(E)-5,5'-di(thiophen-2-yl)-3,3'-bi[thiophen-3(2H)-ylidene]-2,2'-diones--from conspicuous blue impurities to "quasi-metallic" golden-bronze crystals.
(E)-5,5'-Di(thiophen-2-yl)-3,3'-bi[thiophen-3(2H)-ylidene]-2,2'-dione () has caught the eye of several chemists who have encountered it as a trace by-product in a variety of reactions. We report here the first deliberate synthesis of this intense blue dye (λ(max) 635 nm; ε(max) 32,400 L cm(-1) mol(-1)). We prove on the basis of predictions made with TDDFT that 1a has previously been misassigned as a structural isomer and we correct the visible absorption data that was reported. Derivatives of 1a equipped with pentyl (1b) and butylsulfanyl (1c) groups are readily prepared with our divergent synthetic route (3-7% yield over five steps). Crystals of 1b and 1c exhibit an attractive "quasi-metallic" golden-bronze lustre. This effect is rare in molecular crystals and is observed only with the most intense dyes.


Geochemical and Pb isotopic evidence for sources and dispersal of metal contamination in stream sediments from the mining and smelting district of Príbram, Czech Republic.
Stream sediments from the mining and smelting district of Príbram, Czech Republic, were studied to determine the degree, sources and dispersal of metal contamination using a combination of bulk metal and mineralogical determinations, sequential extractions and Pb isotopic analyses. The highest metal concentrations were found 3-4 km downstream from the main polymetallic mining site (9800 mg Pb kg(-1), 26 039 mg Zn kg(-1), 316.4 mg Cd kg(-1), 256.9 mg Cu kg(-1)). The calculated enrichment factors (EFs) confirmed the extreme degree of contamination by Pb, Zn and Cd (EF>40). Lead, Zn and Cd are bound mainly to Fe oxides and hydroxides. In the most contaminated samples Pb is also present as Pb carbonates and litharge (PbO). Lead isotopic analysis indicates that the predominant source of stream sediment contamination is historic Pb-Ag mining and primary Pb smelting (206Pb/207Pb=1.16), while the role of secondary smelting (car battery processing) is negligible.


Facile and Divergent Synthesis of Lamellarins and Lactam-Containing Derivatives with Improved Drug Likeness and Biological Activities.
With the goal to improve the aqueous solubility of lamellarins, the lactone ring in their skeleton was replaced with a lactam moiety in azalamellarins. However, the reported synthetic route produced such derivatives in very low yields. Hence, this study focused on developing an efficient simplified total synthetic scheme that could furnish both azalamellarins and the parent lamellarins from the same pyrrole ester intermediates. Subsequent comparative profiling revealed that the introduced lactone-to-lactam replacement rendered these molecules less lipophilic, whereas their cancer cytotoxicity remained equipotent to that of the parent compounds. Interestingly, their inhibitory activity was significantly enhanced towards the multifaceted GSK-3β enzyme. Our results clearly demonstrate the therapeutic potential of this promising class of marine-derived natural products and justify their further development, especially into anticancer agents.


[Allelic distribution of the HUMCD4 polymorphic system in the Province of Parma].
Allele frequencies of polymorphic system HUMCD4 were determined in a sample from the Province of Parma. Good separation of PCR amplified fragments was performed by non denaturing PAGE; seven allelic variants were found and frequency distribution was in good agreement with previous studies on Caucasian. The statistic tests (Hardy-Weinberg equilibrium -H-W-., Power of Discrimination -PD- and Mean Exclusion Chance -MEC-) and the robustness of the technique suggest the use of this polymorphism in forensic investigations.


[Effect of Yersinia pestis EV 76 lypopolysaccharides with different levels of toxicity on dynamics of TNF-alpha and INF-gamma synthesis by human monocytes].
AIM. To study dynamics of synthesis of TNF-alpha and INF-gamma by cell line U-937 human monocytes under the effect of Yersinia pestis EV 76 lypopolysaccharides (LPS) with different levels of toxicity: original LPS28 and LPS37 as well as their conformationally--changed variants with enhanced toxicity--complex of LPS with murine toxin (MT) of Y. pestis, and LPS modified by biologicall active compound (BAC) obtained from human erythrocytes. Using phenol method, LPS were obtained from Y. pestis EV 76 cells grown at 28 and 37 degrees C. Production of cytokines was measured by ELISA. It was shown that original and modified forms of LPS28 and LPS37 induce synthesis of both TNF-alpha and INF-gamma by human monocytes. Expression of genes for two ways of synthesis of these cytokines points to activation and transmission of signal induced by all studied forms of Y. pestis EV 76 LPS through TLR4. Levels of activity of MyD88-dependent and MyD88-independent signaling pathways are different and depend from chemical structure of LPS28 and LPS37, conformation of their modified forms and duration of their exposition with monocytes. Dynamics ofcytokine synthesis corresponds to response of synergized TLR on activation with profound agonistic/antagonistic effect. It was determined that conformational modifications of Y. pestis EV76 LPS occurring due to effect of MT and BAC accompanied by quantitative, qualitative and temporal changes of TNF-alpha and INF-gamma synthesis by human monocytes and correlate with increase of their toxic properties.


Functional analyses of the C-terminal half of the Saccharomyces cerevisiae Rad52 protein.
The Saccharomyces cerevisiae Rad52 protein is essential for efficient homologous recombination (HR). An important role of Rad52 in HR is the loading of Rad51 onto replication protein A-coated single-stranded DNA (ssDNA), which is referred to as the recombination mediator activity. In vitro, Rad52 displays additional activities, including self-association, DNA binding and ssDNA annealing. Although Rad52 has been a subject of extensive genetic, biochemical and structural studies, the mechanisms by which these activities are coordinated in the various roles of Rad52 in HR remain largely unknown. In the present study, we found that an isolated C-terminal half of Rad52 disrupted the Rad51 oligomer and formed a heterodimeric complex with Rad51. The Rad52 fragment inhibited the binding of Rad51 to double-stranded DNA, but not to ssDNA. The phenylalanine-349 and tyrosine-409 residues present in the C-terminal half of Rad52 were critical for the interaction with Rad51, the disruption of Rad51 oligomers, the mediator activity of the full-length protein and for DNA repair in vivo in the presence of methyl methanesulfonate. Our studies suggested that phenylalanine-349 and tyrosine-409 are key residues in the C-terminal half of Rad52 and probably play an important role in the mediator activity.


Magnetic field characteristics of electric bed-heating devices.
Measurements of the flux density and spectra of magnetic fields (MFs) generated by several types of electric bed heaters (EBH) were made in order to characterize the MFs to which the fetus may be exposed in utero from the mother's use of these devices. Data on MPs were gathered from more than 1,300 in-home and laboratory spot measurements. In-home measurements taken at seven different positions 10 cm from the EBHs determined that the mean flux density at the estimated position of the fetus relative to the device was 0.45 microT (4.5 mG) for electric blankets and 0.20 microT (2.0 mG) for electrically heated water beds. A rate-of-change (RC) metric applied to the nighttime segment of 24 h EMDEX-C personal-dosimeter measurements, which were taken next to the bed of volunteers, yielded an approximate fourfold to sixfold higher value for electric blanket users compared to water-bed heater users. These same data records yielded an approximate twofold difference for the same measurements when evaluated by the time-weighted-average (TWA)MF exposure metric. Performance of exposure meters was checked against standard fields generated in the laboratory, and studies of sources of variance in the in-home measurement protocols were carried out. Spectral measurements showed that the EBH's measured produced no appreciable high-frequency MFs. Data gathered during this work will be used in interpreting results from a component of the California Pregnancy Outcome Study, which evaluates the use of EBHs as a possible risk factor in miscarriage.


Food webs in the litter: effects of food and nest addition on ant communities in coffee agroecosystems and forest.
Community assembly is driven by multiple factors, including resource availability and habitat requirements. Litter nesting ants respond to food and nest site availability, and adding food and nests may increase ant species richness and abundance. However, litter decomposers share food resources with ants, and increasing food availability may speed decomposition processes, eliminating twigs and seeds in which litter ants nest. We manipulated ant food and nest resources in three habitat types (forest, high-shade coffee, and low-shade coffee) to determine ant community responses after 1 and 2 mo. We examined changes in numbers of ant species, colonies, workers, brood, colony growth rate, and ant species composition. Habitat type strongly affected ant communities, influencing ant species richness, numbers of colonies and workers, and ant species composition. However, food addition and nest addition did not affect these community characteristics. Colony growth rate did not differ with food addition but was greater in forest and low-shade coffee compared with high-shade coffee. Habitat differences in colony growth may be because of presence of an aggressive species (Wasmannia auropunctata Roger) in high-shade coffee plots or naturally low arthropod densities during a time when ant colonization was low. Thus, in coffee landscapes, habitat type impacts litter nesting ant community structure, composition, and colony growth rate; however, food and nest addition had small impacts.


Deep Learning for Automated Classification of Inferior Vena Cava Filter Types on Radiographs.
To demonstrate the feasibility and evaluate the performance of a deep-learning convolutional neural network (CNN) classification model for automated identification of different types of inferior vena cava (IVC) filters on radiographs. In total, 1,375 cropped radiographic images of 14 types of IVC filters were collected from patients enrolled in a single-center IVC filter registry, with 139 images withheld as a test set and the remainder used to train and validate the classification model. Image brightness, contrast, intensity, and rotation were varied to augment the training set. A 50-layer ResNet architecture with fixed pre-trained weights was trained using a soft margin loss over 50 epochs. The final model was evaluated on the test set. The CNN classification model achieved a F1 score of 0.97 (0.92-0.99) for the test set overall and of 1.00 for 10 of 14 individual filter types. Of the 139 test set images, 4 (2.9%) were misidentified, all mistaken for other filter types that appear highly similar. Heat maps elucidated salient features for each filter type that the model used for class prediction. A CNN classification model was successfully developed to identify 14 types of IVC filters on radiographs and demonstrated high performance. Further refinement and testing of the model is necessary before potential real-world application.


Sex Differences in 1-Year Rehospitalization for Heart Failure and Myocardial Infarction After Primary Percutaneous Coronary Intervention.
It is unclear whether universal access to primary percutaneous coronary intervention (pPCI) may reduce sex differences in 1-year rehospitalization for heart failure (HF) and myocardial infarction (MI) after ST-elevation myocardial infarction (STEMI). We studied 7,597 consecutive STEMI patients (13.8% women, n = 1,045) who underwent pPCI from January 2007 to December 2013. Cox regression models adjusted for competing risk from death were used to assess sex differences in rehospitalization for HF and MI within 1 year from discharge. Compared with men, women were older (median age 67.6 vs 56.0 years, p < 0.001) with higher prevalence of co-morbidities and multivessel disease. Women had longer median door-to-balloon time (76 vs 66 minutes, p < 0.001) and were less likely to receive drug-eluting stents (19.5% vs 24.1%, p = 0.001). Of the medications prescribed at discharge, fewer women received aspirin (95.8% vs 97.6%, p = 0.002) and P2Y12 antagonists (97.6% vs 98.5%, p = 0.039), but there were no significant sex differences in other discharge medications. After adjusting for differences in baseline characteristics and treatment, sex differences in risk of rehospitalization for HF attenuated (hazard ratio [HR] 1.05, 95% confidence interval [CI] 0.79 to 1.40), but persisted for MI (HR 1.68, 95% CI 1.22 to 2.33), with greater disparity in patients aged ≥60 years (HR 1.83, 95% CI 1.18 to 2.85) than those aged <60 years (HR 1.45, 95% CI 0.84 to 2.50). In conclusion, in a setting of universal access to pPCI, the adjusted risk of 1-year rehospitalization for HF was similar in both sexes, but women had significantly higher adjusted risk of 1-year rehospitalization for MI, especially older women.


Apoptosis and DNA damage in human spermatozoa.
DNA damage is frequently encountered in spermatozoa of subfertile males and is correlated with a range of adverse clinical outcomes including impaired fertilization, disrupted preimplantation embryonic development, increased rates of miscarriage and an enhanced risk of disease in the progeny. The etiology of DNA fragmentation in human spermatozoa is closely correlated with the appearance of oxidative base adducts and evidence of impaired spermiogenesis. We hypothesize that oxidative stress impedes spermiogenesis, resulting in the generation of spermatozoa with poorly remodelled chromatin. These defective cells have a tendency to default to an apoptotic pathway associated with motility loss, caspase activation, phosphatidylserine exteriorization and the activation of free radical generation by the mitochondria. The latter induces lipid peroxidation and oxidative DNA damage, which then leads to DNA fragmentation and cell death. The physical architecture of spermatozoa prevents any nucleases activated as a result of this apoptotic process from gaining access to the nuclear DNA and inducing its fragmentation. It is for this reason that a majority of the DNA damage encountered in human spermatozoa seems to be oxidative. Given the important role that oxidative stress seems to have in the etiology of DNA damage, there should be an important role for antioxidants in the treatment of this condition. If oxidative DNA damage in spermatozoa is providing a sensitive readout of systemic oxidative stress, the implications of these findings could stretch beyond our immediate goal of trying to minimize DNA damage in spermatozoa as a prelude to assisted conception therapy.


Why the Lipid Divide? Membrane Proteins as Drivers of the Split between the Lipids of the Three Domains of Life.
Recent results from engineered and natural samples show that the starkly different lipids of archaea and bacteria can form stable hybrid membranes. But if the two types can mix, why don't they? That is, why do most bacteria and all eukaryotes have only typically bacterial lipids, and archaea archaeal lipids? It is suggested here that the reason may lie on the other main component of cellular membranes: membrane proteins, and their close adaptation to the lipids. Archaeal lipids in modern bacteria could suggest that the last universal common ancestor (LUCA) had both lipid types. However, this would imply a rather elaborate evolutionary scenario, while negating simpler alternatives. In light of widespread horizontal gene transfer across the prokaryotic domains, hybrid membranes reveal that the lipid divide did not just occur once at the divergence of archaea and bacteria from LUCA. Instead, it continues to occur actively to this day.


A collaborative end-of-life care curriculum.
Death and dying in America has received limited attention in medical education. The Southern Arizona VA Health Care System and the University of Arizona have collaborated with three nonprofit community hospice programs to develop an end-of-life care curriculum. This formal and comprehensive program is offered as a one-month elective to senior medical students, residents and fellows. The goal of the program is to improve clinical skills in caring for the dying patient and foster research in palliative and supportive care.


Balance training reduces falls risk in older individuals with type 2 diabetes.
This study assessed the effects of balance/strength training on falls risk and posture in older individuals with type 2 diabetes. Sixteen individuals with type 2 diabetes and 21 age-matched control subjects (aged 50-75 years) participated. Postural stability and falls risk was assessed before and after a 6-week exercise program. Diabetic individuals had significantly higher falls risk score compared with control subjects. The diabetic group also exhibited evidence of mild-to-moderate neuropathy, slower reaction times, and increased postural sway. Following exercise, the diabetic group showed significant improvements in leg strength, faster reaction times, decreased sway, and, consequently, reduced falls risk. Older individuals with diabetes had impaired balance, slower reactions, and consequently a higher falls risk than age-matched control subjects. However, all these variables improved after resistance/balance training. Together these results demonstrate that structured exercise has wide-spread positive effects on physiological function for older individuals with type 2 diabetes.


Hemodialysis Patients' Knowledge of, Beliefs about, and Practices in Using Complementary and Alternative Medicine: An Exploratory Study.
Patients undergoing hemodialysis (HD) are increasingly interested in complementary and alternative medicine (CAM) due to their desire to access symptom-reducing interventions, the inability of most medical teams to devote enough time to their patients, and the cost of treatments. The aim of the study was to determine the knowledge of, beliefs about, and practices in using CAM of HD patients living in eastern Turkey. The research team performed a descriptive, cross-sectional study. The study was carried out between April 2019 and June 2020 in Atatürk University Research Hospital and Regional Training and Research Hospital located in eastern Turkey. A power analysis was performed to determine the sample size of the study, with the 120 HD participants being included in the sample at the 85% confidence range. The research team prepared a questionnaire for determining the identifying characteristics of participants and their knowledge of, beliefs about, and practices in using CAM. Of the 120 participants, 70.8% had information about CAM, and 60.8% of them had obtained it from their families. In general, participants had a positive opinion about CAM, and most didn't obtain approval from their physicians for the use of CAM. Among CAM methods, participants mostly used phytotherapy (80%), especially garlic (57.5%), parsley (56.7%), and linden (50%). Because the participants in the current study usually tended to hide the fact that they used CAM, healthcare professionals should be careful about establishing a proper and reassuring relationship with patients and avoid criticizing them for preferring these methods. Patients should be especially informed about the use of phytotherapy, especially garlic, and be warned about its potential risks.


Prevalence and clinical significance of heparin induced antibodies in chronic hemodialysis patients and cardiac surgery patients.
The prevalence of heparin-induced antibodies (HIA) varies widely among reported series, but is generally higher in cardiac surgery than hemodialysis patients. This study was designed to explore the reasons behind the different prevalence of HIA in these two populations. Blood samples from all hemodialysis and cardiac surgery patients in our hospital were examined for HIA. Heparin-induced thrombocytopenia (HIT) was suspected when platelet count was <150,000 in the hemodialysis group, and >50% decline in platelet count in the cardiac surgery group. 79 hemodialysis and 40 cardiac surgery patients were studied. HIA prevalence was significantly higher in cardiac surgery than in hemodialysis patients (65% v 10.1%, respectively, P<0.00001). Conversely, the prevalence of suspected clinical HIT was 37.5% in the hemodialysis and 11.5% in the cardiac surgery group. Prevalence of HIA was higher in patients who were tested during the first 90 days of hemodialysis than in those tested at later times. One-year mortality was 37% in HIA positive and 19% in HIA negative hemodialysis patients. Prevalence of HIA was significantly lower in hemodialysis as compared with cardiac surgery patients. Our data suggest that the observed difference in HIA prevalence was either population dependent, or due to different timing of heparin administration in the two groups.


Intraoral scanner and computer-aided design/manufacturing technology for the fabrication of double-crown-retained removable dental prosthesis: A clinical report.
This clinical report describes treatment with a double-crown-retained removable dental prosthesis fabricated using an intraoral scanner (IOS) and computer-aided design/manufacturing technology (CAD/CAM). A 68-year-old female patient presented with complaints of missing maxillary right first and left second premolars. CAD/CAM technology was applied to plan treatment with a double-crown-retained removable dental prosthesis. The patient consented to this treatment option but did not want orthodontic treatment for the anterior crossbite of the right side. After the definitive preparation of the abutment teeth, the shape of the provisional restoration was adjusted to match the definitive prosthesis. An IOS was used to obtain digital scans of the provisional restoration, occlusion, antagonist arch, and prepared surface of the abutment teeth. First, the primary crowns were milled from cobalt-chromium alloy. Next, using an intraoral scanner, a pick-up impression of the primary crowns was performed, and the secondary crowns were designed, milled, and veneered. After delivery, the patient expressed satisfaction with the functionality, esthetics, and fit of the double-crown-retained removable dental prosthesis. The surface of the primary crowns was coated with scan spray when the pick-up impression was made using the IOS. Practice is needed to achieve a thin and homogeneous coating with scan spray to improve reproducibility. Double-crown-retained removable dental prostheses can be successfully fabricated using an IOS and CAD/CAM technology, resulting in patient satisfaction.


Roles, regulation and inhibitors of sphingosine kinase 2.
The bioactive sphingolipids ceramide, sphingosine and sphingosine-1-phosphate (S1P) are important signalling molecules that regulate a diverse array of cellular processes. Most notably, the balance of the levels of these three sphingolipids in cells, termed the 'sphingolipid rheostat', can dictate cell fate, where ceramide and sphingosine enhance apoptosis and S1P promotes cell survival and proliferation. The sphingosine kinases (SKs) catalyse the production of S1P from sphingosine and are therefore central regulators of the sphingolipid rheostat and attractive targets for cancer therapy. Two SKs exist in humans: SK1 and SK2. SK1 has been extensively studied and there is a large body of evidence to demonstrate its role in promoting cell survival, proliferation and neoplastic transformation. SK1 is also elevated in many human cancers which appears to contribute to carcinogenesis, chemotherapeutic resistance and poor patient outcome. SK2, however, has not been as well characterized, and there are contradictions in the key physiological functions that have been proposed for this isoform. Despite this, many studies are now emerging that implicate SK2 in key roles in a variety of diseases, including the development of a range of solid tumours. Here, we review the literature examining SK2, its physiological and pathophysiological functions, the current knowledge of its regulation, and recent developments in targeting this complex enzyme.


Developing traps for the overwintering tree-of-heaven weevils Eucryptorrhynchus scrobiculatus and E. brandti (Coleoptera: Curculionidae).
The tree-of-heaven root and trunk weevils, Eucryptorrhynchus scrobiculatus (TRW) and E. brandti (TTW) are important boring pests of Ailanthus altissima in China. Overwintering TRW and TTW adults can continue to damage A. altissima trees and reproduce after they emerge from the soil each year. There is a lack of studies regarding the development of control measures during the overwintering period. A polyethylene terephthalate bottle trap (PETBT) and corrugated paper box trap (CPBT) were evaluated for their ability to trap TRW and TTW adults descending from trees to overwinter in the soil in Wutongshu and Shabatou locations in Ningxia, China. Significantly more overwintering TRW adults were caught by the PETBT than the CPBT. There were no significant differences in the TTW captures in PETBT when compared to the CPBT. Both PETBT and CPBT have little effect on trapping overwintering TTW adults. Further trapping studies showed that PETBT treatments significantly reduced overwintering TRW numbers caught in population monitoring trap nets placed on the A. altissima tree trunks (an average annual reduction of 42% than the untreated trees). These results demonstrate that PETBT is effective for trapping overwintering TRW adults. PETBT could be recommended as an alternative for managing TRW in the framework of integrated pest management. © 2021 Society of Chemical Industry.


Synthesis and anticoagulant activity of polyureas containing sulfated carbohydrates.
Polyurea-based synthetic glycopolymers containing sulfated glucose, mannose, glucosamine, or lactose as pendant groups have been synthesized by step-growth polymerization of hexamethylene diisocyanate and corresponding secondary diamines. The obtained polymers were characterized by gel permeation chromatography, nuclear magnetic resonance spectroscopy, and Fourier transform infrared spectroscopy. The nonsulfated polymers showed similar results to the commercially available biomaterial polyurethane TECOFLEX in a platelet adhesion assay. The average degree of sulfation after reaction with SO3 was calculated from elemental analysis and found to be between three and four -OSO3 groups per saccharide. The blood-compatibility of the synthetic polymers was measured using activated partial thromboplastin time, prothrombin time, thrombin time, anti-IIa, and anti-Xa assays. Activated partial thromboplastin time, prothrombin time, and thrombin time results indicated that the mannose and lactose based polymers had the highest anticoagulant activities among all the sulfated polymers. The mechanism of action of the polymers appears to be mediated via an anti-IIa pathway rather than an anti-Xa pathway.


The influence of cultural variables on treatment retention and engagement in a sample of Mexican American adolescent males with substance use disorders.
Adolescent substance abuse is a serious public health concern, and in response to this problem, a number of effective treatment approaches have been developed. Despite this, retaining and engaging adolescents in treatment are 2 major challenges continuously faced by practitioners and clinical researchers. Low retention and engagement rates are especially salient for ethnic minority adolescents because they are at high risk for underutilization of substance abuse treatment compared to their White peers. Latino adolescents, in particular, are part of the fastest growing ethnic minority group in the United States and experience high rates of substance use disorders. Heretofore, the empirical examination of cultural factors that influence treatment retention and engagement has been lacking in the literature. The goal of this study was to investigate the influence of the cultural variables ethnic identity, familism, and acculturation on the retention and engagement of Latino adolescents participating in substance abuse treatment. This study used data collected from a sample of Latino adolescent males (N = 96), predominantly of Mexican descent, and largely recruited from the juvenile justice system. Analysis was conducted using generalized regression models for count variables. Results indicated that higher levels of exploration, a subfactor of ethnic identity, and familism were predictive of attendance and engagement. In contrast, higher levels of Anglo orientation, a subfactor of acculturation, were predictive of lower treatment attendance and engagement. Clinical implications for the variables of ethnic identity, acculturation, and familism as well as suggestions for future research are discussed.


Comment - Genes and temperament, a shortcut for unravelling the genetics of psychopathology?
Personality is complex and unique, in that people differ greatly from one another in multiple components of personality. Nevertheless, personality can be measured and dissected into a number of quantitative traits. One of the more recent tools is the Temperament and Character Inventory (TCI), which is a self-report personality questionnaire based on Cloninger's psychobiological model of personality (Cloninger et al., 1994). This model consists of four dimensions of temperament and three dimensions of character. Temperament dimensions (novelty-seeking, harm avoidance, reward dependence and persistence) refer to automatic emotional responses to stimuli and are moderately heritable, relatively stable throughout life, and invariant despite sociocultural influences (Svrakic et al., 1996). Individuals high in novelty-seeking tend to be quick-tempered, excitable, exploratory, curious, enthusiastic, impulsive and disorderly. Individuals high in harm avoidance tend to be cautious, careful, fearful, tense, apprehensive, nervous, discouraged, insecure, negativistic and pessimistic, even in situations which do not worry other people. People scoring high on reward dependence seek social contact and are open to communication with other people; they are tender-hearted, sensitive, dedicated and sociable. Highly persistent individuals tend to be industrious, hard-working, persistent, and stable, despite frustration and fatigue. The character dimensions (self- directedness, cooperativeness and self-transcendence) involve differences in social goals and values and seem to be moderately influenced by family environment (Cloninger et al., 1994). Cloninger's psychobiological model of personality shows correlations to other factor models of personality, like the NEO five-factor model. The TCI dimension of novelty-seeking shows positive loading on NEO conscientiousness (Cloninger et al., 1994).


Dental Pulp Revascularization of Necrotic Permanent Teeth with Immature Apices.
The treatment of immature necrotic teeth with apical periodontitis presents challenges in endodontic and pediatric dentistry. Revascularization is a recent treatment for such cases as an alternative to conventional apexification. The purpose is to examine the effect of a pulpal revascularization procedure on immature necrotic teeth with apical periodontitis. Twenty patients were enrolled for pulp revascularization procedure by root canal disinfection using a triple antibiotic mixture for 1-2 weeks, followed by creating a blood clot, sealing the root canal orifice using white mineral trioxide aggregate and a coronal seal of composite resin. Patients were recalled periodically for up to 24 months. During follow-up, all patients were asymptomatic. Three cases of chronic apical periodontitis showed clinical disappearance of the sinus tract 2 weeks after treatment. Radiography revealed progressive periapical radiolucency resolution within the first 12 months. Within 12-24 months, the treated teeth showed progressive increases in dentinal wall thickness, root length and continued root development. Clinical and radiographic evidence showed successful revascularization treatments of immature necrotic permanent teeth with apical periodontitis. More studies are necessary to understand the underlying mechanisms and to perform histopathology of the pulp space contents after revascularization procedures.


Comparison of Point-of-Care and Highly Sensitive Laboratory Troponin Testing in Patients Suspicious of Acute Myocardial Infarction and Its Efficacy in Clinical Outcome.
The use of high-sensitivity troponin (hs-cTnI) assays is recommended in current guidelines for managing patients with acute coronary syndrome (ACS) symptoms. However, point-of-care (POC) assays are frequently used in emergency departments (EDs) to reduce turnaround time and length of stay. This study aimed to compare the results of POC-cTnI testing with those of the gold standard, automated central laboratory testing of troponin (i.e., hs-cTnI). The primary and secondary outcomes were the diagnostic performance of POC-cTnI in diagnosing acute myocardial infarction (AMI) and major adverse cardiovascular events (MACE) during 30 days, respectively. In this diagnostic accuracy study, 136 patients with suspected ACS who were referred or admitted to the Al Zahra Hospital, Shiraz, Iran, were included between March (2020) and July (2020). For the diagnosis of AMI, central laboratory cTnI levels were assessed at the time of presentation (0 hour) and reassessed at least 3 hours later. The POC-cTnI was measured at 0 hour in all patients and at 3 hours if a patient was diagnosed with AMI but had a 0-hour negative result for the POC-cTnI assay. Additionally, the 30-day follow-up period for these participants began on the day of the initial presentation to assess MACE. Out of 180 patients, 136 patients (median age of 59.5 years; 57.5% male) were left for the qualitative POC-cTnI and hs-cTnI assays. In 86 (63.24%) subjects, hs-cTnI was positive (either initial or serial); however, AMI was diagnosed in 85 patients according to positivity of troponin by hs-cTnI and clinical signs and symptoms, which were diagnosed by a cardiologist. The sensitivity, specificity, and negative predictive value of 0-hour POC-cTnI were observed to be 91.76% (95% CI: 83.77-96.62%), 98.04% (95% CI: 89.55-99.95%), and 87.72% (95% CI: 77.82-93.56%), respectively. Moreover, considering both the 0-hour and 3-hour POC-cTnI, all AMI cases were correctly identified, yielding a perfect test performance result. None of the 50 patients with negative cTnI results (by 0-hour and 3-hour POC-cTnI and hs-cTnI) experienced at least one MACE. In this small sample-size study, a new qualitative POC-cTnI assay was statistically equal to a hs-cTnI assay in terms of diagnostic accuracy for AMI or MACE in patients with suspected myocardial infarction. The POC-cTnI was observed to be acceptable for the identification of AMI and prediction of MACE in the ED environment.


Understanding frozen section histopathology in Sinonasal and anterior skull base malignancy and proposed reporting guidelines.
Intraoperative frozen section histopathology (IFSH) in sinonasal and skull base surgery although widely used is not well studied. We reviewed a database of sinonasal and anterior skull base tumors, between 1973 and 2019, and identified 312 suitable operative cases. Clinicopathologic data was collected and analyzed, in addition to descriptive data for histopathological reports classified as "ambiguous," or "limited/insufficient-quality/quantity." Overall, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for IFSH were 90.2%, 97.5%, 94.2%, 95.6%, and 95.2%, respectively. IFSH for adenocarcinoma, salivary carcinoma, and SCC all demonstrated a better clinical utility with a sensitivity of 90% or greater, while it was less than 90% for esthesioneuroblastoma, melanoma, and sarcoma. Other factors such as unclear reporting, poor quality specimens, or limited quality specimens were shown to lower diagnostic performance. Based on limitations identified, we proposed a novel IFSH reporting algorithm to improve IFSH in sinonasal and skull base surgery. IFSH is an accurate and clinically useful technique in sinonasal and skull base surgery patients; however, limitations exist.


General principles of the treatment of infective endocarditis.
The early diagnosis of infective endocarditis is important so that effective antibiotic treatment may be started without delay. When this is achieved other treatment problems are minimised. Heart failure and rhythm changes are treated in the conventional way. The use of necessary surgery at any stage of the disease has greatly improved the prognosis. The timing of surgery is important and is best achieved by close consultation between cardiologist, microbiologist and surgeon. In general, any failure, either haemodynamic or microbiological, of the patient to make a good response will be an indication to consider surgery.


Transfusion of autologous cytotoxic cells leads to failure of unrelated, DLA-nonidentical marrow grafts.
Dogs conditioned with 9.2 Gy total body irradiation (TBI) and given histoincompatible marrow transplants have a high rate of graft failure. Engraftment can be achieved by using 18 Gy fractionated TBI as preparative regimen. In this study, we tested the effects of infusing, at the time of histoincompatible marrow transplantation, autologous cells that had been stored before beginning high-dose (18 Gy) TBI. Our aim was to identify the peripheral blood mononuclear cells (PBMC) that contribute to failure of marrow grafts. Marrow graft failure was observed in three of three dogs receiving a mean of 2.1 x 10(8) unfractionated autologous PBMC/kg body weight as well as in two of two dogs receiving a mean dose of 0.075 x 10(8) PBMC/kg. When the dose of PBMC was decreased to 0.01 x 10(8)/kg, engraftment was seen in two of two dogs. These experiments thus established a cell dose response for causing marrow graft failure; further studies evaluated which subset of cells mediated this effect. Infusion of 0.09 x 10(8) nylon wool-nonadherent, plastic-nonadherent PBMC/kg was effective in causing marrow graft failure in three of three dogs. In contrast, infusion of 0.03 x 10(8) autologous monocytes/kg, enriched threefold above the number contained in the lower dose of PBMC causing graft failure, was associated with engraftment in four of six dogs. Infusion of 0.13 x 10(8) PBMC/kg treated with L-leucyl-L-leucine methyl ester (Leu-Leu-OMe), a drug that depletes canine cytotoxic T-lymphocytes (CTL), natural killer (NK) cells, and monocytes, permitted engraftment in three of four dogs. These data suggest that cytotoxic lymphocytes mediate failure of histoincompatible marrow grafts.


Neuroendocrine tumors of the lung with proposed criteria for large-cell neuroendocrine carcinoma. An ultrastructural, immunohistochemical, and flow cytometric study of 35 cases.
Based on our review of 35 cases and the literature, we found the spectrum of pulmonary neuroendocrine (NE) tumors to be too broad to fit into the traditional three-category classification scheme of typical carcinoid (TC), atypical carcinoid (AC), and small-cell lung carcinoma (SCLC). We found that a spectrum of high- and low-grade tumors exist between TC and SCLC and that in the past many of these tumors have been called AC. We chose to adhere to Arrigoni's definition of AC, as his original criteria characterized a low-grade tumor. For the higher grade non-small-cell tumors (NSCLC), we propose a fourth category of large-cell neuroendocrine carcinoma (LCNEC), which is characterized by: (a) light microscopic NE appearance; (b) cells of large size, polygonal shape, low nuclear-cytoplasmic ratio (N:C), coarse nuclear chromatin, and frequent nucleoli; (c) high mitotic rate [greater than 10/10 high-power fields (HPF)] and frequent necrosis; and (d) NE features by immunohistochemistry (IHC) or electron microscopy (EM). Thus, after deciding that a pulmonary NE tumor is high grade, the major diagnostic issue is separation of LCNEC from SCLC. This distinction is based not only on cell size, but on a variety of morphologic features. We studied 20 TC, six AC, five LCNEC, and four SCLC and characterized the clinical, light microscopic, EM, IHC, and flow cytometric features of each type of tumor. We did not find any advantage to IHC, EM, or flow cytometry over light microscopy in the subclassification or prediction of prognosis; however, these methods were useful in characterizing these four types of pulmonary NE tumors and in demonstrating their NE properties. LCNEC must be distinguished from a fifth category pulmonary NE tumor: NSCLC with NE features in which NE differentiation is not evident by light microscopy and must be demonstrated by EM or IHC. Although the prognosis of LCNEC appears to be intermediate between AC and SCLC, larger numbers of patients will be needed to demonstrate significant differences in survival.


Work clothes as a vector for microorganisms: Accumulation, transport, and resuspension of microorganisms as demonstrated for waste collection workers.
Work clothes may act as a vector for the transport of microorganisms leading to second-hand exposure; however, this has not been studied in work environments. We investigated whether microorganisms accumulate on workers' clothes in environments with elevated microbial exposures, and whether they are transported with the clothes and subsequently resuspended to the air. To study this, we selected waste collection workers and potential transport of bacteria and fungi to waste truck cabs via clothes, and compared the microbial communities within truck cabs, in waste collection workers' personal exposure, and on clean T-shirts worn by the workers. Microbial communities were also investigated for the presence of potentially harmful microorganisms. Results showed that microorganisms accumulated in large quantities (GM = 3.69 × 105 CFU/m2/h for bacteria, GM = 8.29 × 104 CFU/m2/h for fungi) on workers' clothes. The concentrations and species composition of airborne fungi in the truck cabs correlated significantly with the accumulation and composition of fungi on clothes and correlated to concentrations (a trend) and species composition of their personal exposures. The same patterns were not found for bacteria, indicating that work clothes to a lesser degree act as a vector for bacteria under waste collection workers' working conditions compared to fungi. Several pathogenic or allergenic microorganisms were present, e.g.: Klebsiella oxytoca, K. pneumoniae, Proteus mirabilis, Providencia rettgeri, Pseudomonas aeruginosa, and Aspergillus fumigatus, A. glaucus, A. nidulans, A. niger, and various Penicillium species. The potential 'take-home' exposure to these microorganisms are of most concern for immunocompromised or atopic individuals or people with open wounds or cuts. In conclusion, the large accumulation of microorganisms on workers' clothes combined with the overlap between fungal species for the different sample types, and the presence of pathogenic and allergenic microorganisms forms the basis for encouragement of good clothing hygiene during and post working hours.


Prevalence of CYP2C9 polymorphisms in the south of Europe.
CYP2C9 is a major liver enzyme responsible of the metabolism of many clinically important drugs. The presence of CYP2C9 genetic polymorphisms has been associated with marked interindividual variability in its catalytic activity that could result in drug toxicity. Here we present frequencies of the most common CYP2C9 coding variants CYP2C9*2 (C430T) and CYP2C9*3 (A1075C) in representative samples of four regions from Spain (Basque Country, n=358; Catalonia, n=240; Central Spain, n=190 and Galicia, n=288) and one northern Italian region, (Verona, n=164), which range between 0.125 and 0.165 in the case of CYP2C9*2 and between 0.071 and 0.085 for CYP2C9*3. No significant differences between CYP2C9 allele frequencies were found comparing all the sampled populations. A more extensive comparative analysis using allele frequency data of populations widely spread over Europe was performed, showing significant differences in the CYP2C9*2 allele frequencies distribution between some of the regions, being quite homogeneous in the case of CYP2C9*3 variant. The results obtained show that above 40% of our samples carry a mutate allele, which can result in a poor metabolization of low therapeutic index drugs as oral anticoagulants (warfarin, acenocoumarol), oral antidiabetic drugs and some non-steroidal anti-inflammatory drugs. Our study constitutes both a large (n=1240) and robust allele frequency database on CYP2C9 polymorphisms, which represents one of the most numerous CYP2C9*2 and *3 database existing to date.


Effectiveness of the Multidisciplinary Team Model in Treating Colorectal Cancer.
The multidisciplinary team (MDT) model involves multiple medical professionals providing integrated medical care. Colorectal cancer (CRC) has the highest prevalence of cancer in Taiwan. This study examines and evaluates the survival rates of CRC patients treated under the MDT model. In this retrospective and prospective study, 651 CRC patients were recruited. They were divided into 2 groups: the MDT group and the traditional care (TC) group. The MDT group comprised 326 patients who received care from a MDT. The TC group comprised 325 patients who received care from a TC. The outcome variables were survival rates, follow-up appointment compliance, and 14-day readmission rates. Adopting the MDT model for CRC care increased patient follow-up appointment compliance rates at the first week, first month, and third month (p = .032, p = .007, p = .001, respectively). The model also effectively reduced patients' 14-day readmission rates. The results indicated that the survival rates of the MDT care were superior to those of TC. The adoption of the MDT model to treat CRC effectively enhanced clinical treatment adherence, increased survival rates, and reduced the 14-day readmission rate.


Tissue-specific telomere dynamics in hibernating arctic ground squirrels (Urocitellus parryii).
Hibernation is used by a variety of mammals to survive seasonal periods of resource scarcity. Reactive oxygen species (ROS) released during periodic rewarming throughout hibernation, however, may induce oxidative damage in some tissues. Telomeres, which are the terminal sequences of linear chromosomes, may shorten in the presence of ROS, and thus the telomere length of an individual reflects the degree of accrued oxidative damage. This study quantified telomere length dynamics throughout hibernation in arctic ground squirrels (Urocitellus parryii). We hypothesized that telomere dynamics are tissue specific and predicted that telomere shortening would be most pronounced in brown adipose tissue (BAT), the organ that directly supports non-shivering thermogenesis during arousals. We used qPCR to determine relative telomere length (RTL) in DNA extracted from liver, heart, skeletal muscle (SM) and BAT of 45 juvenile and adult animals sampled either at mid- or late hibernation. Age did not have a significant effect on RTL in any tissue. At mid-hibernation, RTL of juvenile females was longer in BAT and SM than in liver and heart. In juvenile females, RTL in BAT and SM, but not in liver and heart, was shorter at late hibernation than at mid-hibernation. At late hibernation, juvenile males had longer RTL in BAT than did juvenile females, perhaps due to the naturally shorter hibernation duration of male arctic ground squirrels. Finally, BAT RTL at late hibernation negatively correlated with arousal frequency. Overall, our results suggest that, in a hibernating mammal, telomere shortening is tissue specific and that metabolically active tissues might incur higher levels of molecular damage.


Transplanted embryonic spinal tissue promotes severed sciatic nerve regeneration in rats.
The effects of transplanted embryonic spinal tissue on host motor nerve regeneration and target muscle reinervation were investigated in severed sciatic nerves of rats. The electromyogram (EMG) responses and number of motor end plates (MEP) in target muscles, number of nerve axons, and retrogradely labeled motor neurons were examined in transplantation-, anastomosis without transplantation-, and naïve groups of the animals. The EMG patterns of the transplantation group returned to nearly normal at the 8th week, but those of the anastomosis group did not. MEP counts in the transplantation group were significantly higher than in the anastomosis group. The myelinated axon counts and myelin sheath thickness in the transplantation group were significantly higher than those in the anastomosis group. The number of retrogradely labeled motor neurons was significantly higher in the transplantation group. We conclude that transplanted embryonic spinal tissue can promote both host motor nerve regeneration and target muscle reinnervation.


Do Alcohol Outlets Mediate the Effects of the Moving to Opportunity Experiment on Adolescent Excessive Drinking? A Secondary Analysis of a Randomized Controlled Trial.
Background: Housing mobility impacts adolescent alcohol use, and the neighborhood built environment may impact this relationship. Methods: Moving to Opportunity (MTO) was a multi-site, three-arm, household-level experiment. MTO randomly assigned one of three treatment arms (1994-1997) allowing families living in public housing to (1) receive a voucher to be redeemed any neighborhood (2) receive a voucher to be redeemed in a neighborhood with less than 10% poverty (3) remain in public housing (control). MTO decreased girls' alcohol use, but increased boys' alcohol use. Treatment groups were pooled because they are similar conceptually and statistically on our primary outcome. Among youth aged 12-19 in 2001-2002 (N = 2829), we estimated controlled direct effects mediation of MTO treatment effects on youth with housing vouchers (N = 1950) vs. controls (N = 879) on past 30-day number of drinks per day on days drank, using gender-stratified Poisson regression. Mediators were density of on- and off-premises alcohol outlets per square mile at the families' census tract of residence in 1997. Results: Treatment group youth were randomized to live in 1997 census tracts with lower off-premises, but higher on-premises, outlet density. MTO treatment (vs. controls) decreased drinking for girls via alcohol outlet density, but only at higher levels of outlet density. Treatment was 18% more beneficial when girls moved to high density neighborhoods, compared to controls who stayed living in public housing in high density neighborhoods. Conclusion: Additional social processes unmeasured in the current study may play an important role in the alcohol use and other health risks for girls.


Enhancing oral and systemic health.
Much published research documents continuing racial and ethnic disparities in health, particularly for African Americans, which apply to both oral and systemic diseases. Current research suggests biologically plausible associations between oral and systemic diseases; however, clear cause-and-effect relationships have not been substantiated. Some researchers and health care providers have noted anecdotal associations between oral and systemic health, as well as compounding adverse effects of oral and systemic diseases and dysfunctions. Historically, African American physicians, dentists, and pharmacists have bonded together under one organizational umbrella to combat discrimination, prejudice, and racism directed at them and their patient populations. This coming together has resulted in a more comprehensive clinical, behavioral, economic, and public health decision-making process related to the general health and well-being of their patient populations, such as maximizing health care visits, treatment plans, reimbursements, and oral and systemic health care follow-ups. According to the 1985 Secretary's Task Force Report, the six causes of excess deaths among African Americans were: cardiovascular disease and stroke; cancer; diabetes; cirrhosis; homicide and accidents; and infant mortality. In 1991, HIV/AIDS became the seventh cause of excess deaths. This article summarizes salient information about cardiovascular diseases, diabetes, cancer, and the social and behavioral factors related to oral and systemic health.


Molecular structure of rat hepatic 3 alpha-hydroxysteroid dehydrogenase. A member of the oxidoreductase gene family.
3-alpha-Hydroxysteroid dehydrogenase (3 alpha-HSD) (EC 184.108.40.206) is an important multifunctional oxidoreductase capable of metabolizing steroid hormones, polycyclic aromatic hydrocarbons, and prostaglandins. 3 alpha-HSD is also required for bile acid synthesis and has been suggested to play an important role in net bile acid transport across the hepatocyte (Stolz, A., Takikawa, H., Ookhtens, M., and Kaplowitz, N. (1989) Annu. Rev. Physiol. 51, 166-177). In order to characterize molecular forms and begin to determine its regulation, we now report the nucleotide sequence, tissue distribution, and homology to other members of the oxidoreductase superfamily. Rat hepatic 3 alpha-HSD cDNA encodes for a 322-amino acid protein with a predicted molecular weight of 37,022 expressed in a 2.4-kilobase (kb) message size. Northern blot analysis of total RNA revealed equivalent steady-state levels in liver and intestine in male rats with lower levels of expression in the colon and minimal expression in stomach, lung, and testis. Female liver contained approximately 2-3-fold greater steady-state levels of mRNA as compared to the male liver with equivalent intestinal expression. Two hybridizing bands, 2.4 and 1.4 kb, were identified in total RNA from the ovary. 3 alpha-HSD exhibits 75% amino acid sequence homology with bovine lung prostaglandin F synthetase and 50% homology with human aldose reductases. Amino acid sequence analysis with short chain alcohol dehydrogenases identified a possible NADP(H) cofactor-binding site at the amino terminus. The significant homology of 3 alpha-HSD with both prostaglandin F synthetase and aldose reductases suggest a subdivision of monomeric, NADPH reductases within the larger oxidoreductases superfamily.


A randomized, clinical trial of education or motivational-interviewing-based coaching compared to usual care to improve cancer pain management.
To test the effectiveness of two interventions compared to usual care in decreasing attitudinal barriers to cancer pain management, decreasing pain intensity, and improving functional status and quality of life (QOL). Randomized clinical trial. Six outpatient oncology clinics (three Veterans Affairs [VA] facilities, one county hospital, and one community-based practice in California, and one VA clinic in New Jersey)Sample: 318 adults with various types of cancer-related pain. Patients were randomly assigned to one of three groups: control, standardized education, or coaching. Patients in the education and coaching groups viewed a video and received a pamphlet on managing cancer pain. In addition, patients in the coaching group participated in four telephone sessions with an advanced practice nurse interventionist using motivational interviewing techniques to decrease attitudinal barriers to cancer pain management. Questionnaires were completed at baseline and six weeks after the final telephone calls. Analysis of covariance was used to evaluate for differences in study outcomes among the three groups. Pain intensity, pain relief, pain interference, attitudinal barriers, functional status, and QOL. Attitudinal barrier scores did not change over time among groups. Patients randomized to the coaching group reported significant improvement in their ratings of pain-related interference with function, as well as general health, vitality, and mental health. Although additional evaluation is needed, coaching may be a useful strategy to help patients decrease attitudinal barriers toward cancer pain management and to better manage their cancer pain. By using motivational interviewing techniques, advanced practice oncology nurses can help patients develop an appropriate plan of care to decrease pain and other symptoms.


CHF1/Hey2 promotes physiological hypertrophy in response to pressure overload through selective repression and activation of specific transcriptional pathways.
We have previously found that CHF1/Hey2 prevents the development of phenylephrine-induced cardiac hypertrophy. To determine the role of CHF1/Hey2 in pressure overload hypertrophy, we performed ascending aortic banding on wild-type and transgenic mice overexpressing CHF1/Hey2 in the myocardium. We found that both wild-type and transgenic mice developed increased ventricular weight to body weight ratios 1 week after aortic banding. Wild-type mice also developed decreased fractional shortening after 1 week when compared to preoperative echocardiograms and sham-operated controls. Transgenic mice, in comparison, demonstrated preserved fractional shortening. Histological examination of explanted heart tissue demonstrated extensive fibrosis in wild-type hearts, but minimal fibrosis in transgenic hearts. TUNEL staining demonstrated increased apoptosis in the wild-type hearts but not in the transgenic hearts. Exposure of cultured neonatal myocytes from wild-type and transgenic animals to hydrogen peroxide, a potent inducer of apoptosis, demonstrated increased apoptosis in the wild-type cells. Gene Set Analysis of microarray data from wild-type and transgenic hearts 1 week after banding revealed suppression and activation of multiple pathways involving apoptosis, cell signaling, and biosynthesis. These findings demonstrate that CHF1/Hey2 promotes physiological over pathological hypertrophy through suppression of apoptosis and regulation of multiple transcriptional pathways. These findings also suggest that CHF1/Hey2 and its downstream pathways provide a variety of targets for novel heart failure drug discovery, and that genetic polymorphisms in CHF1/Hey2 may affect susceptibility to hypertrophy and heart failure.


Spheres from cervical cancer cells display stemness and cancer drug resistance.
Cervical cancer is one of the most common gynecological malignant tumors and is the cause of a serious health problem worldwide. An increasing amount of evidence has shown that cancer stem cells (CSCs) are present in tumors, and that these CSCs may be responsible for tumor metastasis and relapse. The present study aimed to identify and characterize a CSC population from the CaSki cell line. First, a stem cell culture medium was used to selectively expand the cancer stem-like cell spheres, and the putative stemness markers, Oct4 and Sox2, were identified. These markers were all highly expressed in the CaSki sphere-forming cells. Next, target region amplified polymorphism-polymerase chain reaction was performed and the CaSki sphere-forming cells were found to exhibit higher telomerase activity than the CaSki control cells cultured in non-stem cell medium. Using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, it was found that the CaSki sphere-forming cells were more resistant to chemotherapeutic drugs than the control CaSki cells. Using the tumor invasive assay, it was shown that the CaSki sphere-forming cells were more invasive than the control CaSki cells. These characteristics all suggested that the tumor sphere-forming cells mirrored the acknowledged CSC phenotypes. Overall, the use of a suspended sphere culture of CaSki cells may be an easy and feasible approach for enriching cancer stem-like cells in cervical cancer research.


Mitochondrial Functionality and Chemical Compound Action on Sperm Function.
During the last decade, several studies have shown that mitochondrial parameters, such as integrity, respiratory activity, membrane potential and ROS production are intimately linked with sperm quality. Given the limitations of conventional semen analyses in terms of predicting male fertility, an increasing number of studies are focusing on the characterization of sperm mitochondria in order to more accurately assess sperm functionality. Moreover, mitochondria from several organs, such as the liver, have been described as a powerful screening tool for drug safety, being an easy in vitro model to assess the toxicity of distinct families of compounds. Given that mitochondrial functionality is intimately related to sperm homeostasis, it has become important to understand how compounds, ranging from dietary supplements, environmental pollutants, dependency-inducing drugs to pharmacological agents (such as erectile dysfunction-targeted drugs and male contraceptives) affect sperm mitochondrial function. In this review, we discuss studies describing the effects of various chemical agents on spermatozoa, with particular emphasis on mitochondrial function. From the extensive literature analyzed, we conclude that in some cases the role of sperm mitochondria as putative predictors of sperm functionality is very obvious, while in others further studies are needed to clarify this issue.


N-glycosylated catalytic unit meets O-glycosylated propeptide: complex protein architecture in a fungal hexosaminidase.
beta-N-Acetylhexosaminidase from a filamentous fungus Aspergillus oryzae is a secreted enzyme known to be an important component of the binary chitinolytic system. Cloning of the hexA gene and sequencing of the enzyme revealed its unique preproprotein structure. While the enzyme's zincin-like and catalytic domain had significant similarities with members of the glycohydrolase 20 family, the propeptide was unique for the fungal enzyme. Detailed pulse-chase and inhibition studies revealed that propeptide was processed during the biosynthesis of the enzyme. Moreover, the presence of propeptide was necessary for enzyme activation, dimerization and secretion. The catalytic unit was N-glycosylated, and the propeptide was O-glycosylated, both in their C-terminal parts. Deglycosylation experiments revealed that the N-glycosylation increased the stability and solubility of the enzyme. In contrast, O-glycosylated propeptide was necessary to attain the full enzymic activity.


Magnitude and duration of stretch modulate fibroblast remodeling.
Mechanical cues modulate fibroblast tractional forces and remodeling of extracellular matrix in healthy tissue, healing wounds, and engineered matrices. The goal of the present study is to establish dose-response relationships between stretch parameters (magnitude and duration per day) and matrix remodeling metrics (compaction, strength, extensibility, collagen content, contraction, and cellularity). Cyclic equibiaxial stretch of 2-16% was applied to fibroblast-populated fibrin gels for either 6 h or 24 h/day for 8 days. Trends in matrix remodeling metrics as a function of stretch magnitude and duration were analyzed using regression analysis. The compaction and ultimate tensile strength of the tissues increased in a dose-dependent manner with increasing stretch magnitude, yet remained unaffected by the duration in which they were cycled (6 h/day versus 24 h/day). Collagen density increased exponentially as a function of both the magnitude and duration of stretch, with samples stretched for the reduced duration per day having the highest levels of collagen accumulation. Cell number and failure tension were also dependent on both the magnitude and duration of stretch, although stretch-induced increases in these metrics were only present in the samples loaded for 6 h/day. Our results indicate that both the magnitude and the duration per day of stretch are critical parameters in modulating fibroblast remodeling of the extracellular matrix, and that these two factors regulate different aspects of this remodeling. These findings move us one step closer to fully characterizing culture conditions for tissue equivalents, developing improved wound healing treatments and understanding tissue responses to changes in mechanical environments during growth, repair, and disease states.


Escherichia coli tryptophan repressor binds multiple sites within the aroH and trp operators.
DNase I footprinting and methylation protection studies have been used to analyze the binding of Escherichia coli Trp repressor to the trpR, aroH, and trp operators. The methylation protection assay shows that Trp repressor binds in two successive major grooves of the trpR operator, three successive major grooves of the aroH operator, and four successive major grooves of the trp operator. The simplest model that explains the difference in Trp repressor interaction at the three operators is that the aroH and trp operators are composed of multiple, helically stacked binding sites. When viewed in three dimensions, each site is positioned on a different face of the DNA, and together process up the surface of the DNA helix. Analysis of a deletion derivative of the trp operator supports this model.


Spread of the autonomous transposable element hobo in the genome of Drosophila melanogaster.
The transposable element hobo has been introduced into the previously empty Drosophila melanogaster strain Hikone so that its dynamics can be followed and it can be compared with the P element. Five transformed lines were followed over 58 generations. The results were highly dependent on the culture temperature, the spread of hobo element being more efficient at 25 degrees C. The multiplication of hobo sequences resulted in a change in the features of these lines in the hobo system of hybrid dysgenesis. The number of hobo elements remained low (two to seven copies) and the insertions always corresponded to complete sequences. Our findings suggest that, despite their genetic similarities, P and hobo elements differ in many aspects, such as mobility and regulation mechanisms.


Ferrocenes with perfluorinated side chains and ferrocenophanes with fluorinated handles.
Trifluorovinyl groups are introduced onto the cyclopentadienyl ligands of ferrocene at the 1-, 1,1'-, and 1,2-positions by Negishi-type and Stille-type coupling reactions of trifluorovinylzinc chloride and tri-n-butyltrifluorovinyl stannane with several iodoferrocenes. Modification of the trifluorovinyl group by nucleophilic substitution and [2+2] cycloaddition make them versatile building blocks for synthetic transformations. 1,1'-Bis(trifluorovinyl) ferrocene reacts upon contact with silica or oxidizing agents and in the presence of a suitable nucleophile through a redox autocatalytic mechanism to afford ferrocenophanes with fluorinated handles. C(F)(H) and C(F)(OMe) moieties in α-positions allowed further modifications to be performed by nucleophilic substitution of the fluorine atoms. A series of ferrocenes with fluorinated side chains and ferrocenophanes with fluorinated handles were isolated and characterized. Several molecular structures were determined by single-crystal X-ray diffraction. The influence of the fluorine substituents on the redox properties of the iron center were studied by cyclic voltammetry.


Response of bacterial community structure to different ecological niches and their functions in Korean pine forests.
A healthy plant microbiome is diverse, taxonomically-structured, and gives its plant host moderate advantages in growth, development, stress tolerance, and disease resistance. The plant microbiome varies with ecological niches and is influenced by variables that are complex and difficult to separate from each other, such as the plant species, soil, and environmental factors. To explore the composition, diversity, and functions of the bacterial community of Korean pine forests, we used high-throughput sequencing to study five areas with different forest ages from June to October 2017 in northeast China. We obtained 3,247 operational taxonomic units (OTUs) based on 16S rRNA gene sequencing via an Illumina Hi-seq platform. A total of 36 phyla and 159 known genera were classified. The Shannon index of the bacterial community from the rhizospheric soil was significantly higher (p < 0.01, n = 10) than that of the root tips. Beta-diversity analysis confirmed that the bacterial community of the rhizospheric soil was significantly different (p < 0.001) from the root tips. Nine bacterial phyla were dominant (relative richness > 1%) in the rhizospheric soil, but there were six dominant phyla in the root tips. Proteobacteria was the core flora in the root tips with a relative abundance of more than 50%. It is known that the formation of bacterial communities in the rhizospheric soil or the root is mainly caused by the processes of selection, and we found a relatively high abundance of a few dominant species. We further analyzed the correlations between the bacterial community from the rhizospheric soil with that of the root tips, as well as the correlations of the bacterial community with soil physicochemical properties and climate factors. We used Functional Annotation of the Prokaryotic Tax (FAPROTAX) to predict the functions of the bacterial community in the rhizospheric soil and root tips. Five related phototrophic functions, nine nitrogen cycle functions, two related chemoheterotrophic functions, and two others were predicted. The abundance of the bacteria phyla performing relevant functions was different in the rhizospheric soil than in the root tips. These functions were significantly influenced by the contents of nitrogen, phosphorus, and potassium in the soil habitat. The bacterial composition and functions in the rhizospheric soil and root tips of Korean pine were analyzed, and the results demonstrated the importance of soil and plant species on the bacterial community in the below ground plant microbiome.


Thrombosis-associated hypofibrinogenemia: novel abnormal fibrinogen variant FGG c.8G>A with oxidative posttranslational modifications.
Here, we present the first case of fibrinogen variant FGG c.8G>A. We investigated the behaviour of this mutated fibrinogen in blood coagulation using fibrin polymerization, fibrinolysis, fibrinopeptides release measurement, mass spectrometry (MS), and scanning electron microscopy (SEM). The case was identified by routine coagulation testing of a 34-year-old man diagnosed with thrombosis. Initial genetic analysis revealed a heterozygous mutation in exon 1 of the FGG gene encoding gamma chain signal peptide. Fibrin polymerization by thrombin and reptilase showed the normal formation of the fibrin clot. However, maximal absorbance within polymerization was lower and fibrinolysis had a longer degradation phase than healthy control. SEM revealed a significant difference in clot structure of the patient, and interestingly, MS detected several posttranslational oxidations of fibrinogen. The data suggest that the mutation FGG c.8G>A with the combination of the effect of posttranslational modifications causes a novel case of hypofibrinogenemia associated with thrombosis.


Predictors for development of hyperuricemia: an 8-year longitudinal study in middle-aged Japanese men.
To identify the factors responsible for increases in serum uric acid (SUA), a cohort of 1,312 hyperuricemia-free (SUA < 7.5 mg/dL and no medication for hyperuricemia or hypertension) male office workers aged 30 to 52 years were examined annually for 8 successive years. Subjects who were found to have become hyperuricemic (SUA > or = 7.5 mg/dL) or who started medication for hyperuricemia during repeat surveys were defined as incidence cases. The SUA trend was also examined in 1,062 subjects for whom 9 consecutive SUA values were available and who did not start medication for hyperuricemia or hypertension during the observation period. Multivariate analyses, excluding the baseline SUA level as a factor in the Cox proportional-hazards model, indicated that age (negative), body mass index (BMI), log triglyceride level, hemoglobin A(1c) (HbA(1c)) level (negative), white blood cell count, and alcohol intake at study entry were significantly associated with the incidence of hyperuricemia. In the model including the baseline SUA level, baseline SUA level was the strongest factor for the incidence of hyperuricemia, and BMI, white blood cell count, and alcohol intake at study entry remained as independent factors. From stepwise linear regression analyses for SUA slope, excluding the baseline SUA level as a factor, significant correlates with SUA slope were, in order of their relative importance, slopes of BMI, HbA(1c) (negative), blood urea nitrogen, log triglyceride level, total protein, and baseline levels of hematocrit (negative), white blood cells, and HbA(1c) (negative). In stepwise linear regression analyses, including the baseline SUA level as a factor, SUA level (negative) and alcohol intake at study entry emerged as significant factors for SUA slope. The cumulative percentage of variation for SUA slope was 25.6%. In conclusion, obesity, alcohol intake, and multimetabolic disorders were determined to be independent predictors for the development of hyperuricemia. In addition, the white blood cell level may be a contributory factor.


Immunohistochemical study of VEGF expression in oral squamous cell carcinomas: correlation with the mTOR-HIF-1α pathway.
The aim of this study was to clarify the relationship between vascular endothelial growth factor (VEGF) expression and clinicopathological factors in oral squamous cell carcinoma (OSCC). We also examined the correlation between the VEGF expression and the mammalian target of rapamycin (mTOR)-hypoxia inducible factor-1α (HIF-1α) pathway. Formalin-fixed paraffin-embedded tissues from 120 OSCC cases and 10 samples of normal mucosa were stained immunohistochemically for VEGF-A, VEGF-C, p-mTOR and HIF-1α proteins. VEGF-A and VEGF-C protein expression was detected in 76 out of 120 (63%) and 81 of 120 (67.5%) OSCCs, respectively, and their expression was significantly higher in primary OSCC than in normal oral mucosa. VEGF-A expression was significantly associated with the tumor stage and age. VEGF-C expression was significantly associated with the cancer cell invasion. The cases with combined p-mTOR+/HIF-1α(+)/VEGF-A(+) expression had a significantly higher tumor stage and invasion grade, and combined p-mTOR+/HIF-1α(+)/VEGF-C(+) expression was significantly associated with tumor stage, regional lymph node metastasis and invasion grade. In a survival analysis, no obvious correlation was observed with any of the immunohistochemical results. This study indicated that the mTOR-HIF-1α-VEGF pathway affects the progression of OSCC, and inhibition of this pathway may be useful for the treatment of OSCC.


[Effect of deacetylation degree of chitosan on thermosensitive hydrogel via rheological characterization].
To evaluate the effect of deacetylation degree (DDA) on the gelation behavior of thermosensitive chitosan-beta glycerol phosphate disodium salt pentahydrate (CH-GP) system and to compare their rheological behaviors before and after gelation. A series of thermosensitive CH-GP samples with different DDAs (70%, 85%, 90%, 97%) were prepared by dissolving CH with 0.1 mol/L HCl solution, 5 samples for every single DDA, and then all these CH-GP solution samples processed the frequency sweep test and temperature sweep test (10-70 degrees C, 1 degrees C/min) on AR 2000ex rheometer, with pH value of 7.02. Also, all the results of hydrogel samples were processed a frequency sweep test. With CH concentration of 2% (w/v) and pH value of 7.02 , the gelatin temperature of CH-GP systems with different DDAs (85%, 90%, 97%) were (59.90 +/- 0.08), (48.10 +/- 0.08), (37.10 +/- 0.11) degrees C, respectively. While the gelatin temperature of CH-GP system with 70% DDA was over 70 degrees C. There were statistically significant differences in temperature and time of gelation among groups with different DDAs (P < 0.05). Furthermore, storage modulus of such system raised from dozens Pa to a magnitude of several kPa during gelation, while loss modulus kept almost steady. Gelatin temperature and mechanical property of the system could be measured objectively by rheological characterization. Thus during designing tissue engineered scaffolds for various purposes, it is helpful applying selected CH with optimal DDA to different target tissues.


Growth temperature control of the linoleic acid content in safflower (Carthamus tinctorius) seed oil.
The temperature and oxygen regulation of the microsomal oleate desaturase (FAD2) from safflower (Carthamus tinctorius L.) seeds was investigated. Heat-resistance profiles obtained in vivo and in vitro showed that the FAD2 enzyme maintained its maximal activity until 30 degrees C. A temperature increase from 10 to 40 degrees C caused a decrease of the FAD2 activity. However, when the temperature was decreased from 40 to 10 degrees C, no increase in the activity level was detected. The removal of hulls from safflower seeds followed by incubation in air did not change the FAD2 activity level, whereas incubation under nitrogen caused a strong decrease. Air replacement brought about the recovery of the initials levels. Oxygen concentrations less than 3% produced the inactivation of the enzyme. These data indicate that the higher thermal stability and the lower dependence on oxygen availability of the safflower FAD2 enzyme, compared with that of sunflower, could be the main factors to explain why the linoleate content of safflower seeds is more independent of growth temperature than that of sunflower seeds.


Effects of lysine biomass supplementation on growth performance and clinical indicators in broiler chickens.
Production of crystalline amino acids (AA) through microbial fermentation concomitantly provides an AA-enriched biomass that may serve as a cost-effective supplement for broiler chickens. We investigated the effects of feeding a fermentation biomass product containing approximately 62% Lys on growth performance, organ growth, and clinical outcomes of broilers. Beginning at 2 d post-hatch, a total of 360 Ross 308 chicks were randomly assigned to 1 of 5 treatments provided to 12 replicate cages of 6 birds. Practical corn-soybean meal-based dietary treatments included: negative control (NC; no supplementation of L-Lys, 1.01 and 0.86% standardized ileal digestible Lys in starter and grower phases, respectively), NC + 0.23% L-Lys HCl (positive control; PC), and NC supplemented with 0.30, 0.90, or 1.50% Lys biomass (LB) in both phases. Feed and water were provided ad libitum throughout the study. Individual bird and feeder weights were recorded on study day 0, 10, 21, and 35. At study conclusion, birds from each treatment were randomly selected to collect blood and tissue samples. The PC and 0.30% LB diets elicited similar overall (day 0-35) body weight gain and birds were heavier (P < 0.001) than the NC and other LB treatments. The PC, 0.30% LB, and 0.90% LB groups had better (P < 0.001) overall feed conversion ratio than NC. Some LB-supplemented treatments elicited increased (P < 0.001) relative spleen and ileum weight compared with NC and PC. Heterophils were increased (P < 0.001) in LB treatments compared with PC and NC. Lymphocytes were decreased (P < 0.001) in LB treatments compared with NC, and 1.50% LB was similar to PC. This resulted in an increased (P < 0.001) heterophil-to-lymphocyte ratio in some LB treatments, which may have resulted from general AA supplementation or the LB product. Collectively, these results suggest that addition of up to 0.30% LB restored growth performance when added to a Lys-deficient practical diet and elicited results identical to the Lys-adequate PC diet with no negative clinical effects.


Health promotion and disease prevention for the international traveler.
International travel is becoming increasingly popular with Americans, whether for business or pleasure. Approximately 10 to 15 million U.S. citizens travel abroad each year, and more than 8 million of these travel to developing nations. Travelers risk exposure to viral, bacterial and parasitic diseases not often encountered in the United States. Clients planning an international journey should be encouraged to obtain advice from their primary care practitioner. This article reviews the health care needs of the international traveler, including predeparture evaluation, required and recommended immunizations, and advice on disease-prevention measures.


Deubiquitinating Enzyme: A Potential Secondary Checkpoint of Cancer Immunity.
The efficacy of cancer immunotherapy depends on the fine interplay between tumoral immune checkpoints and host immune system. However, the up-to-date clinical performance of checkpoint blockers in cancer therapy revealed that higher-level regulation should be further investigated for better therapeutic outcomes. It is becoming increasingly evident that the expression of immune checkpoints is largely associated to the immunotherapeutic response and consequent prognosis. Deubiquitinating enzymes (DUBs) with their role of cleaving ubiquitin from proteins and other molecules, thus reversing ubiquitination-mediated protein degradation, modulate multiple cellular processes, including, but not limited to, transcriptional regulation, cell cycle progression, tissue development, and antiviral response. Accumulating evidence indicates that DUBs also have the critical influence on anticancer immunity, simply by stabilizing pivotal checkpoints or key regulators of T-cell functions. Therefore, this review summarizes the current knowledge about DUBs, highlights the secondary checkpoint-like role of DUBs in cancer immunity, in particular their direct effects on the stability control of pivotal checkpoints and key regulators of T-cell functions, and suggests the therapeutic potential of DUBs-based strategy in targeted immunotherapy for cancer.


Investigation on traditional medicines of Guarany Indio and studies on diterpenes from Scoparia dulcis.
In interviews on the traditional herbal medicines of Tupi-Guarany Indians at the herbal market of Asuncion and questionnaire from their users, it was clarified that various useful medicinal plants are available in Paraguay and most of them are generally used without drying. In the search for bioactive substances from those plants, a β-glucuronidase-inhibitory diterpene called scoparic acid A (SA) was isolated from Scoparia dulcis L. together with scoparic acid B, scoparic acid C, and the aphidicolin-like tetracyclic diterpenes scopadulcic acid A (SDA) and scopadulcic acid B (SDB). HPLC analysis of diterpenes in the individual plants of Paraguayan and Asian S. dulcis revealed the presence of three chemotypes based on major component, i.e., SA type, SDB type, and SDX type containing mainly scopadiol and scopadulciol (SDC). SA and SDB were elucidated to be mainly biosynthesized in the leaves via 2-C-methyl-D-erythritol- 4-phosphate pathway, and a leaf organ culture system containing methyl jasmonate 10 µM was found to enhance the production of diterpenes by activation of Ca-signal transduction systems such as calmodulin and protein kinase C. On the other hand, SDB and SDC were found to show multifaceted pharmacological effects such as inhibitory effects on gastric acid excretion, bone resorption, replication of herpes simplex virus type 1 (HSV-1), etc. In addition, SDC was suggested to be applicable to cancer gene therapy using ganciclovir or acyclovir and the HSV-1 thymidine kinase gene called the suicide gene.


The Danish version of the questionnaire on pain communication: preliminary validation in cancer patients.
The modified version of the patients' Perceived Involvement in Care Scale (M-PICS) is a tool designed to assess cancer patients' perceptions of patient-health care provider pain communication process. The objective of this study was to examine the psychometric properties of the shortened Danish version of the M-PICS (SDM-PICS). The validated English version of the M-PICS was translated into Danish following the repeated back-translation procedure. Cancer patients were recruited for the study from specialized pain management facilities. Thirty-three patients responded to the SDM-PICS, Danish Barriers Questionnaire II, Hospital Anxiety and Depression Scale, and Brief Pain Inventory Pain Severity Scale. A factor analysis of the SDM-PICS resulted in two factors: Factor one, patient information, consisted of four items assessing the extent to which the patient shared information with his/her health care provider, and Factor two, health care provider information, consisted of four items measuring the degree to which a health care provider was perceived as the one who shares information. Two separate items addressed the perceived level of information exchange between the patient and the health care provider. The SDM-PICS total had an internal consistency of 0.88. The SDM-PICS scores were positively related to pain relief and inversely related to the measures of cognitive pain management barriers, anxiety, and reported pain levels. The SDM-PICS seems to be a reliable and valid measure of perceived patient-health care provider communication in the context of cancer pain.


TRIM50 Inhibits Proliferation and Metastasis of Gastric Cancer via Promoting β-Catenin Degradation.
Gastric cancer (GC) is a common malignancy with a poor prognosis. Tripartite motif-containing 50 (TRIM50) belongs to the TRIM family and is reported to be related to numerous cancers. This study aimed to investigate the function of TRIM50 in GC. Three microarray datasets (GSE13911, GSE79973, and GSE19826) containing GC and adjacent nontumor tissues were used for bioinformatics analysis to screen GC-related genes and assess the associations between GC development and TRIM50 expression. Then, TRIM50 expression in GC cells was detected at mRNA and protein levels. After TRIM50 was knockdown or overexpressed, the effect of TRIM50 on the proliferation and metastasis of GC cells was analyzed using Cell Counting Kit-8 (CCK-8), flow cytometry, scratch, and Transwell assays. The interaction between TRIM50 and β-catenin was analyzed. The expression of cell cycle-, migration-, invasion-, and Wnt/β-catenin signaling pathway-related proteins was detected by Western blot. Furthermore, we measured the role of TRIM50 overexpression on tumor growth as well as the Wnt/β-catenin signaling pathway in vivo. In addition, XAV939 (a WNT/β-catenin signaling pathway inhibitor) was used to clarify the mechanism of TRIM50 on GC. Bioinformatics revealed that TRIM50 expression was decreased in GC samples and associated with GC development. In vitro study revealed that TRIM50 overexpression impeded the GC cell proliferation and metastasis, while TRIM50 knockdown presented the opposite results. In addition, TRIM50 interacted with β-catenin to induce the degradation of β-catenin. In in vivo assay, TRIM50 overexpression inhibited tumor growth and blocked the Wnt/β-catenin signaling pathway. In addition, TRIM50 knockdown-promoted cell proliferation and metastasis in GC cells were inverted by XAV939. TRIM50 overexpression may inhibit cell proliferation and metastasis in GC via β-catenin degradation, indicating that TRIM50 could be a target for the treatment of GC.


Factors that determin color appearance and color classification.
The purpose of this work was to consider the objective and subjective factors involved in color perception and on their basis offer a color classification that would allow for determining which of these factors are significant for each particular class of colors. In the first part of the article it is considered that physical correlates of subjective sensation of color have mainly a dual nature and sometimes correlate with spectral-power content of light coming from a given area of visual scene to retina, and sometimes with surface reflectance of the given area. Other objective and subjective factors which participate in the formation of color appearance are also considered. According to the characteristics of the visual stimulus, viewing conditions and functional state of visual system, composition of objective and subjective factors participating in the formation of color appearance, as well as the share of each factor in this process are changeable. In the second part of the article one of the possible version of color classification according to which it is possible to distinguish nine different classes of colors is proposed. Among differences between these classes, the most noticeable is that in the case of all classes of color except constant colors, the physical parameter that determines the color category of a given area is the spectral-power distribution of the light coming from this area to the retina. However, in the case of constant colors, the physical parameter that determines the color category of a given area is its reflectance. In the case of considered different classes of colors, composition of objective and subjective factors participating in the formation of color appearance is different. The proposed classification allows determining which of these factors are significant in the case of each specific class of color.


Regulation of DNA replication during development.
As development unfolds, DNA replication is not only coordinated with cell proliferation, but is regulated uniquely in specific cell types and organs. This differential regulation of DNA synthesis requires crosstalk between DNA replication and differentiation. This dynamic aspect of DNA replication is highlighted by the finding that the distribution of replication origins varies between differentiated cell types and changes with differentiation. Moreover, differential DNA replication in some cell types can lead to increases or decreases in gene copy number along chromosomes. This review highlights the recent advances and technologies that have provided us with new insights into the developmental regulation of DNA replication.


Work stress in Japanese computer engineers: effects of computer work or bioeducational factors.
To examine whether computer work and bioeducational factors (age and school career) have significant effects on work stress in computer engineers in Japan, we administered a stress questionnaire to 764 male computer engineers and 211 male office workers in a computer-manufacturing factory in Tokyo. Four scales of perceived psychological stress at work examined were work overload, poor human relationships at work, unsuitable job, and competition-dismissal anxiety. The results of the three-way analysis of variance, in which age (20-29, 30-39, and 40-49 years), school career (high school and university graduates), and computer work (computer engineers and office workers) were three variation factors, indicated that: (1) there were no significant differences in all scores of work stress between computer engineers and office workers (P > 0.05); (2) scores for unsuitable job and poor human relationships at work were significantly higher in high school graduates than in university graduates (P < 0.05); and (3) there were significant age differences in scores for three scales of work stress (unsuitable job, competition-dismissal anxiety, and work overload: P < 0.001, P < 0.01, and P < 0.05, respectively). These findings suggest that computer work has no significant effect on perceived work stress in computer engineers; on the other hand, age and school career do have effects.


Electrode dysfunctions in patients with deep brain stimulation: a clinical retrospective study.
Electrode fractures are known hardware problems in patients with deep brain stimulation (DBS) and require surgical revision. Short circuits, loose connections or disconnections of only single contacts of the common quadripolar stimulation electrodes are more subtle dysfunctions and can result in decreased efficacy of DBS. Measuring the impedances of electrodes helps detect such technical dysfunctions. This study evaluates the frequency and clinical implications of abnormal impedance measurements. We retrospectively analyzed findings of systematic impedance checks in 591 consecutive patients with DBS for various movement disorders treated in our DBS center between 2005 and 2010. A technical dysfunction was found in 36 out of 1,142 electrodes (3.2%). Short circuits (22 electrodes) were more frequent than disconnections of single contacts (8 electrodes) or loose contacts (6 electrodes). Moreover, after 109 replacements of impulse generators another 16 electrodes revealed technical dysfunctions, again with short circuits (9 electrodes) exceeding disconnections of single contacts (5 electrodes) and loose contacts (2 electrodes). Most of the short circuits occurred immediately after surgical interventions. In contrast, among dysfunctions occurring later during long-term DBS, disconnections and loose contacts prevailed. Surgical revision was performed in 4 of the overall 52 electrodes with dysfunctions, whereas in the other electrodes adjustment of stimulation parameters resulted in stable and satisfying symptom control. Technical dysfunctions of stimulation electrodes or extension leads are rare but important sources of unsatisfying DBS efficacy. In the majority of cases DBS programming or reprogramming allows avoiding surgical revision.


Clinical Outcomes of Accelerated Corneal Cross-Linking for Pediatric Keratoconus.
To assess the efficacy and safety of accelerated corneal cross-linking in the treatment of pediatric keratoconus. In this retrospective case series, 29 eyes of 20 pediatric patients with keratoconus underwent accelerated corneal cross-linking. Treatment was delivered at 10 mW/cm2 for 9 minutes with a total dose of 5.4 J/cm2. Clinical evaluation included visual acuities and refractive and Scheimpflug corneal tomography assessments. All patients with a minimum follow-up duration of 24 months were included in the study. Mean ± standard deviation age was 15.41 ± 2.13 years (range: 8 to 18 years). Uncorrected distance visual acuity improved significantly from 0.56 ± 0.28 to 0.42 ± 0.29 logMAR (P=0.0003), and corrected distance visual acuity improved significantly from 0.34 ± 0.23 to 0.28 ± 0.22 logMAR (P=0.014). The mean manifest refraction spherical equivalent value was significantly reduced (-0.59 ± 0.95 D, P=0.0024). While mean flat keratometry and steep keratometry values were not significantly altered (P > 0.05 for both), the mean maximum keratometry value was significantly decreased from 56.97 ± 5.24 D preoperatively to 55.84 ± 5.37 D at 24 months postoperatively (P=0.003). Maximum keratometry had progressed by >1 D in two eyes (6.89%). Permanent corneal haze was reported in one case (3.44%). Our 24-month follow-up demonstrated that accelerated corneal cross-linking appears to halt the progression of keratoconus in pediatric patients without apparent complications. Uncorrected and corrected distance visual acuities were also improved.


Clinical outcome of emergency repeat coronary artery bypass surgery.
To determine the clinical outcome of patients requiring emergency repeat coronary artery bypass graft (CABG) procedures, we reviewed 23 such procedures performed for ongoing myocardial ischemia refractory to medical management. The operative mortality was 17%. On follow-up, an average of 24.9 months after emergency reoperation, 14 of the 19 survivors (74%) had recurrent angina. As compared to a randomly selected group of 25 patients who underwent elective repeat CABG procedures during the same time period, the incidence of late cardiac events was significantly higher (79% in the emergency group, 30% in the elective surgery group) and fewer patients had received internal mammary artery (IMA) grafts (9% vs 52%). Emergency repeat CABG operations have considerable operative mortality and poor postoperative functional results with the majority of survivors developing recurrent ischemic syndromes within a short period of time.


Mucoadhesive Interpolyelectrolyte Complexes for the Buccal Delivery of Clobetasol.
This work aimed to investigate the feasibility to design: (a) a mucoadhesive interpolyelectrolyte complex (IPEC) loaded with clobetasol propionate (CP) intended to treat oral lichen planus and (b) individuate an orodispersible dosage form suitable for its administration. IPECs were synthesized by mixing Eudragit® E PO (EPO) and different grades of cross-linked polyacrylate derivatives, in different molar ratios, namely 1:1, 1:2, and 2:1. All IPECs resulted at nanoscale independently of their composition (120⁻200 nm). Both zeta-potentials (ζ) and mucoadhesive performances were influenced by the ratio between polymers. On the bases of the preliminary data, IPECs made of Polycarbophil and EPO in the 1:2 ratio were loaded with CP. The encapsulation efficiency was up 88% independently of the CP-IPEC ratio. The drug encapsulation caused IPEC destabilization in water, as it was noticed by the increase of ζ values and the formation of aggregates. Oral lyophilisates were prepared by freeze-drying slurries made of placebo or CP loaded IPECs, maltodextrin with a dextrose equivalent 38 and Span®80. The optimized formulation permitted to obtain a fast disintegration upon contact with water reducing the tendency of IPECs to aggregate. Moreover, oral lyophilisates allowed improving the apparent solubility of CP throughout the in vitro release experiment.


Polydactylous Bowen's disease of the nail bed.
A case is presented with tender swelling and nail bed hyperplasia in 2 fingers. Histopathology revealed Bowen's disease in both fingers and after amputation, invasive squamous cell carcinoma in one finger.


Functional organ preservation for laryngeal cancer: past, present and future.
Management of laryngeal cancer has focused on improving survival while preserving function. Over the past 20 years, the trends have shifted from surgery to chemoradiotherapy and presently we are facing various challenges. It is imperative to re-examine what has happened and what can be done. Review of the literature along with our experience in the management of functional organ preservation for laryngeal cancer. There was an increasing use of chemoradiotherapy with a decreasing use of surgery. Inappropriate patient selection along with inability to properly apply salvage surgeries have been presumed to be responsible for survival deterioration in laryngeal cancer. Reports concerning late adverse events after chemoradiotherapy are also increasing. Reconfirmation of the multidisciplinary team approach is imperative. Transoral laser microsurgery can be used for early laryngeal cancer and, in some experienced institutes, for advanced-stage cancers. Supracricoid laryngectomy demonstrated satisfactory oncologic and functional outcomes, based on our experience. Treatment selection for larynx preservation should not merely be decided by guidelines but considering each patient's individual condition. Head and neck surgeons are encouraged to take reasonable risks in performing salvage larynx preservation surgery when it is the only option to save a functioning larynx.