Field-compensated michelson spectrometers.
It was first shown by Pierre Connes (1956) that the resolution-luminosity product of a Michelson spec- trometer could be substantially improved by the technique of field compensation. In the present paper, various systems of field compensation are discussed, and an account is given of the tolerances allowed in their operation, together with their areas of usefulness.


Vitamin D in thyroid disorders.
Vitamin D's canonical role are its effects exerted on the musculoskeletal system. In the last decades the importance of this hormone has been studied in the context of extraskeletal health. Hypovitaminosis D and several polymorphic variants of genes coding proteins crucial in the transport, metabolism and effects of vitamin D have been associated with negative health outcomes.In this review the current state of knowledge on the role of vitamin D in thyroid disorders is presented. The review is based on a literature search of the PubMed database performed in December 2014. The following search terms were used in conjunction with 'vitamin D': thyroid cancer, Graves', Hashimoto, thyroiditis, autoimmune thyroid, AITD, nodules, hyperthyroidism, and hypothyroidism.Currently, similarly to other extraskeletal health outcomes, a clear role of vitamin D has not been demonstrated in thyroid disorders. Further research is necessary to fully elucidate the importance of vitamin D in case of thyroid disease.


A novel assessment of population structure and gene flow in grey wolf populations of the Northern Rocky Mountains of the United States.
The successful re-introduction of grey wolves to the western United States is an impressive accomplishment for conservation science. However, the degree to which subpopulations are genetically structured and connected, along with the preservation of genetic variation, is an important concern for the continued viability of the metapopulation. We analysed DNA samples from 555 Northern Rocky Mountain wolves from the three recovery areas (Greater Yellowstone Area, Montana, and Idaho), including all 66 re-introduced founders, for variation in 26 microsatellite loci over the initial 10-year recovery period (1995-2004). The population maintained high levels of variation (H(O) = 0.64-0.72; allelic diversity k=7.0-10.3) with low levels of inbreeding (F(IS) < 0.03) and throughout this period, the population expanded rapidly (n(1995) =101; n(2004) =846). Individual-based Bayesian analyses revealed significant population genetic structure and identified three subpopulations coinciding with designated recovery areas. Population assignment and migrant detection were difficult because of the presence of related founders among different recovery areas and required a novel approach to determine genetically effective migration and admixture. However, by combining assignment tests, private alleles, sibship reconstruction, and field observations, we detected genetically effective dispersal among the three recovery areas. Successful conservation of Northern Rocky Mountain wolves will rely on management decisions that promote natural dispersal dynamics and minimize anthropogenic factors that reduce genetic connectivity.


Oxidative stress in airways: is there a role for extracellular superoxide dismutase?
Airways are exposed to high levels of environmental oxidants, yet they also have enriched extracellular antioxidants. Airways disease such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease have evidence of increased oxidative stress, suggesting that reactive oxygen and nitrogen species may overwhelm antioxidant defenses in airway diseases. Extracellular superoxide dismutase is abundant in pulmonary tissues and protects the lung from increased oxidative stress; however, its role in asthma and other airway diseases has not been fully elucidated. Proteolytic processing of extracellular superoxide dismutase decreases its affinity for the extracellular matrix and may be a mechanism to regulate its distribution during conditions of inflammation or oxidative stress.


Extension of natural reaction orbital approach to multiconfigurational wavefunctions.
Recently, we proposed a new orbital analysis method, natural reaction orbital (NRO), which automatically extracts orbital pairs that characterize electron transfer in reaction processes by singular value decomposition of the first-order orbital response matrix to the nuclear coordinate displacements [Ebisawa et al., Phys. Chem. Chem. Phys. 24, 3532 (2022)]. NRO analysis along the intrinsic reaction coordinate (IRC) for several typical chemical reactions demonstrated that electron transfer occurs mainly in the vicinity of transition states and in regions where the energy profile along the IRC shows shoulder features, allowing the reaction mechanism to be explained in terms of electron motion. However, its application has been limited to single configuration theories such as Hartree-Fock theory and density functional theory. In this work, the concept of NRO is extended to multiconfigurational wavefunctions and formulated as the multiconfiguration NRO (MC-NRO). The MC-NRO method is applicable to various types of electronic structure theories, including multiconfigurational theory and linear response theory, and is expected to be a practical tool for extracting the essential qualitative features of a broad range of chemical reactions, including covalent bond dissociation and chemical reactions in electronically excited states. In this paper, we calculate the IRC for five basic chemical reaction processes at the level of the complete active space self-consistent field theory and discuss the phenomenon of electron transfer by performing MC-NRO analysis along each IRC. Finally, issues and future prospects of the MC-NRO method are discussed.


Mycobacterium tuberculosis Beijing genotype induces differential cytokine production by peripheral blood mononuclear cells of healthy BCG vaccinated individuals.
Members of the Mycobacterium tuberculosis (Mtb) Beijing genotype are a major concern due to their high prevalence in tuberculosis patients and their high rate of multi-drug resistance. Although it has been shown that Beijing modifies macrophage behavior, little is known about how this genotype could affect the cellular immune response. In order to address this issue, peripheral blood mononuclear cells (PBMC) from healthy BCG vaccinated individuals were stimulated with protein extracts from three Mycobacterium tuberculosis genotypes: Canetti, H37Rv and Beijing evaluating T cell proliferation and cytokine production. In this system both CD4+ and CD8+ proliferated in a similar manner independently of the Mtb genotype used for stimulation. Regarding cytokines, all strains induced similar levels of IFN-γ, but were unable to induce IL-4 and TGF-β. Contrasting, Canetti strain induced lower production of IL-10, TNF-α and IL-12 compared to H37Rv and Beijing. Interestingly, PBMC stimulated with the Beijing strain produced the highest levels of IL-12 and IL-10 than those stimulated with other strains. This differential cytokine expression could affect the pathogenesis induced by Beijing strain through the modulation of inflammatory process in the host, but the precise mechanisms by which this cytokine environment affects the Beijing strain pathogenesis needs further characterization.


Spherical Particles of Zirconia-Titania of Hexagonal Structure from a Neutral Amine Route.
Through the sol-gel process, using the so-called neutral amine route, spherical particles of 1:1 zirconia-titania were synthesized from zirconium(IV) and titanium(IV) butoxides as well as 1,12-diaminododecane as precursor species. The obtained product exhibited a hexagonal structure, as determinated by X-ray diffraction data. The obtained material was also characterized by thermogravimetry, differential scanning calorimetry, infrared spectroscopy, scanning electron microscopy, and surface area measurements. Despite the release of template molecules on heating, the spherical morphology was retained up to about 1200 degrees C, at which the disruption of the spheres took place. Copyright 1999 Academic Press.


Tailoring angle dependent ferroelectricity in nanoribbons of group-IV monochalcogenides.
Ferroelectricity is significant in low dimensional structures due to the potential applications in multifunctional nanodevices. In this work, the tailoring angle dependent ferroelectricity is systematically investigated for the nanoribbons and nanowires of puckered group-IV monochalcogenides MX (M =Ge,Sn; X =S,Se). Based on first-principles calculations, it is found that the ferroelectricity of nanoribbon and nanowire strongly depends on the tailoring angle. Firstly, the critical width for the bare nanoribbon of group-IV monochalcogenide is obtained and discussed. As the nanowires are concerned, the ferroelectricity will disappear when the tailoring angle becomes small. At last, H-passivation on the edge and the strain engineering are employed to improve the ferroelectricity of nanoribbon, and it is obtained that H-passivation is beneficial to the enhancement of polarization for nanoribbons tailored near the armchair direction, while the polarization of nanoribbons tailored along the diagonal direction will decrease when the edges are passivated with H atoms, and the tensile strain along the length direction always favors the improvement of ferroelectricity of the considered nanoribbons. Therefore, tailoring angle has great influence on the ferroelectricity of nanoribbons and nanowires, which may be used as an effective way to tune the ferroelectricity and further the electronic structures of nanostructures in the field of nanoelectronics.


Transition in the fractal properties from diffusion-limited aggregation to Laplacian growth via their generalization.
We study the fractal and multifractal properties (i.e., the generalized dimensions of the harmonic measure) of a two-parameter family of growth patterns that result from a growth model that interpolates between diffusion-limited aggregation (DLA) and Laplacian growth patterns in two dimensions. The two parameters are beta that determines the size of particles accreted to the interface, and C that measures the degree of coverage of the interface by each layer accreted to the growth pattern at every growth step. DLA and Laplacian growth are obtained at beta=0, C=0 and beta=2, C=1, respectively. The main purpose of this paper is to show that there exists a line in the beta-C phase diagram that separates fractal (D<2) from nonfractal (D=2) growth patterns. Moreover, Laplacian growth is argued to lie in the nonfractal part of the phase diagram. Some of our arguments are not rigorous, but together with the numerics they indicate this result rather strongly. We first consider the family of models obtained for beta=0, C>0, and derive for them a scaling relation D=2D(3). We then propose that this family has growth patterns for which D=2 for some C>C(cr), where C(cr) may be zero. Next we consider the whole beta-C phase diagram and define a line that separates two-dimensional growth patterns from fractal patterns with D<2. We explain that Laplacian growth lies in the region belonging to two-dimensional growth patterns, motivating the main conjecture of this paper, i.e., that Laplacian growth patterns are two dimensional. The meaning of this result is that the branches of Laplacian growth patterns have finite (and growing) area on scales much larger than any ultraviolet cutoff length.


An academic writing needs assessment of English-as-a-second-language clinical investigators.
Academic writing for publication is competitive and demanding for researchers. For the novice English-as-a-second-language (ESL) researcher, the pressure to publish compounds the difficulties of mastering the English language. Very few studies have used ESL graduate and post-graduate students as academic writing research subjects. The purpose of this project was to assess the learning needs of ESL clinical investigators regarding academic writing for English scholarly publication. A qualitative evaluation approach was used to examine the gap between the current and desired proficiency level for the academic writing of ESL clinical investigators. We considered the perspectives of seven ESL clinical investigators plus three mentors and three writing instructors. Semi-structured questions were asked. Field notes were organized using a field-work recording system. They were analyzed using the constant comparative method. ESL clinical investigators do not accurately perceive their writing deficiencies. They have little knowledge of criteria for academic writing and they are influenced by their prior English learning experiences in their home culture, which engender passive attitudes toward seeking appropriate writing resources. Adequate time is especially needed to develop successful writing skills. Four basic steps are recommended to guide program planners in developing ESL writing activities for professional learning: (1) recognize discrepancies, (2) establish clear standards and performance criteria for scholarly writing, (3) develop individual plans, and (4) organize long-term writing assistance.


Genetic Causes of Craniosynostosis: An Update.
In 1993, Jabs et al. were the first to describe a genetic origin of craniosynostosis. Since this discovery, the genetic causes of the most common syndromes have been described. In 2015, a total of 57 human genes were reported for which there had been evidence that mutations were causally related to craniosynostosis. Facilitated by rapid technological developments, many others have been identified since then. Reviewing the literature, we characterize the most common craniosynostosis syndromes followed by a description of the novel causes that were identified between January 2015 and December 2017.


Arteriovenous fistulas for hemodialysis access in children and adolescents using the proximal radial artery inflow site.
Hemodialysis (HD) for children and adolescents with renal failure is increasingly common in the United States. Consensus opinion views an arteriovenous fistula (AVF) as the best long-term access option, although catheter-based HD remains the most common vascular access in children and has greater risks of complications and higher mortality rates than AVF access. This report reviews our experience with children and adolescents undergoing vascular access operations. We reviewed 721 consecutive vascular access patients who had vascular access surgery by a single surgeon during the previous 5 years. Ten patients 20 years or younger were included in this study. In addition to physical examination, each patient had preoperative vascular ultrasound mapping by the operating surgeon. A radiocephalic AVF (RC-AVF) at the wrist was the first choice for dialysis access when feasible; however, the patients in this report were generally seen after years of intravenous access and venipunctures that necessitated more proximal AVF constructions. A proximal radial artery AVF (PRA-AVF) was our most common choice for vascular access when an RC-AVF was not suitable. Patient ages were 9 to 20 years (mean, 16). Seven were male. Renal failure was caused by glomerulnephitis in 4 patients, 3 had a history of obstuctive uropathy, 2 were diabetic and one had congenital nephrotic syndrome. Eight patients had PRA-AVFs created, 1 had an RC-AVF, and 1 patient required a transposition AVF. Follow-up was 4 to 56 months (mean, 32 months). Primary, primary-assisted, and cumulative patencies were 77.8%, 100%, and 100% at 24 months. No prosthetic grafts were used in any vascular access patient during the study period. We found HD access in children and adolescents was reliably established through use of a PRA-AVF when an RC-AVF was not feasible. Access sites were often possible through the upper arm cephalic veins and/or with retrograde flow into the forearm. Cumulative (secondary) patency was 100% at 24 months.


Between simpatia and malandragem: Brazilian jeitinho as an individual difference variable.
Culture-specific behaviour strategies provide an interesting window into individual differences research, producing a richer conceptualization of personality descriptions. Our aim is to describe the personality dimensions linked to a core socio-cultural behaviour pattern in Brazil: jeitinho. To reach this goal we conducted four studies. Our first set of studies (1a, 1b and 1c) examined the underlying structure of jeitinho as an individual difference variable and its nomological network with social values, the Big-Five, moral attitudes, and social dominance orientation. In Study 2, we confirm this structure and relate personal jeitinho to perceptions of jeitinho norms. Results demonstrated that personal jeitinho has two dimensions: Jeitinho Simpático is an individual's tendency to seek positive social interactions, avoid conflict, and find creative solutions; and Jeitinho Malandro captures behaviours such as the use of deception and trickery. These two behaviours are rooted in the same dimensions of the integrated model of values and personality.


Evaluation of irritation and sensitisation of two 50 microg/day oestrogen patches.
To comparatively assess the irritation and sensitisation of the Estradot transdermal oestrogen patch, in healthy postmenopausal women, using the Menorest transdermal oestrogen patch, as a comparator. In an open-label, single-centre, randomised, active-treatment, within-patient controlled study, 208 healthy postmenopausal women, age range 40-70 years, received and completed simultaneous treatment with a 5 cm(2) (50 microg/day) oestradiol patch (Estradot) and a 14.5 cm(2) (50 microg/day) oestradiol patch (Menorest). The treatment was given for 72 h, then 96 h, for eight successive applications during an induction phase, and for 72 h during a challenge phase. There was a 14-day resting period between phases. Skin irritation (measured by erythema on a scale of 0-4), topical sensitisation, patch adherence and local skin reaction, were assessed and recorded immediately before or after removal of each patch, as appropriate. Most patients experienced a significant difference in irritation with Menorest than with Estradot (P < 0.0001) at the end of the induction phase. Patch loss was also significantly higher for Menorest as compared to Estradot (P = 0.0253) at the end of the induction phase. Most incidences of erythema were classified as slight (score of 1), and there was no significant difference in the percentage of topical sensitisation, or in the incidence of local skin reactions between Estradot and Menorest. Patch loss was low for both systems. Estradot demonstrates reduced skin irritation, superior adhesion and a lower rate of patch loss compared to Menorest.


Design, synthesis and evaluation of 3-quinoline carboxylic acids as new inhibitors of protein kinase CK2.
In this article, the derivatives of 3-quinoline carboxylic acid were studied as inhibitors of protein kinase CK2. Forty-three new compounds were synthesized. Among them 22 compounds inhibiting CK2 with IC50 in the range from 0.65 to 18.2 μM were identified. The most active inhibitors were found among tetrazolo-quinoline-4-carboxylic acid and 2-aminoquinoline-3-carboxylic acid derivatives.


Management and long-term outcomes of sarcoidosis-associated pulmonary hypertension.
Studies reporting the effects of modern strategies with pulmonary arterial hypertension (PAH)-targeted therapies in sarcoidosis-associated pulmonary hypertension (S-APH) are limited.Clinical and haemodynamic data from newly diagnosed patients with severe S-APH (mean pulmonary artery pressure (mPAP) >35 mmHg or mPAP 25-35 mmHg with cardiac index <2.5 L·min-1·m-2) were collected from the French Pulmonary Hypertension Registry between 2004 and 2015.Data from 126 patients with severe S-APH were analysed (mean±sd age 57.5±11.6 years, 74% radiological stage IV). 97 patients (77%) received PAH-targeted therapy and immunosuppressive therapy was initiated or escalated in 33 patients at the time of pulmonary hypertension diagnosis. Four months after PAH-targeted therapy initiation, mean±sd pulmonary vascular resistance decreased from 9.7±4.4 to 6.9±3.0 Wood units (p<0.001), without significant improvement in exercise capacity. Among the 11 patients treated only with immunosuppressive therapy, a haemodynamic improvement was observed in four patients, including two with compressive lymph nodes. After a median follow-up of 28 months, 39 patients needed PAH-targeted therapy escalation, nine underwent lung transplantation and 42 had died. Survival at 1, 3 and 5 years was 93%, 74% and 55%, respectively.PAH-targeted therapy improved short-term pulmonary haemodynamics in severe S-APH without change in exercise capacity. Immunosuppressive therapy improved haemodynamics in selected patients. Pulmonary hypertension in sarcoidosis remains associated with a poor prognosis.


Male patients presenting with rapidly progressive puberty associated with malignant tumors.
In males, precocious puberty (PP) is defined as the development of secondary sexual characteristics before age 9 years. PP is usually idiopathic; though, organic abnormalities including tumors are more frequently found in male patients with PP. However, advanced puberty in male also can be an important clinical manifestation in tumors. We report 2 cases of rapidly progressive puberty in males, each associated with a germ-cell tumor. First, an 11-year-old boy presented with mild fever and weight loss for 1 month. Physical examination revealed a pubertal stage of G3P3 with 10-mL testes. Investigations revealed advanced bone age (16 years) with elevated basal luteinizing hormone and testosterone levels. An anterior mediastinal tumor was identified by chest radiography and computed tomography, and elevated α-fetoprotein (AFP) and β-human chorionic gonadotropin (β-hCG) levels were noted. Histopathologic analysis confirmed a yolk-sac tumor. Second, a 12-year-old boy presented with diplopia, polydipsia, and polyuria for 4 months. Physical examination revealed a pubertal stage of G3P3 with 8-mL testes. Bone age was advanced (16 years) and laboratory tests indicated panhypopituitarism with elevated testosterone level. A mixed germ-cell tumor was diagnosed with elevated AFP and β-hCG levels. Of course, these patients also have other symptoms of suspecting tumors, however, rapidly progressive puberty can be the more earlier screening sign of tumors. Therefore, in male patients with accelerated or advanced puberty, malignancy should be considered, with evaluation of tumor markers. In addition, advanced puberty in male should be recognized more widely as a unique sign of neoplasm.


Downregulation of Mcl-1 synergizes the apoptotic response to combined treatment with cisplatin and a novel fiber chimeric oncolytic adenovirus.
The aim of this study was to examine the effects of SG511, a novel fiber chimeric oncolytic adenovirus with E1B 55-kDa deleted, combined with cisplatin on cancer cells and to identify their underlying mechanisms. The combined effect of SG511 and cisplatin on HeLa and HT-29 cells was assessed by a crystal violet assay and an MTT assay, followed by combination index analysis. Cell apoptosis was evaluated by DAPI staining and visualized by fluorescein-mediated signal detection. Mitochondrial membrane potential was detected by flow cytometric analysis of Rhodamine 123 accumulation. The activation of the caspase pathway and the expression of Bcl-2 family proteins were examined by western blotting. Results show that SG511 vector infected various human cancer cell lines and induced growth inhibition effectively. Of note, SG511 synergistically enhanced the anti-proliferative activity of cisplatin, a DNA-damaging agent, against HeLa and HT-29 cells in vitro, concomitantly with increased apoptosis and activation of the mitochondrial pathway. Furthermore, treatment with SG511 alone or in combination with cisplatin resulted in reduced expression the anti-apoptotic Bcl-2 family member Mcl-1 in HeLa and HT-29 cells. Importantly, this combination did not increase the growth inhibitory effects of cisplatin on human normal liver cells. Collectively, SG511, a novel fiber chimeric oncolytic adenovirus, sensitizes cancer cells to apoptosis by reducing anti-apoptotic Mcl-1 protein levels.


Integrated analysis of senescence-associated genes in pancreatic ductal adenocarcinoma.
Background: Cellular senescence plays a critical role in the occurrence and development, and immune modulation of cancer. This research primarily investigated the role of senescence-associated genes (SAGs) in the survival and tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC). Methods: From the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) database, the gene expression profiles and clinical data of PDAC samples were downloaded. SAGs in the TCGA cohort were used to build a novel prognostic model and validated in the ICGC cohort. The relationship of signature with the immune landscape, tumor mutational burden (TMB), as well as the sensitivity of different therapies, was explored. Moreover, a nomogram was developed to predict the overall survival of PDAC patients. Results: A prognostic signature was constructed on basis of three SAGs, and patients in the low-risk score group had a longer survival time. The accuracy of the signature to distinguish different score groups was confirmed through principal component analysis (PCA) and the Receiver operator curves curve. The mRNA expression of the three signature genes was also verified in normal pancreatic and PDAC cell lines by RT-qPCR. The signature could independently predict the prognosis of PDAC patients and had broad applicability. Meanwhile, the nomogram predicted that 1- and 3-years survival rates were in good agreement with the observed overall survival rates. Low-risk patients had lower tumor mutational burden, and low-TMB patients had a better prognosis. Low- and high-risk patients exhibit distinct immune cell infiltration and immune checkpoint changes. By further analyzing the risk score, patients in the low-risk group were more responsive to immunotherapy and a variety of commonly used chemotherapeutic drugs. Conclusion: The prognostic signature can well predict the prognosis and assess the possibility of immunotherapy in personalized PDAC treatment.


Analysis of the relationship between workability traits and functional longevity in Canadian dairy breeds.
The aim of this study was to assess the effect of workability traits like milking speed and temperament on functional longevity of Canadian dairy cattle using a Weibull proportional hazards model. First-lactation data consisted of the following: 1,728,289 and 2,426,123 Holstein cows for milking temperament and milking speed, respectively, from 18,401 herds and sired by 8,248 sires; 39,618 and 60,121 Jersey cows for milking temperament and milking speed, respectively, from 1,845 herds and sired by 2,413 sires; and 54,391 and 94,847 Ayrshire cows for milking temperament and milking speed, respectively, from 1,316 herds and sired by 2,779 sires. Functional longevity was defined as the number of days from the first calving to culling, death, or censoring adjusted for production. Milking temperament and milking speed were recorded on a 1- to 5-point scale from very nervous to very calm and from very slow to very fast, respectively. The statistical model included the effects of stage of lactation; season of production; the annual change in herd size; type of milk recording supervision; age at first calving; effects of milk, fat, and protein yields calculated as within herd-year-parity deviations; herd-year-season of calving; sire; and milking temperament or milking speed class. The relative culling rate was calculated for animals in each milking temperament or milking speed class after accounting for the above-mentioned effects. The study showed that there was a statistically significant association between workability traits and functional longevity. Very nervous cows were 26, 23, and 46% more likely to be culled than very calm cows in Holstein, Ayrshire, and Jersey breeds, respectively. Similarly, very slow milkers were 36, 33, and 28% more likely to be culled than average milkers in Holstein, Ayrshire, and Jersey breeds, respectively. Additionally, very fast milkers were 11, 13, and 15% more likely to be culled than average milkers in Holstein, Ayrshire, and Jersey breeds, respectively. Producers might want to avoid consequences associated with the fast milkers such as udder health problems.


Getting ready to leave: transition readiness in adolescent kidney transplant recipients.
To develop a measure of transition readiness and assess factors associated with perceived readiness for transition of healthcare responsibility and transfer among adolescent kidney transplant recipients. The Readiness for Transition Questionnaire (RTQ-teen; RTQ-parent) was created to assess overall transition readiness, adolescent healthcare behavior, and familial involvement in healthcare. Participants were 48 adolescent kidney transplant recipients ages 15-21 years. Thirty-two (66.7%) of the adolescents' caregivers also participated. Adolescents completed the RTQ-teen, as well as self-reported measures of adherence and barriers to adherence. Parents completed the RTQ-parent. The RTQ showed good internal consistency, inter rater reliability, and demonstrated construct validity. Increased adolescent responsibility and decreased parental involvement predicted higher transition readiness. Additionally, greater adolescent adherence factors predicted greater transition readiness. The preliminary psychometrics of the RTQ appear to be supported. Additional research should evaluate healthcare transition programming to identify clinical components related to improved transition readiness, adolescent responsibility, and medical outcomes.


Young Children's Self-Concepts Include Representations of Abstract Traits and the Global Self.
There is debate about the abstractness of young children's self-concepts-specifically, whether they include representations of (a) general traits and abilities and (b) the global self. Four studies (N = 176 children aged 4-7) suggested these representations are indeed part of early self-concepts. Studies 1 and 2 reexamined prior evidence that young children cannot represent traits and abilities. The results suggested that children's seemingly immature judgments in previous studies were due to peculiarities of the task context not the inadequacy of children's self-concepts. Similarly, Studies 3 and 4 revealed that, contrary to claims of immaturity in reasoning about the global self, young children update their global self-evaluations in flexible, context-sensitive ways. This evidence suggests continuity in the structure of self-concepts across childhood.


Applications of Carbon Dots in Optoelectronics.
Carbon dots (CDs) are an attractive class of nanomaterials due to the ease of their synthesis, biocompatibility, and superior optical properties. The electronic structure of CDs and hence their optical transitions can be controlled and tuned over a wide spectral range via the choice of precursors, adjustment of the synthetic conditions, and post-synthetic treatment. We summarize recent progress in the synthesis of CDs emitting in different colors in terms of morphology and optical properties of the resulting nanoparticles, with a focus on the synthetic approaches allowing to shift their emission to longer wavelengths. We further consider formation of CD-based composite materials, and review approaches used to prevent aggregation and self-quenching of their emission. We then provide examples of applications of CDs in optoelectronic devices, such as solar cells and light-emitting diodes (LEDs) with a focus on white LEDs.


A conceptual model of the role of communication in surrogate decision making for hospitalized adults.
To build a conceptual model of the role of communication in decision making, based on literature from medicine, communication studies and medical ethics. We proposed a model and described each construct in detail. We review what is known about interpersonal and patient-physician communication, described literature about surrogate-clinician communication, and discussed implications for our developing model. The communication literature proposes two major elements of interpersonal communication: information processing and relationship building. These elements are composed of constructs such as information disclosure and emotional support that are likely to be relevant to decision making. We propose these elements of communication impact decision making, which in turn affects outcomes for both patients and surrogates. Decision making quality may also mediate the relationship between communication and outcomes. Although many elements of the model have been studied in relation to patient-clinician communication, there is limited data about surrogate decision making. There is evidence of high surrogate distress associated with decision making that may be alleviated by communication-focused interventions. More research is needed to test the relationships proposed in the model. Good communication with surrogates may improve both the quality of medical decisions and outcomes for the patient and surrogate.


An immortalized drug-resistant cell line established from 12-13-day mouse embryos for the propagation of human embryonic stem cells.
Human embryonic stem (ES) cells are usually co-cultivated with supporting cells consisting of short-term cultures of fibroblasts (not an immortalized line) in a medium lacking serum. This method has promoted important progress in the field, but suffers from certain disadvantages. By serial cultivation for 27 consecutive transfers and about 63 cell generations, we have evolved an immortalized line from fibroblastic cells of 12-13-day mouse embryos. This line (MMM) supports the multiplication of H9 cells better than the 3T3 line. It supports the growth of H9 cells as well as do available short-term fibroblast cultures, but maintains more effectively the stem cell character of the H9 cells, judging by their better retention of Oct4. We have made MMM cells resistant to blasticidin and zeocin, the most efficient antibiotics for selection of stable transformants. In the presence of zeocin, the resistant MMM were able to support multiplication and selection of ES cells transfected with an exogenous gene encoding zeocin resistance.


Evaluation of the effect of N-acetyl-glucosamine administration on biomarkers for cartilage metabolism in healthy individuals without symptoms of arthritis: A randomized double-blind placebo-controlled clinical study.
The present study aimed to evaluate the effect of N-acetyl-glucosamine (GlcNAc) on the joint health of healthy individuals without arthritic symptoms. A randomized double-blind placebo-controlled clinical trial was performed to investigate the effect of oral administration of a GlcNAc-containing test supplement (low dose, 500 mg/day and high dose, 1,000 mg/day) on cartilage metabolism in healthy individuals with a mean age of 48.6±1.3 years (range, 23-64 years) by analyzing the ratio of type II collagen degradation to type II collagen synthesis using type II collagen degradation (C2C) and synthesis (PIICP) markers. The results indicated that the changes in C2C/PIICP ratios from the baseline were suppressed in the treated with low and high doses of GlcNAc, compared with the placebo group at week 16 during intervention. To further elucidate the effect of GlcNAc, subjects with impaired cartilage metabolism were evaluated. Notably, the changes in the C2C/PIICP ratios were markedly suppressed in the groups treated with low and high doses of GlcNAc at week 16. Finally, to exclude the effect of heavy body weight on joint loading, subjects weighing <70 kg with impaired cartilage metabolism were analyzed. Notably, the changes in the C2C/PIICP ratios were suppressed in the groups treated with low and high doses of GlcNAc at weeks 12 and 16. No test supplement-related adverse events were observed during or following the intervention. Together, these observations suggest that oral administration of GlcNAc at doses of 500 mg and 1,000 mg/day exhibits a chondroprotective effect on healthy individuals by reducing the C2C/PIICP ratio (relatively decreasing type II collagen degradation and increasing type II collagen synthesis) without any apparent adverse effects.


Socialization of coping with community violence: influences of caregiver coaching, modeling, and family context.
A socialization model of coping with community violence was tested in 101 African American adolescents (55% male, ages 9-13) and their maternal caregivers living in high-violence areas of a mid-sized, southeastern city. Participants completed interviews assessing caregiver coping, family context, and child adjustment. Caregiver-child dyads also discussed a film clip depicting community violence. Parental coaching (caregivers' strategies suggesting how to cope) and child-reported coping were coded from the discussion. Coaching, modeling (caregivers' own coping), and family context each contributed to children's coping with violence. Children's problem-focused coping in response to violence had the strongest associations with changes in their adjustment 6 months later. Implications for interventions with youth and families are discussed.


TARGETING LEUKEMIA STEM CELL RESISTANCE IN CHRONIC MYELOGENOUS LEUKEMIA.
A major limitation of current leukemia treatment is that most patients ultimately relapse. Leukemia cells show heterogeneous potential and response to treatment. We have shown that primitive leukemia stem cells (LSC) in chronic myelogenous leukemia resist elimination by treatment, and persist as a source of relapse. The bone marrow microenvironment (BMM) plays a critical role in of hematopoietic stem cell maintenance and regulation. There is increasing interest in the role of the BMM in promoting LSC maintenance, resistance to therapy, and ultimately disease relapse. Recent studies have shown that leukemia-induced changes in the BMM provide a competitive growth advantage to LSC, and support their preservation after treatment. We are studying mechanisms of niche regulation of LSC to guide development of novel approaches to target LSC and enhance cures.


Effect of dietary calcium and milk consumption on risk of thromboembolic stroke in older middle-aged men. The Honolulu Heart Program.
Evidence suggests that dietary calcium is protective against hypertension. This report examines whether the effect has an influence on thromboembolic stroke. Since 1965, the Honolulu Heart Program has followed a cohort of men in a study of cardiovascular disease. This report examines the effect of baseline dietary calcium and milk intake on stroke risk in 22 years of follow-up in 3150 older middle-aged men (55 to 68 years). Men who were nondrinkers of milk experienced stroke at twice the rate (P < .05) of men who consumed 16 oz/d or more (7.9 versus 3.7 per 100, respectively). While the rate of stroke decreased with increasing milk intake (P < .05), the decline in stroke risk with increased consumption was modest for those who consumed under 16 oz/d. Intake of dietary calcium was also associated with a reduced risk of stroke (P < .01), although its association was confounded with milk consumption. Calcium intake from nondairy sources was not related to stroke, suggesting that other constituents or covariates related to milk consumption may be important. We conclude that an association between milk consumption and a reduced risk of stroke in older middle-aged men cannot be explained by intake of dietary calcium. Since milk is often part of a diverse pattern of dietary intake, it is difficult to determine whether milk consumption has a direct role in reducing the risk of stroke. Data suggest that consumption of milk in older middle age is not harmful, and when combined with a balanced diet, weight control, and physical activity, reductions in the risk of stroke may occur.


Regional differences in interstitial glycerol concentration in subcutaneous adipose tissue of women.
The aims of this study were to 1) compare two methods of determining interstitial glycerol concentration in subcutaneous adipose tissue (AT) and 2) determine whether there are regional differences in interstitial glycerol concentration in subcutaneous AT of nonobese, premenopausal women. Microdialysis probes were inserted under local anesthesia into the abdominal (2 probes) and femoral (1 probe) subcutaneous AT in each subject (n = 5) and perfused with a Ringer solution containing 2.5 mM glucose and glycerol in concentrations ranging from 0 to 900 microM. Microdialysis probe relative recoveries and interstitial glycerol concentrations were determined by the no-net-flux method (NNF) and the internal reference method (IR) with the use of [13C]glycerol. Microdialysis probe relative recoveries were 57.4 +/- 3.6% by NNF and 61.2 +/- 10.1% by IR in femoral AT [P = not significant (NS)] and were 55.2 +/- 6.0% by NNF and 66.6 +/- 4.2% by IR in abdominal AT (P = NS). The calculated interstitial glycerol concentrations determined by NNF and IR were 236.4 +/- 42.7 and 241.1 +/- 39.6 microM (P = NS) in femoral AT and 151.4 +/- 29.7 and 129.4 +/- 18.7 microM in abdominal AT (NNF vs. IR, P = NS; femoral vs. abdominal, P < 0.05). It can be concluded that the interstitial glycerol concentration in the femoral AT of nonobese, premenopausal females is approximately 240 microM and is higher than in abdominal AT (140 microM). Furthermore, the use of a stable isotope of glycerol as an internal reference is suitable for determining interstitial glycerol concentrations in subcutaneous adipose tissue in humans at rest.


Combining multiscale niche modeling, landscape connectivity, and gap analysis to prioritize habitats for conservation of striped hyaena (Hyaena hyaena).
Identifying spatial gaps in conservation networks requires information on species-environment relationships, and prioritization of habitats and corridors. We combined multi-extent niche modeling, landscape connectivity, and gap analysis to investigate scale-dependent environmental relationships, and identify core habitats and corridors for a little-known carnivore in Iran, the striped hyaena (Hyaena hyaena). This species is threatened in Iran by road vehicle collisions and direct killing. Therefore, understanding the factors that affect its habitat suitability, spatial pattern of distribution, and connectivity among them are prerequisite steps to delineate strategies aiming at human-striped hyaena co-existence. The results showed that the highest predictive power and extent of habitats was obtained at the extent sizes of 4 and 2 km, respectively. Also, connectivity analysis revealed that the extent and number of core habitats and corridors changed with increasing dispersal distance, and approximately 21% of the landscape was found to support corridors. The results of gap analysis showed that 15-17% of the core habitats overlapped with conservation areas. Given the body size of the species, its mobility, and lack of significant habitat specialization we conclude that this species would be more strongly influenced by changes in habitat amount rather than landscape configuration. Our approach showed that the scale of variables and dispersal ability must be accounted for in conservation efforts to prioritize habitats and corridors, and designing conservation areas. Our results could facilitate the conservation of striped hyaena through the identification and prioritization of habitats, establishment of conservation areas, and mitigating conflicts in corridors.


Inter-joint coordination in producing kicking velocity of taekwondo kicks.
The purpose of this study was to investigate joint kinematics of the kicking leg in Taekwondo and to examine the role of inter-joint coordination of the leg in producing the kicking velocity. A new inter-joint coordination index that encompasses three- dimensional hip and knee motions, was defined and applied to the joint kinematic results. Twelve elite Taekwondo athletes participated in this study and performed the back kick, thrashing kick, turning-back kick and roundhouse kick. Our results indicate that the back kick utilized a combination of hip and knee extension to produce the kicking velocity, and was characterized by a pushlike movement. The thrashing kick and turning-back kick utilized a greater degree of hip abduction than the roundhouse kick and back kick, and included complicated knee motions. The new index successfully categorized the thrashing kick and turning-back kick into a push-throw continuum, indicating a change from negative index (opposite direction) to positive index (same direction) of hip and knee motions at the end of the movement. This strategy of push-throw continuum increases the kicking velocity at the moment of impact by applying a throwlike movement pattern. Key pointsA variety of Taekwondo kicks have unique inter-joint coordination of the kicking leg.The back kick used a combination of hip and knee extension to produce the kicking velocity, and was characterized by a pushlike movement.The new index explained well the inter-joint coordination of three DOF joint motions of two joints in producing kicking velocity (positive values for throwlike movements and negative values for pushlike movements).The index successfully categorized the thrashing kick and turning-back kick into a push-throw continuum.


On the evolution of calculation abilities.
Some numerical knowledge, such as the immediate recognition of small quantities, is observed in animals. The development of arithmetical abilities found in man's evolution as well as in child's development represents a long process following different stages. Arithmetical abilities are relatively recent in human history and are clearly related with counting, i.e., saying aloud a series of number words that correspond to a collection of objects. Counting probably began with finger sequencing, and that may explain the 10-base found in most numerical systems. From a neuropsychological perspective, there is a strong relationship between numerical knowledge and finger recognition, and both are impaired in cases of left posterior parietal damage (angular or Gerstmann's syndrome). Writing numbers appeared earlier in human history than written language. Positional digit value is clearly evident in Babylonians, and around 1,000 BC the zero was introduced. Contemporary neuroimaging techniques, specifically fMRI, have demonstrated that the left parietal lobe, particularly the intraparietal sulcus, is systematically activated during a diversity of tasks; other areas, particularly the frontal lobe, are also involved in processing numerical information and solving arithmetical problems. It can be conjectured that numerical abilities continue evolving due to advances in mathematical knowledge and the introduction of new technologies.


[Analysis of association of human endothelial nitric oxide synthase gene polymorphism with myocardial infraction].
The aim of this study was an assessment of association of human endothelial nitric oxide synthase gene Ban II polymorphism with the myocardial infarction in 178 patients and 136 healthy individuals. These polymorphism were studied using polymerase chain reaction (PCR) and Ban II restriction fragment length polymorphism (RFLP). It was found that TT and GT genotypes and allele T were associated with myocardial infarction patients under 50 years. We did not observed this association for older myocardial infarction patients. Allele T might be used as a genetic marker in the prophylaxis of myocardial infarction among people under 50 years.


Emissions of chromium, copper, arsenic, and PCDDs/Fs from open burning of CCA-treated wood.
Aged and weathered chromated copper arsenate (CCA) treated wood was burned in an open burn research facility to characterize the air emissions and residual ash. The objectives were to simulate, to the extent possible, the combustion of such waste wood as might occur in an open field or someone's backyard; to characterize the composition and particle size distribution (PSD) of the emitted fly ash; to determine the partitioning of arsenic, chromium, and copper between the fly ash and residual ash; and to examine the speciation of the CCA elements. This work reports preliminary air emission concentrations and estimated emission factors for total particulate matter, arsenic (As), chromium (Cr), copper (Cu), and polychlorinated dibenzodioxins/dibenzofurans (PCDD/F) totals and toxic equivalents (TEQs). The partitioning of As, Cr, and Cu between the emitted fly ash and residual ash is examined and thermochemical predictions from the literature are used to explain the observed behavior. Results indicate a unimodal fly ash PSD between 0.1 and 1.0 microm diameter. In addition to a large carbonaceous component, between 11 and 14% of the As present in the burned CCA treated wood was emitted with the air emissions, with the remainder present in the residual ash. In contrast, less than 1% of both the Cr and Cu present in the wood was emitted with the air emissions. PCDD/F levels were unremarkable, averaging 1.7 ng TEQ/kg of treated wood burned, a value typical for wood combustion. Scanning electron microscopy (SEM) was unable to resolve inorganic particles consisting of Cu, Cr, or As in the wood samples, but X-ray absorption fine structure (XAFS) spectroscopy confirmed that the oxidation states of the CCA elements in the wood were Cu2+, Cr3+, and As5+. SEM examination of the fly ash samples revealed some inorganic microcrystals within the mostly carbonaceous fly ash, while XAFS spectroscopy of the same samples showed that the oxidation states after combustion were mixed Cu+ and Cu2+, Cr3+, and mixed As3+ and As5+. Estimates of the ratios of the mixed oxidation states based on the XAFS spectra were As3+/(total As) = 0.8-0.9 and Cu+/(total Cu) = 0.65-0.7. The Cu and Cr present in the fly ash were determined to coexist predominantly in the two oxide phases CuCrO2 and CuCr2O4. These results indicate that the open burning of CCA-treated wood can lead to significant air emissions of the more toxic trivalent form of As in particle sizes that are most respirable.


Long-term Efficacy of Dacryoendoscopy-guided Recanalization and Silicone Tube Intubation.
To investigate the long-term efficacy of dacryoendoscopy-guided recanalization and silicone tube intubation in patients with obstruction in the lacrimal drainage system and to identify factors related to surgical outcome. We retrospectively reviewed the medical records of patients with primary nasolacrimal duct obstruction and canalicular obstruction who underwent dacryoendoscopy-guided recanalization and silicone tube intubation between August 2014 and March 2016. Factors related to surgical outcome were examined and compared between the success group (eyes with complete response and partial response) and the failure group. Kaplan-Meier survival analysis and multivariable logistic regression analysis were used to analyze the success rate according to the factors found to have statistical significance. The study included 74 eyes of 51 patients. The mean age of the patients was 60.3 ± 10.0 years (range, 34-80 years). The success group consisted of 66 eyes (89.2%) (complete response, 56 eyes, 75.7%; partial response, 10 eyes, 13.5%) and the failure group consisted of eight eyes (10.8%). The median follow-up period was 58 months (range, 6.5-72 months), and the overall success rate was 89.2%. Compared to the eyes with preoperative lacrimal irrigation test of partial passage, the eyes with no passage were associated with a lower success rate (95.9% vs. 76.0%, p = 0.01). Postoperative inflammation was also associated with a lower success rate (96.6% vs. 60.0%, p < 0.001). Dacryoendoscopy-guided recanalization and silicone tube intubation is effective and can be considered a first choice of treatment for eyes which show partial passage in the lacrimal irrigation test. The management of postoperative inflammation is essential to ensure surgical success.


Astemizole--a new, non-sedating antihistamine for hayfever.
Astemizole, a new histamine H1 receptor blocker, was compared with placebo in an eight week, double-blind trial in the treatment of seasonal allergic rhinitis. Sixty-five patients of either sex were randomized to either astemizole (32 patients: 10 mg t.i.d. on day 1, 10 mg b.i.d. on day 2, 10 mg o.d. for the remainder of the study) or placebo (33 patients). Patients were seen bi-weekly and maintained a daily diary record of symptoms throughout the study. Significantly more patients in the placebo group (12) compared to the astemizole group (2) dropped out of the study due to treatment failure (p less than 0.05). Astemizole significantly reduced the frequency and severity of allergic symptoms. In subjective evaluations of each treatment by both the investigator and the patients, astemizole was judged good to excellent by 68% compared to 30% for placebo (p less than 0.05). One patient in each group experienced drowsiness. The only significant side effect of astemizole was weight gain (20 patients compared to 1 in the placebo group), although only one patient discontinued astemizole for this reason.


Regulation of photosynthesis in nitrogen deficient wheat seedlings.
Nitrogen effects on the regulation of photosynthesis in wheat (Triticum aestivum L., cv Remia) seedlings were examined. Ribulose 1,5-bisphosphate carboxylase/oxygenase was rapidly extracted and tested for initial activity and for activity after incubation in presence of CO(2) and Mg(2+). Freeze clamped leaf segments were extracted for determinations of foliar steady state levels of ribulose 1,5-bisphosphate, triose phosphate, 3-phosphoglycerate, ATP, and ADP. Nitrogen deficient leaves showed increased ATP/ADP and triose phosphate/3-phosphoglycerate ratios suggesting increased assimilatory power. Ribulose 1,5-bisphosphate levels were decreased due to reduced pentose phosphate reductive cycle activity. Nevertheless, photosynthesis appeared to be limited by ribulose 1,5-bisphosphate carboxylase/oxygenase, independent of nitrogen nutrition. Its degree of activation was increased in nitrogen deficient plants and provided for maximum photosynthesis at decreased enzyme protein levels. It is suggested that ribulose 1,5-bisphosphate carboxylase/oxygenase activity is regulated according to the amount of assimilatory power.


Colon stroma mediates an inflammation-driven fibroblastic response controlling matrix remodeling and healing.
Chronic inflammation is often associated with the development of tissue fibrosis, but how mesenchymal cell responses dictate pathological fibrosis versus resolution and healing remains unclear. Defining stromal heterogeneity and identifying molecular circuits driving extracellular matrix deposition and remodeling stands to illuminate the relationship between inflammation, fibrosis, and healing. We performed single-cell RNA-sequencing of colon-derived stromal cells and identified distinct classes of fibroblasts with gene signatures that are differentially regulated by chronic inflammation, including IL-11-producing inflammatory fibroblasts. We further identify a transcriptional program associated with trans-differentiation of mucosa-associated fibroblasts and define a functional gene signature associated with matrix deposition and remodeling in the inflamed colon. Our analysis supports a critical role for the metalloprotease Adamdec1 at the interface between tissue remodeling and healing during colitis, demonstrating its requirement for colon epithelial integrity. These findings provide mechanistic insight into how inflammation perturbs stromal cell behaviors to drive fibroblastic responses controlling mucosal matrix remodeling and healing.


Small things from small places.
The federal government has recently acknowledged that more highly skilled GPs would reduce the health bill by decreasing the level of specialist referral. Practical procedures should form part of every day practice, however, gaining skills and the practical tips that make procedures easier can be difficult. This article describes the skills required for the removal of foreign bodies from children. The retrieval of foreign bodies from children requires patience, preparation and confidence. Plan your approach carefully and take your time as you may only have one chance at grasping the object before the child becomes uncooperative.


Leukocyte rolling: a prominent feature of venules in intact skin of anesthetized hairless mice.
Leukocyte (white blood cell; WBC) rolling in postcapillary venules is a frequently reported phenomenon in the microvasculature of experimental preparations. In most reports where this phenomenon has been systematically studied the confounding effects of various procedures associated with tissue preparation have been present. Thus there is sparse information on the extent of WBC rolling under fairly normal conditions. Here observations and features of this phenomenon in venules in the intact skin microvasculature of the homozygous hairless mouse ear are described. One venule in each of 10 mice was observed and continuously video recorded for 90 min. The parameters determined (mean +/- SD) were diameter, 15.9 +/- 3.1 microns; red blood cell velocity, 359 +/- 227 micron/s; flux of rolling WBCs, 3.2 +/- 2.6/min; velocity of rolling WBCs, 9.6 +/- 1.1 micron/s; systemic WBC count (CWBC), 3,220 +/- 1,072/microliters; and total WBC flux, estimated as the product of CWBC and calculated venule blood flow, 8.5 +/- 3.0/min. Overall, 44.8 +/- 13.8% of the total WBC flux exhibited rolling with a velocity that was 3.6 +/- 2.9% of the red blood cell velocity. During the total 15-h combined observation time, no WBCs were seen to be adherent. These findings establish that in small venules of normal skin, WBC rolling is common, since on the average nearly one of two WBCs delivered to the venule exhibits rolling. Furthermore, because the translational rolling speed is very low, they contribute to the marginated pool, which, according to the present data, might be better termed the "rolling" pool.


Autonomic dysfunction in multiple sclerosis.
Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system. Autonomic dysfunction in MS patients may cause significant morbidity. The aim of this controlled cross sectional study was to investigate the prevalence, pattern and severity of autonomic dysfunction in Iraqi MS patients and to correlate them with patient`s age, disease course, duration and severity. Fifty-five patients with clinically definite MS according to Poser`s criteria attending Baghdad MS clinic at Baghdad Teaching Hospital were studied between July 2000 and August 2001. Each patient was assessed according to a detailed protocol paper. Expanded disability status scale was used to assess the severity of the disease. The severity of autonomic symptoms was classified according to autonomic nervous system disability scale (ANSDS). Five standardized autonomic cardiovascular (Ewing) tests were performed for every patient which included: heart rate responses to deep breathing, Valsalva maneuver and standing, and blood pressure responses to standing and sustained hand grip. Forty matched healthy subjects were studied as a control group who were assessed with the same protocol paper, ANSDS and Ewing tests. Autonomic symptoms were significantly more prevalent in MS patients than in the controls. Cardiovascular, urinary and gastrointestinal symptoms were highly prevalent. The severity of the different autonomic symptoms as assessed by ANSDS, were higher in the patients than the controls. All 5 Ewing tests in the patients showed highly significant abnormal results as compared to those of the control. Definite parasympathetic derangement was found in 45.5% of the patients while combined sympathetic and parasympathetic derangements were found in 34.5% of the patients. There were significant correlations between the finding of definite autonomic dysfunctions and the age of the patients at the time of assessment and the duration of the disease. Autonomic dysfunctions as assessed by a formal interview, ANSDS and by Ewing tests were common in Iraqi MS patients. Careful attention to autonomic disturbances should be considered in the routine evaluation of MS patients which might help in improving their quality of life.


Predictors of clinical outcome in MCI.
It remains an open issue in old age psychiatry whether or not persons with mild cognitive impairment (MCI) are at increased risk for developing a dementia syndrome, and if so, to what extent and under what circumstances. The purpose of the present study was to examine a population of older patients 5 years after a diagnosis of MCI. From an initial group of 158 older patients from our clinic who had been tested neuropsychologically and diagnosed with MCI between 1994 and 1996, and who meet the inclusion and exclusion criteria, 52 were available for follow-up five years later. Of the 52 subjects we successfully recruited, 12 had developed dementia within the five-year follow-up period, including 8 with DAT, 3 with mixed dementia, and 1 with vascular dementia. The rate of cognitive decline is a good predictor of later dementia. Patients with MCI are at some risk of developing a dementia syndrome, most commonly DAT. Evaluating both the cognitive and neuropsychological functioning of individuals affected with MCI, as well as their global functioning, can be useful in terms of predicting the clinical outcome in these patients.


Major histocompatibility complex antigens, maternal and paternal immune responses, and chronic habitual abortions in humans.
Women with recurrent consecutive spontaneous abortions of unknown etiology compared with those with recurrent spontaneous abortions of known etiology had a significantly increased frequency of sharing HLA antigens at the A, B, and D/DR loci with their spouses. This major histocompatibility complex (MHC) homozygosity was generally associated with female (responder) and male (stimulator) hyporeactivity in mixed lymphocyte culture reactions. The results indicate that MHC homozygosity between spouses is associated with postfertilization pregnancy wastage in humans.


Disease-specific changes in equine ground reaction force data documented by use of principal component analysis.
To assess the force plate as a diagnostic aid in equine locomotor abnormalities, particularly for abnormalities such as navicular disease that do not have specific diagnostic criteria. 17 Thoroughbreds without observable locomotor abnormalities (group A), 6 Thoroughbreds with superficial digital flexor tendon injury (group B), and 8 Thoroughbreds with navicular disease (group C). Using a force plate, ground reaction force patterns were recorded at the trot. Peak limb vertical force and force/time curve parameters were derived from 4 identifiable points at the beginning and end of vertical and craniocaudal horizontal plots. Principal component analysis (PCA) of group-A data was undertaken on beginning and end of stride data, and the first 2 components were represented graphically. The PCA rotation matrices were applied to equivalent data for horses of groups B and C. Asymmetry of peak vertical force (PVF) could not be differentiated among groups A, B, and C. Values for group-B horses, however, were significantly outside mean group-A values on the PCA plot for beginning of stride phase variables. Group-B data were within the group-A range for end of stride phase variables. Values for group-C horses were significantly outside the group-A range for beginning of stride phase variables and were outside mean group-A values for end of stride phase variables. PCA of force/time data provides a sensitive method to evaluate the force/time curve associated with 2 specific injury/disease processes. Horses alter weight-bearing in biomechanically distinct ways, thus creating potential for the force plate to become an important diagnostic and prognostic tool.


Probiotics against neoplastic transformation of gastric mucosa: effects on cell proliferation and polyamine metabolism.
Gastric cancer is still the second leading cause of cancer death worldwide, accounting for about 10% of newly diagnosed neoplasms. In the last decades, an emerging role has been attributed to the relations between the intestinal microbiota and the onset of both gastrointestinal and non-gastrointestinal neoplasms. Thus, exogenous microbial administration of peculiar bacterial strains (probiotics) has been suggested as having a profound influence on multiple processes associated with a change in cancer risk. The internationally accepted definition of probiotics is live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. The possible effects on the gastrointestinal tract following probiotic administration have been investigated in vitro and in animal models, as well as in healthy volunteers and in patients suffering from different human gastrointestinal diseases. Although several evidences are available on the use of probiotics against the carcinogen Helicobacter pylori, little is still known about the potential cross-interactions among probiotics, the composition and quality of intestinal flora and the neoplastic transformation of gastric mucosa. In this connection, a significant role in cell proliferation is played by polyamines (putrescine, spermidine, and spermine). These small amines are required in both pre-neoplastic and neoplastic tissue to sustain the cell growth and the evidences here provided suggest that probiotics may act as antineoplastic agents in the stomach by affecting also the polyamine content and functions. This review will summarize data on the most widely recognized effects of probiotics against neoplastic transformation of gastric mucosa and in particular on their ability in modulating cell proliferation, paying attention to the polyamine metabolism.


Thermodynamic and kinetic characterization of host-guest association between bolaform surfactants and alpha- and beta-cyclodextrins.
The thermodynamics and kinetics of formation of host-guest complexes between a series of bolaform surfactants of type C n Me 6 (2+)2Br (-) ( n = 8, 10, and 12) and alpha-cyclodextrin and beta-cyclodextrin were studied with the aid of isothermal titration calorimetry (ITC) at 298.15 and 308.20 K. The association constant, the enthalpy, and the entropy of formation were determined. The obtained thermodynamic parameters are compared with parameters for the micelle formation of a related cationic surfactant. The difference in magnitude and sign between the parameters of the alpha-CD and beta-CD complexes is discussed based on the curvature of the cavity of the CD. We suggest that the water molecules inside the alpha-CD cavity are not able to maintain their hydrogen bond network. Upon complex formation these water molecules are expelled and reform their hydrogen bond network. The situation is different in the larger beta-CD cavity where water has the possibility of a more extensive hydrogen bonding. The kinetics for alpha-CD is slow, associated with high activation energies for both association and dissociation of the complex. The rates increased with a decrease in the number of methylene groups in the hydrocarbon chain. The slow kinetics is argued to originate from the fact that the charged headgroup needs to be pushed through a relative nonpolar cavity. A comparison is made with the Born energy.


Using Virtual Reality and Videogames for Traumatic Brain Injury Rehabilitation: A Structured Literature Review.
This article reviews the available literature about the use of novel methods of rehabilitation using virtual reality interventions for people living with posttraumatic brain injuries. The MEDLINE, EMBASE, SCOPUS, and Cochrane Library databases were searched using the terms "virtual reality" OR "video games" AND "traumatic brain injury." Included studies investigated therapeutic use of virtual reality in adults with a brain trauma resulting from acquired closed head injury, reported outcomes that included measures of motor or cognitive functionality, and were published in a peer-reviewed journal written in English. Eighteen articles fulfilled inclusion criteria. Eight were case studies, five studies had a quasi-experimental design with a pre-post comparison, and five were pilot randomized control trials or comparative studies. The virtual reality systems used were commercial or custom designed for the study and ranged from expensive, fully immersive systems to cheap online games or videogames. In before-after comparisons, improvements in balance were seen in four case studies and two small randomized control trials. Between-group comparisons in these randomized control trials showed no difference between virtual reality and traditional therapy. Post-training improvements were also seen for upper extremity functions (five small studies) and for various cognitive function measures (four case studies and one pilot randomized control trial). Attitudes of participants toward virtual reality interventions was more positive than for traditional therapy (three studies). The evidence that the use of virtual reality in rehabilitation of traumatic brain injury improves motor and cognitive functionality is currently very limited. However, this approach has the potential to provide alternative, possibly more affordable and available rehabilitation therapy for traumatic brain injury in settings where access to therapy is limited by geographical or financial constraints.


Stroke and migraine is there a possible comorbidity?
The association between migraine and stroke is still a dilemma for neurologists. Migraine is associated with an increased stroke risk and it is considered an independent risk factor for ischaemic stroke in a particular subgroup of patients. The pathogenesis is still unknown even if several studies report some common biochemical mechanisms between these two diseases. A classification of migraine-related stroke that encompasses the full spectrum of the possible relationship between migraine and stroke includes three main entities: coexisting stroke and migraine, stroke with clinical features of migraine, and migraine-induced stroke. The concept of migraine-induced stroke is well represented by migrainous infarction and it is described in the revised classification of the International Headache Society (IHS), representing the strongest demonstration of the relationship between ischaemic stroke and migraine. A very interesting common condition in stroke and migraine is patent foramen ovale (PFO) which could play a pathogenetic role in both disorders. The neuroradiological evidence of subclinical lesions most typical in the white matter and in the posterior artery territories in patients with migraine, opens a new field of research. In conclusion the association between migraine and stroke remains an open question. Solving the above mentioned issues is fundamental to understand the epidemiologic, pathogenetic and clinical aspects of migraine-related stroke.


High-speed non-invasive measurement of tibial rotation during the impact phase of running.
Several injuries to the lower extremity in runners have been linked to excessive rates of internal rotation of the tibia just after ground impact. This study presents an improved method of capturing internal/external tibial rotation, and investigates whether estimates of rates of internal tibial rotation during the first 50 ms of contact during running are influenced by the sampling rate and processing of tibial displacement data. A lightweight plate was moulded to the shape of each subject's right anterior-medial tibia. Nine male subjects ran barefoot (3.35 m.s(-1)) and the landing kinematics of the right leg were recorded at 1000 Hz. The group mean value for the total range of internal rotation of the tibia for the whole stance phase was consistent with the literature (15.4 degrees ), but peak angular velocities (8.3 rad.s(-1)) were substantially higher than previously reported. The cut-off frequency of the low-pass filter influenced the peak angular velocity values obtained with the largest changes occurring between 15 and 40 Hz. Typically, researchers using lower sample rates have to filter around 10 Hz and consequently are likely to underestimate peak angular velocities. These findings have implications for obtaining a sound quantitative foundation for transient tibial motion before furthering our understanding of injury mechanisms.


[Anti-HLA antibodies after bone graft and their impact on kidney transplant programs].
Immunological evaluation by panel reactive antibody (PRA) and determination of anti-HLA specificity is an important phase in the assessment of patients awaiting kidney transplant. The main causes of immunization are previous solid organ transplants, blood transfusions, and pregnancy; immunogenicity can also be triggered by vascularized tissue grafts. Immune induction by cryopreserved bone allografts is not yet fully understood. We report the case of a 19-year-old patient with osteosarcoma who underwent resection of the left proximal tibia with reconstruction using human bone in 1997 (donor typing: A3, A29 (19) - B44 (12), Bw4 - DR13 (6), DR7, DR52, DR53). The patient was subsequently placed on the waiting list for a cadaver donor kidney transplant because of chronic kidney failure caused by cisplatin toxicity. Pretransplant immunological screening using the CDC (complement dependent cytotoxicity) technique revealed a PRA of 63% and anti-A3 and anti-A68 antibodies. The presence of IgG antibody specificity against class I and class II donor antigens (specifically anti-A3, B44, DR7 antibodies) was highlighted using flow cytometry (Tepnel-Luminex). Further immunological studies using single HLA specificity analysis (LSA Class I - II - Tepnel-Luminex) detected direct antibodies against all donor antigen specificities. This is the first reported case of immune induction after a bone graft in a kidney transplant candidate. It underlines the importance of the availability of HLA typing data of all human allograft donors.


Microstructure-controlled aerosol-gel synthesis of ZnO quantum dots dispersed in SiO2 nanospheres.
ZnO quantum dots dispersed in a silica matrix were synthesized from a TEOS:Zn(NO(3))(2) solution by a one-step aerosol-gel method. It was demonstrated that the molar concentration ratio of Zn to Si (Zn/Si) in the aqueous solution was an efficient parameter with which to control the size, the degree of agglomeration, and the microstructure of ZnO quantum dots (QDs) in the SiO(2) matrix. When Zn/Si ≤ 0.5, unaggregated quantum dots as small as 2 nm were distributed preferentially inside SiO(2) spheres. When Zn/Si ≥ 1.0, however, ZnO QDs of ∼7 nm were agglomerated and reached the SiO(2) surface. When decreasing the ratio of the Zn/Si, a blue shift in the band gap of ZnO was observed from the UV/Visible absorption spectra, representing the quantum size effect. The photoluminescence emission spectra at room temperature denoted two wide peaks of deep-level defect-related emissions at 2.2-2.8 eV. When decreasing Zn/Si, the first peak at ∼2.3 eV was blue-shifted in keeping with the decrease in the size of the QDs. Interestingly, the second visible peak at 2.8 eV disappeared in the surface-exposed ZnO QDs when Zn/Si ≥ 1.0.


Losartan inhibits STAT1 activation and protects human glomerular mesangial cells from angiotensin II induced premature senescence.
Human glomerular mesangial cells (HMCs) have a finite lifespan, and eventually enter irreversible growth arrest known as cellular senescence, which is thought to contribute to kidney ageing and age-related kidney disorders, such as chronic kidney disease. The signal transducer and activator of transcription 1 (STAT1) is a latent transcription factor involved in a variety of signal transduction pathways, including cell proliferation, apoptosis, and differentiation, but whether it could regulate HMC senescence still remains to be explored. In our study, the induction of angiotensin II (Ang II)-accelerated HMC senescence, as judged by increased senescence-associated β-galactosidase (SA-β-gal)-positive staining cells, morphological changes, and G0/G1 cell cycle arrest. STAT1 activity and the expression of p53 and p21(Cip1) were increased after Ang II treatment. STAT1 knockdown using RNA interference significantly inhibited the progression of HMC senescence and decreased the elevated expression of p53 and p21(Cip1). Pretreating HMCs with Ang II receptor blocker losartan also inhibited the progression of HMC senescence and STAT1 activity. Our results indicate that STAT1 is implicated in the mediation of Ang II-induced HMC senescence through p53/ p21(Cip1) pathway, and that losartan could attenuate HMC senescence by regulating STAT1. The antioxidant N-acetyl-L-cysteine reduced ROS production and STAT1 activity induced by Ang II, indicating that Ang II uses ROS as a second messenger to regulate STAT1 activity.


Loss of recovery capacity of plasmalemma k influx after cutting in chlorsulfuron pretreated maize roots.
Active K(+) influx was studied in apical segments from maize (Zea mays L., hybrid lines XL 342) and pea (Pisum sativum L. var Laxton superbo) seedlings pretreated with the herbicide chlorsulfuron (2-chloro-N-[(4-methoxy-6-methyl-1,3,5-triazin-2-yl) aminocarbonyl]benzenesulfonamide).Even though both plants were sensitive to chlorsulfuron, a strong inhibition of K(+) uptake only was evident in maize root segments after 12 hours pretreatment with 10 micromolar chlorsulfuron. The inhibition was revealed only when maize root segments were washed for 2 hours before uptake measurements. This was done in order to recover K(+) influx inhibited by cutting injury. Consequently, we demonstrated that roots from chlorsulfuron pretreated maize seedlings lost the capacity to recover from cutting injury by washing. By contrast, K(+) influx in pea roots was not inhibited by chlorsulfuron because pea roots notoriously do not exhibit the ;washing' effect.


High frequency of brain metastases after adjuvant therapy for high-risk melanoma.
The incidence of CNS progression in patients with high-risk regional melanoma (stages IIIAN2a-IIIC) is not well characterized. Data from the S0008 trial provided an opportunity to examine the role of CNS progression in treatment failure and survival. All patients were surgically staged. Following wide excision and full regional lymphadenectomy, patients were randomized to receive adjuvant biochemotherapy (BCT) or high-dose interferon alfa-2B (HDI). CNS progression was retrospectively identified from data forms. Survival was measured from date of CNS progression. A total of 402 eligible patients were included in the analysis (BCT: 199, HDI: 203). Median follow-up (if alive) was over 7 years (range: 1 month to 11 years). The site of initial progression was identifiable in 80% of relapsing patients. CNS progression was a component of systemic melanoma relapse in 59/402 patients (15% overall). In 34/402 patients (9%) CNS progression represented the initial site of treatment failure. CNS progression was a component of initial progression in 27% of all patients whose melanoma relapsed (59/221). The risk of CNS progression was highest within 3 years of randomization. The difference in CNS progression rates between treatment arms was not significant (BCT = 25, HDI = 34, P = 0.24). Lymph node macrometastases strongly associated with CNS progression (P = 0.001), while ulceration and head and neck primaries were not significant predictors. This retrospective analysis of the S0008 trial identified a high brain metastasis rate (15%) in regionally advanced melanoma patients. Further studies are needed to establish whether screening plus earlier treatment would improve survival following CNS progression.


Influence of chronotype on responses to a standardized, self-paced walking task in the morning vs afternoon: a pilot study.
The response to sub-maximal physical activity performed in the morning and late afternoon by individuals with different chronotypes was investigated. 22 participants filled out the Morningness-Eveningness Questionnaire and underwent a self-paced walking task that consisted of walking from the top to the bottom of a hill and back three times (1,836 meters, with a slope of 14.16%). The task was repeated twice: late afternoon (16:30) and early morning (08:30). Walking speed (time for completion in seconds), heart rate, and perceived exertion were measured during each task, with overall results given as a general descriptive analysis. Preliminary findings suggest that chronotype is likely to influence the responses to exercise, mostly with evening-types seeming at a disadvantage when performing a physical task in the morning. Individuals can be classified by circadian typology or chronotype, which is the propensity to be a morning-type, evening-type, or neither-type. The circadian typology, commonly referred to as being a morning person or an evening person or somewhere in between, is involved not only in the expression of physiological rhythms, but also in habits and lifestyles, such as sleeping patterns (Park, Matsumoto, Seo, & Shinkoda, 1999) that emerge especially during adolescence (Park, Matsumoto, Seo, Kang, & Nagashima, 2002) and remain throughout adult life (Koukkari & Sothern, 2006).


Laboratory evaluations of the thermal degradation properties of toxic organic materials in sewage sludge.
Laboratory thermal decomposition studies were performed to evaluate potential emissions from sewage sludge incinerators. Precisely controlled thermal decomposition experiments were conducted on sludge spiked with mixtures of hazardous organic compounds, on mixtures of pure compounds without sludge, and on unspiked sludge. Experiments were conducted in nitrogen and air atmospheres with gas phase reaction times of 2.0 seconds over the temperature range 300 degrees C-1000 degrees C. It was found that sludge inhibited the decomposition of moderately stable spiked contaminants but accelerated the decomposition of the most stable components. This effect was attributed to radical scavengers produced by the sludge matrix at lower temperatures which then decomposed at higher temperatures. A multiple hearth simulation study suggested that most of the organic material present in the sludge matrix is vaporized within the upper hearths that are held at lower temperatures and may consequently escape from such incinerators undestroyed. A number of stable byproducts resulted from the sludge decomposition that may be of environmental concern.


Synaptic pathology in Alzheimer's disease: relation to severity of dementia, but not to senile plaques, neurofibrillary tangles, or the ApoE4 allele.
Alzheimer's disease (AD) is characterised by an increased number of senile plaques (SP) and neurofibrillary tangles (NFT) as compared with that found in non-demented individuals of the same age, and a marked degeneration and loss of synapses. One of the main risk-factors for the disorder is inheritance of the apolipoprotein E4 (ApoE4) allele. To further study the relation between these pathogenetic substrates for AD, we quantified the synaptic vesicle membrane protein rab3a in brain tissue from 19 patients with AD and 9 age-matched control subjects. Rab3a levels were reduced in AD, both in the hippocampus (60% of control level, p < 0.0001), and in the frontal cortex (68% of control level, p < 0.01), but not in the cerebellum (92% of control level). Within the AD group, lower rab3a levels were found both with increasing duration and severity of dementia. These findings further support that synaptic pathology is closely correlated to the clinical dementia in AD. In contrast, no significant correlations were found between SP counts and duration or severity of dementia, while higher NFT counts in the frontal cortex were found with increasing severity of dementia (r = 0.54, p < 0.05). There were no significant correlations between the rab3a level and SP or NFT counts, and by immunohistochemistry, reduced rab3a immunostaining was found throughout the neuropil in AD brain, without relation to SP or NFT. These findings suggest that the synaptic pathology in AD is not closely related to the presence of SP and NFT. No significant differences in rab3a levels were found in any brain region between AD patients possessing different numbers of the ApoE4 allele, suggesting that, although ApoE4 is A risk factor for earlier development of AD, the degree of synaptic pathology does not differ between patients with or without the ApoE4 allele.


Ventricular arrhythmias in competitive athletes: risk stratification with T-wave alternans.
Aim of our study is to evaluate the role of TWA to stratify the risk of sudden cardiac death in athletes (Ath) with complex ventricular arrhythmias (VA), and to document a possible correlation between TWA and electrophysiological testing (EES) results. We studied 43 Ath with VA (31 M, mean age 34 ± 12 years). In all cases a cardiological evaluation was performed, including TWA and EES. The patients were evaluated during a follow-up of 25 ± 22 months. The end-point was the occurrence of sudden death or malignant ventricular tachyarrhythmias (VT). TWA was negative in 28 Ath (65%), positive in 8 (19%) and indeterminate in 7 (16%). All subjects with negative TWA did not show induction of VT at EES, with significant correlation between negative TWA and negative EES (p<0.001). All Ath with positive TWA also had VT induced by a EES, but without significant correlation between positive TWA and positive EES. In 2 Ath with undetermined TWA (29%) VT were induced at EES. Our data did not show significant correlation between indeterminate TWA and positive or negative EES. However, logistic regression analysis showed significant correlation between abnormal TWA test (positive or indeterminate) and inducibility of VT at EES (p<0.001). During follow-up we observed a significant difference in end-point occurrence between Ath with negative or positive TWA and between Ath with negative or positive EES. TWA confirm its role as a simple and non-invasive test, and it seems useful for prognostic stratification of Ath with VA.


Factors affecting the survival of implants placed in grafted maxillary sinuses: a clinical report.
Many factors affect the survival rate of osseointegrated implants placed in grafted maxillary sinuses. This clinical report describes the retrospective evaluation of 60 patients with 228 implants placed in 84 grafted maxillary sinuses at the Loma Linda University School of Dentistry. The factors used to determine the survival rates of these implants were implant type, simultaneous/delayed implant placement, pretreatment bone height, oral hygiene, and cigarette smoking habits. Out of the total 228 implants, 205 (89.9%) remained in function after a mean follow-up period of 41.6 months (range 0 to 60 months). A higher failure rate was associated with the use of non-threaded implants, poor oral hygiene, and smoking. This information may facilitate treatment planning and enhance communication between the dentist and patient regarding the risk/benefit ratio and outcomes of implants placed in grafted maxillary sinuses.


Development of an Online 2D Ultrahigh-Pressure Nano-LC System for High-pH and Low-pH Reversed Phase Separation in Top-Down Proteomics.
The development of novel high-resolution separation techniques is crucial for advancing the complex sample analysis necessary for high-throughput top-down proteomics. Recently, our group developed an offline 2D high-pH RPLC/low-pH RPLC separation method and demonstrated good orthogonality between these two RPLC formats. Specifically, ultrahigh-pressure long capillary column RPLC separation has been applied as the second dimensional low-pH RPLC separation for the improvement of separation resolution. To further improve the throughput and sensitivity of the offline approach, we developed an online 2D ultrahigh-pressure nano-LC system for high-pH and low-pH RPLC separations in top-down proteomics. An online microtrap column with a dilution setup was used to collect eluted proteins from the first dimension high-pH separation and inject the fractions for ultrahigh-pressure long capillary column low-pH RPLC separation in the second dimension. This automatic platform enables the characterization of 1000+ intact proteoforms from 5 μg of intact E. coli cell lysate in 10 online-collected fractions. Here, we have demonstrated that our online 2D pH RP/RPLC system coupled with top-down proteomics holds the potential for deep proteome characterization of mass-limited samples because it allows the identification of hundreds of intact proteoforms from complex biological samples at low microgram sample amounts.


Current Perspectives on Antithrombotic Therapy for the Treatment of Acute Coronary Syndrome.
Acute coronary syndrome (ACS) is one of the leading causes of death worldwide. Percutaneous coronary intervention (PCI) is the treatment of choice for ACS as this procedure reduces the morbidity and mortality rates of patients in clinical trials and daily practice. However, patients with a history of prior ACS who undergo PCI are still at high risk for recurrent major adverse cardiac events (MACE). Because the antithrombotic drugs reduce the rate of MACE and minimize stent-related complications such as target vessel failure or stent thrombosis, the utilization of these agents is the cornerstone treatment for secondary prevention of ACS patients after PCI. Unfortunately, using the antithrombotic agents may be associated with bleeding complications, including major or fatal bleeding. Therefore, premature discontinuation of antithrombotic regimens regarding the hemorrhagic events is sometimes inevitable and possibly leads to fatal complications such as stent thrombosis. To minimize the bleeding issues, shorten antithrombotic regimens have been proposed, which theoretically offers improved safety. Nevertheless, inappropriate withdrawal of antithrombotic drugs may increase the rate of ischemic events. On the other hand, an unnecessary prolonged antithrombotic regimen may cause avoidable bleeding. Balancing the risk of bleeding against the benefits of using antithrombotic drugs is therefore challenging especially for the patients who contain both bleeding and ischemic risks such as ACS patients who are concomitant using the anticoagulants. Currently, the treatment paradigms are shifting from the "one size fits all approach" toward the "tailored approach". This means that the antithrombotic regimens can be adjustable individually. As a result, various clinical risk scoring systems have been established to help physicians with their decision-making. However, besides the development of these dedicated scoring tools, clinical judgment for balancing the safety versus the efficacy before deciding on the antithrombotic plan is still imperative.


Contact hypersensitivity to hydrocortisone-free-alcohol in patients with allergic patch test reactions to tixocortol pivalate.
It has been suggested that contact allergy to hydrocortisone alcohol is a frequent phenomenon. A recent study showed that all patients with allergic patch reactions to tixocortol pivalate reacted to intradermal hydrocortisone sodium phosphate. We studied patients with positive patch test reactions to tixocortol pivalate but negative to hydrocortisone alcohol, with penetration enhancers in hydrocortisone alcohol patch tests and oral challenges with hydrocortisone alcohol. Additionally, prick and intradermal tests with hydrocortisone sodium succinate were used. Using penetration enhancers and oral challenges enabled detection of more contact allergies to hydrocortisone alcohol compared to conventional patch testing alone. 9/12 patients with allergic reactions to tixocortol pivalate reacted to intradermal hydrocortisone sodium succinate. No immediate reactions were seen in prick or intradermal tests, suggesting that hydrocortisone contact hypersensitivity is probably not associated with immediate allergy to hydrocortisone. The present study suggests that allergic patch test reactions to tixocortol pivalate are caused by hypersensitivity to hydrocortisone alcohol itself or to one of its metabolites in the skin.


Conversion of excision-repairable DNA lesions to micronuclei within one cell cycle in human lymphocytes.
The human lymphocyte micronucleus (MN) assay is relatively insensitive to genotoxic agents that predominantly induce excision-repairable lesions such as adducts and abasic sites. In this study we have explored the possibility of using cytosine arabinoside (ARA) to convert excision-repairable DNA lesions to micronuclei (MN) within one cell cycle. The system consisted of human lymphocytes as target cells, the cytokinesis-block (CB) method for identifying cells that had completed one nuclear division only, and X-rays, methylnitrosourea (MNU), and ultraviolet light (UV) as mutagens. With each mutagen we have observed significant increments in induced MN in the cultures that had also been treated with ARA during G1. The slope of the dose-response curves for induction of MN was increased by a factor of approximately 1.8 for X-rays and 10.3 for UV and significant MNU induction of MN was only achieved in the cultures treated with ARA. Furthermore, a 24-hr gap between mutagen exposure and the start of the assay did not abolish the increased sensitivity in the cultures treated with ARA. These observations suggested that the combined ARA and cytokinesis-block micronucleus (CBMN) method may enhance the detection of exposure to genotoxic agents that predominantly induce excision-repairable lesions.


Branchial cleft-like cysts in Hashimoto's thyroiditis: A case report and literature review.
We report an extremely rare case of branchial cleft-like cysts in Hashimoto's thyroiditis. The patient was a 77-year-old man with a growing mass in the anterior neck. Ultrasonography and computed tomography revealed a cystic lesion with septum in the left thyroid and multiple small cystic lesions in the right thyroid. Lymph node swelling of the cervical region, supraclavicular fossa and submandibular region was also observed. Left thyroidectomy and lymph node dissection were performed. Histologically, cysts were lined by stratified squamous epithelium and dense lymphoid tissue having conspicuous follicle formation surrounded the epithelial lining. Solid cell nest (SCN)-like aggregations were seen in the thyroid parenchyma adjacent to the cyst walls and a small number of thyroid follicles were observed in the fibrous wall. Immunohistochemically, it is suggested that both the cyst lining and SCN-like aggregations are originally from thyroid follicles. Although, the exact histogenesis of branchial cleft-like cysts remains unclear, there are probably two different processes for its development, one is of branchial cleft origin and the other is mere squamous metaplasia, while in our case the latter is suggested. Herein, we report our new case and update information about branchial cleft-like cysts that appears in the literature.


Sialic acid on the neuronal glycocalyx prevents complement C1 binding and complement receptor-3-mediated removal by microglia.
Microglial cells are professional phagocytes of the CNS responsible for clearance of unwanted structures. Neuronal processes are marked by complement C1 before they are removed in development or during disease processes. Target molecules involved in C1 binding and mechanisms of clearance are still unclear. Here we show that the terminal sugar residue sialic acid of the mouse neuronal glycocalyx determines complement C1 binding and microglial-mediated clearance function. Several early components of the classical complement cascade including C1q, C1r, C1s, and C3 were produced by cultured mouse microglia. The opsonin C1q was binding to neurites after enzymatic removal of sialic acid residues from the neuronal glycocalyx. Desialylated neurites, but not neurites with intact sialic acid caps, were cleared and taken up by cocultured microglial cells. The removal of the desialylated neurites was mediated via the complement receptor-3 (CR3; CD11b/CD18). Data demonstrate that mouse microglial cells via CR3 recognize and remove neuronal structures with an altered neuronal glycocalyx lacking terminal sialic acid.


A natural tetrahydropyrimidine protects small bowel from cold ischemia and subsequent warm in vitro reperfusion injury.
Ischemia/reperfusion (I/R) injury is a major difficulty in small bowel transplantation. Many postoperative complications are caused by damage to the intestinal mucosa following organ retrieval and during cold storage. Here we investigate whether 1-, 4-, 5-, 6-tetrahydro-2-methyl-4-pyrimidine carboxylic acid (THP) can protect ileal mucosa and muscularis against cold ischemia and subsequent warm in vitro reperfusion injury. Small rat bowels were stored in the absence or presence of THP or its synthetic derivative lauryl-THP for 18 h at 4 degrees C. Several biochemical parameters were evaluated following isolated reperfusion in tissue grafts and/or effluent solution. Graft morphology was analyzed by electron microscopy. Ceramide was quantified as a potential target of THP action. THP considerably inhibited apoptosis and improved all parameters illustrating membrane and subcellular integrity and functionality. Parallel studies with lauryl-THP failed to show a similar protective effect. Lauryl-THP, in contrast to THP, also failed to decrease tissue ceramide content, indicating the involvement of this well-known mediator of cellular stress response. THP effectively protects ileal mucosa and muscularis against ischemia and reperfusion injury, indicating for the first time the clinical relevance of this new and promising molecule that might become a central component in tissue and organ protection in the near future.


Utilization of Medicare services by beneficiaries having partial Medicare coverage.
With the rapid increases in Medicare expenditures, policymakers are constantly reevaluating the use of and the need for services provided. One approach to better understand these issues is to identify major subgroups of the Medicare population for more detailed evaluation. A disaggregation of the data can pinpoint critical high expenditure areas for further study and may suggest potential cost containment strategies. With funding from the Health Care Financing Administration (HCFA), a series of investigations were designed to study utilization of services by particular types of Medicare beneficiaries. These include: Those who are continuously enrolled in the program over time. Those who died. Those who recently joined Medicare. Those who have one part of Medicare without the other part. This article discusses findings concerning beneficiaries who have only partial Medicare coverage (such as those who are enrolled under one part of Medicare without the other part).