Soil ingestion estimates for children residing on a superfund site.
Soil ingestion estimates were obtained from a stratified, simple random sample of 64 children aged 1-4 years residing on a superfund site in Montana. The study was conducted during the month of September for 7 consecutive days. The study utilized a mass-balance methodology in which eight naturally occurring soil tracers (Al, Si, Ti, Ce, Nd, La, Y, and Zr) believed to be poorly absorbed by the gastrointestinal tract were employed to provide soil ingestion estimates. Food and fecal samples were analyzed on a daily basis. Soil/dust samples representative of where the children played during the study period were obtained. Very high compliance among the participants was maintained throughout the study. The identical methodology employed in the childrens' study was used in an adult study of tracer recovery in 10 subjects over 28 days of observation to provide validation that soil ingestion over the range of 20 to 500 mg/day could be detected. Soil ingestion was estimated by each soil tracer via traditional methods as well as by an improved approach using five trace elements (Al, Si, Ti, Y, and Zr), called the Best Tracer Method (BTM), which substantially corrects for error due to misalignment of tracer input and output as well as error occurring from ingestion of tracers from nonfood, nonsoil sources, while being insensitive to the particle size of the soil/dust ingested. According to the BTM, the median soil ingestion was less than 1 mg/day while the upper 95% was 160 mg/day. No significant age (1 year vs 2, vs 3) or sex-related differences in soil ingestion were observed. These estimates are lower than estimates observed in another study in Massachusetts during September and October. Significant methodological improvements in this study as compared to previously conducted soil ingestion studies include the selection of a representative sample of children, longer study duration, inclusion of dietary recommendations to reduce food tracer input and variability, use of the BTM, and a stronger adult validation study with respect to number of subjects, and duration and range of possible soil ingestion rates. Despite these methodological improvements, evidence exists that this study displays a net residual negative error, suggesting that the above estimates are below the true soil ingestion. The magnitude of this residual negative error cannot be quantified with the BTM but is likely to not affect the median by more than 40 mg/day, while the impact of such an error on the upper end of the distribution is more uncertain.


Predicting development of adolescent drinking behaviour from whole brain structure at 14 years of age.
Adolescence is a common time for initiation of alcohol use and development of alcohol use disorders. The present study investigates neuroanatomical predictors for trajectories of future alcohol use based on a novel voxel-wise whole-brain structural equation modeling framework. In 1814 healthy adolescents of the IMAGEN sample, the Alcohol Use Disorder Identification Test (AUDIT) was acquired at three measurement occasions across five years. Based on a two-part latent growth curve model, we conducted whole-brain analyses on structural MRI data at age 14, predicting change in alcohol use score over time. Higher grey-matter volumes in the caudate nucleus and the left cerebellum at age 14 years were predictive of stronger increase in alcohol use score over 5 years. The study is the first to demonstrate the feasibility of running separate voxel-wise structural equation models thereby opening new avenues for data analysis in brain imaging.


Possible solution of capturing viable Enterohemorrhagic Escherichia coli (EHEC) in clinical patient stool.
For clinical diagnosis of enterohemorrhagic Escherichia coli (EHEC), it needs to capture viable EHEC cells from stool sample in the view of medical fee points. However, there is no comprehensive solution for the detection of viable EHEC cells since there are wide variety of serotype and susceptibility against potassium tellurite which is commonly used for selective agent in selective medium for EHEC. In these background, EHEC Clear-HT System (EHEC-CHT), a novel effective chromogenic medium system for screening comprehensive viable EHEC, was developed. When EHEC-CHT was assessed using 128 microbes including 49 clinical isolated EHEC strains, EHEC-CHT detected all 49 EHEC strains as typical blue-colored colony regardless of both serotype and susceptibility to potassium tellurite. EHEC-CHT was compared with Japanese commercially available tellurite-based EHEC selective media using 107 clinical patient stool samples. EHEC-CHT showed higher detection ratio than conventional tellurite-based selective media compared, and 7% improvement at least in detection ratio in this study.


Effects of hypertonic saline on myocardial contractility in anaesthetized pigs.
The cardiac effects of hypertonic saline (HS, 7.5% NaCl) were evaluated using a number of indices derived from the left ventricular (LV) pressure-volume relationship. Left ventricular end-systolic elastance (elastance), the slope of the end-systolic pressure-volume relationship, end-systolic elastance normalized for end-diastolic volume (elastance(norm)), the rate of rise of LV pressure (dP/dtmax), and dP/dtmax/end-diastolic volume were used to assess myocardial contractility. Pigs were anaesthetized with isoflurane and instrumented for haemodynamic measurements, LV pressure, and volume (conductance catheter) determinations. Elastance was determined during transient (8-10 s) caudal vena caval balloon occlusion. Following instrumentation, the end-tidal isoflurane concentration was reduced and maintained at 1 minimum alveolar concentration (1.5%). Pigs were randomly administered either 0.9% NaCl (n = 7) or HS (n = 9) at a dose of 4 ml/kg, over 3 min into the right atrium. There were no significant differences in LV or haemodynamic measurements between isotonic saline and HS treated pigs at any time point. Elastance, elastase(norm) and dP/dtmax/end-diastolic volume did not change in either treatment group. In contrast, dP/dtmax increased significantly (P < 0.015) at 5 min compared to baseline after treatment with HS. End-diastolic volume increased significantly from 5 to 30 min following treatment with HS. Left ventricular end-diastolic pressure increased significantly at 5 and 60 min in HS treated pigs. Central venous and pulmonary arterial wedge pressures,and cardiac index increased significantly at 5 min after treatment with HS. Total peripheral resistance decreased significantly at 5 min, followed by a return to baseline in the HS group.(ABSTRACT TRUNCATED AT 250 WORDS)


Polyphenol Intake from Beverages in Japan over an 18-Year Period (1996-2013): Trends by Year, Age, Gender and Season.
An association between the dietary intake of polyphenols and human health has been shown in many epidemiological studies. Since beverages are rich sources of polyphenols, we aimed to evaluate the polyphenol intake from beverages in Japanese individuals with a focus on differences according to year, age, gender and season. More than 10,000 Japanese male and female subjects aged 1-99 y old participated in this survey every year from 1996 to 2013, and their beverage consumption and amount of polyphenol intake were calculated. Polyphenol intake from beverages in Japan showed no tendency to increase or decrease over the 18-y period, and the major sources of polyphenols in Japanese daily life were coffee and green tea. Polyphenol intake was larger in participants with higher age up to 59 y old in both male and female subjects. There was a slight difference in polyphenol intake by gender, with adult males consuming more polyphenols than adult females. Polyphenols were consumed slightly more in the winter than the summer, although the seasonal difference in polyphenol intake was not large. Our results suggest that polyphenol intake from beverages is influenced by age rather than gender or season in Japan, and may not have changed over time, at least over the 18-y period beginning in 1996 in Japan.


[Cystic dystrophy in an antro-duodenal heterotopic antroduodenal pancreas].
The authors report a case of cystic dystrophy in heterotopic pancreas in the absence of disease of the proper pancreas. This case is particular in regard of its association to pancreas divisum, its antro-bulbous localization, and its evolutive character marked by hyperamylasemia, ascite, and sharped inflammatory lesions of resection specimen. The diagnostic usefulness of endoscopic ultrasonography is outlined.


Genotoxicity of N-nitroso-N-methylurea and acetone oxime in the transgenic Drosophila carrying the human gene encoding a subunit of glutathione S-transferase.
The genotoxic effects of N-nitroso-N-methylurea (MNU) and acetone oxime (ACOX) were tested in the Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster. We have performed the same assay on transgenic flies expressing the human gene encoding a glutathione S-transferase alpha subunit (HGST). The SMART assay is used here to demonstrate genotoxicity and to determine the effect of human glutathione S-transferase on the genotoxic response. Three types of Drosophila strains were used: non-transgenic strains first described by Szabad (1986), transgenic strains derived from the Szabad strains but expressing the bacterial lacZ gene, and similarly derived transgenic strains expressing the HGST gene. MNU was highly genotoxic in both transgenic and non-transgenic flies. The non-transgenic lies were significantly more sensitive to the genotoxic effects of MNU compared to both types of transgenic flies. There were statistically significant differences between the transgenic HGST crosses and transgenic lacZ and non-transgenic control crosses but there was no significant difference between the genotoxic response to MNU in flies from the transgenic cross with lacZ and from the cross carrying three copies of HGST. ACOX also proved to be genotoxic to both non-transgenic and transgenic flies. However, flies carrying three copies of the gene were significantly more resistant to the genotoxic effect of ACOX than those transgenic flies with two or no copies of the human gene.


The impact of sociodemographic factors and PSA screening among low-income Black and White men: data from the Southern Community Cohort Study.
Variation in PSA screening is a potential source of disparity in prostate cancer survival, particularly among underserved populations. We sought to examine the impact of race and socioeconomic status (SES) on receipt of PSA testing among low-income men. Black (n=22 167) and White (n=9588) men aged ⩾40 years completed a baseline questionnaire from 2002 to 2009 as part of the Southern Community Cohort Study. Men reported whether they had ever received PSA testing and had testing within the prior 12 months. To evaluate the associations between SES, race and receipt of PSA testing, odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from the multivariable logistic models where age, household income, insurance status, marital status, body mass index and educational level were adjusted. Black men were younger, had a lower income, less attained education and were more likely to be unmarried and uninsured (all P<0.001). Percentages of men having ever received PSA testing rose from <40% under the age of 45 years to ~90% above the age of 65 years, with Whites >50 more likely than Blacks to have received testing. Lower SES was significantly associated with less receipt of PSA testing in both groups. After adjustment for SES, White men had significantly lower odds of PSA testing (OR 0.81; 95% CI: 0.76-0.87). Greater PSA testing among White than Black men over the age of 50 years in this low-income population appears to be mainly a consequence of SES. Strategies for PSA screening may benefit from tailoring to the social circumstances of the men being screened.


MEMS Mirrors for LiDAR: A review.
In recent years, Light Detection and Ranging (LiDAR) has been drawing extensive attention both in academia and industry because of the increasing demand for autonomous vehicles. LiDAR is believed to be the crucial sensor for autonomous driving and flying, as it can provide high-density point clouds with accurate three-dimensional information. This review presents an extensive overview of Microelectronechanical Systems (MEMS) scanning mirrors specifically for applications in LiDAR systems. MEMS mirror-based laser scanners have unrivalled advantages in terms of size, speed and cost over other types of laser scanners, making them ideal for LiDAR in a wide range of applications. A figure of merit (FoM) is defined for MEMS mirrors in LiDAR scanners in terms of aperture size, field of view (FoV) and resonant frequency. Various MEMS mirrors based on different actuation mechanisms are compared using the FoM. Finally, a preliminary assessment of off-the-shelf MEMS scanned LiDAR systems is given.


Vibrational frequency scaling factors for correlation consistent basis sets and the methods CC2 and MP2 and their spin-scaled SCS and SOS variants.
We present scaling factors for vibrational frequencies calculated within the harmonic approximation and the correlated wave-function methods coupled cluster singles and doubles model (CC2) and Møller-Plesset perturbation theory (MP2) with and without a spin-component scaling (SCS or spin-opposite scaling (SOS)). Frequency scaling factors and the remaining deviations from the reference data are evaluated for several non-augmented basis sets of the cc-pVXZ family of generally contracted correlation-consistent basis sets as well as for the segmented contracted TZVPP basis. We find that the SCS and SOS variants of CC2 and MP2 lead to a slightly better accuracy for the scaled vibrational frequencies. The determined frequency scaling factors can also be used for vibrational frequencies calculated for excited states through response theory with CC2 and the algebraic diagrammatic construction through second order and their spin-component scaled variants.


Geographical variation of bacterial and ciliophoran communities in tidal flats in a continental archipelago.
In tidal flats, which are located at the transition zone between terrestrial and marine ecosystems, environmental factors such as temperature, sediment particle size, and tidal range exhibit geographic variation. Accordingly, the composition and structure of the microbial communities in the tidal flats are likely to vary in geographically different habitats. To clarify these differences with environmental factors causing them, we analyzed microbial communities consisting of bacteria and ciliates in sediments collected from nine tidal flats in geographical diverse region from Hokkaido to Kagoshima, Japan. The results confirmed that the community structures of bacteria and ciliophora in tidal flat sediments differed at the geographical scale of the Japanese archipelago. However, the variation could not be explained by the physical distance between the tidal flats nor by the differences in the trophic conditions among the tidal flats. Instead, the OTU richness of both the bacterial and ciliophoran communities was significantly related to the tidal range. The results also showed that bacteria and ciliophora tended to form similar communities among the tidal flats with similar median particle sizes. Furthermore, ciliophoran communities were similar among the tidal flats with similar bacterial communities. The results suggest that bacteria and ciliophora interact each other through trophic relationships or physical and chemical processes in the sediment habitats.


Diabetic myonecrosis: a diagnostic challenge in patients with long-standing diabetes.
A 51-year-old female with a history of type 1 diabetes mellitus (DM) presented with sudden onset of pain and swelling of the left thigh. Her initial evaluation revealed mildly elevated erythrocyte sedimentation rate and creatine phosphokinase. Venous and arterial Doppler studies were negative for DVT and arterial thrombus. Further imaging with CT scan and then MRI revealed an irregular, enhancing space-occupying lesion of the left upper and mid-thigh. Subsequent muscle biopsy showed myonecrosis and proliferative myositis. Both findings are consistent with diabetic myonecrosis, which is a microvascular complication of long-standing poorly controlled DM. The patient was treated with analgesics, supportive care, and optimization of glycemic control. While short-term prognosis is good with adequate healing in a few weeks to several months, long-term prognosis is poor due to underlying extensive vascular disease. Although radiological findings are very suggestive of the diagnosis, most clinicians still need tissue biopsy to rule out other serious conditions such as infections and malignancy.


DNA analysis in Finnish patients with hereditary neuropathy with liability to pressure palsies (HNPP).
Hereditary neuropathy with liability to pressure palsies (HNPP) is a dominantly inherited disorder that presents as recurrent mononeuropathies precipitated by apparently trivial traumas. The presence of a deletion in 17p11.2 was analysed in 13 Finnish families with HNPP. The deletion was found in all patients who were neurologically and neurophysiologically confirmed to have HNPP. In the problematic cases the detection of the gene defect is the method of choice in the diagnosis of HNPP. Analysis of DNA can also be used to detect clinically unaffected family members.


Primary large cell lymphoma of the mediastinum. A histologic and immunophenotypic study of 29 cases.
We studied the morphologic and immunologic features of 29 cases of primary nonlymphoblastic non-Hodgkin's lymphoma of the mediastinum. The patients ranged in age from 15 to 73 years, with a median of 32 years. The mean age for the 11 men (50 years) was significantly higher than that for the 18 women (32 years) (p less than 0.05). All had diffuse large cell lymphomas (six immunoblastic, 14 large cell not otherwise specified, six large cell noncleaved, one large cell cleaved, and two not subclassifiable). Sclerosis was prominent in 11 cases, none of them immunoblastic, and did not correlate with superior vena cava syndrome. The mean age (54 years) of patients with immunoblastic lymphomas was higher than that for patients with other subtypes (35 years) (p less than 0.02). Frozen-section immunoperoxidase staining disclosed monotypic immunoglobulin in 13 cases, with a high frequency of heavy-chain class switching (seven IgG, two IgA, four IgM). Sixteen cases were immunoglobulin negative; 14 of 15 cases expressed B-lineage antigens, and none expressed T-lineage antigens. Three of four cases showed immunoglobulin heavy- or light-chain gene rearrangement by the Southern blot technique. None showed rearrangement of the T-cell receptor beta-chain-gene constant region. There was no correlation between immunophenotype and morphologic subtype. The immunoglobulin-negative group was predominantly female (13 of 16 cases; p less than 0.02), and younger (mean age, 34 years versus 44 years; p = NS) than the immunoglobulin-positive group; however, the difference in age was not statistically significant. The actuarial 5-year survival was 57%, and there was no correlation between survival and either histologic subtype or immunophenotype. Mediastinal large cell lymphoma is a B-cell tumor, which frequently lacks immunoglobulin, may be primary in the thymus, has a predilection for young women, and can be cured with aggressive therapy.


Isolation and Genome Characterization of the Virulent Staphylococcus aureus Bacteriophage SA97.
A novel bacteriophage that infects S. aureus, SA97, was isolated and characterized. The phage SA97 belongs to the Siphoviridae family, and the cell wall teichoic acid (WTA) was found to be a host receptor of the phage SA97. Genome analysis revealed that SA97 contains 40,592 bp of DNA encoding 54 predicted open reading frames (ORFs), and none of these genes were related to virulence or drug resistance. Although a few genes associated with lysogen formation were detected in the phage SA97 genome, the phage SA97 produced neither lysogen nor transductant in S. aureus. These results suggest that the phage SA97 may be a promising candidate for controlling S. aureus.


Interactome Mapping Guided by Tissue-Specific Phosphorylation in Age-Related Macular Degeneration.
The current study aims to determine the molecular mechanisms of age-related macular degeneration (AMD) using the phosphorylation network. Specifically, we examined novel biomarkers for oxidative stress by protein interaction mapping using in vitro and in vivo models that mimic the complex and progressive characteristics of AMD. We hypothesized that the early apoptotic reactions could be initiated by protein phosphorylation in region-dependent (peripheral retina vs. macular) and tissue-dependent (retinal pigment epithelium vs. retina) manner under chronic oxidative stress. The analysis of protein interactome and oxidative biomarkers showed the presence of tissue- and region-specific post-translational mechanisms that contribute to AMD progression and suggested new therapeutic targets that include ubiquitin, erythropoietin, vitronectin, MMP2, crystalline, nitric oxide, and prohibitin. Phosphorylation of specific target proteins in RPE cells is a central regulatory mechanism as a survival tool under chronic oxidative imbalance. The current interactome map demonstrates a positive correlation between oxidative stress-mediated phosphorylation and AMD progression and provides a basis for understanding oxidative stress-induced cytoskeletal changes and the mechanism of aggregate formation induced by protein phosphorylation. This information could provide an effective therapeutic approach to treat age-related neurodegeneration.


Climate change promotes parasitism in a coral symbiosis.
Coastal oceans are increasingly eutrophic, warm and acidic through the addition of anthropogenic nitrogen and carbon, respectively. Among the most sensitive taxa to these changes are scleractinian corals, which engineer the most biodiverse ecosystems on Earth. Corals' sensitivity is a consequence of their evolutionary investment in symbiosis with the dinoflagellate alga, Symbiodinium. Together, the coral holobiont has dominated oligotrophic tropical marine habitats. However, warming destabilizes this association and reduces coral fitness. It has been theorized that, when reefs become warm and eutrophic, mutualistic Symbiodinium sequester more resources for their own growth, thus parasitizing their hosts of nutrition. Here, we tested the hypothesis that sub-bleaching temperature and excess nitrogen promotes symbiont parasitism by measuring respiration (costs) and the assimilation and translocation of both carbon (energy) and nitrogen (growth; both benefits) within Orbicella faveolata hosting one of two Symbiodinium phylotypes using a dual stable isotope tracer incubation at ambient (26 °C) and sub-bleaching (31 °C) temperatures under elevated nitrate. Warming to 31 °C reduced holobiont net primary productivity (NPP) by 60% due to increased respiration which decreased host %carbon by 15% with no apparent cost to the symbiont. Concurrently, Symbiodinium carbon and nitrogen assimilation increased by 14 and 32%, respectively while increasing their mitotic index by 15%, whereas hosts did not gain a proportional increase in translocated photosynthates. We conclude that the disparity in benefits and costs to both partners is evidence of symbiont parasitism in the coral symbiosis and has major implications for the resilience of coral reefs under threat of global change.


Thermoregulation responses of broiler chickens to humidity at different ambient temperatures. I. One week of age.
Three trials were conducted to investigate the effect of RH (35, 60, and 85%) on thermoregulation of 1-wk-old broiler chickens at different temperatures (35, 30, and 25 degrees C). The response to humidity in rectal temperature and plumage temperature at the back and breast within 24 h after exposure were recorded at 5 time points (1,4,8,16, and 24 h). Humidity affected the thermoregulation of 1-wk-old broiler chickens by redistributing heat within the body at high, low, and thermoneutral temperatures. The redistribution of heat resulted in decreased rectal temperature and increased peripheral temperature, which were, respectively, beneficial and unfavorable at high and low temperatures. These results suggested that feedback effects of surface temperature on core temperature also exist in poultry, as already observed in mammals, and could be induced not only by changed ambient temperature but also by the changes in humidity at high temperature. The disturbance of thermal equilibrium could not be established solely by changes in RT, but rather core and surface temperatures had to be considered. The daily rhythms in rectal and surface temperatures were affected by humidity.


Effects of rare gases on sonoluminescence spectrum of the K atom.
Multibubble-sonoluminescence spectra from Ar-saturated KCl aqueous solutions were measured in the temperature range of 15-40 °C at frequencies of 48 kHz, 148 kHz, and 1 MHz. The effects of dissolved rare gases and the ultrasonic frequency on the shape of the K atom emission spectrum were examined. The line width of the K doublet was independent of the solution temperature, whereas the K line intensity decreased with increasing temperature. The spectra from Xe- and Ar-saturated solutions at 148 kHz exhibited a red-shifted and asymmetrically broadened doublet of K lines. The spectrum from a He-saturated solution, on the other hand, exhibited symmetrically broadened K lines, which were slightly blue-shifted. The observed effects of rare gases are in good agreement with those obtained by gas-phase spectroscopy. These results strongly indicate that the excited K atoms are perturbed by rare gases inside bubbles. The spectra from Xe- and Ar-saturated solutions also indicated that the K doublet is composed of two types of peaks, shifted broadened lines and unshifted narrow lines. These two types of peaks were clearly separated at a frequency of 48 kHz with a high acoustic power in the case of Ar-saturated solutions. The intensity of the broadened lines relative to that of the narrow lines markedly decreased at 1 MHz. Although the narrow lines as well as the broadened lines may have originated from inside the bubbles, the exact mechanism is still unclear.


Strength of integration of transmembrane alpha-helical peptides in lipid bilayers as determined by atomic force spectroscopy.
In this study we address the stability of integration of proteins in membranes. Using dynamic atomic force spectroscopy, we measured the strength of incorporation of peptides in lipid bilayers. The peptides model the transmembrane parts of alpha-helical proteins and were studied in both ordered peptide-rich and unordered peptide-poor bilayers. Using gold-coated AFM tips and thiolated peptides, we were able to observe force events which are related to the removal of single peptide molecules out of the bilayer. The data demonstrate that the peptides are very stably integrated into the bilayer and that single barriers within the investigated region of loading rates resist their removal. The distance between the ground state and the barrier for peptide removal was found to be 0.75 +/- 0.15 nm in different systems. This distance falls within the thickness of the interfacial layer of the bilayer. We conclude that the bilayer interface region plays an important role in stably anchoring transmembrane proteins into membranes.


Nicholas reactions with carboxylic acids for the synthesis of macrocyclic diolides.
[reaction: see text] We have developed a new strategy for the preparation of diolides using a cascade of Nicholas reactions. The carboxylic acid nucleophiles in these reactions are virtually unstudied participants in transformations of this type. Using this methodology, a 16-membered cobalt-complexed cyclic diyne is available in 28% yield over eight steps (an average of 85% per step). We can also easily access the uncomplexed diolide in one additional step.


Carbon nanotubes: an example of multiscale development--a mechanistic view from the subnanometer to the meter scale.
We summarize the catalytic synthesis of multiwall carbon nanotubes (MWCNTs). The current understanding of the reaction mechanism is presented, in particular the catalyst design for the CCVD process is analyzed. To complement that, kinetics and reaction engineering aspects are discussed along with the impact of the reaction and reactor operation on the product properties. All these issues are analyzed from the perspective of the industrial synthesis and implications for the application of carbon nanotubes. Carbon-nanotube technology is a perfect example of multi-scale development and covers challenges from the nanometer to the meter scale. Problems, methods, and solutions characteristic for different scales will be highlighted. The Co/Mn catalyst is used as reference as one of the first commercially used technologies for the scalable production of multiwall carbon nanotubes.


Gas phase anion photoelectron spectroscopy and theoretical investigation of gold acetylide species.
We conducted gas phase anion photoelectron spectroscopy and density functional theory studies on a number of gold acetylide species, such as AuC2H, AuC2Au, and Au2C2H. Based on the photoelectron spectra, the electron affinities of AuC2H, AuC2Au, and Au2C2H are measured to be 1.54(±0.04), 1.60(±0.08), and 4.23(±0.08) eV, respectively. The highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) gaps of AuC2H and AuC2Au are measured to be about 2.62 and 2.48 eV, respectively. It is interesting that photoelectron spectra of AuC2H- and AuC2Au- display similar spectral features. The comparison of experimental and theoretical results confirms that the ground-state structures of AuC2H-, AuC2Au-, and their neutrals are all linear with Au-C≡C-H and Au-C≡C-Au configurations. The similar geometric structures, spectral features, HOMO-LUMO gaps, and chemical bonding between AuC2H-/0 and AuC2Au-/0 demonstrate that Au atom behaves like H atom in these species. The photoelectron spectrum of Au2C2H- shows that Au2C2H has a high electron affinity of 4.23(±0.08) eV, indicating Au2C2H is a superhalogen. Further, we found an unusual similarity between the terminal Au atom of Au2C2H- and the iodine atom of IAuC2H-.


Humoral sensitization in parous women: cytotoxic antibodies to non HL-A antigens.
From sera of parous women, we selected 100 samples that lacked cytotoxic antibodies to human peripheral lymphocytes from at least 80 unrelated persons. These sera were then reacted with a panel of 17 cultured human lymphoid cells in the complement-dependent cytotoxic test. Forty-six sera contained cytotoxic antibodies apparently directed to an antigenic system distinct from HL-A antigens, and other known cell surface markers. Rabbit serum was the most efficient source of complement with these cytotoxic antibodies which did not appear to be directed to tumor associated antigens: in fact, no lysis of melanoma cells or leukemic cells could be detected. Ten specificities could be identified which were represented on the cultured human lymphoid cells in various combinations. It is suggested that antigens detected by this approach may be similar to the Ia antigens of the mouse.


Assessing health literacy of hypertensive patients in a primary care setting using a self-administered questionnaire.
The Newest Vital Sign (NVS) assesses health literacy in clinical settings. This exploratory study examined the feasibility of using the NVS as a self-administered questionnaire (SAQ) in a low-income, primary care setting. Adult hypertensive patients were recruited in 2011-2012 (n=238). Quantitative and qualitative analyses were conducted to examine potential issues with self-administration. Patients had low rates of adequate health literacy (28.4%). Only half of respondents completed the NVS (54.4%). Being Black, female, and having additional chronic illnesses increased the likelihood of being a partial responder as opposed to being a completer. Easier math problems and reading comprehension items were attempted in greater numbers by partial responders. Results indicate issues with interpretation and the need for better scoring instructions. Future studies that self-administer the NVS should consider slight modifications. The NVS provides important information about patients' health literacy and it is a valuable tool to assess patients' understanding of food labels.


Mycoplasma genitalium in the cervices of Japanese women.
Mycoplasma genitalium is considered a cause of nongonococcal urethritis in men. This organism also is a cause of genital infections in women, and has been detected in women attending sexually transmitted disease clinics in the United Kingdom and Denmark, although its prevalence is unknown in Japanese women. To determine the prevalence of M. genitalium in the cervices of women with cervicitis or adnexitis as well as in asymptomatic pregnant women in Japan. Two hundred women who attended obstetric and gynecologic clinics were recruited. Sixty-four women had cervicitis, 53 had adnexitis, and 3 had both. Eighty pregnant women were asymptomatic for infection. Cervical swab specimens were examined for M. genitalium using a polymerase chain reaction-based assay. Five (7.8%) of 64 women with cervicitis and 3 (5.7%) of 53 women with adnexitis were positive for M. genitalium. After exclusion of Chlamydia-positive women, 5 (8.8%) of 57 women with cervicitis, and 2 (4.1%) of 49 women with adnexitis were positive for M. genitalium. In none of 80 asymptomatic pregnant women, including a Chlamydia-positive woman, was M. genitalium detected. Overall, 7 (6.6%) of 106 women with Chlamydia-negative genital infections were positive for the M. genitalium. This prevalence was significantly greater than that in asymptomatic pregnant women (P < 0.05). A significantly greater prevalence of M. genitalium was demonstrated in Japanese women with Chlamydia-negative cervicitis or adnexitis, compared with that in asymptomatic pregnant women. This study suggests that M. genitalium may play a pathogenic role in a portion of cases with Chlamydia-negative genital infections.


Ever-present threats from information technology: the Cyber-Paranoia and Fear Scale.
Delusions involving technology, and specifically the internet, are increasingly common, and fear-reality statistics suggest computer-related fears are very widespread. These fears form a continuum from the widely understandable and realistic to the unrealistic, and frankly paranoid. The present study investigated the validity of this construct in a non-clinical population by constructing a novel self-report measure. The new Cyber-Paranoia and Fear Scale aims to measure the perception of information technology-related threats originating from or enabled by computers, smartphones, social networks, and digital surveillance. Psychometric properties of the new Cyber-Paranoia and Fear Scale are reported alongside an established measure of suspiciousness and paranoia in 181 participants including a sub-group of fifty information technology professionals. Exploratory factor analysis suggested the presence of two, related, dimensions that we term cyber-paranoia and cyber-fear. Both sub-scales were internally consistent and produced a normal distribution of scores. The relationships of the sub-scales with age, gender, trait paranoia, digital literacy, and digital inclusion are supportive of construct validity. The distinctiveness of 'cyber-paranoia' from general trait paranoia appears to mirror the clinical distinctiveness of 'internet' and other technology-fuelled delusions. Knowledge provision to increase technological proficiency and awareness may bring about a reduction in cyber-paranoia.


Rural-Urban Disparities in Multimorbidity Associated With Climate Change and Air Pollution: A Longitudinal Analysis Among Chinese Adults Aged 45.
Chronic conditions and multimorbidity are increasing worldwide. Yet, understanding the relationship between climate change, air pollution, and longitudinal changes in multimorbidity is limited. Here, we examined the effects of sociodemographic and environmental risk factors in multimorbidity among adults aged 45+ and compared the rural-urban disparities in multimorbidity. Data on the number of chronic conditions (up to 14), sociodemographic, and environmental factors were collected in 4 waves of the China Health and Retirement Longitudinal Study (2011-2018), linked with the full-coverage particulate matter 2.5 (PM2.5) concentration data set (2000-2018) and temperature records (2000-2018). Air pollution was assessed by the moving average of PM2.5 concentrations in 1, 2, 3, 4, and 5 years; temperature was measured by 1-, 2-, 3-, 4-, and 5-year moving average and their corresponding coefficients of variation. We used the growth curve modeling approach to examine the relationship between climate change, air pollution, and multimorbidity, and conducted a set of stratified analyses to study the rural-urban disparities in multimorbidity related to temperature and PM2.5 exposure. We found the higher PM2.5 concentrations and rising temperature were associated with higher multimorbidity, especially in the longer period. Stratified analyses further show the rural-urban disparity in multimorbidity: Rural respondents have a higher prevalence of multimorbidity related to rising temperature, whereas PM2.5-related multimorbidity is more severe among urban ones. We also found temperature is more harmful to multimorbidity than PM2.5 exposure, but PM2.5 exposure or temperature is not associated with the rate of multimorbidity increase with age. Our findings indicate that there is a significant relationship between climate change, air pollution, and multimorbidity, but this relationship is not equally distributed in the rural-urban settings in China. The findings highlight the importance of planning interventions and policies to deal with rising temperature and air pollution, especially for rural individuals.


Recent Advances in Mesoporous Silica Nanoparticles for Targeted Drug Delivery Applications.
Nanotechnology provides the means to design and fabricate delivery vehicles capable of overcoming physiologically imposed obstacles and undesirable side effects of systemic drug delivery. This protocol allows maximal targeting effectiveness and therefore enhances therapeutic efficiency. In recent years, Mesoporous Silica Nanoparticles (MSNPs) have sparked interest in nanomedicine research community, particularly for their promising applications in cancer treatment. The intrinsic physio-chemical stability, facile functionalization, high surface area, low toxicity, and great loading capacity for a wide range of chemotherapeutic agents make MSNPs very appealing candidates for controllable drug delivery systems. Importantly, the peculiar nanostructures of MSNPs enabled them to serve as an effective drug, gene, protein and antigen delivery vehicle for a variety of therapeutic regimens. For these reasons, in this review article, we underscore the recent progress in the design and synthesis of MSNPs along with the parameters influencing their characteristic features and activities. In addition, the process of absorption, dissemination and secretion by injection or oral management of MSNPs are also discussed, as they are key directions for potential utilization of MSNPs. Factors influencing the in vivo fate of MSNPs will also be highlighted, with a main focus on particle size, morphology, porosity, surface functionality and oxidation. Given that combining other functional materials with MSNPs may increase their biological compatibility, monitor drug discharge, or improve absorption by tumor cells coated MSNPs; these aspects are also covered and discussed herein.


In vitro maturation using αMEM with reduced NaCl enhances maturation and developmental competence of pig oocytes after somatic cell nuclear transfer.
Compared to medium containing 108 mM sodium chloride (NaCl), in vitro maturation (IVM) using a simple medium with reduced (61.6 mM) NaCl increases the cytoplasmic maturation and embryonic development of pig oocytes. This study determines the effect of a complex medium containing reduced NaCl on the IVM and embryonic development of pig oocytes. Pig oocytes were matured in Minimum Essential Medium Eagle-alpha modification (αMEM) supplemented with 61.6 (61αMEM) or 108 (108αMEM) mM NaCl, and containing polyvinyl alcohol (PVA) (αMEMP) or pig follicular fluid (PFF) (αMEMF). Medium-199 (M199) served as the control for conventional IVM. Cumulus cell expansion, nuclear maturation, intra-oocyte glutathione (GSH) contents, size of perivitelline space (PVS), and embryonic development after parthenogenesis (PA) and somatic cell nuclear transfer (SCNT) were evaluated after IVM. Regardless of PVA or PFF supplementation, oocytes matured in 61αMEM showed increased intra-oocyte GSH contents and width of PVS (p < 0.05), as well as increased blastocyst formation (p < 0.05) after PA and SCNT, as compared to oocytes matured in 108αMEMP and M199. Under conditions of PFF-enriched αMEM, SCNT oocytes matured in 61αMEMF showed higher blastocyst formation (p < 0.05), compared to maturation in 108αMEMF and M199, whereas PA cultured oocytes showed no significant difference. IVM in αMEM supplemented with reduced NaCl (61.6 mM) enhances the embryonic developmental competence subsequent to PA and SCNT, which attributes toward improved oocyte maturation.


Soundscapes influence the settlement of the common Caribbean coral Porites astreoides irrespective of light conditions.
The settlement of reef-building corals is critical to the survival and recovery of reefs. Recent evidence indicates that coral larvae orient towards reef sound, yet the components of the acoustic environment that may attract coral larvae and induce settlement are unknown. Here we investigated the effects of ambient soundscapes on settlement of Porites astreoides coral larvae using in situ chambers on reefs differing in habitat quality (coral and fish abundance). Mean larval settlement was twice as high in an acoustic environment with high levels of low-frequency sounds, typical of a high-quality, healthy reef; this result was observed in both natural light and dark treatments. Overall, the enhancement of coral settlement by soundscapes typical of healthy reefs suggests a positive feedback where soundscape properties of reefs with elevated coral and fish abundance may facilitate coral recruitment.


Carotid Artery Stenting-Historical Context, Trends, and Innovations.
Surgical carotid endarterectomy (CEA) has been proven effective in both primary and secondary stroke prevention and, until recently, has been considered the standard treatment approach for patients with severe carotid artery disease. Because of its technical limitations and less favorable outcomes, carotid artery stenting (CAS) has been offered preferably to patients considered to be too comorbid to undergo surgical treatment. However, CAS has evolved over time into a reliable method and is currently considered an alternative to CEA. The aim of this review was to discuss the historical aspects, trends, and innovations in CAS.


Diagnostic value of procalcitonin levels as an early indicator of sepsis.
Researchers and clinicians have been investigating and implementing various methods of early diagnosis for sepsis before documentation of infection. The aim of this study was to outline the efficiency of procalcitonin (PCT), C-reactive protein (CRP), and white blood cell count (WBC) in determining the early diagnosis of sepsis in the emergency department. Between January 1999 and September 2000, 34 patients with signs of systemic inflammatory response syndrome (SIRS) were enrolled in the study. The patients were divided into 2 groups according to non-suspected sepsis and suspected sepsis clinically. Admission PCT was significantly higher in suspected sepsis group (median 68.7 microg/L; lower [L] = 15.24 microg/L, upper [U] = 120.54 microg/L) compared with the unsuspected sepsis group (.23 microg/L; L =.10 microg/L, U =.44 microg/L). PCT values were compared with WBC and CRP levels. Predictive accuracy for sepsis expressed as area under the receiver operating characteristic (ROC) curve was.88 for PCT,.44 for WBC, and.34 for CRP. PCT can probably be used as a predictive marker in bacterial infections in emergency departments.


[Identification of clinical isolates of Burkholderia cepacia and assessment of their pathogenicity in animal experiments].
In experiments on animals study of pathogenicity of 9 clinical strains of Burkholderia cepacia isolated from patients with chronic lung diseases was performed. Preliminary identification of studied strains by means of biochemical and genetic methods allowed to establish their belonging to B. cepacia species. It was determined that 6 of 9 strains are epidemiologically significant. Experiments showed that bacteria of studied strains are not able to cause infectious process in white mice and hamadryas baboons. Conclusion about appropriateness of development and use of other biological models was made.


LLPS of SQSTM1/p62 and NBR1 as outcomes of lysosomal stress response limits cancer cell metastasis.
Liquid droplet has emerged as a flexible intracellular compartment that modulates various cellular processes. Here, we uncover an antimetastatic mechanism governed by the liquid droplets formed through liquid-liquid phase separation (LLPS) of SQSTM1/p62 and neighbor of BRCA1 gene 1 (NBR1). Some of the tyrosine kinase inhibitors (TKIs) initiated lysosomal stress response that promotes the LLPS of p62 and NBR1, resulting in the spreading of p62/NBR1 liquid droplets. Interestingly, in the p62/NBR1 liquid droplet, degradation of RAS-related C3 botulinum toxin substrate 1 was accelerated by cellular inhibitor of apoptosis protein 1, which limits cancer cell motility. Moreover, the antimetastatic activity of the TKIs was completely overridden in p62/NBR1 double knockout cells both in vitro and in vivo. Thus, our results demonstrate a function of the p62/NBR1 liquid droplet as a critical determinant of cancer cell behavior, which may provide insight into both the clinical and biological significance of LLPS.


Sustained Neuromuscular Blockade after Vecuronium Use in a Premature Infant.
Background Prolonged use of neuromuscular blocking agents (NMBAs) is very common in critically ill children both in pediatric and neonatal intensive care units. There are no guidelines available for use of NMBAs in children or neonates in the US, and the data for their safety in this age group is limited. Case Description Our case describes prolonged neuromuscular blockade following concurrent use of a NMBA along with aminoglycosides and steroids in the setting of renal failure in a premature infant. Conclusion Prolonged use of NMBAs in preterm infants should be avoided if possible or should be restricted to the shortest possible duration and the smallest possible physiologically effective dose. Concurrent use of NMBAs with aminoglycoside and steroids should be avoided, especially in the setting of renal failure.


The effect of an acidic, copper sulfate-based commercial sanitizer on indicator, pathogenic, and spoilage bacteria associated with broiler chicken carcasses when applied at various intervention points during poultry processing.
Studies were conducted to evaluate 1) the effect of an acidic, copper sulfate-based commercial sanitizer on pathogenic, indicator, and spoilage bacteria in a model scalder system, 2) the effect of this sanitizer on total aerobic bacteria (APC) and Escherichia coli counts, and Salmonella prevalence on broiler chicken carcasses when applied during scalding or scalding and postpick dipping, and 3) the ability of sanitizer to extend the shelf-life of broiler chicken carcasses. Exposure of Salmonella Typhimurium, Listeria monocytogenes, Staphylococcus aureus, Pseudomonas fluorescens, or Shewanella putrefaciens to the sanitizer in scalder water at 54 degrees C for 2 min resulted in complete elimination of these bacterial species. Exposure of E. coli to the treated scald water resulted in a 4.9 log(10) reduction. These data suggest that this sanitizer would be effective for use in scalders. When applied during scalding in a commercial processing plant, APC and E. coli counts were significantly (P <or= 0.05) reduced on all days of sampling. The average log10 reduction overall was 3.80 and 3.05 for APC and E. coli, respectively. Salmonella prevalence was reduced by an average of 30%. For carcasses that were scalded, picked, and dipped postpick using this sanitizer, APC were significantly P <or= 0.05) reduced on all days of sampling by an average of 1.19 log10. Escherichia coli counts were reduced on all but 2 d of sampling for carcasses scalded, picked, and dipped in this sanitizer, except for d 2 and 10. Averages on these days were higher for controls, but were not significantly different. Salmonella prevalence was not consistently impacted overall. For the shelf-life study, odor scores were significantly (P <or= 0.05) reduced for treated carcasses at d 8 through 14 of storage. The psychrotrophic plate counts were significantly (P <or= 0.05) lower on treated carcasses at d 6 through 14 of storage. This sanitizer suppressed spoilage bacteria with a 99.99% reduction at d 10 and a 99.9% reduction at d 12 of storage. This effect could result in an extension of the shelf life of the poultry carcasses by up to 4 d.


Reticulocyte response to endogenous erythropoietin after renal transplantation.
We determined in a prospective study reticulocyte counts and serum erythropoietin concentrations after renal transplantation in 37 recipients of renal allografts. Erythropoietin decreased in 35 patients out of 37 during surgery. Results concerning reticulocyte counts allowed us to define two groups of patients. Group 1: 33 patients had a reticulocyte peak before d29. Among them the reticulocyte peak followed the first Epo peak in 22 patients (1a) and occurred after several Epo peaks in 11 patients (1b). Patients of groups 1b had a serum creatinine level above 300 mumol/l at the time of the first Epo peak. Group 2: 4 patients with acute tubular necrosis had no reticulocytes peak before d29 despite one or several erythropoietin peaks. Post-operative erythropoietin reduction was not entirely explained by hemodilution or by per-operative blood transfusions. The erythropoietin peak appeared to be efficient only when creatinine at the time of the peak was under 200 mumol/l according to the inhibition of erythropoiesis during renal failure.


[A new technique of aortic occlusion in patient with severe aortic calcification].
A 63-year-old woman with severe aortic valve insufficiency and bilateral subclavian artery occlusion underwent ascending aorta-to-biaxillary artery bypass and aortic valve replacement, simultaneously. Because of severe aortic calcification, a hand-made aortic occluder was utilized to prevent embolic stroke. We believe that the new technique of aortic occllusion might be very useful for patients with severe aortic calcification.


Sternal closure after median sternotomy: a new technique using titanium hooks and wires applied parasternally.
Osteosynthetic closure of the chest after median sternotomy is usually performed with steel wires. We describe, for the first time, a case series in which titanium hooks were implanted from the sternal surface in patients who required secondary or additional stabilization. In comparison to the classic wires, the diameters of the hooks are approximately three times bigger and therefore reduce the risk of cutting through the bones. Additionally, there is no need to dissect retrosternal adhesions, which may reduce the risk of injuring mediastinal tissues. The hooks are shaped like fishing hooks and can be inserted parasternally into the intercostal spaces. They can be pulled to the contralateral side of the sternum by the attached wires and then intertwined with a second hook. In 13 patients, the system was used to provide additional stabilization, while in two patients the hooks were implanted for exclusive stabilization of sternal fractures. In all cases but one, the implantation was able to eliminate the sternal problems. No infections, necrosis or bleeding of neighbouring tissues occurred. One patient developed chronic sternal infection, which necessitated explantation of the hooks. This sternal closure system using titanium hooks inserted parasternally is an effective alternative to conventional techniques and may increase stability of the breastbone and reduce the risk of injury to retrosternal tissues.


Accurate Sampling of Macromolecular Conformations Using Adaptive Deep Learning and Coarse-Grained Representation.
Conformational sampling of protein structures is essential for understanding biochemical functions and for predicting thermodynamic properties such as free energies. Where previous approaches rely on sequential sampling procedures, recent developments in generative deep neural networks rendered possible the parallel, statistically independent sampling of molecular configurations. To be able to accurately generate samples of large molecular systems from a high-dimensional multimodal equilibrium distribution function, we developed a hierarchical approach based on expressive normalizing flows with rational quadratic neural splines and coarse-grained representation. Furthermore, system specific priors and adaptive and property-based controlled learning was designed to diminish the likelihood for the generation of high-energy structures during sampling. Finally, backmapping from a coarse-grained to fully atomistic representation is performed through an equivariant transformer model. We demonstrate the applicability of the method on the one-shot configurational sampling of a protein system with more than a hundred amino acids. The results show enhanced expressivity that diminish the invertibility constraints inherent in the normalizing flow framework. Moreover, the capacity of the hierarchical normalizing flow model was tested on a challenging case study of the folding/unfolding dynamics of the peptide chignolin.


Cost of illness of cystic fibrosis in Germany: results from a large cystic fibrosis centre.
Cystic fibrosis (CF) is the most common life-shortening genetic disorder among Whites worldwide. Because many of these patients experience chronic endobronchial colonization and have to take antibiotics and be treated as inpatients, societal costs of CF may be high. As the disease severity varies considerably among patients, costs may differ between patients. Our objectives were to calculate the average total costs of CF per patient and per year from a societal perspective; to include all direct medical and non-medical costs as well as indirect costs; to identify the main cost drivers; to investigate whether patients with CF can be grouped into homogenous cost groups; and to determine the influence of specific factors on different cost categories. Resource utilization data were collected for 87 patients admitted to an inpatient unit at a CF treatment centre during the first 6 months of 2004 and 125 patients who visited the centre's CF outpatient unit during the entire year. Fifty-four patients were admitted to the hospital and also visited the outpatient unit. Since all patients were exclusively treated at the centre, data could be aggregated. Costs that varied greatly between patients were measured per patient. The remaining costs were summarized as overhead costs and allocated on the basis of days of treatment or contacts per patient. Costs of the outpatient and inpatient units and costs for drugs patients received at the outpatient pharmacy were summarized as direct medical costs. Direct non-medical costs (i.e. travel expenses), as well as indirect costs (i. e. absence from work, productivity losses), were also included in the analysis. Main cost drivers were detected by the analysis of different cost categories. Patients were classified according to a diagnosis-related severity model, and median comparison tests (Wilcoxon-Mann-Whitney tests) were performed to investigate differences between the severity groups. Generalized least squares (GLS) regressions were used to identify variables influencing different cost categories. A sensitivity analysis using Monte Carlo simulation was performed. The mean total cost per patient per year was &U20AC;41 468 (year 2004 values). Direct medical costs accounted for more than 90% of total costs and averaged &U20AC;38 869 (&U20AC;3876 to &U20AC;88 096), whereas direct non-medical costs were minimal. Indirect costs amounted to &U20AC;2491 (6% of total costs). Costs for drugs patients received at the outpatient pharmacy were the main cost driver. Costs rose with the degree of severity. Patients with moderate and severe disease had significantly higher direct costs than the relatively milder group. Regression analysis revealed that direct costs were mainly affected by the diagnosis-related severity level and the expiratory volume; the coefficient indicating the relationship between costs for mild CF patients and other patients rose with the degree of severity. A similar result was obtained for drug costs per patient as the dependent variable. Monte Carlo simulation suggests that there is a 90% probability that annual costs will be lower than &U20AC;37 300. The share of indirect costs as a percentage of total costs for CF was rather low in this study. However, the relevance of indirect costs is likely to increase in the future as the life expectancy of CF patients increases, which is likely to lead to a rising work disability rate and thus increase indirect costs. Moreover we found that infection with Pseudomonas aeruginosa increases costs substantially. Thus, a decrease of the prevalence of P. aeruginosa would lead to substantial savings for society.


Interval breast cancers: prognostic features and survival by subtype and time since screening.
To investigate the hypothesis that interval cancers arising soon after the previous screen and true interval cancers are biologically aggressive and have a relatively poor prognosis compared with other interval cancers, and to assess which prognostic features are relevant to interval cancers. Analysis of prognostic pathological features (grade, lymph node stage, size, vascular invasion, oestrogen receptor [ER] status and histological type), radiological features (comedo/non-comedo calcification and spiculation) and survival for 538 invasive interval breast cancer cases by type and time since previous screen. Late interval cancers were less likely to be lymph node positive (13 versus 43%, P = 0.003). Type 1 interval cancers were more likely to be histological grade 3 than type 2 (minimal signs) and type 3 (false-negative) intervals (52 versus 35%, P = 0.05). Type 3 interval cancers were more likely to have lobular features than other intervals (47 versus 20%, P < 0.0001). There was no significant survival difference by interval cancer type (P = 0.64) or interval year (P = 0.83). At univariate analysis of all interval cancers, tumour size, grade, nodal stage, ER status, vascular invasion and comedo calcification were associated with survival. On multivariate analysis of prognostic features significant at univariate analysis, nodal stage (P value = 0.009), tumour size (P = 0.001), ER status (P < 0.0001) and vascular invasion (P < 0.0001) maintained independent significance. Our study shows that true intervals and interval cancers arising quickly after screening do not have a worse prognosis than other interval cancers, and that interval cancers have a unique set of prognostic features.


In vitro effects of waterpipe smoke condensate on endothelial cell function: a potential risk factor for vascular disease.
Despite its increasing popularity, little is known about the health effects of waterpipe smoking (WPS), particularly on the cardiovascular system. To investigate the role of WPS as a risk factor for vascular disease, we evaluated its effect on endothelial cell function, which is an early event in vascular disease pathogenesis. We assessed the changes in cell viability, ROS generation, inflammatory and vasodilatory markers and in vitro angiogenesis of human aortic endothelial cells in response to waterpipe smoke condensate exposure. Mainstream waterpipe smoke condensate (WSC) was generated using a standard laboratory machine protocol. Compared to control, WSC induced cell cycle arrest, apoptosis, and oxidative stress in human primary endothelial cells. In addition, we assayed for impaired endothelium-dependent vasodilation and induced inflammation by studying the effect of WPS on the content and activity of AMPK, eNOS proteins and NF-κB p65 ser536 phosphorylation, respectively. WSC inhibited AMPK/eNOS phosphorylation and induced phosphorylation of p65. Moreover, we evaluated endothelial cells repair mechanism related properties that include migration/invasion and in vitro tube formation upon treatment with WSC. WSC reduced the motility and inhibited angiogenic potential of HAEC cells. WPS induced endothelial cell dysfunction as evident by exerting oxidative stress, inflammation, and impaired endothelial vasodilatory function and repair mechanisms. All together these data provide evidence for the potential contribution of WPS to endothelial dysfunction and thus to vascular disease.


Non-renin dependent hypertension in renal allograft rejections. A structural and functional analysis.
A 25-year-old recipient of a cadaveric renal allograft underwent three acute rejection episodes within the first 40 days after transplant, the final episode necessitating nephrectomy. The saralasin acetate infusion test and plasma renin activity (as measured by radioimmunoassay of angiotensin I) were used as functional tests of the renin-angiotensin axis. Biopsy specimens of the allograft one hour after implantation and sections of the nephrectomy specimen were fixed and stained with hematoxylin-eosin for structural analysis. On three separate dates, during the final rejection episode, saralasin acetate infusion of up to 20 micrograms/kg/min failed to lower BP significantly. The final two trials were preceded by furosemide administration the previous day to reduce fluid volume. Plasma renin activity was low on all three dates. On nephrectomy, the allograft was noted grossly to be infarcted. Histologic examination revealed cortical necrosis, markedly narrowed or occluded intrarenal vessels, and extremely narrowed large vessels within the renal pelvis. The allograft renal artery was thickened and narrowed. From our structural and functional analysis we conclude that (1) hypertension, in this case, was probably volume dependent and was clearly renin independent; and (2) the low renin levels are explainable on the basis of extensive vascular occlusion producing renal infarction and resulting in a kidney incapable of producing significant amounts of renin (autonephrectomy).


Satisfiability, sequence niches and molecular codes in cellular signalling.
Biological information processing as implemented by regulatory and signalling networks in living cells requires sufficient specificity of molecular interaction to distinguish signals from one another, but much of regulation and signalling involves somewhat fuzzy and promiscuous recognition of molecular sequences and structures, which can leave systems vulnerable to crosstalk. A simple model of biomolecular interactions that reveals both a sharp onset of crosstalk and a fragmentation of the neutral network of viable solutions is examined as more proteins compete for regions of sequence space, revealing intrinsic limits to reliable signalling in the face of promiscuity. These results suggest connections to both phase transitions in constraint satisfaction problems and coding theory bounds on the size of communication codes.


Sensitive Analysis of Nitroguanidine in Aqueous and Soil Matrices by LC-MS.
Nitroguanidine, a widely used nitramine explosive, is an environmental contaminant that is refractory, persistent, highly mobile in soils and aquifers, and yet under-researched. Nitroguanidine determination in water and soil poses an analytical challenge due its high hydrophilicity, low volatility, charge neutrality over a wide pH range, and low proton affinity which results in low electrospray interface (ESI)-MS sensitivity. A sensitive method for the determination of nitroguanidine in aqueous and soil matrices was developed. The method is based on reduction by zinc in acidic solution, hydrophobization by derivatization, preconcentration on C18 cartridge, and LC-MS quantification. The demonstrated limit of detection (LOD) reaches 5 ng/L and 22 ng/g in water and soil, respectively. Analysis of a contaminated site demonstrates that it is possible to map a contamination plume that extends over 1 km from the source of the contamination.


The Sicilian Wolf: Genetic Identity of a Recently Extinct Insular Population.
Historically, many local grey wolf (Canis lupus) populations have undergone substantial reductions in size or become extinct. Among these, the wolf population once living in Sicily, the largest island in the Mediterranean Sea, was completely eradicated by human activity in the early decades of the 20th century. To gain a better understanding of the genetic identity of the Sicilian wolf, we used techniques for the study of ancient DNA to analyze the mitochondrial (mt) variability of six specimens stored in Italian museums. We were able to amplify a diagnostic mtDNA fragment of the control region (CR) in four of the samples. Two of the samples shared the same haplotype, differing by two substitutions from the currently most diffused Italian wolf haplotype (W14) and one substitution from the only other Italian haplotype (W16). The third sample showed a previously unreported wolf-like haplotype, and the fourth a haplotype commonly found in dogs. All of the wolf haplotypes analyzed in this study belonged to the mitochondrial haplogroup that includes haplotypes detected in all the known European Pleistocene wolves and in several modern southern European populations. Unfortunately, this endemic island population, which exhibited unique mtDNA variability, was definitively lost before it was possible to understand its taxonomic uniqueness and conservational value.


CBIR-SAR System Using Stochastic Distance.
This article proposes a system for Content-Based Image Retrieval (CBIR) using stochastic distance for Synthetic-Aperture Radar (SAR) images. The methodology consists of three essential steps for image retrieval. First, it estimates the roughness (α^) and scale (γ^) parameters of the GI0 distribution that models SAR data in intensity. The parameters of the model were estimated using the Maximum Likelihood Estimation and the fast approach of the Log-Cumulants method. Second, using the triangular distance, CBIR-SAR evaluates the similarity between a query image and images in the database. The stochastic distance can identify the most similar regions according to the image features, which are the estimated parameters of the data model. Third, the performance of our proposal was evaluated by applying the Mean Average Precision (MAP) measure and considering clippings from three radar sensors, i.e., UAVSAR, OrbiSaR-2, and ALOS PALSAR. The CBIR-SAR results for synthetic images achieved the highest MAP value, retrieving extremely heterogeneous regions. Regarding the real SAR images, CBIR-SAR achieved MAP values above 0.833 for all polarization channels for image samples of forest (UAVSAR) and urban areas (ORBISAR). Our results confirmed that the proposed method is sensitive to the degree of texture, and hence, it relies on good estimates. They are inputs to the stochastic distance for effective image retrieval.


Phonon-Assisted Auger-Meitner Recombination in Silicon from First Principles.
We present a consistent first-principles methodology to study both direct and phonon-assisted Auger-Meitner recombination (AMR) in indirect-gap semiconductors that we apply to investigate the microscopic origin of AMR processes in silicon. Our results are in excellent agreement with experimental measurements and show that phonon-assisted contributions dominate the recombination rate in both n-type and p-type silicon, demonstrating the critical role of phonons in enabling AMR. We also decompose the overall rates into contributions from specific phonons and electronic valleys to further elucidate the microscopic origins of AMR. Our results highlight potential pathways to modify the AMR rate in silicon via strain engineering.


Syndecan-2 enhances E-cadherin shedding and fibroblast-like morphological changes by inducing MMP-7 expression in colon cancer cells.
E-cadherin plays a mechanical role in mediating cell-cell interactions and maintaining epithelial tissue integrity, and the loss of E-cadherin function has been implicated in cancer progression and metastasis. Syndecan-2, a cell-surface heparan sulfate proteoglycan, is upregulated during the development of colon cancer. Here, we assessed the functional relationship between E-cadherin and syndecan-2. We found that stable overexpression of syndecan-2 in a human colorectal adenocarcinoma cell line (HT29) enhanced the proteolytic shedding of E-cadherin to conditioned-media. Either knockdown of matrix metalloproteinase 7 (MMP-7) or inhibition of MMP-7 activity using GM6001 significantly reduced the extracellular shedding of E-cadherin, suggesting that syndecan-2 mediates E-cadherin shedding via MMP-7. Consistent with this notion, enhancement of MMP-7 expression by interleukin-1α treatment increased the shedding of E-cadherin. Conversely, the specific reduction of either syndecan-2 or MMP-7 reduced the shedding of E-cadherin. HT29 cells overexpressing syndecan-2 showed significantly lower cell-surface expression of E-cadherin, decreased cell-cell contact, a more fibroblastic cell morphology, and increased expression levels of ZEB-1. Taken together, these data suggest that syndecan-2 induces extracellular shedding of E-cadherin and supports the acquisition of a fibroblast-like morphology by regulating MMP-7 expression in a colon cancer cell line.


Occlusal Traits of Primary Dentition among Pre-School Children of Mehsana District, North Gujarat, India.
Aesthetic and functional problems in the dentofacial complex among children are often attributed to the disturbances in the dentofacial growth and development. This can be recognized during routine dental visits. This study pursued to assess the occlusion of the primary dentition in three to five-year-old children. To study the occlusal traits of the primary dentition in a group of three to five-year-old North Gujarat children of Mehsana district and the variation in their occlusion relative to age and gender in the same group. The study was a cross-sectional survey based on clinical examination and photographic evaluation of the primary dentition, 383 preschool children aged three to five years who were randomly selected from preschools in Mehsana district, Gujarat, India, using a multistage sampling technique. The study group was evaluated for the several occlusal parameters that include primary molar relation based on Baume classification and canine relation, overjet, overbite were assessed using Foster and Hamilton criteria. Chi-square test was performed to carry out statistical analysis. The p-value<0.05 was taken as statistically significant. Out of 383 participants, 55.35% had flush terminal plane; 43.34% mesial step molar relationship and 1.31% distal step molar relationship, 63.2% had straight profile, 95.8% had Class I canine relationship, 71.3% primate spaces, 56.7% physiologic spaces. Flush terminal plane was common at three years while, mesial step at four to five years, and Class I canine relationship was prevalent in both age groups. Flush terminal plane was more common in female participants than the males. Amongst other occlusal characteristics, increased overbite and open bite were prevalent. It was found that the flush terminal plane molar relationship, straight profile, Class I canine relationship, primate spacing, increased overbite and open bite predominated.


Effect of Organ Scandal on Corneal Donation Rate and Organ Donors at a German University Hospital.
BACKGROUND The purpose of this study was to assess the effect of an organ transplantation scandal on the rate of corneal donations and organ donors at the University Hospital Tübingen. MATERIAL AND METHODS Data from all hospital deaths from January 2012 to December 2013 were analyzed retrospectively. Each deceased patient was considered as a potential corneal donor. The corneal donor procurement was handled by an ophthalmic resident on a full-time basis with standard used unchanged set of procedures. Each patient who died due to cerebral complications was considered as a potential organ donor. During the two-year period, a German transplantation scandal occurred at the end of 2012 and received worldwide attention. The rates of corneal donation and organ donation in 2012 and 2013 were examined and evaluated. RESULTS Among the 1685 deceased patients, approval for corneal donation was received in 220 cases (13.1%): 124 cases (15.0%) in 2012 and 96 cases (11.2%) in 2013. This corresponds to a decline of 23%. The leading causes of nonfulfillment of corneal donations were refusal to donation: 401 cases (48.4%) in 2012 and 445 cases (52.0%) in 2013; and medical contraindications: 201 cases (24.2%) in 2012 and 212 cases (24.8%) in 2013. During the two-year period, consent for organ donation was obtained in 25 cases (1.5%): 15 cases (1.8%) in 2012 and 10 cases (1.2%) in 2013. The number of realized organ donors was 20 cases (1.2%): 12 cases (1.4%) in 2012 and 8 cases (0.9%) in 2013. This corresponds to a decline of 33%. CONCLUSIONS After a transplantation scandal, the number of realized corneal donors and realized organ donors decreased significantly. It seems that increasing professional performance is very important to gaining trust inside and outside the hospital and improving corneal and organ donation rate.


System-wide mapping of peptide-GPCR interactions in C. elegans.
Neuropeptides and peptide hormones are ancient, widespread signaling molecules that underpin almost all brain functions. They constitute a broad ligand-receptor network, mainly by binding to G protein-coupled receptors (GPCRs). However, the organization of the peptidergic network and roles of many peptides remain elusive, as our insight into peptide-receptor interactions is limited and many peptide GPCRs are still orphan receptors. Here we report a genome-wide peptide-GPCR interaction map in Caenorhabditis elegans. By reverse pharmacology screening of over 55,384 possible interactions, we identify 461 cognate peptide-GPCR couples that uncover a broad signaling network with specific and complex combinatorial interactions encoded across and within single peptidergic genes. These interactions provide insights into peptide functions and evolution. Combining our dataset with phylogenetic analysis supports peptide-receptor co-evolution and conservation of at least 14 bilaterian peptidergic systems in C. elegans. This resource lays a foundation for system-wide analysis of the peptidergic network.


Osteogenesis imperfecta: fibronectin in dentin matrix.
Deciduous and permanent teeth from seven patients with five different osteogenesis imperfecta (OI) syndromes and three normal subjects were demineralized with ethanolic trimethylammonium EDTA, enzymatically pretreated and immunostained with antihuman plasma fibronectin (FN) sera. Staining for FN in the dentin matrix was positive in halo and reticular patterns in the one patient with Sillence type I B OI and in two patients of three with type IV B OI, all with dentinogenesis imperfecta (DI). The staining was negative in type I A OI without DI, in type III, in one patient with type IV B, and in an unidentified type of OI, all with DI. In normal control teeth no staining of the dentin matrix was observed. The staining differences between OI types (also with DI) may reflect genetic heterogeneity. The diverse results in type IV B OI were suggestive of interfamilial variability within the OI syndrome. The presence of FN in the dentin matrix in OI may be due to its continuous synthesis or decreased degradation during dentin development.


Advantages of FDM and gamma irradiation to manufacture personalized medical devices for airway obstructions.
In the early childhood population, congenital airway conditions like bronchomalacia (BM) can pose a life-threatening threat. A breakthrough technology called additive manufacturing, or 3D printing, makes it feasible to create a biomedical device that aids in the treatment of airway obstruction. This article describes how a polycaprolactone (PCL) splint for the upper airways can be created using the fusion deposition technique (FDM) and sterilized using gamma radiation. It is presented as a simple, accessible, and cost-reduced alternative that complements other techniques using more expensive and sophisticated printing methods. Thermomechanical and morphological analysis proved that FDM and sterilizing by gamma irradiation are both appropriate methods for producing splints to treat life-threatening airway blockages. Additionally, the 3D-printed splints' effectiveness in treating a young patient with BM that was life-threatening was assessed by medical professionals. In this regard, the case report of a patient with 34 months of follow-up is presented. Splints manufactured by this affordable 3D printing method successfully surpass breathing arrest in life-threatening airway obstruction in pediatric patients. The success of this procedure represents a fundamental contribution to the treatment of the population in countries where access to expensive and complex technologies is not available.


Ubiquitin-specific peptidase 10 attenuates the ferroptosis to promote thyroid cancer malignancy by facilitating GPX4 via elevating SIRT6.
Ubiquitin-specific peptidase 10 (USP10) has been found to have oncogenic activity in several human tumors. This study first revealed the exact function of USP10 on the progression of thyroid cancer (THCA) by researching its effect on the ferroptosis. USP10 expression in THCA patients was analyzed by online data analysis and in 75 THCA cases was scrutinized by real-time quantitative reverse transcription-polymerase chain reaction and Western blot. Influence of USP10 on the viability, colony formation, migration and invasion of THCA cells was demonstrated by cell counting kit-8, colony formation, wound healing and Transwell invasion assays. Effect of USP10 on the Erastin-induced ferroptosis in THCA cells was evaluated by detecting the ferroptosis-related indicators. Intrinsic mechanism of USP10, glutathione peroxidase 4 (GPX4) and sirtuin 6 (SIRT6) in regulating THCA progression was identified. In vivo xenograft experiment was implemented. USP10 was abundantly expressed in THCA patients, linking to poor outcome. USP10 overexpression enhanced the viability, colony formation, migration and invasion of THCA cells. USP10 mitigated the Erastin-induced ferroptosis in THCA cells, decreased the levels of iron, Fe2+ , malondialdehyde, lipid reactive oxygen species, reduced mitochondrial superoxide level, and increased mitochondrial membrane potential. USP10 facilitated the expression of ferroptosis suppressor GPX4 by elevating SIRT6. Loss of USP10 repressed the in vivo growth of THCA cells. USP10 might attenuate the ferroptosis to promote thyroid cancer malignancy by facilitating GPX4 via elevating SIRT6. It might be novel target for the treatment of THCA.


Synthesis of acyloxy-2H-azirine and sulfonyloxy-2H-azirine derivatives via a one-pot reaction of β-enamino esters, PIDA and carboxylic acid or sulfonic acid.
PIDA mediated oxidative acyloxylation/azirination and sulfonyloxylation/azirination of β-enamino esters were investigated. A series of functionalized acyloxy-2H-azirine and sulfonyloxy-2H-azirine derivatives was synthesized in moderate to good yields. This represents the first oxidative sulfonyloxylation/azirination of β-enamino esters with PIDA and sulfonic acid for access to sulfonyloxy-2H-azirine. Hypervalent iodine reagents enable cascade C-O/C-N bond formation. Furthermore, a possible reaction pathway was proposed based on the experimental results.


Four factors that accurately predict hearing loss in "high risk" neonates.
Two simple overall measures of health--length of stay in the Intensive Care Nursery (ICN) and gestational age--predict hearing loss in ICN graduates. Craniofacial anomalies, congenital perinatal infections, and meconium aspiration are strong predictors of hearing loss, especially in term infants. Findings are based on univariate and multivariate analyses of a number of variables that might be associated with permanent hearing loss. Study variables included all seven High Risk Register items and a number of other features of the ICN history. They were examined in 799 ICN graduates whose hearing had been monitored in their first few years of life. These babies composed 40% of the ICN population and were selected because they had one or more "high risk" factors in their neonatal history. Prevalence of hearing loss in this high risk sample was similar to that found in other ICN samples. Prevalence of hearing loss associated with individual Risk Register items was similar to other published findings for some items and not for others.


Mechanisms of organophosphate toxicity and detoxication with emphasis on studies in Croatia.
This review comprises studies on the mechanisms of toxicity and detoxication of organophosphorus (OP) compounds done in Croatia in different research areas. One area is the synthesis of antidotes against OP poisoning and their in vivo testing in experimental animals. In vitro studies included in this review focus on the mechanisms of reversible inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), protection of cholinesterases from inhibition by OPs, and reactivation of phosphylated cholinesterases. The third area comprises distribution profiles of BChE and paraoxonase (PON) phenotypes in selected population groups and the detection of OPs and metabolites in humans. Finally, methods are described for the detection of OP compounds in human blood and other media by means of cholinesterase inhibition.


Developing a university-wide institutional response to sexual assault and relationship violence.
This article presents a process case study for developing a university-wide response to sexual assault and relationship violence. Following Kelly's (1988) approach to prevention work in community-settings, we began our work with in-depth ecological reconnaissance to understand our local context. Our case study described the processes used to develop an inclusive task force, conduct an environmental scan, and carry out a quantitative-qualitative needs assessment. Our processes for developing an institutional response for both direct services interventions and prevention are discussed in the context of Kelly's (1966, 1968, 2006) ecological principles of interdependence and cycling of resources.


Effects of multi-components released from S-PRG filler on the activities of human dental pulp-derived stem cells.
Numerous studies have shown that the sustained release of ions from dental restorative materials have acid buffering capacity, prevents tooth enamel demineralization, and inhibits bacterial adhesion. Herein, the release behavior and bioresponsiveness of ions released from surface pre-reacted glass-ionomer (S-PRG) fillers were investigated in different types of media based on human dental pulp-derived stem cell (hDPSC) responses. The hDPSCs were cultured for 1-7 days in S-PRG eluates diluted with varying amounts of cell culture media. S-PRG released several types of ions, such as F-, Sr2+, Na+, Al3+, BO33-, and SiO32-. The balance of eluted ions differed depending on the dilution and solvent, which in turn affected the cytotoxicity, cell morphology, cell proliferation, and alkane phosphatase activity of hDPSCs, among other properties. The results suggest that tailored S-PRG filler eluates could be designed and prepared for application in dental practice.


Simultaneous determination of in vivo plastoquinone and ubiquinone redox states by HPLC-based analysis.
For a better understanding of the metabolic interaction between chloroplasts and mitochondria, it is important to analyze the in vivo redox states of the electron transport chains in both organelles at the same time. For this purpose, we devised an HPLC-based measurement system simultaneously analyzing plastoquinone (PQ) and ubiquinone (UQ) contents and redox states. Using this system, we discovered that, in addition to PQ, the reduction levels of UQ were elevated under high-light conditions. We also provide direct evidence that mitochondrial alternative oxidase contributes to alleviate UQ over-reduction under such conditions.


Orthorhombic modification of triphenyltin 3-ureidopropionate.
The Sn atom in catena-poly[triphenyltin(IV)-micro-(3-ureidopropionato-O(1):O(3))], [Sn(C(6)H(5))(3)(C(4)H(7)N(2)O(3))](n), is five-coordinate and has a trans-C(3)SnO(2) trigonal-bipyrmidal geometry arising from bridging through the O atom of the ureido fragment of an adjacent carboxylate group. Infinite chains propagate helically along the c axis and adjacent chains are linked by N-H.O [N.O 2.851 (4) A] hydrogen bonds into layers.


Oral Delivery of Cholic Acid-Derived Amphiphile Helps in Combating Salmonella-Mediated Gut Infection and Inflammation.
A major impediment to developing effective antimicrobials against Gram-negative bacteria like Salmonella is the ability of the bacteria to develop resistance against existing antibiotics and the inability of the antimicrobials to clear the intracellular bacteria residing in the gastrointestinal tract. As the critical balance of charge and hydrophobicity is required for effective membrane-targeting antimicrobials without causing any toxicity to mammalian cells, herein we report the synthesis and antibacterial properties of cholic acid-derived amphiphiles conjugated with alkyl chains of varied hydrophobicity. Relative to other hydrophobic counterparts, a compound with hexyl chain (6) acted as an effective antimicrobial against different Gram-negative bacteria. Apart from its ability to permeate the outer and inner membranes of bacteria; compound 6 can cross the cellular and lysosomal barriers of epithelial cells and macrophages and kill the facultative intracellular bacteria without disrupting the mammalian cell membranes. Oral delivery of compound 6 was able to clear the Salmonella-mediated gut infection and inflammation, and was able to combat persistent, stationary, and multi-drug-resistant clinical strains. Therefore, our study reveals the ability of cholic acid-derived amphiphiles to clear intracellular bacteria and Salmonella-mediated gut infection and inflammation.


Penetration of Ufenamate into Intact, Stripped, or Delipidized Skin Using Different Vehicles.
The purpose of this study was to clarify the effect of skin condition on skin penetration of the very high lipophilic drug, ufenamate (UF). UF was applied to stripped or delipidized skin using liquid paraffin (LP) or purified water containing polysorbate 80 at a dose of 2 µL/cm(2). We found that UF penetration into intact and stripped skin using a water vehicle was respectively 5 and 10 times higher than that using LP. UF is freely soluble in oil and insoluble in water; thus, activity in water is higher than that in LP. Therefore, it is useful to use a water-based vehicle for both intact sites and those with defective stratum corneum (SC). Conversely, we found that delipidization of SC decreased the penetration of UF significantly with both LP and water, and the amount measured in the epidermis was 1 µg/cm(2) with both vehicles. This indicates that UF is not suitable for so-called "dry skin." This study revealed clinically relevant differences in the penetration of UF into intact, stripped, or delipidized skin conditions.


Amplification of virus-induced antimelanoma T-cell reactivity by high-dose interferon-alpha2b: implications for cancer vaccines.
The therapeutic effectiveness of cancer vaccines, composed of tumor antigens that are also self-antigens, may be limited by the normal mechanisms that preserve immunological tolerance. Consistent with this notion, we found that vaccination of melanoma patients with recombinant viral vaccines expressing gp100 (a melanoma antigen also expressed by normal melanocytes) produced only transient increases in noncytotoxic T cells specific for immunodominant gp100 epitopes. To improve the therapeutic effects of these vaccines, IFN-alpha2b (IFN-alpha) was administered to some high-risk patients. 7 HLA-A*0201(+) patients were injected with high doses of IFN-alpha (20 MU/m(2) x 20 doses) at various times after completing the vaccination protocol. Clinical toxicity and responses were documented, and the effects on gp100-reactive T cells were measured by IFN-gamma enzyme-linked immunospot assays, tetramers of HLA-A*0201 and gp100 epitopes, and cellular cytotoxicity assays. In patients who had previously responded to vaccination, high doses of IFN-alpha recalled gp100-reactive T cells with the ability to kill gp100-expressing tumor targets in vitro. Concomitant with the reappearance of these cytotoxic T cells, tumor regression was observed in the two patients with clinically evident metastatic disease. The finding that high-dose IFN recalls previously activated tumor-reactive T cells with potent killing ability suggests a strategy to maintain antitumor responses initiated by cancer vaccines.


MicroRNA-200b Impacts Breast Cancer Cell Migration and Invasion by Regulating Ezrin-Radixin-Moesin.
BACKGROUND Ezrin-radixin-moesin (ERM) plays an important role in multiple links of tumors. It also involved in breast cancer invasion and metastasis, and might be a potential biomarker of breast cancer. Another study suggested that ERM expression was regulated directly by miR-200c, and had a critical role in miR-200c suppressing cell migration. This study aimed to investigate the effect of miR-200b on ERM expression in a breast cancer cell line and its influence on invasion and metastasis ability in vitro. MATERIAL AND METHODS Breast cancer cell lines MCF-7 and MDA-MB-231 with different metastatic potentials were selected as a model. MiR-200b overexpression or inhibition was achieved by Lipofectamine™ 2000-mediated miRNA transfection. RT-PCR was used to test miR-200b level, while Western blot was selected to detect ERM protein expression. Wound healing assay and Transwell assay were performed to determine cell migration and invasion ability. RESULTS RT-PCR revealed that miR-200b level in MDA-MB-231 was obviously lower than that in MCF-7, while Western blot analysis showed that ERM expression was significantly higher. MiR-200b inhibition by transfection in MCF-7 markedly decreased miR-200b level, elevated ERM expression, and enhanced cell migration and invasion. MiR-200b overexpression in MDA-MB-231 obviously increased miR-200b level, reduced ERM expression, and weakened cell migration and invasion. CONCLUSIONS MiR-200b participates in breast cancer cell migration and invasion through regulating ERM in MCF-7 and MDA-MB-231.


Pupillary examination.
Examination of the pupils is an essential part of the evaluation of patients in optometric practice. In this article, the normal pupil and pupillary reflexes are reviewed, along with a discussion of anisocoria and specific anomalies of the pupils. Explanation of step by step office examination techniques is presented, as well as a discussion of the pathophysiology of abnormal pupils.


Gene expression caused by alkylating agents and cis-diamminedichloroplatinum(II) in Escherichia coli.
Previous work has demonstrated heterogeneous effects of methylating agents on induction of DNA damage inducible genes in Escherichia coli. These studies employed E. coli mutants that have fusions of the lac operon to genes induced by treatment with sublethal levels of alkylating agents. These mutants were selected from random insertions of the Mu-dl (Apr lac) phage by screening for induction of beta-galactosidase activity in the presence of methylmethanesulfonate or N-methyl-N'-nitro-N-nitrosoguanidine. The current report extends these findings by analyzing gene expression caused by mechlorethamine, chloroethylnitrosoureas and cis-diamminedichloroplatinum(II) (cis-DDP). The results demonstrate heterogeneous effects by these agents on gene expression. While 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea induces alkA, other nitrosoureas, mechlorethamine, and cis-DDP do not cause expression of this gene. Further, while all nitrosoureas caused expression of aidC, mechlorethamine and cis-DDP did not. Lastly, cis-DDP caused marked expression of a sulA fusion mutant while not inducing any of the other E. coli fusion mutants.


The influence of visual motion on motor learning.
How does visual perception shape the way we coordinate movements? Recent studies suggest that the brain organizes movements based on minimizing reaching errors in the presence of motor and sensory noise. We present an alternative hypothesis in which movement trajectories also result from acquired knowledge about the geometrical properties of the object that the brain is controlling. To test this hypothesis, we asked human subjects to control a simulated kinematic linkage by continuous finger motion, a completely novel experience. This paradigm removed all biases arising from influences of limb dynamics and past experience. Subjects were exposed to two different types of visual feedback; some saw the entire simulated linkage and others saw only the moving extremity. Consistent with our hypothesis, subjects learned to move the simulated linkage along geodesic lines corresponding to the geometrical structure of the observed motion. Thus, optimizing final accuracy is not the unique determinant of trajectory formation.


Nonlinear aspects of the BOLD response in functional MRI.
Functional magnetic resonance imaging (fMRI) using blood oxygenation level-dependent (BOLD) contrast has progressed rapidly and is commonly used to study function in many regions of the human brain. This paper introduces a method for characterizing the linear and nonlinear properties of the hemodynamic response. Such characterization is essential for accurate prediction of time-course behavior. Linearity of the BOLD response was examined in the primary visual cortex for manipulations of the stimulus amplitude and duration. Stimuli of 1, 2, 4, and 8 s duration (80% contrast) and 10, 20, 40, and 80% contrast (4 s duration) were used to test the hemodynamic response. Superposition of the obtained responses was performed to determine if the BOLD response is nonlinear. The nonlinear characteristics of the BOLD response were assessed using a Laplacian linear system model cascaded with a broadening function. Discrepancies between the model and the observed response provide an indirect measure of the nonlinearity of the response. The Laplacian linear system remained constant within subjects so the broadening function can be used to absorb nonlinearities in the response. The results show that visual stimulation under 4 s in duration and less than 40% contrast yield strong nonlinear responses.


Association of macrophage migration inhibitory factor gene -173 G/C polymorphism with prognosis in Turkish children with juvenile rheumatoid arthritis.
The objectives of this study were to determine genotypic and allelic frequencies of macrophage migration inhibitory factor (MIF) gene -173 G/C polymorphism in patients with juvenile rheumatoid arthritis (JRA) and to evaluate the association of the MIF -173 C allele with the outcome of JRA. Genomic DNA was collected from 67 JRA patients and 153 healthy individuals. To evaluate the association of the MIF -173 polymorphism with the outcome, we analyzed the data concerning the treatment regimen, duration of glucocorticoid treatment, score on the childhood health assessment questionnaire (C-HAQ) and the number of joints with active arthritis. Nonsignificant differences were observed between the study and control groups in the distribution of genotype and allele frequencies of the MIF gene -173 G/C polymorphism. In JRA patients, carrying a MIF -173 C allele, the number of disease modifying antirheumatic drugs required for the treatment was more, the duration of glucocorticoid treatment was significantly longer, and at the last visits the C-HAQ scores and the number of joints with active arthritis were significantly higher. MIF gene -173 C allele frequency did not differ between the controls and JRA patients. MIF -173 C allele did not confer increased susceptibility to JRA in our study group. Carriage of the MIF -173 C allele was found to be a strong predictor of poor outcome in all types of JRA.


Borrelia burgdorferi vlsE antigenic variation is not mediated by RecA.
RecA is a key protein linking genetic recombination to DNA replication and repair in bacteria. Previous functional characterization of Borrelia burgdorferi RecA indicated that the protein is mainly involved in genetic recombination rather than DNA repair. Genetic recombination may play a role in B. burgdorferi persistence by generation of antigenic variation. We report here the isolation of a recA null mutant in an infectious B. burgdorferi strain. Comparison of the in vitro growth characteristics of the mutant with those of the wild-type strain under various conditions showed no significant differences. While the RecA mutant was moderately more sensitive to UV irradiation and mitomycin C than the wild-type strain, the lack of RecA abolished allelic exchange in the mutant. Absence of RecA did not affect the ability of the mutant to infect mice. However, the RecA mutant was attenuated for joint infection in competitive-infection assays with the wild-type strain. vlsE sequence variation in mice was observed in both wild-type and RecA mutant spirochetes, indicating that the mechanism of antigenic variation is not homologous genetic recombination.