind") 222Rn concentrations that could be related to U.S. national standards. The standardized sample additions were obtained with a calibrated 226Ra source and a specially-designed manifold used to obtain well-known dilution factors from simultaneous flow-rate measurements. The additions were introduced over sampling periods of several hours (typically 4 h) into a common streamline on a sampling tower used by the participating laboratories for their measurements. The standardized 222Rn activity concentrations for the intercomparison ranged from approximately 2.5 Bq · m-3 to 35 Bq · m-3 (of which the lower end of this range approached concentration levels for ambient Bermudian air) and had overall uncertainties, approximating a 3 standard deviation uncertainty interval, of about 6 % to 13 %. This paper describes the calibration and methodology for the standardized sample additions.


Unidirectional Wetting of Liquids on "Janus" Nanostructure Arrays under Various Media.
We report the unidirectional wetting behavior of liquids (water and oil) on Janus silicon cylinder arrays (Si-CAs) under various media (air, water, and oil). The Janus cylinders were prepared by chemical modification of nanocylinders with different molecules on two sides. Through adjusting surface energies of the modified molecules, the as-prepared surfaces could control the wetting behavior of different types of liquids under various media. We discuss the regularity systematically and propose a strategy for preparing anisotropic wetting surfaces under arbitrary media. That is, to find two surface modification molecules with different surface energies, one of the molecules is easy to be wetted by the liquid under the corresponding media, while the other one is difficult. Additionally, by introducing thermal-responsive polymer brushes onto one part of Janus Si-CAs, the surfaces show thermal-responsive anisotropic wetting property under various media. We believe that due to the excellent unidirectional wettability under various media, the Janus surfaces could be applied in water/oil transportation, oil-repellent and self-cleaning coatings, water/oil separation, microfluidics, and so on.


[Rapid determination of optimal time for peripheral blood stem cell harvest by detecting hematopoietor progenitor cell during mobilization].
To develop a simple method to rapidly determine the optimal time of perpheral blood stem cell harvest. We selected 5 healthy donors mobilized with granulocyte colony-stimulating factor (G-CSF) in allogenic peripheral blood stem cell transplantation (allo-PBSCT) to continuously monitor the variety of hematopoietic stem/progenitor cells (HSC/HPC) in the peripheral blood. HPC in the peripheral blood was detected by Sysmex XE-2100 fully automated hematology analyzer with an immature myeloid information channel and the CD34+ cells and colony-forming unit-granulocyte-macrophage (CFU-GM) were determined by flow cytometry and colony culture during mobilization. HPC was positively correlated with the CD34+ cells or CFU-GM in the peripheral blood (r = 0.82 or r = 0.85, respectively). HPC, CD34+ cells, and CFU-GM in allo-PBSCT donors obviously increased on the 4th day after the mobilization, and their peaks were on the 5th day after the mobilization. But HPC varied more than CD34+ cells and CFU-GM did. Sysmex XE-2100 can rapidly monitor the variety of HSC/HPC in allo-PBSCT donors mobilizated with G-CSF, and can provide a simple and economic method to determine the optimal time of peripheral blood stem cell harvest.


Outcome of patients with post acute myocardial infarction ischemia hospitalized in intensive cardiac care units with and without on-site catheterization laboratories.
This study addresses the impact of availability of on-site catheterization laboratories on the 1-year survival of patients with post-acute myocardial infarction ischemia (P-AMI-I), a high-risk subgroup of AMI patients. A prospective 5 month national survey was conducted in 1996 in all operating intensive care units (ICCUs) in Israel (N=26) and included 2377 patients. Four hundred and three (17%) had P-AMI-I, 317 of them were admitted to 18 ICCUs with on-site catheterization laboratories (CATH+) and 86 patients to 8 ICCUs without such facilities (CATH-). A retrospective analysis was performed comparing the in-hospital course and 7 day, 1 month and 1 year mortality data of CATH+ vs. CATH- patients. Patient characteristics in both groups were similar with regard to age, gender AMI location, risk factors, hemodynamic parameters on admission and rate of thrombolytic therapy. Of patients in CATH+, 79% were catheterized before hospital discharge vs. 42% in CATH- (P<0.0001), 45 vs. 15% had PTCA (P<0.0001) and 19 vs. 9% had CABG (P<0.05). At 30 days, patients in CATH+ still had significantly more revascularization procedures (71 vs. 48%, P<0.001). Patients hospitalized in ICCUs with CATH+ and CATH- facilities had similar cardiac mortality rates at 7 days (2.0 vs. 2.3%), 30 days (5.7 vs. 4.7%) and at 1 year (7.6 vs. 7.0%). Despite a more invasive strategy used during the index hospitalization of patients with P-AMI-I hospitalized in CATH+ ICCUs, their survival was similar to CATH- patients at 7 days, 30 days and at 1 year follow-up.


Socioeconomic aspects of hepatic transplantation.
The outcome, cost, length of hospital stay, and extent of rehabilitation were assessed in a series of 55 consecutive patients who received hepatic transplants between May 1982 and June 1985. In the same geographic region, medical costs for patients dying of hepatic failure without transplantation were studied for years 1979 through 1984. One-yr survival in all patients transplanted without cancer was 71%, and the mean cost was $92,866. The mean cost of hospitalization for the last 12 months of life in patients who did not receive transplants was $45,643. Eight-two percent of patients surviving the first yr are fully rehabilitated and restored to pre-illness activity. Length of hospital stay, hospital costs, and the extent of rehabilitation closely correlate with a grading system based on preoperative medical status. We conclude that hepatic transplantation restores high-quality, useful life to patients with endstage liver disease in a predictable and cost-effective manner.


Prediction of recurrence in operable breast cancer by postoperative changes in prolactin secretion.
It has been demonstrated that breast surgery may induce prolactin (PRL) increase. Because of the potential stimulatory role of PRL on breast cancer cells, its postoperative increase may influence the prognosis of breast cancer patients. This study was performed to evaluate the influence of surgery-induced hyperprolactinemia on recurrence rate in operable breast cancer. The study included 250 consecutive breast cancer patients, clinical stage T1-3 N0-2M0, who were observed for a median follow-up of 72 months. Surgery-induced hyperprolactinemia occurred in 108/250 patients (43%). Irrespectively of node involvement, hormonal receptor, type of surgery and adjuvant therapies, the relapse rate was significantly higher in patients who had no surgery-induced hyperprolactinemia than in those with postoperative PRL increase (64/142 vs. 23/108; p < 0.001). This difference was also significant in relation to node status (N0:22/63 vs. 5/56, p < 0.001; N+:42/79 vs. 18/52, p < 0.05). The present study shows that a surgery-induced rise of PRL, despite its potential stimulation of cancer cell growth, is paradoxically associated with a longer disease-free survival in operable breast carcinoma in both patients with or without axillary node involvement. Moreover, this study suggests that the prognosis of node-negative patients who did not show postoperative hyperprolactinemia tends to be similar to that of patients with node involvement and surgery-induced PRL enhancement. Therefore, the lack of surgery-induced hyperprolactinemia would have to be grouped together with the unfavorable prognostic factors of breast cancer.


MDPHnet: secure, distributed sharing of electronic health record data for public health surveillance, evaluation, and planning.
Electronic health record systems contain clinically detailed data from large populations of patients that could significantly enrich public health surveillance. Clinical practices' security, privacy, and proprietary concerns, however, have limited their willingness to share these data with public health agencies. We describe a novel distributed network for public health surveillance called MDPHnet. The system allows the Massachusetts Department of Public Health (MDPH) to initiate custom queries against participating practices' electronic health records while the data remain behind each practice's firewall. Practices can review proposed queries before execution and approve query results before releasing them to the health department. MDPH is using the system for routine surveillance for priority conditions and to evaluate the impact of public health interventions.


Working Harder than Others to Prove Yourself: High-Effort Coping as a Buffer between Teacher-Perpetrated Racial Discrimination and Mental Health among Black American Adolescents.
High-effort coping (feeling like one must work harder than others to succeed due to anticipated discrimination) is an understudied concept in adolescence. The current study examined among Black American adolescents surveyed in eighth and 11th grade (N = 630, 49% female) how high-effort coping moderated the relations between teacher-perpetrated racial discrimination and psychological distress across time, and whether the buffering role of high-effort coping varied by adolescent gender and socioeconomic status. Experiencing racial discrimination from teachers in eighth grade was positively related with depressive symptoms, anger, and suicidal ideation in 11th grade. High-effort coping buffered against teacher discrimination for suicidal ideation among low socioeconomic status youth, as well as for anger among high socioeconomic status youth. Findings underscore the harmful influence of racial discrimination on Black American adolescents' mental health, as well as suggest that among certain subpopulations, high-effort coping may be one psychologically protective resource through which Black American youth retain positive feelings that are undermined by racial discrimination, and thus promote mental well-being.


Cytomegalovirus-associated periodontitis and Guillain-Barré syndrome.
Guillain-Barré syndrome (GBS), an autoimmune disorder of the peripheral nervous system, is characterized by rapidly ascending neural paralysis, hyporeflexia, and areflexia. The polyneuropathy of the GBS affects one to four humans per 100,000 of the population annually throughout the world (adults and children). The pathogenesis of GBS remains unclear. However, there are increasing indications that the disease is triggered by a preceding well-established febrile infection by cytomegalovirus (CMV). The present report describes active CMV within the periodontium of a 37-year-old patient affected by GBS. Real-time reverse transcriptase-polymerase chain reaction (real-time RT-PCR) was performed to detect CMV, Epstein-Barr virus-1 (EBV-1), herpes simplex 1 (HSV-1) and 2 (HSV-2) virus, and enteroviruses (polio-, coxsackie-, echo-, and enteroviruses 68 and 71) from periodontal sites demonstrating advanced attachment loss. Healthy sites and sites with inflamed gingival tissue were not included in the study. Anaerobic bacterial culture determined the occurrence of potential major periodontal pathogens. Real-time RT-PCR and microbiologic analysis revealed the presence of a dual infection of CMV and specific bacterial plaque. CMV, Porphyromonas gingivalis, Tannerella forsythensis, and Campylobacter species were associated with periodontitis active sites, loss of attachment, and gingival bleeding. Furthermore, periodontal sites infected by active CMV had no visible radiographic crestal lamina dura. The periodontium may serve as a reservoir for CMV and a source of viral replication. However, further research is needed to test whether viral replication in the periodontium precedes the GBS symptoms.


Mapping of a major locus that determines telomere length in humans.
Telomere length is a crucial factor for both normal chromosomal function and senescence. Mean telomere length in humans shows considerable interindividual variation and strong genetic determination. To see if a locus (or loci) affecting telomere length in humans could be mapped, we performed a quantitative-trait linkage analysis of mean leukocyte telomere-restriction-fragment (TRF) lengths, measured by Southern blotting, in 383 adult subjects comprising 258 sib pairs. Heritability of mean (+/-SE) TRF was 81.9%+/-11.8%. There was significant linkage (LOD score 3.20) of mean TRF length to a locus on chromosome 12, which explained 49% of the overall variability in mean TRF length. We present preliminary analysis of a strong candidate gene in the region, the DNA helicase DDX11. In conclusion, we report mapping of the first locus that determines mean telomere length in humans. Identification of the gene involved and elucidation of its mechanism of action could have important implications for our understanding of chromosomal assembly, telomere biology, and susceptibility to age-related diseases.


Adolescent Emotional Maturation through Divergent Models of Brain Organization.
In this article we introduce the hypothesis that neuropsychological adolescent maturation, and in particular emotional management, may have opposing explanations depending on the interpretation of the assumed brain architecture, that is, whether a componential computational account (CCA) or a dynamic systems perspective (DSP) is used. According to CCA, cognitive functions are associated with the action of restricted brain regions, and this association is temporally stable; by contrast, DSP argues that cognitive functions are better explained by interactions between several brain areas, whose engagement in specific functions is temporal and context-dependent and based on neural reuse. We outline the main neurobiological facts about adolescent maturation, focusing on the neuroanatomical and neurofunctional processes associated with adolescence. We then explain the importance of emotional management in adolescent maturation. We explain the interplay between emotion and cognition under the scope of CCA and DSP, both at neural and behavioral levels. Finally, we justify why, according to CCA, emotional management is understood as regulation, specifically because the cognitive aspects of the brain are in charge of regulating emotion-related modules. However, the key word in DSP is integration, since neural information from different brain areas is integrated from the beginning of the process. Consequently, although the terms should not be conceptually confused, there is no cognition without emotion, and vice versa. Thus, emotional integration is not an independent process that just happens to the subject, but a crucial part of personal growth. Considering the importance of neuropsychological research in the development of educational and legal policies concerning adolescents, we intend to expose that the holistic view of adolescents is dependent on whether one holds the implicit or explicit interpretation of brain functioning.


Interleukin-2 and granulocyte-macrophage-colony-stimulating factor immunomodulation with high-dose chemotherapy and autologous hematopoietic stem cell transplantation for patients with metastatic breast cancer.
Immunomodulation with cytokines was used to improve the result of high-dose chemotherapy (HDC)/autologous hematopoietic stem cell transplantation (AHST). We examined the use of IL-2 and growth factors for mobilization, ex vivo activation of peripheral blood stem cell (PBSC) and maintenance therapy after HDC/AHST in metastatic breast cancer. Eligible patients with metastatic breast cancer for HDC/AHST were assigned to 1 of 3 protocols for PBSC mobilization: G-CSF (group 1); IL-2 + G-CSF (group 2); or IL-2 + G-CSF + GM-CSF (group 3). HDC with cyclophosphamide, carmustine and thiotepa was given from day -7 to -5. PBSCs were treated ex vivo with IL-2 for 24 h and reinfused on day 0. Maintenance therapy included low-dose IL-2, followed by 2 courses of intermediate-dose IL-2. GM-CSF was given from day 1 until neutrophil recovery. Thirty-four patients (10 in group 1, 14 in group 2, and 10 in group 3) were included. Comparable numbers of CD34(+) cells were collected from all 3 groups; incremental increases of CD3(+) cells were collected from groups 1 to 2 and to 3 (p = 0.03). Major adverse effects from IL-2 were fever, hypotension and fatigue; no treatment-related mortality was seen. At a median follow-up of 790.5 days (range 150-2,722 days), median progression-free survival was 434 days and median overall survival was 1,432 days. Estimated 3-year progression-free and overall survival rates were 31 and 57%. Our study suggested that the use of IL-2 and growth factors immunomodulation with HDC/AHST was feasible with comparable survival rates.


Pharmacologic regression of cardiac hypertrophy in experimental hypertension.
The normal heart has the capacity to either augment or reduce its mass in relation to long-term alterations in hemodynamic and metabolic demands. However, once cardiac hypertrophy is established, as in hypertensive heart disease, it is less clear whether the augmented mass can revert to normal with control of arterial pressure. In experimental models in which systemic hypertension is induced in genetically normotensive animals, left ventricular weight generally returns toward normal with the removal of the inciting stimulus for the hypertension. However, when arterial pressure control is achieved by pharmacologic therapy, and the inciting stimulus (mechanical or genetic) is intact, the results of pressure reduction on ventricular weight are much more variable than that observed with the removal of a mechanical stimulus for hypertension. It is hypothesized that pharmacologic pressure reduction elicits secondary adjustments in cardiorenal and neurohumoral function which have important influences on ventricular hypertrophy.


Circadian vulnerability of cisplatin-induced ototoxicity in the cochlea.
The chemotherapeutic agent cisplatin is renowned for its ototoxic effects. While hair cells in the cochlea are established targets of cisplatin, less is known regarding the afferent synapse, which is an essential component in the faithful temporal transmission of sound. The glutamate aspartate transporter (GLAST) shields the auditory synapse from excessive glutamate release, and its loss of function increases the vulnerability to noise, salicylate, and aminoglycosides. Until now, the involvement of GLAST in cisplatin-mediated ototoxicity remains unknown. Here, we test in mice lacking GLAST the effects of a low-dose cisplatin known not to cause any detectable change in hearing thresholds. When administered at nighttime, a mild hearing loss in GLAST KO mice was found but not at daytime, revealing a potential circadian regulation of the vulnerability to cisplatin-mediated ototoxicity. We show that the auditory synapse of GLAST KO mice is more vulnerable to cisplatin administration during the active phase (nighttime) when compared to WT mice and treatment during the inactive phase (daytime). This effect was not related to the abundance of platinum compounds in the cochlea, rather cisplatin had a dose-dependent impact on cochlear clock rhythms only after treatment at nighttime suggesting that cisplatin can modulate the molecular clock. Our findings suggest that the current protocols of cisplatin administration in humans during daytime may cause a yet undetectable damage to the auditory synapse, more so in already damaged ears, and severely impact auditory sensitivity in cancer survivors.


[Calculating of critical loads of sulfur deposition for surface waters in southern China using a steady-state acidification model].
In order to study the response of Chinese surface waters to acid deposition, a steady-state model based on acidity balance was applied in this paper to calculate critical loads of sulphur deposition for surface waters in southern China. An empirical equation for Chinese surface waters was obtained to calculate the background sulfate concentration. The results showed that the critical loads of sulphur deposition for most surface waters in southern China were more than 2.0 keq.(hm2.a)-1, indicating that they were not sensitive to acidification. Surface waters with critical loads less than 2.0 keq.(hm2.a)-1 were those waters located on mountains. Except these mountain waters, the critical loads of sulphur deposition for other surface waters were not exceeded by the present sulphur deposition, indicating acidification will not occur in the near future for these waters. The spatial distribution of critical load exceedance was similar with that of the critical loads, showing the trend of increasing from the southeastern provinces, such as Fujian, Guangdong and Jiangxi, to the southwestern and the central region. The uncertainty analysis of the model results indicated that, the errors of the results caused by the uncertainty of parameters and the input data were minor and acceptable so long as the input data were among the appropriate ranges.


[Pulmonary Pseudomonas infections].
145 strains of pathogenic pseudomonas had been isolated from the sputum or bronchoscopic aspirate of 1423 patients with pulmonary infections. They were classified into 8 types, among which 31.7% was pseudomonas aeruginosa. Pseudomonas aeruginosa was the dominant causative organism in pulmonary infections of the aged while in presenile ones the organism was mainly Pseudomonas fetid. The incidence of nosnocomial pseudomonas infection in patients of COPD with respiratory failure was 40%, of COPD with pulmonary infection 9.1% and of others 6.6%. 24 pseudomonas carriers with COPD (colonies less than or equal to 10(6)/ml in sputum) had been followed up. 16 out of them became negative in sputum culture without any treatment, while the remaining 8 developed pulmonary pseudomonas infections. 21 patients (14.5%) were found to have other types of pseudomonas infections during antibiotic treatment. Sensitivity tests showed that third-generation cephalosporins and aminoglycosides had definite antimicrobial activity against pseudomonas, the former being more stable and effective than the latter.


Intrinsic inhomogeneities in manganite thin films investigated with scanning tunneling spectroscopy.
Thin films of La0.7Sr0.3MnO3 on MgO show a metal insulator transition and colossal magnetoresistance. The shape of this transition can be explained by intrinsic spatial inhomogeneities, which give rise to a domain structure of conducting and insulating domains at the submicrometer scale. These domains then undergo a percolation transition. The tunneling conductance and tunneling gap measured by scanning tunneling spectroscopy were used to distinguish and visualize these domains.


The effect of a shear force on the cell shedding rate of the corneal epithelium.
During blinking the lids apply a shear force to the corneal epithelium. The aim of this study was to determine if a shear force applied to the epithelial surface increases the rate at which cells shed. The shedding rate was studied in perfused whole rabbit eyes, and the effect of a shear force examined by exposing the corneas to a stirred solution. Control corneas were exposed to a static solution. The shedding rate and size of shed cells were measured, and the number of terminally differentiated cells on the corneal surface determined after 6 h of perfusion using ethidium bromide. Compared with controls, the shear force increased the cell shedding rate from the corneal surface significantly (p < 0.01, paired t-test). The increase was due to small cells with a longest dimension less than 25 microm. The number of terminally differentiated cells on the epithelial surface did not increase. Because of the decrease in size, and the change in appearance of shedding cells, it is proposed that the increase in cell shedding rate was due to an increase in the number of apoptotic cells, and not to an increase in terminally differentiated cells. It is suggested that in the human eye, under adverse conditions, shear forces due to blinking may play a role in creating apoptotic cells.


Giant proliferating trichilemmal tumor of the gluteal region.
Proliferating trichilemmal tumors are rare cutaneous neoplasms that show features of typical pilar cysts but also show extensive epithelial proliferation, variable cytologic atypia, and mitotic activity. Proliferating trichilemmal tumors are benign lesions; however, there are numerous reports of malignant proliferating trichilemmal tumors. We present a case of benign proliferating trichilemmal tumor of an 81-year-old woman that was located on the left superior gluteal region for 30 years. A tumor measuring 9 x 7 cm was surgically excised with a 1 cm conservative margin of normal tissue. Based on the histopathologic findings of tumor, this case was diagnosed as proliferating trichilemmal tumor. The patient's condition was successfully treated with total excision. Our case is an unusual presentation of proliferating trichilemmal tumor. Physicians should be aware of this entity while differentiating cutaneous tumor located on the gluteal region.


Taste test: children rate flavoring agents used with activated charcoal.
To compare flavoring agents added to activated charcoal (AC) to determine which mixture is most palatable to children. Healthy volunteers between the ages of 3 and 17 years participated in a prospective masked trial. Five identical pitchers were prepared containing AC alone, AC with chocolate milk, AC with Coca-Cola (Coca-Cola Corp, Atlanta, Ga), AC with cherry-flavored syrup, and AC with sorbitol. Subjects tasted all 5 substances in random order. Children younger than 8 years rated taste on a 10-point Faces Scale. Children 8 years and older used a 100-point visual analog scale to rate taste and, separately, ease of swallowing. All children were asked which mixture was best. Ratings were compared using 1-way analysis of variance, and comparisons for all pairs were made using the Tukey test. P<.05 was considered significant. Mean age among the 53 children enrolled was 8.3 years; 23 children were younger than 8 years. Girls made up 52% of the group. Taste scores for chocolate milk, Coca-Cola, and cherry-flavored syrup were significantly better than those for no flavoring agent. The scores for ease of swallowing for Coca-Cola, chocolate milk, and cherry-flavored syrup were significantly better than those for either no flavoring agent or sorbitol. When asked to choose a single best flavoring agent, 39% chose chocolate milk, 23% picked Coca-Cola, and 23% chose cherry-flavored syrup. The addition of chocolate milk, Coca-Cola, or cherry-flavored syrup to AC improves palatability for children and is favored over no flavoring agent or sorbitol.


Sweet's syndrome in a granulocytopenic patient with acute myeloid leukemia on FLT3 inhibitor.
Gilteritinib is a FLT3 kinase inhibitor approved for FLT3-mutated acute myeloid leukemia (AML). We present a case of febrile neutropenia and neutrophilic dermatosis consistent with Sweet's syndrome (SS). A 55-year-old woman presented with fever and skin lesions after 4 weeks of initiation of Gilteritinib for AML. She was febrile, pancytopenic and neutropenic with absolute neutrophil count (ANC) of 0.1x10E3/UI. Examination revealed reddish and violaceous rashes on her extremities. Pathology showed superficial dermal edema, widespread epidermal spongiosis and multiple neutrophils in the dermal infiltrate. Rash improved with prednisone 60 mg daily and started to flare with taper. She was still on Gilteritinib all this time. Gilteritinib was finally stopped due to non-response and possible contribution in flaring her SS. Shortly after, the patient succumbed to progressive disease and complications of sepsis. There have been reports of SS in neutropenic patients although SS is typically a neutrophilic dermatosis. The pathogenesis of SS in neutropenia remains uncertain. Our study represents an additional medication-associated cutaneous complication of AML therapy. Clinicians need to be aware of potential neutrophilic dermatoses with FLT-3 inhibition, even with peripheral neutropenia.


Previous Homologous and Heterologous Stress Exposure Induces Tolerance Development to Pulsed Light in Listeria monocytogenes.
As one of the emerging non-thermal technologies, pulsed light (PL) facilitates rapid, mild and residue-free microbial surface decontamination of food and food contact materials. While notable progress has been made in the characterization of the inactivation potential of PL, experimental data available on the tolerance development to the same (homologous) stress or to different (heterologous) stresses commonly applied in food manufacturing (e.g., acid, heat, salt) is rather controversial. The findings of the present study clearly indicate that both the homologous tolerance development against PL as well as the heterologous tolerance development from heat to PL can be triggered in Listeria monocytogenes. Further, conducted kinetic analysis confirmed that the conventionally applied log-linear model is not well suited to describe the inactivation of L. monocytogenes, when exposed to PL. Instead, the Weibull model as well as the log-linear + tail model were identified as suitable models. Transmission electron microscopic (TEM) approaches allow suggestions on the morphological alterations in L. monocytogenes cells after being subjected to PL.


Characterization of various immunoglobulin preparations for intravenous application. II. Complement activation and binding to staphylococcus protein A.
14 immunoglobulin preparations for intravenous use were tested to assess functions of their Fc portion. Inhibition of the hemolytic activity of complement, C1q binding and the interaction of IgG subclasses with Staphylococcus protein A were investigated. Complement studies were done on both the ready-for-infusion and the heat-aggregated preparations. Three groups of products could be distinguished: (1) Enzymatically and chemically treated products were devoid of complement-activating capacity, both when tested and ready-for-infusion and as heat-aggregated preparations. The chemically treated preparations showed atypical binding properties to Staphylococcal protein A. (2) The poly-(ethylene glycol) (PEG)-treated preparations and the untreated reference activated complement before and after heat-aggregation. (3) The albumin protected and the pH 4-treated product did not spontaneously activate complement in the ready-for-infusion state but did so after heat-aggregation. These results suggest that only the albumin-protected and the pH 4-treated products can be expected both to be well tolerated when given intravenously to high-risk agammaglobulinemic patients and to exhibit normal Fc functions in vivo.


Pigment analysis of chloroplast pigment-protein complexes in wheat.
Pigment-protein complexes separated from wheat (Triticum aestivum L. selection ND96-25 by two gel electrophoresis techniques were analyzed by high-performance liquid chromatography for chlorophylls and carotenoids. The two techniques are compared, and pigment analyses are given for the major reaction centers and light-harvesting complexes. Reaction centers contain mostly chlorophyll a, carotene, and lutein, whereas light-harvesting complexes contain chlorophyll a, chlorophyll b, lutein, and neoxanthin. The amounts of violaxanthin are variable.


Exaggerated sympathetic and pressor responses to handgrip exercise in older hypertensive humans: role of the muscle metaboreflex.
Recent animal studies have reported that exercise pressor reflex (EPR)-mediated increases in blood pressure are exaggerated in hypertensive (HTN) rodents. Whether these findings can be extended to human hypertension remains unclear. Mean arterial pressure (MAP), muscle sympathetic nerve activity (MSNA), and venous metabolites were measured in normotensive (NTN; n = 23; 60 ± 1 yr) and HTN (n = 15; 63 ± 1 yr) subjects at baseline, and during static handgrip at 30 and 40% maximal voluntary contraction (MVC) followed by a period of postexercise ischemia (PEI) to isolate the metabolic component of the EPR. Changes in MAP from baseline were augmented in HTN subjects during both 30 and 40% MVC handgrip (P < 0.05 for both), and these group differences were maintained during PEI (30% PEI trial: Δ15 ± 2 NTN vs. Δ19 ± 2 HTN mmHg; 40% PEI trial: Δ16 ± 1 NTN vs. Δ23 ± 2 HTN mmHg; P < 0.05 for both). Similarly, in HTN subjects, MSNA burst frequency was greater during 30 and 40% MVC handgrip (P < 0.05 for both), and these differences were maintained during PEI [30% PEI trial: 35 ± 2 (NTN) vs. 44 ± 2 (HTN) bursts/min; 40% PEI trial: 36 ± 2 (NTN) vs. 48 ± 2 (HTN) bursts/min; P < 0.05 for both]. No group differences in metabolites were observed. MAP and MSNA responses to a cold pressor test were not different between groups, suggesting no group differences in generalized sympathetic responsiveness. In summary, compared with NTN subjects, HTN adults exhibit exaggerated sympathetic and pressor responses to handgrip exercise that are maintained during PEI, indicating that activation of the metabolic component of the EPR is augmented in older HTN humans.


Fine Mapping, Candidate Gene Identification and Co-segregating Marker Development for the Phytophthora Root Rot Resistance Gene RpsYD25.
Phytophthora root rot (PRR) caused by Phytophthora sojae is a serious disease of soybean. The most effective disease-control strategy is to deploy resistant cultivars carrying Rps genes. Soybean cultivar Yudou25 can effectively resist pathotypes of P. sojae in China. Previous studies have mapped the Rps gene in Yudou25, RpsYD25, on chromosome 3. In this study, at first RpsYD25 was located between SSR markers Satt1k3 (2.2 cM) and BARCSOYSSR_03_0253 (4.5 cM) by using an F2:3 population containing 165 families derived from Zaoshu18 and Yudou25. Then the recombination sites were identified in 1127 F3:4 families derived from Zaoshu18 and Yudou25 using the developed PCR-based SNP, InDel and SSR markers, and RpsYD25 was finely mapped in the a 101.3 kb genomic region. In this region, a zinc ion binding and nucleic acid binding gene Glyma.03g034700 and two NBS-LRR genes Glyma.03g034800 and Glyma.03g034900 were predicted as candidate genes of RpsYD25, and five co-segregated SSR markers with RpsYD25 were identified and validated to be diagnostic markers. Combined with the resistance reaction to multiple P. sojae isolates, seven of 178 soybean genotypes were detected to contain RpsYD25 using the five co-segregated SSR markers. The soybean genotypes carrying RpsYD25 and the developed co-segregated markers can be effectively applied in the breeding for P. sojae resistance in China.


New Solutions for the Sample Transport and Results Delivery: A Digital Lab.
The consolidation of laboratories, the evolution to integrated care network as well as an environment of consumerization are disrupting laboratory services and operations. The switch to SMART (Speed Metrics Automation Remote Technologies) digital laboratories based health ecosystems depends on several prerequisites for successes. Intelligent processes, integration of big data and real-time data management, automation, blockchain, Internet of things and enhancement of user experiences are key element of the smart digital laboratory. Safety, security and cost-effectiveness are pillars for the credibility and transferability of such smart digital laboratory environment. This transforming ecosystem will also trigger novel human - machine interfaces and we will be the gatekeepers for this new "click to brick" ecosystem.


Decrease of trabecular bone score reflects severity of Crohn's disease: results of a case-control study.
Osteoporosis and osteopaenia are known chronic complications of inflammatory bowel diseases. The trabecular bone score (TBS) provides an indirect measurement of bone microarchitecture, independent of bone mineral density (BMD). The study was designed as a case-control study with the aim to assess and compare bone quantity and quality in patients with Crohn's disease (CD). We purposefully excluded postmenopausal women and patients on long-term corticosteroid therapy. The cohort consisted of 50 CD patients and 25 healthy controls who matched in age, sex, weight, or vitamin D status. There was no significant difference between CD patients versus controls in the mean lumbar BMD of 0.982±0.119 versus 0.989±0.12 g/cm and the mean TBS score of 1.37±0.12 versus 1.38±0.12. We observed significantly lower TBS, but not lumbar BMD, in CD patients with stricturing (B2, 1.36±0.08) or penetrating (B3, 1.32±0.11) disease compared with those with luminal disease (B1, 1.42±0.11; P=0.003 and <0.0001, respectively). We also observed lower mean±SD TBS in patients on versus not on anti-tumour necrosis factor-α therapy: 1.341±0.138 versus 1.396±0.099, respectively. However, the difference between these groups failed to reach statistical significance (P=0.11). No similar finding was seen comparing lumbar BMD in these groups. For the first time, it was observed that TBS, but not BMD, correlates with the severity of CD. Our results therefore suggest that TBS can potentially help to identify high fracture risk CD patients better than BMD alone.


Viral tracing identifies distributed columnar organization in the olfactory bulb.
Olfactory sensory neurons converge onto glomeruli in the olfactory bulb (OB) to form modular information processing units. Similar input modules are organized in translaminar columns for other sensory modalities. It has been less clear in the OB whether the initial modular organization relates to a columnar structure in the deeper layers involved in local circuit processing. To probe synaptic connectivity in the OB, we injected a retrograde-specific strain of the pseudorabies virus into the rat OB and piriform cortex. The viral-staining patterns revealed a striking columnar organization that extended across all layers of the OB from the glomeruli to the deep granule cell layer. We hypothesize that the columns represent an extension of the glomerular unit. Specific patterning was observed, suggesting selective, rather than distance-dependent, center-surround connectivity. The results provide a previously undescribed basis for interpreting the synaptic connections between mitral and granule cells within the context of a columnar organization in the OB and have implications for olfactory coding and network organization.


Influence of the type of cerebral infarct and timing of intervention in the early outcomes after carotid endarterectomy for symptomatic stenosis.
Our objectives were to compare early postoperative outcomes after carotid endarterectomy for symptomatic carotid stenosis and to analyze the impact of time to treatment between patients with a territorial or a border-zone infarct. This is a single-center, retrospective study carried out on data from a single-center, prospective database. Patients undergoing carotid endarterectomy for symptomatic carotid stenosis after an ipsilateral acute ischemic stroke were included between January 1, 2009 and December 31, 2013. The only exclusion criterion was a mixed-topography stroke. We included 114 patients who were retrospectively divided into groups according to the location of the infarct: group TI for territorial infarction and group BZ for border-zone infarction. The primary end point was the 30-day death or stroke rate. Ninety patients were included in the TI group (79%) and 24 in the BZ group (21%) with a mean age of 73 ± 11 years. All demographic data were similar between the two groups except for dyslipidemia, which was greater in the BZ group (72% vs 47%, P = .03) and the subocclusive feature of carotid stenosis (14% in the TI group vs 33% in the BZ group, P .04). There was one death and one stroke in each group, with a 30-day death and stroke rate of 2% in the TI group and 8% in the BZ group (P = .18). Multivariate analysis showed that the National Institute of Health Stroke Score (NIHSS) score was the only independent predictive factor of complications with an increase of 36% per additional point in this score. Sixty-eight patients (76%) in the TI group and 14 (58%) in the BZ group were operated on during the first 2 weeks after the neurological event. In this subgroup, the 30-day death or stroke rate was 2% in the TI group (one stroke) vs 14% in the BZ group (one stroke and one death; P = .06). The preoperative NIHSS score was again the only factor significantly associated with the postoperative complication rate (P = .03). In our series, surgery for patients with symptomatic carotid stenosis after border-zone infarction resulted in more complications than after territorial infarction, although no significant differences were found. This study nonetheless raised questions concerning the optimal timing of carotid surgery depending on the type of the original stroke. Other larger-scale studies are necessary to determine whether the type of cerebral infarction needs to be taken into account in decisions whether to operate on the diseased carotid as early as possible.


Combined Laparoscopic and CT Monitoring of the Ice-Ball Margin during Cryoablation for Renal Cell Carcinoma Associated with von Hippel-Lindau Disease: First Case.
We report a 47-year-old Japanese female with 10 previous treatments for multiple bilateral renal cell carcinoma (RCC) associated with von Hippel-Lindau disease. The 14-mm right lower pole renal tumor was in contact with the right ureter. Laparoscopic cryoablation was performed to protect the ureter wrapped with gauze. Computed tomography (CT) monitoring was used to confirm the precise ≥ 6 mm ice-ball margin. There was no local progression at 6-months post-surgery. The serum creatinine has been stable. This is apparently the first report of combined laparoscopic and CT monitoring of an ice-ball formation and its margin during cryoablation for RCC.


Incorporating nutritional risk screening with case management initiatives.
Keystone 65, the Medicare Program of Keystone Health Plan East, has designed case management programs around the needs of America's seniors. Keystone 65 utilizes a health risk assessment tool to aid in determining a member's health risk profile. This tool, the Health Risk Assessment Form, consists of the Short Form 36, the Nutrition Screening Initiative Nutrition Checklist, self-reported disease questions, and questions related to the health plan. Preliminary analysis has led Keystone to believe that the use of such an assessment tool will aid in identifying those members who need proactive case management and intervention. The increased use of the Checklist may provide the case management department with an important element in the assessment of Keystone 65 members.


The role of transesophageal echocardiography in identifying anomalous coronary arteries.
The study objective was to evaluate the role of transesophageal echocardiography in identifying the origin of anomalous coronary arteries and confirming their course in relation to the great vessels. The diagnosis of coronary anomalies is made by angiography. The anomalous left main artery with a course between the pulmonary artery and the aorta has been associated with myocardial infarction and sudden death. The course of these anomalous coronary arteries is difficult to demonstrate by angiography alone. Nine patients with angiographically confirmed anomalous coronary arteries were studied by transesophageal echocardiography with color flow Doppler. The abnormal origin of the anomalous coronary arteries was confirmed by transesophageal echocardiography in all nine patients. In four patients, the left main coronary artery originated from the right sinus of Valsalva. In all of these patients, transesophageal echocardiography demonstrated the course of the anomalous left main coronary artery between the aorta and pulmonary artery better than angiography. Other anomalies that were visualized included two patients with origin of the right coronary arteries from the left aortic sinus, one patient with origin of the left anterior descending from the right sinus, one patient with origin of circumflex from the right sinus, and one patient with origin of the left main coronary artery from the pulmonary artery. Transesophageal echocardiography is a useful noninvasive test for diagnosing anomalous origin of the coronary arteries. Furthermore, it is a valuable adjunct to angiography in demonstrating the abnormal course of the left main coronary artery interposed between the aorta and the pulmonary artery, a potentially life-threatening entity.


Neuropsychological rehabilitation of memory deficits and activities of daily living in patients with Alzheimer's disease: a pilot study.
Patients with Alzheimer's disease (AD) gradually lose their cognitive competence, particularly memory, and the ability to perform daily life tasks. Neuropsychological rehabilitation is used to improve cognitive functions by facilitating memory performance through the use of external aids and internal strategies. The effect of neuropsychological rehabilitation through memory training - motor movements, verbal association, and categorization - and activities of daily living (ADL) training was tested in a sample of 5 elderly out-patients (mean age: 77.4 +/- 2.88 years), with mild AD (Mini-Mental State Examination score: 22.20 +/- 2.17) and their caregivers. All patients had been taking rivastigmine (6-12 mg/day) for at least 3 months before being assigned to the rehabilitation sessions, and they continued to take the medication during the whole program. Just before and after the 14-week neuropsychological rehabilitation program all patients were assessed by interviewers that did not participate in the cognitive training, using the Mini-Mental State Examination, Montgomery-Alsberg Depression Rating Scale, Hamilton Anxiety Scale, Interview to Determine Deterioration in Functioning in Dementia, Functional Test, Memory Questionnaire of Daily Living for patient and caregiver, Quality of Life Questionnaire for patient and caregiver, and a neuropsychological battery. The results showed a statistically significant improvement in ADL measured by Functional Test (P = 0.04), and only a small improvement in memory and psychiatric symptoms. Our results support the view that weekly stimulation of memory and training of ADL is believed to be of great value in AD treatment, not only delaying the progress of the disease, but also improving some cognitive functions and ADL, even though AD is a progressively degenerative disease.


Immune modulation by non-hodgkin lymphoma in a patient with two primary intestinal T-cell lymphomas and long-standing celiac disease.
Tumors may influence immunologic reactions. Here, we report on a 72-year-old patient who suffered from celiac disease (CD) that had been diagnosed 20 years before. Under a normal diet but without any evidence of enteropathy or CD-associated antibodies, the patient developed a jejunal T-cell lymphoma. It was resected due to perforation and four courses of IMVP-16 were added. The patient started and kept a strict gluten-free diet (GFD). Two years later, he presented with weight loss and a clonally divergent refractory sprue type II with loss of antigen (CD8; T-cell receptor-beta) expression in intraepithelial lymphocytes. At this time point, he showed high titers of CD-associated antibodies, although he was on a strict GFD. This case report highlights several questions: the missing enteropathy under a gluten-containing diet supports the notion of immune suppression in malignant diseases, especially non-Hodgkin lymphoma. Secondly, the patient developed an early form of a second independent T-cell lymphoma (refractory sprue type II) under a strict GFD, then with CD-associated antibodies, which raises the question whether the clonal intraepithelial lymphocytes were stimulating antibody production. Thus, the single detection of CD-associated antibodies in patients with CD is not itself proof of noncompliance with GFD.


Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer.
Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.


Theoretical study on diradical characters and nonlinear optical properties of 1,3-diradical compounds.
We investigate the relationships between the diradical character (y) and nonlinear optical (NLO) properties of open-shell 1,3-diradical compounds using the broken-symmetry density functional theory method. The 2,2-substituent effects on the structure-property relationship are clarified for several 1,3-diphenylcyclopentane-1,3-diyl derivatives, which are known as the systems with weak or intermediate π-single-bonding characters. The parent 1,3-diphenylcyclopentane-1,3-diyl (1a: X = H) is found to be almost pure diradical (y ∼ 1) owing to the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO). The energy gap is determined by the balance of the through-space coupling with the through bond coupling effect. On the other hand, the introduction of the electron-withdrawing substituents X at the C2 position of cyclopentane-1,3-diyls (1b: X = OH, 1c: X = F) is found to decrease the y-value owing to the effects of additional through-bond interactions. As a result, 1b and 1c are found to have intermediate y. Static second hyperpolarizabilities (γ) of 1b and 1c are found to be enhanced by a factor of ∼4.5 and ∼6.4, respectively, compared with those of the pure singlet diradical 1a and those of the triplet 1a-1c. From the analysis of the third-order responses of electron density, the introduction of the 2,2-substituents is found to enhance the field-induced third-order polarizations over the whole system. We also investigate the effects of asymmetric donor/acceptor substitutions at the para positions of phenyl rings on the response properties. Although the asymmetric donor/acceptor substitutions have no significant impact on y in the present systems, they are found to provide the increase of γ from the corresponding nonsubstituted analogues. The present results have revealed strong correlation between the π-bonding character (diradical character) and third-order NLO properties in the real 1,3-diradical compounds. On the basis of the theoretically predicted correlation in the real systems, NLO measurements are speculated to be utilized as a new probe of the unique chemical bonding nature in such localized diradical compounds, which is one of the fundamental subjects in chemistry.


Structural characteristics and anticancer activity of fucoidan from the brown alga Sargassum mcclurei.
Three different fucoidan fractions were isolated and purified from the brown alga, Sargassum mcclurei. The SmF1 and SmF2 fucoidans are sulfated heteropolysaccharides that contain fucose, galactose, mannose, xylose and glucose. The SmF3 fucoidan is highly sulfated (35%) galactofucan, and the main chain of the polysaccharide contains a →3)-α-L-Fucp(2,4SO₃⁻)-(1→3)-α-L-Fucp(2,4SO₃⁻)-(1→ motif with 1,4-linked 3-sulfated α-L-Fucp inserts and 6-linked galactose on reducing end. Possible branching points include the 1,2,6- or 1,3,6-linked galactose and/or 1,3,4-linked fucose residues that could be glycosylated with terminal β-D-Galp residues or chains of alternating sulfated 1,3-linked α-L-Fucp and 1,4-linked β-D-Galp residues, which have been identified in galactofucans for the first time. Both α-L-Fucp and β-D-Galp residues are sulfated at C-2 and/or C-4 (and some C-6 of β-D-Galp) and potentially the C-3 of terminal β-D-Galp, 1,4-linked β-D-Galp and 1,4-linked α-L-Fucp residues. All fucoidans fractions were less cytotoxic and displayed colony formation inhibition in colon cancer DLD-1 cells. Therefore, these fucoidan fractions are potential antitumor agents.


A radio transient with unusually slow periodic emission.
The high-frequency radio sky is bursting with synchrotron transients from massive stellar explosions and accretion events, but the low-frequency radio sky has, so far, been quiet beyond the Galactic pulsar population and the long-term scintillation of active galactic nuclei. The low-frequency band, however, is sensitive to exotic coherent and polarized radio-emission processes, such as electron-cyclotron maser emission from flaring M dwarfs1, stellar magnetospheric plasma interactions with exoplanets2 and a population of steep-spectrum pulsars3, making Galactic-plane searches a prospect for blind-transient discovery. Here we report an analysis of archival low-frequency radio data that reveals a periodic, low-frequency radio transient. We find that the source pulses every 18.18 min, an unusual periodicity that has, to our knowledge, not been observed previously. The emission is highly linearly polarized, bright, persists for 30-60 s on each occurrence and is visible across a broad frequency range. At times, the pulses comprise short-duration (<0.5 s) bursts; at others, a smoother profile is observed. These profiles evolve on timescales of hours. By measuring the dispersion of the radio pulses with respect to frequency, we have localized the source to within our own Galaxy and suggest that it could be an ultra-long-period magnetar.


FHSA in Wales trains receptionists and practice nurses.
Local health strategies had identified training for GP and clinic receptionists as a way to help meet targets on reducing unwanted teenage pregnancy and sexual health. As the "gateway" to the surgery, receptionists have a vital part to play in making young people feel welcome. The practice nurse is also a frontline contact person, often being the first health professional that a young person sees. Gwynedd Family Health Services Authority asked the FPA (Family Planning Association) to provide a pilot course for a group of receptionists and practice nurses to address their awareness of young people's needs. The two-day course covered legal issues, such as contraception and the under-16s, as well as looking at young people's feelings about relationships, sexuality, pregnancy, sexually transmitted diseases, and risk-taking. Participants worked on communication skills and came up with practical ways of making their practice more approachable for young people. The course concluded with the enthusiastic compiling of action plans to take back for discussion with practice managers. Suggestions included: using more empathy when dealing with teenagers requesting emergency contraception; having a supply of condoms in the surgery; displaying more leaflets in the surgery; stressing that advice is available specifically for young people in the practice leaflet; trying to encourage more teenage boys to come in; starting a teenage clinic. Evaluation forms showed that participants found the course "very enjoyable and informative," and that it gave an "excellent insight into the law." "Most invaluable," commented one participant, "I have certainly learned a great deal about young people and their sexual behavior." Further courses are now planned as part of a rolling program for other receptionists and practice nurses in the Gwynedd area.


[The diagnostic value of 99mTc-MIBI myocardial perfusion imaging for coronary artery disease: a systematic review].
This review aims to evaluate the quality of studies assessing the value of 99mTc-MIBI myocardial perfusion imaging in the diagnosis of coronary artery disease. OVID (1956 to 2006), CBMdisc (1978 to 2006), CNKI (2005 to 2006) and VIP (2005 to 2006) for relevant studies in English and Chinese were searched and identified. Quality assessment of diagnostic accuracy studies (QUADAS) items were used. Studies were classified and Meta-disc software was used to analyze sensitivity, specificity, positive likelihood ratio and negative likelihood ratio for the pooled analysis and heterogeneity test, then Asymmetric SROC curves were drawn for those without heterogeneity. In 29 articles included, the results of the pooled analysis showed that, as for rest, exercise and drug myocardial perfusion imaging, the pooled LR + were 2.209, 4.334 and 5.508, the pooled LR- were 0.224, 0.141 and 0.195, and for dipyridamole myocardial perfusion imaging, the pooled LR+ and LR- were 5.031 and 0.193, respectively. Besides, for stress myocardial perfusion imaging among the patients without myocardial infarction history, the pooled LR+ and LR- were 6.176 and 0.199, respectively. The biases from the 29 studies were mainly due to diagnostic test results review bias; variations were probable and were correlated with the spectrum of disease and inclusion criteria; the quality of report was moderate. The conclusion is that 99mTc-MIBI stress MPI, especially dipyridamole MPI, is valuable for diagnosing coronary artery disease.


Pressurization of bioactive bone cement in vitro.
We have developed a bioactive bone cement consisting of MgO-CaO-SiO2-P2O5-CaF2 glass-ceramic powder (AW glass-ceramic powder), silica glass powder as an inorganic filler, and bisphenol-a-glycidyl methacrylate (bis-GMA) based resin as an organic matrix. The efficacy of this bioactive bone cement was investigated by evaluating its pressurization in a 5-mm hole and small pores using a simulated acetabular cavity. Two types of acetabular components were used (flanged and unflanged sockets) and a commercially available polymethylmethacrylate (PMMA) bone cement (CMW 1 Radiopaque Bone Cement) was selected as a comparative control. Bioactive bone cement exerted greater intrusion volume in 5-mm holes than PMMA bone cement in both the flanged and unflanged sockets 10 minutes after pressurization (p < 0.05). In the small pores the bioactive and PMMA bone cements exerted almost identical intrusion volumes in flanged and unflanged sockets 10 min after pressurization. The intrusion volume in the flanged socket 10 minutes after pressurization was greater than that in the unflanged socket in all groups (p < 0.05). These results show that bioactive bone cement intrudes deeper into anchor holes than PMMA bone cement.


Diagnostic value of repeated sputum examinations in pulmonary tuberculosis: how many sputum specimens are adequate?
The aim of this study was to assess the value of examining multiple sputum specimens in the diagnosis of pulmonary tuberculosis (PTB). We analyzed sputum smear and culture results of patients diagnosed with culture-proven PTB during 2002. In 1027 patients, the diagnosis was established by detection of Mycobacterium tuberculosis bacilli in sputum samples. The number of sputum specimens submitted to laboratory was one in 634 cases, two in 167 cases, three in 186 cases and more than three in 48 cases. 760 (74%) cases had positive smear examination result. The first sputum smear examination was positive in 82.3% of smear positive cases. Either the first or the second sputum was diagnostic in 94.9% of these cases. Smear examination of third sputum revealed 4.2% additional diagnostic yield. In 863 (84%) cases, culture examination of the first sputum was positive. The second and the third sputum culture examinations revealed additional diagnostic yield of 11% and 4.5%, respectively. Percent 95 of culture-proven cases were diagnosed with the first two sputum cultures. In conclusion the majority of PTB cases can be diagnosed with the examination of two sputum specimens. Three or more sputum specimens submitted obtain a small additional diagnostic yield.


On the Metabolic Relationship between the Calvin Cycle and the Tricarboxylic Acid Cycle: IV. A Plant Survey for Anomalous Acetyl Coenzyme A.
Leaves of 10 randomly selected plants representing eight dicotyledonous families were exposed to (14)CO(2) for a 10-minute period in the light. Citrate and alanine were isolated, purified isotopically, and degraded to obtain the (14)C-isotope distribution of corresponding carbon atoms, i.e. citrate (C-1,2) and alanine (C-2,3). The cited carbon atoms of alanine were equally labeled as is typical of a 3-carbon intermediate derived from photosynthetic 3-phosphoglycerate. The carbon atoms of citrate, equivalent to acetyl-CoA, were unequally labeled. The citrate (C-1,2) isotope ratio ranged from 1.20 to 1.78 for the various plants compared to a ratio of unity in the uniformly labeled control. The results infer that 3-phosphoglycerate produced in the chloroplast is not the singular precursor of mitochondrial citrate.


Ontogeny of the expression of some catecholamine synthesising enzymes in the female porcine preoptic area.
Ontogeny of the catecholaminergic system of the preoptic area (PA) was studied in various animal species including mice, rats, cats and lower vertebrates. Until now, there has been no data about development of catecholaminergic structures in the porcine PA. To study this problem, hypothalami from six groups of animals were collected. Three groups of foetuses (70, 84 and 112 days old) and three groups of female pigs (1 day, 10 weeks and 7-8 months old) were used. Nerve structures immunoreactive for the studied substances: tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DbetaH) and phenylethanoloamine-N-metylthransferase (PNMT) were observed in different periods. In PA, TH-IR (immunoreactive) structures appeared before 70th day of foetal life, DbetaH-IR between 70th and 84th day of foetal live and PNMT-IR only in 10-week old and adult animals. In the PA of 70-day old foetuses, single smooth and varicose nerve fibres immunoreactive only to TH were found. In PA of 84-day old foetuses, additionally, single nerve cell bodies immunoreactive to TH were shown and some of them also contained immunoreactivity to DbetaH. In PA of 1-day old piglets, moderate numbers of nerve fibres immunoreactive to TH and only single TH/DbetaH-IR nerve terminals were observed. TH-IR nerve cell bodies were also moderate in number and many of them contained simultaneously immunoreactivity to DbetaH. In PA of 10-week old pigs, a moderate number of immunopositive nerve fibres was observed. They contained mainly TH, but part of them stained also for TH/DbetaH. Only very few nerve fibres containing exclusively DbetaH were found. These nerve terminals were observed in a close vicinity of blood vessels. In PA, moderate numbers of TH-IR nerve cell bodies were found, some of them contained also immunoreactivity to DH but never to PNMT. Perikarya containing PNMT were TH-negative. In the PA of sexually mature sows, additional, single, large nerve cell bodies (about 35 microm in a diameter) containing TH only were found. In many cases, TH- and DbetaH-IR "basket-like" structures surrounding nerve cell bodies were seen, suggesting an influence of those fibres on the neuronal activity.


Effects of fluoxetine at antidepressant doses on short-term outcome of detoxified alcoholics.
Compulsivity in alcohol-dependent patients is a frequent cause of early relapse in the post-detoxification period. The present study is a 2-month trial on detoxified alcoholics undergoing a double-blind placebo-controlled treatment with fluoxetine (20 mg/day). The rating instruments were the Hamilton Depression and Anxiety Scales, a visual analogue scale for alcohol craving and an original scale for evaluating alcohol withdrawal. The abstinence rate for fluoxetine-treated patients was significantly higher than in the placebo group, whereas no difference between treatments was found on the rating scales. Medical problems, additional psychiatric diagnoses, and family alcoholism were negatively correlated with abstinence. Two subgroups of patients having significantly different characteristics were identified as to the outcome, by means of cluster analysis. They are likely to represent two different stages in the evolution of alcoholism. Our results show that, independently from craving, fluoxetine at antidepressant doses is able to prevent relapses in weaned alcoholics. The anticompulsive therapy can positively influence the short-term outcome, while other factors are negatively associated with abstinence.


The cell as single-hit detector.
The common manifestation of shoulders to survival curves, particularly for mammalian cells, has diverted attention from the importance of single-hit action as a radiobiological mechanism. Exponential survival is diagnostic for that mode of action. Of various interpretations of shouldered curves, the one best fitted by experimental facts is that single energy deposits can indeed be lethal; but many cells have capacity for a specific type of repair that is depleted, in a dose-dependent manner, until it ceases to function. The curve then assumes its exponential 'tail'. Genomic DNA seems an obvious target for the scoring of lethal hits. But a body of evidence indicates the presence in the cell of a second, chemically different, target, one in which oxygen interacts at the sites of energy deposits to fix damage, so causing radiosensitization. The nuclear membrane is a likely candidate. In cells proficient at repairing DNA, and irradiated with oxygen present, only a minority of lethal events are attributable to energy deposited in DNA. The hypothesis that hits are scored by .OH, based to a large extent on the phenomenon of chemical protection, is not justified by all the facts and is in conflict with some experimental observations. On the other hand, e-aq may well be damaging to DNA unless oxygen is present to act as scavenger.


Cardiothoracic CTA in Infants Referred for Aortic Arch Evaluation-Retrospective Comparison of Iomeprol 350, Ioversol 350, Iopromide 370 and Iodixanol 320.
Computed tomography angiography (CTA) in infants is considered one of the most challenging radiological examinations due to difficulties in balancing start delay, contrast agent (CA) volume and flow in order to achieve optimal opacification of the large vessels. This study aimed to compare the contrast enhancement achieved by four CAs when taking into consideration CA injection parameters and patient characteristics. We performed a retrospective assessment of forty-eight consecutive cardiothoracic CTAs performed for aortic arch evaluation on children aged 0-1 year. All examinations were performed using the same 64-slice scanner and power injector using the bolus tracking technique. Axial 0.6 mm slices were used to measure large vessel enhancement using regions of interest at the level of the main pulmonary artery, ascending and descending aorta. The recorded variables included anthropometric measurements, CA type, flow rate, volume, and the average Hounsfield unit (HU) values of the blood pool. Descriptive statistics are presented as averages and standard deviations (SD) for normal distributed data or otherwise as medians and interquartile ranges (IQRs). We found no statistically significant differences between age and anthropometric parameters when looking at different CAs. The median CA volume was 7 (IQR, 7-9) mL with the average flow rate of 0.94 (SD, 0.23) mL/s. Ascending aorta average HU values were 605.9 (SD, 177.23) for Iomeprol 350, 626 (SD, 183.83) for Ioversol 350, 530.83 (SD, 175.56) for Iopromide 370 and 354.91 (SD, 115.81) for Iodixanol 320. The difference in HU value for Iodixanol 320 compared to the other CAs was statistically significant. Similar differences were found for the other vascular structures. In CTA of infants suspected of aortic arch hypoplasia/coarctation, Iodixanol 320 provided up to 40% less enhancement of the great vessels when compared to Iomeprol 350, Ioversol 350 and Iopromide 370.


Role of the N terminus in RNase A homologues: differences in catalytic activity, ribonuclease inhibitor interaction and cytotoxicity.
A number of biochemical properties differ dramatically among homologues within the pancreatic ribonuclease superfamily. Human pancreatic ribonuclease (hRNase) has high enzyme activity, extreme sensitivity to ribonuclease inhibitor (RI) and is non-toxic, whereas a homologous RNase from frog eggs, called onconase, has much lower enzyme activity, is not sensitive to RI and is cytotoxic to cancer cell lines and animals. To explore the structural basis of these differences among members in the RNAse family we synthesized genes for onconase, hRNase, a mutant onconase (K9Q) and onconase-hRNase N-terminal hybrids and expressed the proteins in Escherichia coli with final yields of 10 to 50 mg per liter of culture after purification. A recombinant version of onconase with an N-terminal methionine instead of the native pyroglutamyl residue had decreased cytotoxicity and enzyme activity. Cleavage of the recombinant onconase Met-1 residue, and cyclization of the Gln1 residue to reform the pyroglutamyl N terminus, reconstituted cytotoxicity and enzyme activity. Thus a unique role of the pyroglutamyl residue in the active site of amphibian RNases is indicated. Replacement of one to nine residues of onconase with the homologous residues of hRNase increased the enzymatic activity against most of the substrates tested with a simultaneous shift in the enzyme specificity from high preference for poly(U) to slight preference for poly(C). Cytotoxicity of the chimera decreased, dissociating cytotoxicity from enzymatic activity. The molecular basis for the low binding affinity of onconase for RI has been examined experimentally with the recombinant RNases and by fitting onconase and RNase A structures to the coordinates from the recently published RNase A-RI complex.


A novel choline cotransporter sequestration compartment in cholinergic neurons revealed by selective endosomal ablation.
The sodium-dependent, high affinity choline transporter - choline cotransporter - (ChCoT, aka: cho-1, CHT1, CHT) undergoes constitutive and regulated trafficking between the plasma membrane and cytoplasmic compartments. The pathways and regulatory mechanisms of this trafficking are not well understood. We report herein studies involving selective endosomal ablation to further our understanding of the trafficking of the ChCoT. Selective ablation of early sorting and recycling endosomes resulted in a decrease of approximately 75% of [3H]choline uptake and approximately 70% of [3H]hemicholinium-3 binding. Western blot analysis showed that ablation produced a similar decrease in ChCoTs in the plasma membrane subcellular fraction. The time frame for this loss was approximately 2 h which has been shown to be the constitutive cycling time for ChCoTs in this tissue. Ablation appears to be dependent on the intracellular cycling of transferrin-conjugated horseradish peroxidase and the selective deposition of transferrin-conjugated horseradish peroxidase in early endosomes, both sorting and recycling. Ablated brain slices retained their capacity to recruit via regulated trafficking ChCoTs to the plasma membrane. This recruitment of ChCoTs suggests that the recruitable compartment is distinct from the early endosomes. It will be necessary to do further studies to identify the novel sequestration compartment supportive of the ChCoT regulated trafficking.


Rapid dephosphorylation of eIF4E by dietary protein in the skeletal muscle and liver of food-deprived rats.
The effect of dietary protein on eIF4E phosphorylation was examined in rats starved for 18 h and then fed on either a 20% casein diet (20C) or a protein-free diet (0C). Refeeding with the 20C diet, but not the 0C diet, resulted in partial dephosphorylation of eIF4E in both the skeletal muscle and liver. The results suggest that the dephosphorylation of eIF4E in response to food intake was regulated by the increase in plasma amino acid concentration that occurred after feeding with the 20C diet.


Characterization of rotavirus strains isolated from children with acute gastroenteritis in Rawalpindi, Pakistan.
Diarrhea is the leading cause of childhood morbidity and mortality particularly in developing countries and rotavirus has been identified as the major pathogen associated with diarrheal infections. This study was conducted to detect genotypic distribution of predominant rotavirus strains circulating in children suffering from acute gastroenteritis in Rawalpindi, Pakistan. Stool specimens were collected from children ≤5 years of age, visiting Military Hospital, Rawalpindi, with signs and symptoms of acute gastroenteritis. Two hundred and eighty-four specimens were collected during the period from April 2017 to March 2018. Enzyme immunoassay was performed for detection of rotavirus and reverse transcription-PCR (RT-PCR) was carried out for amplification of VP7 and VP4 gene segments followed by multiplex PCR using genotype-specific primers. Out of 284 children, 71 were found rotavirus positive and among them, 54% were females and 46% males. Our findings showed 92% of infection among children ≤2 years of age, while, the peak age of rotavirus incidence was found to be 6-12 months. Although, rotavirus infection was observed throughout the year but frequency increased in winter. Subtype G1P[8] was more prevalent followed by G2P[4], G3P[8], and G4P[6] subtypes. The results of this study provide insight into the disease burden as well as information on rotavirus diversity which will be useful to develop future strategies to control and prevent diarrheal infections among children.


Wearing a mask-For yourself or for others? Behavioral correlates of mask wearing among COVID-19 frontline workers.
Human behavior can have effects on oneself and externalities on others. Mask wearing is such a behavior in the current pandemic. What motivates people to wear face masks in public when mask wearing is voluntary or not enforced? Which benefits should the policy makers rather emphasize in information campaigns-the reduced chances of getting the SARS-CoV-2 virus (benefits for oneself) or the reduced chances of transmitting the virus (benefits for others in the society)? In this paper, we link measured risk preferences and other-regarding preferences to mask wearing habits among 840 surveyed employees of two large Swiss hospitals. We find that the leading mask-wearing motivations change with age: While for older people, mask wearing habits are best explained by their self-regarding risk preferences, younger people are also motivated by other-regarding concerns. Our results are robust to different specifications including linear probability models, probit models and Lasso covariate selection models. Our findings thus allow drawing policy implications for effectively communicating public-health recommendations to frontline workers during the COVID-19 pandemic.


Effects of hydralazine and increased cardiac output on recombinant tissue plasminogen activator-induced thrombolysis in canine pulmonary embolism.
We employed a canine model of pulmonary embolism, induced by injection of autologous radiolabelled blood clots, to investigate effects of hydralazine and an increase in cardiac output per se on recombinant tissue plasminogen activator-induced thrombolysis. Emboli increased pulmonary artery pressure (PAP) and decreased CO from 2.7 to 1.8 L/min-1. Following embolization, dogs were randomly divided into three groups. Group 1 received .5 mg/kg of rtPA over 30 minutes. Group 2 received the same dose of rtPA and were pretreated with hydralazine to increase CO approximately 50 percent. In the group 3 dogs, CO was increased by opening a systemic A-V fistula. Following embolization, CO remained low in group 1, the mean 2 h time-averaged CO was 1.9 L/min-1. The CO was 2.9 and 3.1 L/min-1 in groups 2 and 3, respectively. Corresponding to the increased flow in groups 2 and 3, rate and extent of pulmonary thrombolysis significantly increased. These results indicate that an increase in CO augments rtPA-induced pulmonary thrombolysis.


Spectrum and burden of severe Haemophilus influenzae type b diseases in Asia.
The validity of the commonly held view that Haemophilus influenzae type b (Hib) diseases are rare in Asia is challenged in this article by a thorough analysis of the data available, often in languages other than English. The entire spectrum of Hib disease, not only meningitis, was taken into account, and over 100 reports from 25 countries were explored. Hib was the leading agent among nontuberculous childhood meningitis cases in two-thirds of 48 studies from 22 countries. Data from six countries showed that all the classical manifestations of invasive Hib diseases are also found in Asia, except epiglottitis, which was nearly absent. In Hong Kong Special Administrative Region of China Hib disease is rare, but otherwise the incidences seemed not to deviate much from those in Europe until recently, around 25 per 100,000 for meningitis and at least 40 per 100,000 per year for the classical Hib manifestations combined at age 0-4 years. In total, more than 200,000 cases of Hib disease are estimated to occur annually in Asia. Because nonbacteraemic Hib pneumonia remains mostly undetected, the total burden is probably significantly greater. The issue will be fully elucidated only by prospective epidemiological and clinical studies, but awaiting them should not delay large-scale vaccinations against Hib throughout Asia.


The impact of lowering the cut-off value on the sensitivity of the Platelia Elisa IgG (Bio-Rad) test for toxoplasmosis diagnosis.
Determining specific immune status against Toxoplasma gondii is essential for assessing the risk of reactivation in immunocompromised patients or defining serological monitoring and appropriate prophylactic measures during pregnancy. In France, toxoplasmosis serological screening requires systematic testing for IgM and IgG antibodies. The Platelia Toxo IgG and IgM test (Bio-Rad) is one of the most widely used tests for anti-toxoplasmic antibody detection. We performed a study on 384 sera, including 123 IgG negative (<6 IU/mL) and 261 IgG equivocal (6-9 IU/mL) sera tested with Platelia Toxo IgG and collected during routine screening at Pitié-Salpêtrière Hospital, Paris, France to determine the best-performing IgG titer cut-off value. Out of these 383 sera, 298 were IgM negative by Platelia Toxo IgM and 86 were IgM positive. All sera were also tested against Toxo IgG II LD BIO western blot test as confirmation. Our results indicated that an IgG titer cut-off value of ≥4.4 IU/mL for the Platelia Toxo IgG met the definition of positivity, a value significantly lower than that indicated by the manufacturers. In the presence of IgM antibodies, the IgG titer cut-off decreased significantly to a value ≥0.2 IU/mL. This latter cut-off also allowed adequate diagnosis of proven toxoplasmosis seroconversion in 76.7% of cases (33/43). Our findings may improve toxoplasmosis care by reducing therapeutic intervention time and eliminating the need for further serological monitoring.


Expedient synthesis of chiral α-amino acids through nickel-catalyzed reductive cross-coupling.
A novel method for the synthesis of non-natural L- and D-amino acids by a Ni-catalyzed reductive cross-coupling reaction is described. This strategy enables the racemization-free cross-coupling of serine/homoserine- derived iodides with aryl/acyl/alkyl halides. It provides convenient access to varieties of enantiopure and functionalized amino acids, which are important building blocks in bioactive compounds and pharmaceuticals.


RAGE antagonism by FPS‑ZM1 attenuates postoperative cognitive dysfunction through inhibition of neuroinflammation in mice.
Neuroinflammation triggered by surgical trauma contributes to postoperative cognitive dysfunction (POCD). The receptor for advanced glycation end‑products (RAGE), a multiligand inflammatory receptor, is involved in the damaging effects of various cellular processes, contributing to neuroinflammation and neurodegeneration. However, the potential role of RAGE in the acute period of POCD has not been fully investigated. C57BL/6 male mice undergoing surgery of the tibia under isoflurane anesthesia were treated with the RAGE antagonist FPS‑ZM1 or vehicle control intraperitoneally for a period of 7 days. The cognitive function of the animals was tested using trace fear conditioning on the third postoperative day. To determine astrocytic activation, microgliosis, p65 expression, inflammatory factor levels and postsynaptic density protein‑95 (PSD‑95) expression in the hippocampus, the animals were euthanized on either the first, third or seventh postoperative day. Compared with the control group, the cognitive function of the surgical animals was impaired on the third postoperative day. Astrocytic activation, microgliosis and the expression levels of p65, interleukin (IL)‑1β, IL‑6, and PSD‑95 were significantly increased on the first, and third postoperative days. However, tumor necrosis factor‑α expression was significantly increased only on postoperative day 1. All of the surgical effects observed were partially inhibited by treatment with FPS‑ZM1. In summary, the results of the present study suggest that RAGE serves an important role in the acute inflammatory process of POCD, and blocking RAGE can inhibit neuroinflammation and attenuate POCD. Thus, the RAGE signaling pathway may be a novel target in the prevention, and treatment of POCD.


Healthy and unhealthy aging on kidney structure and function: human studies.
This review is intended to provide an up-to-date analysis of the structural and functional alterations of the kidneys that accompany healthy and unhealthy aging in humans. Macro- and micro- structural changes and glomerular filtration rate (whole kidney and single nephron) accompanying aging will be stressed. Comparative findings concerning distribution of anatomic changes of the kidney healthy and unhealthy aging are reviewed. Challenges concerning definition of chronic kidney disease (CKD) in otherwise healthy aging patients are discussed. The complex interactions of CKD and aging are discussed. The role of podocyte dysbiosis in kidney aging is reviewed. Kidney aging is a complex phenomenon often difficult to distinguish from CKD. Nonetheless, phenotypes of healthy and unhealthy aging are evident. Much more information concerning the molecular characteristics of normal kidney aging and its relevance to chronic kidney disease is needed.


A national-level analysis of neighborhood form metrics.
Interest in urban neighborhood form is strong among scholars trained in multiple disciplines. The increasing popularity of this field calls for a set of metrics that can be used to describe meaningful patterns of built features in neighborhood environments. This study employs national-level datasets from Add Health, the National Land Cover Dataset (NLCD) 2001, the U.S. Census TIGER, and the U.S. Geological Survey to construct neighborhood form metrics for 20,467 residents, whose residential environments cover a wide array of geographic areas representative of comprehensive neighborhood types across the United States. Buffers of different sizes (1 km, 3 km, 5 km, and 8 km, respectively) are drawn around each resident's location as the unit of analysis. For the four sets of 20,467 neighborhood environments, 27 neighborhood form metrics are selected, computed, and further reduced through factor analysis. The results suggest that the derived subsets of univariate metrics can be applied across neighborhood types to characterize diverse neighborhood environments.


Exposure assessment of cattle via roughages to plants producing compounds of concern.
Food producing animals are exposed to biologically active plant compounds through feed and roughages, presenting a potential risk to the animal but also consumers of food of animal origin. To evaluate to which plant compounds of concern dairy cows in the Netherlands are exposed, a ranking filter model was developed, combining information on abundance of plant species in vegetation plots in the Netherlands (183,905 plots of three different vegetation types) with plant-compound combinations (700), and with consumption data of fresh grass, grass silage and corn silage by cattle. The most abundant plant genera are those producing cyanogenic glycosides, coumarins and benzofuranocoumarins, being predominantly fodder plants (alfalfa, clover and some grasses) considered to be safe. Highest exposures were estimated for plant genera producing piperidine alkaloids (horsetail), furanocoumarins (parsley and relatives), pyrrolizidine alkaloids (Symphytum, Senecio, Leucanthemum, Eupatorium) and essential oils. The current results allow to prioritise future scientific research on these compounds.


Investigation of nanoscratch processes in semiconductor materials for application to maskless patterning.
Features of nanoscratching processes with a diamond 90 degrees cube corner tip in semiconductor materials have been studied with different tip orientations and scratch procedures: constant and linearly increasing normal load during scratching, multi-scratching and the direct analysis of the generated scratch by re-scanning the scratch with a strongly reduced normal load. These scratch functions allowed a detailed investigation of the materials response due to the mechanical deformation process. Elastic material recovery, plastic deformation and material removal contribute to the generation of scratch groove profiles. For low applied normal loads mainly elastic deformation occurs whereas for larger normal loads stick-slip processes with periodic hillocks at the groove bottom and irregular pile-up along the scratch rim dominate the process. From the analysis of the scratch groove profile in Si(100), GaAs(100) and thin InSb films, quantitative values for the elastic deformation, the friction coefficient, stick-slip pattern, material removal and scratch depth as a function of the applied normal load are obtained. With multi-scratching a definite removal pattern with a reproducible scratch depth is obtained. These results can be used to optimise the scratch technique for application to maskless patterning.


Acute lipoprotein lipase deletion in adult mice leads to dyslipidemia and cardiac dysfunction.
The most energy-requiring organ in the body, the cardiac muscle, relies primarily on lipoprotein-derived fatty acids. Prenatal loss of cardiac lipoprotein lipase (LPL) leads to hypertriglyceridemia, but no cardiac dysfunction, in young mice. Cardiac specific loss of LPL in 8-wk-old mice was produced by a 2-wk tamoxifen treatment of MerCreMer (MCM)/Lpl(flox/flox) mice. LPL gene deletion was confirmed by PCR analysis, and LPL mRNA expression was reduced by approximately 70%. One week after tamoxifen was completed, triglyceride was increased with LPL deletion, 162 +/- 53 vs. 91 +/- 21 mg/dl, P < 0.01. Tamoxifen treatment of Lpl(flox/flox) mice did not cause a significant increase in triglyceride levels. Four weeks after tamoxifen, MCM/Lpl(flox/flox) mice had triglyceride levels of 190 +/- 27 mg/dl, similar to those of mice with prenatal LPL deletion. One week after the tamoxifen, MCM/Lpl(flox/flox), but not Lpl(flox/flox), mice had decreases in carnitine palmitoyl transferase I mRNA (18%) and pyruvate dehydrogenase kinase 4 mRNA (38%). These changes in gene expression became more robust with time. Acute loss of LPL decreased ejection fraction and increased mRNA levels for atrial natriuretic factor. Our studies show that acute loss of LPL can be produced and leads to rapid alteration in gene expression and cardiac dysfunction.


Molecular Comparison of Pyrophosphate- and ATP-Dependent Fructose 6-Phosphate 1-Phosphotransferases from Potato Tuber.
The aim of this work was to compare the molecular properties of pyrophosphate:fructose 6-phosphate 1-phosphotransferase (PFP) and ATP:fructose 6-phosphate 1-phosphotransferase (PFK). Both enzymes were purified to apparent homogeneity from potato tubers (Solanum tuberosum cv Record). Neither PFP nor PFK preparations contained detectable activity of the other enzyme. PFP was composed of two polypeptides of apparent molecular weight 58,000 and 55,700 whereas PFK contained four polypeptides of apparent molecular weight between 46,300 and 53,300. Chemical cleavage of individual PFP and PFK polypeptides gave a different set of fragments for each polypeptide. On Western blots antisera against PFP failed to cross-react with any of the four PFK polypeptides, and antibodies against PFK failed to bind to either of the PFP polypeptides. Antibodies that immunoprecipitate PFP activity had no effect on PFK activity. Conversely, antibodies against the four PFK polypeptides precipitated the activity of PFK, but not that of PFP. This work shows that potato tuber PFP and PFK are composed of distinct, unrelated polypeptides and indicate that interconversion between PFP and PFK is unlikely.