Automated measurement of red blood cell microcytosis and hypochromia in iron deficiency and beta-thalassemia trait.
Some routine red blood cell (RBC) measurements and indexes (count, mean volume, volume dispersion, and mean hemoglobin [HGB] concentration) can be used to differentiate iron deficiency from heterozygous beta-thalassemia. A number of formulas that incorporate two or more of these measurements have been described to amplify such differences. The H*1 hematology analyzer directly measures volume and HGB concentration of individual RBCs. We have assessed the diagnostic usefulness of conventional and new RBC measurements provided by the H*1 on a learning data set that comprised 119 patients with iron deficiency and 172 patients with beta-thalassemia trait, both untreated and uncomplicated. The most striking finding was the inverse behavior of percentages of microcytes (volume, less than 60 fL) and hypochromic RBCs (HGB concentration, less than 280 g/L) in the two conditions. In 162 of 172 patients with beta-thalassemia trait, the percentage of microcytes (mean, 33.1%; central 95th percentile range, 9.2% to 54.5%) was higher than the percentage of hypochromic RBCs (mean, 13.9%; central 95th percentile range, 1.7% to 24.7%). In 105 of 119 patients with iron deficiency, on the contrary, the percentage of hypochromic cells (mean, 34.6%; central 95th percentile range, 9.7% to 73.1%) was higher than the percentage of microcytes (mean, 12.8%; central 95th percentile range, 1.7% to 29.6%). The ratio between the percentage of microcytes and the percentage of hypochromic cells provided by the H*1 (microcytic-hypochromic ratio) was useful in differentiating the two types of microcytic anemia: with the use of a discriminant value of 0.9, the discriminant efficiency of the microcytic-hypochromic ratio was 92.4% (95% confidence interval, 88.8% to 95.2%), higher than that of the five previously described discriminant formulas and simple RBC measurements. When assessed on a test data set that comprised 149 unselected cases of microcytic anemia, a microcytic-hypochromic ratio lower than 0.9 demonstrated high sensitivity (94.0%), specificity (92.3%), and predictive value (94.0%) for the presence of iron-deficient erythropoiesis in patients with isolated iron deficiency, polycythemia vera treated by phlebotomy, and iron deficiency complicating heterozygous thalassemia. In conclusion, our results showed that iron-deficient erythropoiesis is characterized by the production of RBCs with a severely decreased HGB concentration, while microcytes of beta-thalassemia trait are generally smaller, with a more preserved HGB concentration. Such properties, as assessed by the H*1 hematology analyzer, are very useful in distinguishing these two common types of microcytic anemia.


Shell disorder, immune evasion and transmission behaviors among human and animal retroviruses.
This study involves measurements of percentages of intrinsic disorder (PIDs) in the GAG protein shells of various retroviruses. Unique patterns of shell protein disorder can be seen especially when GAG proteins (matrix M, capsid C, and nucleocapsid N) of primate and non-primate retroviruses are compared. HIV-1 presents the most unique pattern of disorder distribution with generally high levels of disorder in all three proteins, while EIAV (PIDs:: 26, 29, 13) is diametrically different from HIV-1 (N C M PIDs: 39.5 ± 3.0, 44.5 ± 2.6, 56.5 ± 10.8). The HTLV viruses (CPID: 32.8 ± 3.4) resemble HIV-2 (C PID: 26.6 ± 2.9) with a moderately disordered capsid. Totally distinct patterns, however, are seen for the non-primate retroviruses. They generally have highly disordered nucleocapsids (PID > 65%) and more ordered outer shells especially the matrix. These characteristics might be attributed to the differences in the way the retroviruses are transmitted, with non-primate viruses having greater non-sexual transmission components such as oral-fecal transmission. These differences are also evolutionarily related to the ways the viruses evade the host immune systems, and thus, have implications for oncolytic virotherapy and animal models in vaccine research. The importance of protein shell disorder in immune evasion, as related to the case of HIV-1, and the difficult search for its vaccines are highlighted.


Advances in mapping population and demographic characteristics at small-area levels.
Temporally and spatially highly resolved information on population characteristics, including demographic profile (e.g. age and sex), ethnicity and socio-economic status (e.g. income, occupation, education), are essential for observational health studies at the small-area level. Time-relevant population data are critical as denominators for health statistics, analytics and epidemiology, to calculate rates or risks of disease. Demographic and socio-economic characteristics are key determinants of health and important confounders in the relationship between environmental contaminants and health. In many countries, census data have long been the source of small-area population denominators and confounder information. A strength of the traditional census model has been its careful design and high level of population coverage, allowing high-quality detailed data to be released for small areas periodically, e.g. every 10 years. The timeliness of data, however, becomes a challenge when temporally and spatially highly accurate annual (or even more frequent) data at high spatial resolution are needed, for example, for health surveillance and epidemiological studies. Additionally, the approach to collecting demographic population information is changing in the era of open and big data and may eventually evolve to using combinations of administrative and other data, supplemented by surveys. We discuss different approaches to address these challenges including (i) the US American Community Survey, a rolling sample of the US population census, (ii) the use of spatial analysis techniques to compile temporally and spatially high-resolution demographic data and (iii) the use of administrative and big data sources as proxies for demographic characteristics.


Autoimmune lymphoproliferative syndrome; a case report.
Autoimmune lymphoproliferative syndrome is a disorder of lymphoid system regulation characterized by chronic splenomegaly, lymphadenopathy and autoimmune phenomena especially immune-mediated cytopenias. The hallmark of the disease is the presence in peripheral blood and lymphoid tissue of increased numbers of a normally rare T lymphocyte subset, usually referred to as "double-negative" T cells. Here the authors report a 16-year-old boy when he was first hospitalized for diffuse petechiae, purpura and epistaxis at 9 years of age. One year later,he was readmitted for high fever and recurring cytopenia. On examination several enlarged, nontender lymph nodes involving cervical and submandibular areas and a huge spleen were detected. Lymph node biopsy was performed two times. According to flowcytometry of peripheral blood and immunophenotyping of lymph node tissues which revealed increased numbers of CD3+CD4-CD8- T-lymphocytes autoimmune lymphoproliferative syndrome was suggested for him. Autoimmune lymphoproliferative syndrome should be considered in differential diagnosis of any patient with unexplained Coomb's positive cytopenias, hypergammaglobulinemia, generalized lymphadenopathy and splenomegaly. The confirmation of the diagnosis should be based upon genetic analysis and detection of the affected genes involved in fas pathway.


Relaxation dynamics of 3He and 4He clusters and droplets studied using near infrared and visible fluorescence excitation spectroscopy.
The relaxation dynamics of electronically excited 3He and 4He clusters and droplets is investigated using time-correlated near-infrared and visible (NIR/VIS) fluorescence excitation spectroscopy. A rich data set spanning a wide range of cluster and droplet sizes is produced. The spectral features broadly follow the vacuum ultraviolet excitation (VUV) spectra. However, when the NIR/VIS spectra are normalised to the VUV fluorescence, regions with distinctly different cluster size and isotope dependence are identified, enabling deeper insight into the relaxation mechanism. Particle density, location of atomic-like states and their principal quantum number, n, are found to play an important role in the relaxation. For states with n = 3 and higher, only energy within the surface region is transferred to excited atoms which are subsequently ejected from the surface and fluoresce in vacuum. For states with n = 2, energy from the entire region within clusters and droplets is transferred to the surface, leading to the ejection of excited atoms and excimers. Here, the energy is transferred by excitation hopping, which competes with radiative and non-radiative decay, making ejection and NIR/VIS fluorescence inefficient in increasingly larger droplets.


Unravelling the rate of action of hits in the Leishmania donovani box using standard drugs amphotericin B and miltefosine.
In recent years, the neglected diseases drug discovery community has elected phenotypic screening as the key approach for the identification of novel hit compounds. However, when this approach is applied, important questions related to the mode of action for these compounds remain unanswered. One of such questions is related to the rate of action, a useful piece of information when facing the challenge of prioritising the most promising hit compounds. In the present work, compounds of the "Leishmania donovani box" were evaluated using a rate of action assay adapted from a replicative intracellular high content assay recently developed. The potency of each compound was determined every 24 hours up to 96 hours, and standard drugs amphotericin B and miltefosine were used as references to group these compounds according to their rate of action. Independently of this biological assessment, compounds were also clustered according to their minimal chemical scaffold. Comparison of the results showed a complete correlation between the chemical scaffold and the biological group for the vast majority of compounds, demonstrating how the assay was able to bring information on the rate of action for each chemical series, a property directly linked to the mode of action. Overall, the assay here described permitted us to evaluate the rate of action of the "Leishmania donovani box" using two of the currently available drugs as references and, also, to propose a number of fast-acting chemical scaffolds present in the box as starting points for future drug discovery projects to the wider scientific community. The results here presented validate the use of this assay for the determination of the rate of action early in the discovery process, to assist in the prioritisation of hit compounds.


Mechanism for isaxonine hepatitis. II. Protective role of glutathione and toxicological studies in mice.
Coincubation of 0.4 mM [3H]glutathione with 4 mM isaxonine , an NADPH-generating system, glutathione S-transferase and mouse liver microsomes, followed by thin-layer chromatography of the incubation mixture, resulted in the appearance of a 3H-labeled peak with characteristics consistent with a glutathione- isaxonine metabolite adduct: this peak was absent if either isaxonine or the NADPH-generating system was omitted and was decreased if the transferase was omitted. In vivo, the concentrations of hepatic glutathione and glutathione disulfide were markedly decreased 2.5 hr after administration of isaxonine (4 mmol X kg-1 i.p.); this depletion of glutathione was prevented essentially by pretreatment with piperonyl butoxide. In vitro, addition of 4 mM glutathione decreased markedly the amount of [14C] isaxonine metabolite that bound to microsomal proteins during incubation of 1 mM [2-14C] isaxonine with hepatic microsomes and an NADPH-generating system. In vivo, pretreatment with diethylmaleate decreased further hepatic glutathione concentration and markedly increased the amount of [14C] isaxonine metabolite covalently bound to hepatic proteins, 2.5 hr after administration of [2-14C] isaxonine (4 mmol X kg-1 i.p.). Administration of isaxonine (4 mmol X kg-1 i.p.) decreased hepatic cytochrome P-450 concentration, but failed to produce liver cell necrosis, even in mice pretreated with phenobarbital, 3-methylcholanthrene or diethylmaleate, despite high levels of in vivo covalent binding in pretreated animals. We conclude that the reactive metabolite of isaxonine may be conjugated with glutathione or may covalently bind to hepatic proteins. The metabolite, however, has limited hepatotoxic potential in mice.


[Contasure Needleless: a single incision tot for the surgical treatment of stress urinary incontinence].
The aim of this study is to describe the surgical technique, and assess the complications and middle-term results of the Contasure Needleless (Neomedic International), a single incision TOT sling for the surgical treatment of stress urinary incontinence. The main concept of this device is that it is not a mini-sling, it has 138% more surface area. We are analyzing the results of a minimally invasive solution that is a TOT like sling with the same known benefits of a TOT and the advantages of a single incision technique. The surface area to support the urethra of the Needleless is very similar to the surface area of the TOT. (16% less surface area of tissue ingrowths) It is 100% macroporous polypropylene without any additional material. 120 patients were evaluated retrospectively. They were all treated of SUI with the Contasure Needleless.Female patients were evaluated under clinical study protocol consisting in cough test, urodynamic and Quality Of Life questionnaire, before and after the procedure. patients with genuine SUI and patients with SUI plus concomitant procedures as prolapse. patients with ISD and or neurogenic incontinence. Anesthesia used: general (30%) or epidural (70%), patients with associated pathology. The 114 mm long and tension-free mesh was placed beneath the midurethra. The central part is 12 mm wide. The sling can be repositioned during surgery due to the 22 mm wide T-Pocket Positioning System located at the 2 edges. These pockets fixed the sling to the surrounding tissue in order to have the proper tissue in growth and anchoring. A 20mm sub urethral incision was made to dissect the paraurethral spaces only up to the ischiopubic ramus. A surgical forceps with the T-pocket folded was inserted into the dissected spaces and penetrates at the contra lateral side, like the standard transobturator technique. The forceps was introduced until the fascia of the Internal Obturator muscle was perforated. Then the forceps is opened to extend the pocket inside the muscle fibers for fixation. 120 patients with a mean age of 55 years (from 36 to 79) and a mean number of deliveries of 3 (0-7). Follow-up period: 24 months. SUCCESS RATE: 100 patients (84%) Improved rate: 10 patients (8%) Failure rate: 10 (8%) Mean operating time of sling procedure alone: 9 minutes (4-12). 3 patients had mesh extrusion solved with estrogens and 2 patients required short term catheterization due to voiding difficulties and no patients had inguinal pain. The results of the study suggest that the Contasure Needleless can be considered a minimally invasive TOT with no-needles and maintaining the same cure rate than our TOT cases at 2 years follow up.


The Dural Tube Continues to Expand after Muscle-Preserving Cervical Laminectomy.
The purpose of this study was to elucidate the duration for which the dural tube continues to expand after muscle-preserving cervical laminectomy and the extent to which the expansion affects surgical outcomes. We analyzed 83 patients with cervical myelopathy who underwent muscle-preserving selective laminectomy of three consecutive laminae between C4 and C6. On the lateral radiographs, parameters considered were C2-7 Cobb angles, range of flexion-extension neck motions, and C2-7 sagittal vertical axis. Neck alignment was classified into four types with lateral radiographs. Anteroposterior (AP) diameter of the dural tube was measured at mid-level of the C5 vertebral body on T2 sagittal image. Expansion ratio (ER) was defined as the extent of expansion at a particular time divided by the final extent of expansion of the dural tube diameter. Operative outcomes were examined using the Japanese Orthopaedic Association scores. The mean age was 62.3 years, and the mean follow-up period was 2 years and 9 months. AP diameter of the dural tube had been expanding until 1-year after surgery. ER in cases with kyphosis was lower at 6 months than that in cases without kyphosis, indicating that the speed of dural expansion was slower in cases with kyphosis. There was no correlation between the extent of expansion of the dural tube and neurological recovery. The dural tube continued to expand for approximately 1-year after surgery. The dural tube of patients with kyphosis slowly expanded possibly because of the hardness of the dura mater. A small extent of dural expansion does not necessarily indicate bad surgical outcomes.


Microcirculatory changes in term newborns with suspected infection: an observational prospective study.
Background. In adults severely disturbed microcirculatory flow can be observed by Orthogonal Polarized Spectral (OPS) imaging techniques during sepsis. Therefore we set out to assess for microcirculatory changes in term newborns with suspected early onset infection using OPS. Methods. OPS images were obtained prospectively from the vascular bed of the ear conch and upper arm of 47 newborns on their 1st, 2nd, and 3rd day of life. OPS sequences were analyzed semiquantitatively offline and blinded to clinical status of the infant. Flow in vessels was classified as continuous or noncontinuous flow and given as proportion of total vessels per image as in the studies in adults. Results. The proportion of vessels with continuous flow was significantly lower in the infants with infection (69% [56-81] versus 90% [87-94] (P = 0.0003)). None of the infants with infection was in shock or severely septic. Conclusion. In term neonates the microcirculatory flow is impaired in a large proportion of vessels even in mild to moderate infection. These changes can be observed at the onset of disease at the external ear, an optimal site for microcirculatory measurements in term infants.


Clinical Outcomes in High-Gradient, Classical Low-Flow, Low-Gradient, and Paradoxical Low-Flow, Low-Gradient Aortic Stenosis After Transcatheter Aortic Valve Implantation: A Report From the SwissTAVI Registry.
Background In view of the rising global burden of severe symptomatic aortic stenosis, its early recognition and treatment is key. Although patients with classical low-flow, low-gradient (C-LFLG) aortic stenosis have higher rates of death after transcatheter aortic valve implantation (TAVI) when compared with patients with high-gradient (HG) aortic stenosis, there is conflicting evidence on the death rate in patients with severe paradoxical low-flow, low-gradient (P-LFLG) aortic stenosis. Therefore, we aimed to compare outcomes in real-world patients with severe HG, C-LFLG, and P-LFLG aortic stenosis undergoing TAVI. Methods and Results Clinical outcomes up to 5 years were addressed in the 3 groups of patients enrolled in the prospective, national, multicenter SwissTAVI registry. A total of 8914 patients undergoing TAVI at 15 heart valve centers in Switzerland were analyzed for the purpose of this study. We observed a significant difference in time to death at 1 year after TAVI, with the lowest observed in HG (8.8%) aortic stenosis, followed by P-LFLG (11.5%; hazard ratio [HR], 1.35 [95% CI, 1.16-1.56]; P<0.001) and C-LFLG (19.8%; HR, 1.93 [95% CI, 1.64-2.26]; P<0.001) aortic stenosis. Cardiovascular death showed similar differences between the groups. At 5 years, the all-cause death rate was 44.4% in HG, 52.1% in P-LFLG (HR, 1.35 [95% CI, 1.23-1.48]; P<0.001), and 62.8% in C-LFLG aortic stenosis (HR, 1.7 [95% CI, 1.54-1.88]; P<0.001). Conclusions Up to 5 years after TAVI, patients with P-LFLG have higher death rates than patients with HG aortic stenosis but lower death rates than patients with C-LFLG aortic stenosis.


Dormancy Associated Translation Inhibitor (DATIN/Rv0079) of Mycobacterium tuberculosis interacts with TLR2 and induces proinflammatory cytokine expression.
Mycobacterium tuberculosis, the cause of tuberculosis in humans, is present approximately in one third of the world's population, mostly in a dormant state. The proteins encoded by the dormancy survival regulon (DosR regulon) are mainly responsible for survival of the bacilli in a latent form. To maintain latency, mycobacteria orchestrate a balanced interplay of different cytokines secreted by immune cells during the granulomatous stage. The function of most of the DosR regulon proteins of M. tuberculosis is unknown. In this study, we have shown that one of the DosR regulon proteins, DATIN, encoded by the gene Rv0079, can stimulate macrophages and peripheral blood mononuclear cells (PBMC) to secrete important cytokines that may be significant in granuloma formation and its maintenance. The expression level of DATIN in Mycobacterium bovis BCG was found to be upregulated in pH stress and microaerobic conditions. Computational modeling, docking and simulation study suggested that DATIN might interact with TLR2. This was further confirmed through the interaction of recombinant DATIN with TLR2 expressed by HEK293 cells. When in vitro differentiated THP-1 cells were treated with recombinant DATIN, increased secretion of TNF-α, IL-1β and IL-8 was observed in a dose dependent manner. When differentiated THP-1 cells were infected with a modified BCG strain that overexpressed DATIN, augmented secretions of TNF-α, IL-1β and IL-8 were observed as compared to a reference BCG strain containing empty vector. Similarly, human PBMCs when infected with M. bovis BCG that overexpressed DATIN, upregulated secretion of proinflammatory cytokines IFN-γ, TNF-α, IL-1β and IL-8. The cytokine profiles dissected herein point to a possible role of DATIN in maintenance of latency with the help of the proinflammatory responses.


Hepatomegaly induced by the pulsatile, but not continuous, intravenous administration of purified chicken growth hormone in broiler pullets: liver composition and nucleic-acid content.
The present study determined the composition and nucleic-acid content of livers obtained from 11-wk-old, broiler-strain pullets infused with pituitary-derived chicken growth hormone (p-cGH) in either a pulsatile (Study 1) or continuous (Study 2) manner for 21 days. Pulsatile p-cGH administration resulted in a decrease in ratios for liver DNA to wet weight (P less than .01), DNA to protein (P less than .03), and DNA to RNA (P less than .002), compared with controls. Total RNA-to-liver ratio (P less than .003) and liver weight (P less than .007) were significantly elevated, compared with controls. Total grams of protein (P less than .0007), water (P less than .004), and ash (P less than .01) were also elevated, with no significant differences in the percentage of composition. Continuous growth-hormone (GH) administration resulted in a decrease in the DNA-to-protein ratio (P less than .04) and a modest increase in the mass of liver protein (P less than .11) in comparison with controls, suggestive of cell hypertrophy. On a mass and percentage basis, liver composition was otherwise unaffected by the continuous administration of GH. In summary, pulsatile administration of GH induced hepatomegaly, largely due to cell hypertrophy, with no change in relative tissue composition. The continuous administration of GH had no effect on liver size, tissue composition, or most nucleic-acid-based indicators of cell hypertrophy or hyperplasia. Thus, previously observed differences in overall growth performance due to pattern of GH administration were also reflected in selected target-tissue response.


Transthyretin Stimulates Tumor Growth through Regulation of Tumor, Immune, and Endothelial Cells.
Early detection of lung cancer offers an important opportunity to decrease mortality while it is still treatable and curable. Thirteen secretory proteins that are Stat3 downstream gene products were identified as a panel of biomarkers for lung cancer detection in human sera. This panel of biomarkers potentially differentiates different types of lung cancer for classification. Among them, the transthyretin (TTR) concentration was highly increased in human serum of lung cancer patients. TTR concentration was also induced in the serum, bronchoalveolar lavage fluid, alveolar type II epithelial cells, and alveolar myeloid cells of the CCSP-rtTA/(tetO)7-Stat3C lung tumor mouse model. Recombinant TTR stimulated lung tumor cell proliferation and growth, which were mediated by activation of mitogenic and oncogenic molecules. TTR possesses cytokine functions to stimulate myeloid cell differentiation, which are known to play roles in tumor environment. Further analyses showed that TTR treatment enhanced the reactive oxygen species production in myeloid cells and enabled them to become functional myeloid-derived suppressive cells. TTR demonstrated a great influence on a wide spectrum of endothelial cell functions to control tumor and immune cell migration and infiltration. TTR-treated endothelial cells suppressed T cell proliferation. Taken together, these 13 Stat3 downstream inducible secretory protein biomarkers potentially can be used for lung cancer diagnosis, classification, and as clinical targets for lung cancer personalized treatment if their expression levels are increased in a given lung cancer patient in the blood.


A Review of Remote Sensing Approaches for Monitoring Blue Carbon Ecosystems: Mangroves, Seagrassesand Salt Marshes during 2010⁻2018.
Blue carbon (BC) ecosystems are an important coastal resource, as they provide a range of goods and services to the environment. They play a vital role in the global carbon cycle by reducing greenhouse gas emissions and mitigating the impacts of climate change. However, there has been a large reduction in the global BC ecosystems due to their conversion to agriculture and aquaculture, overexploitation, and removal for human settlements. Effectively monitoring BC ecosystems at large scales remains a challenge owing to practical difficulties in monitoring and the time-consuming field measurement approaches used. As a result, sensible policies and actions for the sustainability and conservation of BC ecosystems can be hard to implement. In this context, remote sensing provides a useful tool for mapping and monitoring BC ecosystems faster and at larger scales. Numerous studies have been carried out on various sensors based on optical imagery, synthetic aperture radar (SAR), light detection and ranging (LiDAR), aerial photographs (APs), and multispectral data. Remote sensing-based approaches have been proven effective for mapping and monitoring BC ecosystems by a large number of studies. However, to the best of our knowledge, this is the first comprehensive review on the applications of remote sensing techniques for mapping and monitoring BC ecosystems. The main goal of this review is to provide an overview and summary of the key studies undertaken from 2010 onwards on remote sensing applications for mapping and monitoring BC ecosystems. Our review showed that optical imagery, such as multispectral and hyper-spectral data, is the most common for mapping BC ecosystems, while the Landsat time-series are the most widely-used data for monitoring their changes on larger scales. We investigate the limitations of current studies and suggest several key aspects for future applications of remote sensing combined with state-of-the-art machine learning techniques for mapping coastal vegetation and monitoring their extents and changes.


Allergen source materials and quality control of allergenic extracts.
Allergen extracts are prepared from a wide variety of source materials including pollens, fungi, arthropods, animal danders, foods, and dusts. The composition of allergen extracts can vary depending on the allergen source, manufacturing process, and storage conditions. Allergen-specific immunoglobulin E (IgE) assays and skin tests employ a variety of allergen-containing reagents that confer specificity on the test. Given that the allergen source materials are heterogenous mixtures of proteins, glycoproteins, carbohydrates, and other substances that are not allergenic, it is not unexpected that variability exists between test results obtained with different allergen-containing reagents. Variability within a single manufacturer's allergen product can be controlled by using reproducible extraction and processing procedures, single large lots of allergen source materials, and solid-phase supports. These controls do not, however, ensure the consistency of products between manufacturers or laboratories because allergen source materials, manufacturing procedures, and acceptance criteria for allergen reagents may vary.


Using ring-recovery and within-season recapture data to estimate fecundity and population growth.
Tag-recovery data from organisms captured and marked post breeding are commonly used to estimate juvenile and adult survival. If annual fecundity could also be estimated, tagging studies such as European and North American bird-ringing schemes could provide all parameters needed to estimate population growth. I modified existing tag-recovery models to allow estimation of annual fecundity using age composition and recapture probabilities obtained during routine banding operations of northern pintails (Anas acuta) and dark-eyed juncos (Junco hyemalis), and I conducted simulations to assess estimator performance in relation to sample size. For pintails, population growth rate from band-recovery data (λ = 0.93, SD: 0.06) was similar but less precise than count-based estimates from the Waterfowl Breeding Pair and Habitat Survey (λ: 0.945, SE: 0.001). Models with temporal variation in vital rates indicated that annual population growth in pintails was driven primarily by variation in fecundity. Juncos had lower survival but greater fecundity, and their estimated population growth rate (λ: 1.01, SD: 0.19) was consistent with count-based surveys (λ: 0.986). Simulations indicated that reliable (CV < 0.10) estimates of fecundity could be obtained with >1,000 within-season live encounters. Although precision of survival estimates depended primarily on numbers of adult recoveries, estimates of fecundity and population growth were most sensitive to total number of live encounters. Synthesis and applications: Large-scale ring-recovery programs could be used to estimate annual fecundity in many species of birds, but the approach requires better data curation, including accurate assessment of age, better reporting of banding totals, and greater emphasis on obtaining and reporting within-season live encounters.


Enhanced activation of human dendritic cells by inducible CD40 and Toll-like receptor-4 ligation.
Despite the potency of dendritic cells (DC) as antigen-presenting cells for priming adaptive immunity, DC-based cancer vaccines have been largely insufficient to effectively reduce tumor burden or prevent tumor progression in most patients. To enhance DC-based vaccines, we used the combination of a synthetic ligand-inducible CD40 receptor (iCD40) along with Toll-like receptor-4 (TLR-4) ligation in human monocyte-derived DCs. The iCD40 receptor permits targeted, reversible activation of CD40 in vivo, potentially bypassing the essential role of CD4(+) T cells for activation of DCs. As a rigorous preclinical study of this approach, we evaluated key parameters of DC activation and function. Whereas neither iCD40 nor TLR-4 signaling alone led to high levels of interleukin (IL)-12p70 and IL-6, using iCD40 in combination with lipopolysaccharide (LPS) or monophosphoryl lipid A led to strongly synergistic production of both. Furthermore, this approach led to high expression of DC maturation markers, epitope-specific CTL and T helper 1 responses, as well as DC migration in vitro and in vivo. Moreover, use of iCD40-modified and LPS-stimulated DCs led to targeted expansion of autologous T cells against tumor-associated antigens, including prostate-specific membrane antigen, and elimination of preestablished tumors, supporting this technology as a potent strategy for DC-based cancer immunotherapy.


Armored brain in patients with hydrocephalus after shunt surgery: review of the literatures.
Armored brain or chronic calcified subdural hematoma is a rare complication of cerebrospinal fluid diversion with few cases reported in the literature. Seventeen patients with this pathology have been published. A complete review of the literatures regarding this topic has been collected and discussed. The author also presents a 12- year old boy with triventricular hydrocephalus who had undergone ventriculoperitoneal medium pressure shunt system since birth. The patient presented to our clinic with a 2-year history of seizures. The patient was conscious and without neurological deficits on examination. Computed tomography of the brain showed bilateral high density mass with surface calcification. X ray skull and MRI confirmed the calcified subdural hematoma bilaterally. We preferred conservative treatment and the patient continued his antiepileptic treatment. At one year follow up, the patient had the same neurological state. The case highlights the importance of frequent follow up CT brain after shunt surgery.


Analysis of DNA endoreplication in the brain neurons in the terrestrial slug, Limax valentianus.
DNA endoreplication is the DNA synthesis without cell division, resulting in the generation of a nucleus containing a larger amount of genomic DNA compared to a normal diploid genome. There are many such giant neurons in the molluscan brain that are generated as a result of repeated endoreplication. However, it has been controversial whether the endoreplication is the whole genome replication (polyploidy) or the local amplification of the genes that are necessary for the neuron's function (polyteny/polysomy). Here in this study, we investigated these two possibilities by (1) immunohistochemical analysis of the distribution of 5'-bromodeoxyuridine incorporated into the nuclei of the brain neurons, and by (2) quantitative genomic PCR directed to two different genes expressed in specific brain regions. Our data supported the view that the DNA endoreplication is the whole genome replication rather than the local amplification of a specific genomic region.


Crowdsourcing healthcare costs: Opportunities and challenges for patient centered price transparency.
Efforts to improve health care price transparency have garnered significant attention from patients, policy makers, and health insurers. In response to increasing consumer demand, state governments, insurance plans, and health care providers are reporting health care prices. However, such data often do not provide consumers with the most salient information: their own actual out-of-pocket cost for medical care. Although untested, crowdsourcing, a mechanism for the public to help answer complex questions, represents a potential solution to the problem of opaque hospital costs. This article explores, the challenges and potential opportunities for crowdsourcing out-of-pocket costs for healthcare consumers.


Mass spectrometry imaging identifies metabolic patterns associated with malignant potential in pheochromocytoma and paraganglioma.
Within the past decade, important genetic drivers of pheochromocytoma and paraganglioma (PPGLs) development have been identified. The pathophysiological mechanism that translates these alterations into functional autonomy and potentially malignant behavior has not been elucidated in detail. Here we used MALDI-mass spectrometry imaging (MALDI-MSI) of formalin-fixed paraffin-embedded tissue specimens to comprehensively characterize the metabolic profiles of PPGLs. MALDI-MSI was conducted in 344 PPGLs and results correlated with genetic and phenotypic information. We experimentally silenced genetic drivers by siRNA in PC12 cells to confirm their metabolic impact in vitro. Tissue abundance of kynurenine pathway metabolites such as xanthurenic acid was significantly lower (P = 2.35E-09) in the pseudohypoxia pathway cluster 1 compared to PPGLs of the kinase-driven PPGLs cluster 2. Lower abundance of xanthurenic acid was associated with shorter metastasis-free survival (log-rank tests P = 7.96E-06) and identified as a risk factor for metastasis independent of the genetic status (hazard ratio, 32.6, P = 0.002). Knockdown of Sdhb and Vhl in an in vitro model demonstrated that inositol metabolism and sialic acids were similarly modulated as in tumors of the respective cluster. The present study has identified distinct tissue metabolomic profiles of PPGLs in relation to tumor genotypes. In addition, we revealed significantly altered metabolites in the kynurenine pathway in metastatic PPGLs, which can aid in the prediction of its malignant potential. However, further validation studies will be required to confirm our findings.


CT-guided injection for ganglion impar blockade: a radiological approach to the management of coccydynia.
To evaluate the role of computed tomography (CT) in needle placement for ganglion impar blocks, and to determine the efficacy of CT-guided ganglion impar blocks in the management of coccydynia. The results of ganglion impar blockade in eight patients with coccydynia secondary to trauma or unknown cause were reviewed. The diagnosis of coccydynia was based on clinical history, location of pain, and response to previous diagnostic and therapeutic procedures. The eight patients were treated with CT-guided ganglion impar blocks to manage their coccyx pain after conservative procedures, including oral medication and cushions, failed to provide relief. All patients were subjected to ganglion impar blocks under a thin-section CT-guided technique for needle placement, using a mixture of bupivacaine and triamcinolone. The patients were followed-up for a period of 6-months. Eight patients were treated in this study with a total of 11 injections. A technical success of 100% was achieved in all cases with accurate needle placement without any complications and all the patients tolerated the procedure well. Out of eight, three patients (37%) had complete relief of pain on the follow-up intervals up to 6 months. Three out of eight patients (37%), had partial relief of symptoms and a second repeat injection was given at the 3 month interval of the follow-up period. At the end of the 6-month follow-up period, six out of eight patients (75%) experienced symptomatic relief (four complete relief and two partial relief) without any additional resort to conventional pain management. Twenty-five percent (two out of eight) did not have any symptomatic improvement. The mean visual analogue score (VAS) pre-procedure was 8 (range 6-10) and had decreased to 2 (range 0-5) in six out of eight patients. CT can be used as an imaging method to identify the ganglion and guide the needle in ganglion impar blockade. The advantages of CT-guided injection over those performed under fluoroscopy may include accurate and confident needle placement in the sacro-coccygeal region, ease of wide area coverage, lesser risk of complications due to inadvertent injections into the major pelvic structures, and increased likelihood of reaching the ganglion impar, especially in cases with anatomical variation in the ganglion impar location. These factors may have implications in the overall success rate of ganglion impar blockade.


Mapping QTLs for seedling characteristics under different water supply conditions in rice (Oryza sativa).
A greater understanding of the genetics of responses to water deficit/drought may be helpful in improving water-deficit resistance in the early stages of growth in rice. A recombinant inbred population derived from a cross between Zhenshan 97 and Minghui 63 was grown in hydroponic culture to characterize the responses of seedlings to water deficit imposed by PEG 6000 and to identify quantitative trait loci (QTLs) for seedling characteristics under both well-watered and water-deficit conditions. Generally, the two parents showed significant differences in plant height (PH), maximum root length (MRL), shoot fresh weight (SFW), root fresh weight (RFW), number of roots and root:shoot ratio based on fresh weight under both well-watered and water-deficit conditions. For two parents, PH and SFW were significantly inhibited under water deficit. However, the other four traits had larger values under water deficit. Among 26 and 34 QTLs detected for the six traits studied under the well-watered and water-deficit conditions, respectively, a total of 14 QTLs for SFW, PH, RFW and MRL (23% of total QTLs detected) were detected in similar or tight linkage regions in both conditions. Among 11 intervals on 7 chromosomes identified to harbor multiple QTLs, 8 intervals were found to affect related traits under the two water supply conditions and 3 intervals were observed to be water supply-specific regions and had effects only under well-watered conditions, suggesting that water supply-specific regions or QTLs may be closely associated with the responses of lines to water deficit in the study. Several regions for the traits studied were also found to affect the root-related traits in previous studies and might be used in marker-assisted selection for drought-resistant rice in breeding programs.


Fungal arthritis simulating juvenile rheumatoid arthritis.
Petriellidium boydii is often isolated from maduromycosis but has recently been associated with arthritis. A previously healthy 6-year-old boy developed chronic purulent arthritis of the knee after a bicycle accident. Culture of aspirate grew no pathogens and antibiotic treatment had no effect. Culture of synovial fluid grew P boydii, which responded initially to amphotericin but reappeared after six months. Subsequent treatment with miconazole was stopped after development of haematuria. The fungus was sensitive to ketoconazole, and treatment with this drug cured the infection. With the introduction of ketoconazole it is of practical importance to recognise fungal infections.


Cefotaxime treatment of skin and skin structure infections: a multicenter study.
The efficacy, safety, and tolerability of cefotaxime, a new parenteral cephalosporin resistant to beta-lactamase, were evaluated in a multicenter open trial. The study population comprised 594 hospitalized patients with infections of the skin or subcutaneous tissue. Of these, 409 patients fulfilled the protocol requirements for assessment of clinical efficacy. Usual dosages of cefotaxime were in the range of 1.5 to 12 gm/day for 5 to 85 days. Staphylococcus aureus was the most frequent gram-positive organism; Proteus mirabilis, Escherichia coli, and Pseudomonas aeruginosa, the most frequent gram-negative bacilli; and Peptococcus sp, the most frequent anaerobic organism isolated. Of the 409 evaluable patients, 382 (93.4%) were clinically cured. Bacteriological cures were obtained in 316 of 372 (84.9%) patients. Reactions to cefotaxime included asymptomatic eosinophilia, rash, drug fever, phlebitis, and elevated hepatic enzyme levels. All reactions were transient, and drug therapy had to be terminated in only eight patients. Cefotaxime proved effective for treating a variety of skin and soft tissue infections. The lack of serious toxicity and adverse reactions associated with cefotaxime, together with its broad antimicrobial spectrum, makes it a suitable substitute for aminoglycosides in certain clinical settings.


Transient inactivation of Rb and ARF yields regenerative cells from postmitotic mammalian muscle.
An outstanding biological question is why tissue regeneration in mammals is limited, whereas urodele amphibians and teleost fish regenerate major structures, largely by cell cycle reentry. Upon inactivation of Rb, proliferation of postmitotic urodele skeletal muscle is induced, whereas in mammalian muscle this mechanism does not exist. We postulated that a tumor suppressor present in mammals but absent in regenerative vertebrates, the Ink4a product ARF (alternative reading frame), is a regeneration suppressor. Concomitant inactivation of Arf and Rb led to mammalian muscle cell cycle reentry, loss of differentiation properties, and upregulation of cytokinetic machinery. Single postmitotic myocytes were isolated by laser micro-dissection-catapulting, and transient suppression of Arf and Rb yielded myoblast colonies that retained the ability to differentiate and fuse into myofibers upon transplantation in vivo. These results show that differentiation of mammalian cells is reversed by inactivation of Arf and Rb and support the hypothesis that Arf evolved at the expense of regeneration.


Dissemination and benefits of a replicable Tai Chi and Qigong program for older adults.
Tai Chi and Qigong (TCQG) show promise for improving many health outcomes and are recommended for dissemination to older adults. A simplified, easy-to-replicate version of TCQG, "Tai Chi Easy," was tested using a train-the-trainer method to demonstrate feasibility of dissemination to a widespread population of older adults through community sites and achievement of perceived outcomes. Nonexpert facilitators known as "practice leaders" were trained to implement Tai Chi Easy sessions at 18 sites across the United States. Outstanding facilitator (100%) and participant (94%) adherence was achieved. With 330 completers, mean age 73 years, significant improvements were found for participants' perceived stress levels (P = .003). Sleep quality and energy/vitality were markedly improved. Eighty-nine percent enjoyed the program, 91% were committed to continue, and 67% stated that they had increased their weekly levels of physical activity. A train-the-facilitator model for Tai Chi Easy is easily disseminated to older adults and may promote a sustainable alternative exercise, yielding favorable quality of life benefits.


Combined structural and biochemical analysis of the H-T complex in the glycine decarboxylase cycle: evidence for a destabilization mechanism of the H-protein.
The lipoate containing H-protein plays a pivotal role in the catalytic cycle of the glycine decarboxylase complex (GDC), undergoing reducing methylamination, methylene transfer, and oxidation. The transfer of the CH(2) group is catalyzed by the T-protein, which forms a 1:1 complex with the methylamine-loaded H-protein (Hmet). The methylamine group is then deaminated and transferred to the tetrahydrofolate-polyglutamate (H(4)FGlu(n)) cofactor of T-protein, forming methylenetetrahydrofolate-polyglutamate. The methylamine group is buried inside the protein structure and highly stable. Experimental data show that the H(4)FGlu(n) alone does not induce transfer of the methylene group, and molecular modeling also indicates that the reaction cannot take place without significant structural perturbations of the H-protein. We have, therefore, investigated the effect of the presence of the T-protein on the stability of Hmet. Addition of T-protein without H(4)FGlu(n) greatly increases the rate of the unloading reaction of Hmet, reducing the activation energy by about 20 kcal mol(-1). Differences of the (1)H and (15)N chemical shifts of the H-protein in its isolated form and in the complex with the T-protein show that the interaction surface for the H-protein is localized on one side of the cleft where the lipoate arm is positioned. This suggests that the role of the T-protein is not only to locate the tetrahydrofolate cofactor in a position favorable for a nucleophilic attack on the methylene carbon but also to destabilize the H-protein in order to facilitate the unlocking of the arm and initiate the reaction.


Value of treating primary causes of syrinx in scoliosis associated with syringomyelia.
Retrospective chart and radiologic analysis. To analyze the value and risks of neurosurgical procedures for syringomyelia and of fusion procedures for scoliosis. There are few reports on the benefit of neurosurgical procedures on scoliosis, as well as the risk of fusion procedures on scoliosis related to syringomyelia. The 105 patients who had both scoliosis and syringomyelia were subdivided into three groups: (I) 59 patients without congenital scoliosis or myelomeningocele, (II) 20 patients with congenital scoliosis and syringomyelia, and (III) 26 patients with myelomeningocele and syringomyelia. The study evaluated: (1) The effect of either suboccipital craniectomy or direct shunting on the syrinx, the curvature, and the neurologic status; (2) the neurologic risk of scoliosis fusion surgery; and (3) the curve status after fusion surgery. In Group I (patients without congenital scoliosis or myelomeningocele), suboccipital craniectomy resulted in curve improvement in seven, worsening in three, and no change in two, whereas direct syrinx shunting gave curve improvement in none, curve worsening in six, and no change in two. In Groups II and III, no patient had curve improvement after neurosurgery. Group III had the highest rate of subsequent neurosurgery (50%). The subsequent neurosurgery was nearly always suboccipital craniectomy or detethering of the cord. Three of 38 patients (8%) had neurologic worsening when scoliosis fusion surgery was done without previous syrinx decompression. In patients without myelomeningocele or congenital scoliosis, but with Arnold-Chiari malformation and syringomyelia, suboccipital craniectomy gave the best chance for syrinx reduction and scoliosis improvement, particularly in children younger than 10 years. Syrinx shunting improved none of the scolioses. For syrinxes in patients with congenital scoliosis or myelomeningocele, neither neurosurgical procedure resulted in curve improvement, as other causes of scoliosis (vertebra anomalies, paralysis) remained untreated. Patients with myelomeningocele require a multipronged surgical approach to address all causes of syrinx, thus minimizing the potential need for repeat neurosurgery. Scoliosis correction without prior syrinx decompression carries a high neurologic risk.


Lymphocyte subset ratios and factor VIII usage in haemophilia.
Type and quantity of replacement treatment, together with haematological and immunological parameters were determined in 37 boys with severe haemophilia A and 41 children with other bleeding disorders. The quantity of factor VIII concentrate given to boys with severe haemophilia A (mean U/year) showed a significant inverse correlation with total white cell counts, lymphocyte counts, platelet counts, and the ratio of monoclonal antibody defined T lymphocyte subsets, T4 and T8 (T4:T8). Of the boys with severe haemophilia A, 49% had inversed T4:T8 ratios and 24% had thrombocytopenia. Treatment with high dose factor VIII concentrate (more than 25 000 U/year) was associated with low platelet counts, low lymphocyte counts, low T4:T8 ratios, and hypergammaglobulinaemia. In addition, six patients with severe haemophilia A and factor VIII inhibitors had inversed T4:T8 ratios. Patients treated exclusively with cryoprecipitate or prothrombin complex concentrates had normal T4:T8 ratios and platelet counts. The severity of the haematological and immunological abnormalities observed seems to be associated with high usage of factor VIII concentrates. Similar abnormalities have been described in patients with the acquired immune deficiency syndrome (AIDS). Prospective study of haemophiliacs is required to assess long term sequelae of factor concentrate usage, including the possible development of AIDS.


Promoting Effects of Heparin on ex vivo Expansion of Megakaryocytopoiesis from Human Cord Blood CD34+ Cells.
Transfusion of ex vivo expanded megakaryocytes (MKs) has been proposed to sustain platelet recovery after cord blood (CB) hematopoietic stem cell transplantation. In this study, we investigated the effects of heparin on ex vivo colony forming unit-megakaryocytes (CFU-MKs) and MKs expansion from CB CD34+ cells. CB CD34+ cells were stimulated by a combination of thrombopoietin (TPO), stem cell factor (SCF), Flt3-Ligand (FL), IL-6, and IL-11 supplemented with autologous serum and heparin during 14 days. Expanded cells were analyzed by flow cytometry and cultured in a CFU-MK assay. Compared to control cultures, the 5-factor combination with heparin induced significantly (p ≤ 0.05) higher numbers of: CFU-MKs and CD41+ cells on days 7 and 14; CD41+ cells displaying hyperploidy levels (≥8N) on day 14; platelets on day 14. The culture-derived platelets were activated upon collagen stimulation. Heparin can significantly enhance the stimulating effects of a combination of TPO, SCF, FL, IL-6, and IL-11 supplemented with autologous serum on CFU-MK, MK, and platelet production from CB CD34+ cells. This expansion system could represent a promising method to generate CFU-MKs and MKs cells for transfusion to sustain platelet reconstitution following CB transplantation.


MmoD regulates soluble methane monooxygenase and methanobactin production in Methylosinus trichosporium OB3b.
Aerobic methanotrophs play a critical role in the global carbon cycle, particularly in controlling net emissions of methane to the atmosphere. As methane is a much more potent greenhouse gas than carbon dioxide, there is increasing interest in utilizing these microbes to mitigate future climate change by increasing their ability to consume methane. Any such efforts, however, require a detailed understanding of how to manipulate methanotrophic activity. Herein, we show that methanotrophic activity is strongly controlled by MmoD, i.e., MmoD regulates methanotrophy through the post-transcriptional regulation of the soluble methane monooxygenase and controls the ability of methanotrophs to collect copper. Such data are likely to prove quite useful in future strategies to enhance the use of methanotrophs to not only reduce methane emissions but also remove methane from the atmosphere.


Understanding internalizing and externalizing symptoms in trauma exposed community members.
Posttraumatic stress disorder (PTSD) is highly comorbid with internalizing and externalizing symptoms, but few studies have examined risk factors that can account for these comorbidities. The primary aim of this study is to investigate the role of blame attribution (i.e., self-blame and other blame) and impulsivity dimensions (i.e., negative and positive urgency) in predicting internalizing (i.e., social anxiety, depression, and worry) and externalizing symptoms (i.e., aggression, risky thrill-seeking, risky substance use, and sexual risk-taking) when statistically controlling for PTSD. Participants were 63 trauma-exposed community members (47.6% diagnosed with PTSD; Mage = 27.17, 84.1% female) interviewed using the Clinician-Administered PTSD Scale-5. We hypothesized that self- and other blame would predict internalizing symptoms and that self-blame, negative urgency, and positive urgency would predict externalizing symptoms after controlling for PTSD. Findings showed that self-blame was associated with all three internalizing symptoms and risky sex and that negative urgency predicted risky aggression. This study provides evidence that self-blame is an important risk factor for a broad range of internalizing symptoms and for at least one type of externalizing symptom and that the effects of self-blame are not fully explained by PTSD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Pharmacogenomics of maternal tobacco use: metabolic gene polymorphisms and risk of adverse pregnancy outcomes.
To assess whether functional maternal or fetal genotypes along well-characterized metabolic pathways (ie, CYP1A1, GSTT1, and CYP2A6) may account for varying associations with adverse outcomes among pregnant women who smoke. DNA samples from 502 smokers and their conceptuses, alongside women in a control group, were genotyped for known functional allelic variants of CYP1A1 (Ile462Val AA>AG/GG), GSTT1(del), and CYP2A6 (Lys160His T>A). Modification of the association between smoking and outcome by genotype was evaluated. Outcomes included birth weight, pregnancy loss, preterm birth, small for gestational age, and a composite outcome composed of the latter four components plus abruption. No interaction between maternal or fetal genotype of any of the polymorphisms and smoking could be demonstrated. In contrast, the association of smoking with gestational age-adjusted birth weight (birth weight ratio) was modified by fetal GSTT1 genotype (P for interaction=.02). Fetuses with GSTT1(del) had a mean birth weight reduction among smokers of 262 g (P=.01), whereas in fetuses without the GSTT1(del) the effect of tobacco exposure was nonsignificant (mean reduction 87 g, P=.16). After adjusting for confounding, results were similar. Fetal GSTT1 deletion significantly and specifically modifies the effect of smoking on gestational age-corrected birth weight.


Nature of electrogenerated intermediates in nitro-substituted nor-β-lapachones: the structure of radical species during successive electron transfer in multiredox centers.
Electrochemical, spectroelectrochemical, and theoretical studies of the reduction reactions in nor-β-lapachone derivatives including a nitro redox center showed that reduction of the compounds involves the formation of several radical intermediates, including a biradical dianion resultant from the separate reduction of the quinone and nitro groups in the molecules. Theoretical descriptions of the corresponding Fukui functions f(αα)⁺ and f(ββ)⁺(r) and LUMO densities considering finite differences and frozen core approximations for describing the changes in electron and spin densities of the system allowed us to confirm these results. A description of the potential relationship with the obtained results and biological activity selectivity indexes suggests that both the formation of stable biradical dianion species and the stability of the semiquinone intermediates during further reduction are determining factors in the description of their biological activity.


Nanoscale Structural Organization of Plant Epicuticular Wax Probed by Atomic Force Microscope Infrared Spectroscopy.
The cuticle covers external surfaces of plants, protecting them from biotic and abiotic stress factors. Epicuticular wax on the outer surface of the cuticle modifies reflectance and water loss from plant surfaces and has direct and indirect effects on photosynthesis. Variation in epicuticular wax accumulation, composition, and nanoscale structural organization impacts its biological function. Atomic force microscope infrared spectroscopy (AFM-IR) was utilized to investigate the internal and external surfaces of the cuticle of Sorghum bicolor, an important drought-tolerant cereal, forage, and high-biomass crop. AFM-IR revealed striking heterogeneity in chemical composition within and between the surfaces of the cuticle. The wax aggregate crystallinity and distribution of chemical functional groups across the surfaces was also probed and compared. These results, along with the noninvasive nondestructive nature of the method, suggest that AFM-IR can be used to investigate mechanisms of wax deposition and transport of charged molecules through the plant cuticle.


Age and time effects on implicit and explicit learning.
BACKGROUND/STUDY CONTEXT: It has been proposed that effects of aging are more pronounced for explicit than for implicit motor learning. The authors evaluated this claim by comparing the efficacy of explicit and implicit learning of a movement sequence in young and older adults, and by testing the resilience against fatigue and secondary tasking after learning. It was also examined whether explicit learning in older adults can be promoted by alleviating time constraints during learning. The alternating serial reaction time task (ASRTT) was used. Experiment 1 compared the benefits of receiving full instructions about the stimulus sequence relative to receiving no instructions in young (20-25 years) and older (50-65 years) adults during retention and during transfer to fatigue and secondary task conditions. Experiment 2 alleviated time constraints during the initial bouts of practice with full instructions. Experiment 1 indicated that the older adults learned on the ASRTT and achieved similar performance as young adults when no instructions were given. In contrast to the young adults, learning was not superior in older adults who received full instructions compared with those who did not. Experiment 2 indicated that alleviating time constraints allowed some of the older adults to gain from instruction but only under relatively low time constraints, but there was no retention with rigorous time constraints. Explicit learning, but not implicit learning, declines in older adults. This is partly due to older adults difficulties to apply explicit knowledge. Less rigorous time constraints can help to ameliorate some of these difficulties and may induce levels of explicit learning in older adults that will result in superior performance compared with implicit learning. Implicit learning did occur under time constraints that prevented explicit learning.


[Combined treatment of hepatocarcinoma with chemoembolization and alcohol administration. Long-term results].
We investigated the long-term outcome of combined transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) for the treatment of hepatocellular carcinoma (HCC). A series of 86 patients with biopsy-proved HCC were treated at our Institution January, 1991, to June, 1996. All patients had a single primary tumor bigger than 3 cm, occurring solitary or associated with no more than 2 daughter nodules. Forty-eight patients were in Child class A and 38 patients were in Child class B. The diameter of the lesions ranged 3 to 8 cm (mean: 5.3 cm). The treatment schedule included a single TACE performed via a segmental approach by injecting an emulsion of 20-70 mg adriblastin or farmorubicin and 5-20 ml Lipiodol followed by gelatin sponge particles. Four weeks later, CT and MR follow-up studies were performed and PEI was subsequently started. PEI included 4-16 treatment sessions (mean: 6.8 sessions) performed under US guidance. The total amount of alcohol administered ranged 16 to 215 ml (mean: 69 ml). All patients were followed after therapy with clinical examinations. laboratory tests, and US, CT, and MR studies performed at regular time intervals. The follow-up period ranged 4 to 65 months (mean: 27.8 months; median: 26 months). No major treatment-related complication occurred. The therapeutic response, as assessed with imaging studies performed after the end of treatment, was complete tumor necrosis in 71 of 86 patients (82%) and partial tumor necrosis in the remaining 15. Overall survival rates by the Kaplan-Meier method were 92% at 1 year, 83% at 2 years, 69% at 3 years, 58% at 4 years, and 47% at 5 years. The survival of Child A patients (75% at 3 years and 59% at 5 years) was significantly longer (p < .01) than that of Child B patients (61% at 3 years and 35% at 5 years). During the follow-up, a recurrence of the treated tumors was observed in 5 patients, and new HCCs appeared in 46 patients. The 1-, 2-, 3-, 4-, and 5-year recurrence rates by the Kaplan-Meier method were 14%, 35%, 56%, 69%, and 82%, respectively. The long-term results of combined treatment with TACE and PEI confirm the effectiveness of this therapeutic approach in patients with large uninodular HCC.


Genetic variation and population structure of Sudanese populations as indicated by 15 Identifiler sequence-tagged repeat (STR) loci.
There is substantial ethnic, cultural and linguistic diversity among the people living in east Africa, Sudan and the Nile Valley. The region around the Nile Valley has a long history of succession of different groups, coupled with demographic and migration events, potentially leading to genetic structure among humans in the region. We report the genotypes of the 15 Identifiler microsatellite markers for 498 individuals from 18 Sudanese populations representing different ethnic and linguistic groups. The combined power of exclusion (PE) was 0.9999981, and the combined match probability was 1 in 7.4 × 1017. The genotype data from the Sudanese populations was combined with previously published genotype data from Egypt, Somalia and the Karamoja population from Uganda. The Somali population was found to be genetically distinct from the other northeast African populations. Individuals from northern Sudan clustered together with those from Egypt, and individuals from southern Sudan clustered with those from the Karamoja population. The similarity of the Nubian and Egyptian populations suggest that migration, potentially bidirectional, occurred along the Nile river Valley, which is consistent with the historical evidence for long-term interactions between Egypt and Nubia. We show that despite the levels of population structure in Sudan, standard forensic summary statistics are robust tools for personal identification and parentage analysis in Sudan. Although some patterns of population structure can be revealed with 15 microsatellites, a much larger set of genetic markers is needed to detect fine-scale population structure in east Africa and the Nile Valley.


Three-dimensional plant architecture and sunlit-shaded patterns: a stochastic model of light dynamics in canopies.
Diurnal changes in solar position and intensity combined with the structural complexity of plant architecture result in highly variable and dynamic light patterns within the plant canopy. This affects productivity through the complex ways that photosynthesis responds to changes in light intensity. Current methods to characterize light dynamics, such as ray-tracing, are able to produce data with excellent spatio-temporal resolution but are computationally intensive and the resulting data are complex and high-dimensional. This necessitates development of more economical models for summarizing the data and for simulating realistic light patterns over the course of a day. High-resolution reconstructions of field-grown plants are assembled in various configurations to form canopies, and a forward ray-tracing algorithm is applied to the canopies to compute light dynamics at high (1 min) temporal resolution. From the ray-tracer output, the sunlit or shaded state for each patch on the plants is determined, and these data are used to develop a novel stochastic model for the sunlit-shaded patterns. The model is designed to be straightforward to fit to data using maximum likelihood estimation, and fast to simulate from. For a wide range of contrasting 3-D canopies, the stochastic model is able to summarize, and replicate in simulations, key features of the light dynamics. When light patterns simulated from the stochastic model are used as input to a model of photoinhibition, the predicted reduction in carbon gain is similar to that from calculations based on the (extremely costly) ray-tracer data. The model provides a way to summarize highly complex data in a small number of parameters, and a cost-effective way to simulate realistic light patterns. Simulations from the model will be particularly useful for feeding into larger-scale photosynthesis models for calculating how light dynamics affects the photosynthetic productivity of canopies.


Dexamethasone and cyclosporin A modulation of human retinal pigment epithelial cell monocyte chemotactic protein-1 and interleukin-8.
To examine the modulation of interleukin-1 beta (IL-1 beta)- and tumor necrosis factor-alpha (TNF-alpha)-stimulated monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) secretion and transcription in human retinal pigment epithelial (HRPE) cells by dexamethasone (DEX) and cyclosporin A (CSA). Cultured HRPE cells were stimulated with IL-1 beta (0.2 to 20 ng/ml) or TNF-alpha (0.2 to 20 ng/ml) for 8 or 24 hours without (control) and with DEX (10(-8) to 10(-6) M) or with CSA (0.3 to 30 ng/ml). Secreted levels of HRPE MCP-1 and IL-8 were measured in the media using enzyme-linked immunosorbent assay (ELISA). Both MCP-1 and IL-8 mRNA were analyzed by Northern blot. Although DEX (10(-8) to 10(-6) M) inhibited IL-1 beta-stimulated MCP-1 and IL-8 production, it did not inhibit TNF-alpha-stimulated chemokine secretion. In contrast, CSA significantly inhibited TNF-alpha-stimulated, but not IL-1 beta-stimulated, HRPE MCP-1 and IL-8 secretion. Both DEX and CSA inhibitions showed dose dependence. Northern blot analysis of HRPE steady state MCP-1 and IL-8 mRNA corroborated the ELISA measurements of secreted MCP-1 and IL-8. Although DEX and CSA inhibit HRPE MCP-1 and IL-8 secretion, this is dependent on whether the inducing inflammatory mediator is IL-1 beta or TNF-alpha. IL-1 beta-induced chemokine secretion is sensitive to DEX, whereas MCP-1 and IL-8 induced by TNF-alpha are inhibited by CSA. This information may be useful in explaining in vivo observations and in suggesting targeted clinical treatments and combinations of immunosuppressive agents.


Protein adsorption onto CF(3)-terminated oligo(ethylene glycol) containing self-assembled monolayers (SAMs): the influence of ionic strength and electrostatic forces.
Oligo(ethylene glycol) (OEG) containing self-assembled monolayers (SAMs) on gold are known for their protein resistant properties. The underlying molecular mechanisms and the contributions of the interactions involved, however, are still not completely understood. It is known that electrostatic, van der Waals, hydrophobic, and hydration forces all play a role in the interaction between proteins and surfaces, but it is difficult to study their influence separately and to quantify their contributions. In the present study we investigate five different OEG containing SAMs and the influence of the ionic strength and the electrostatic component on the amount of a negatively charged protein (fibrinogen) that adsorbs onto them. Atomic force microscopy (AFM) was employed to record force-distance curves with hydrophobic probes depending on the ion concentration, and the amount of the protein that adsorbs relative to a hydrophobic surface was quantified using ellipsometry. The findings suggest that electrostatic forces can create a very low energy barrier thus only slightly decreasing the number of negatively charged proteins in solution with sufficient energy to approach the surface closely, and have a rather small influence on the amount that adsorbs. The films we investigated were not protein resistant. This supports other studies, reporting that a strong short-range repulsion as for example caused by hydration forces is required to make these films resistant to the non-specific adsorption of proteins.


Action-dependent plasticity in peripersonal space representations.
The space immediately around the body is represented by multisensory integrative processes implemented in frontal and parietal lobes. This network has basically a motor function-that is, planning an approaching or defensive motor response to stimuli presented close to the body. Peripersonal space representations are highly plastic as a function of experience. Indeed, using a tool to act in far space can drive an elongation of peripersonal space representation towards the acting space. In this review functional and dynamic properties of such plasticity are reviewed in light of recent experimental findings from our own group and other laboratories.


[Determination of carotenoids in flue-cured tobacco leaves during its growth by reversed-phase high performance liquid chromatography].
A reversed-phase high performance liquid chromatographic (RP-HPLC) method for the determination of carotenoids in flue-cured tobacco leaves was developed. Carotenoids were extracted from flue-cured tobacco leaves by acetone-water (90:10, v/v) solution containing 0.1% butylated hydroxytoluene (BHT). Plant proteins were eliminated by adding 0.1 g Pb(Ac)2 and by centrifugation (10000 r/min) for 5 min at 4 degrees C. Lutein, beta-carotene, neoxanthin, violaxanthin and other plant pigments were separated on a reversed-phase C18 column (3.9 mm i.d. x 150 mm, 5 microm), with a mobile phase of (A) methanol-isopropyl alcohol (1:1, v/v) and (B) water using a gradient elution at a flow rate of 0.5 mL/min. The optimum elution gradient was as follows: 0-10 min, 70% A + 30% B; 10-17 min, 100% A; 17-30 min, 90% A + 10% B. The recoveries of carotenoids in flue-cured tobacco leaves were 91.77%-97.42%, and relative standard deviations were 3. 46%-0.98%. This method was applied to determine carotenoids in flue-cured tobacco leaves during its growth with satisfactory results.


Total transmission of incident plane waves that satisfy the Brewster conditions at a free-space-chiral interface.
The common definition of the Brewster angles for dielectric and magnetic achiral materials are the angles at which the vertically and horizontally polarized reflection coefficients vanish. We examine broader definitions of the Brewster conditions for waves that are incident on a free-space-chiral interface. Besides the common definition, the Brewster angles have been defined as the angles at which the polarizations of the reflected waves are independent of the polarizations of the incident waves. We consider total transmission of incident plane waves that satisfy the Brewster conditions at a free-space-chiral medium planar interface. In this case we determine the polarization of the incident wave for which the reflected vertically and horizontally polarized waves vanish simultaneously. Thus with this definition of the Brewster conditions the polarization of the reflected wave is undefined. The conditions for the excitation of surface waves are considered. The characteristic polarizations that are the same for the reflected and incident waves are also examined subject to the Brewster conditions. Potential applications of this analysis are to experimentally determine the chiral or geotropic measure of the medium and to identify and characterize biological and chemical materials through their optical activity in real time. Several independent measurements can be taken with the same polarimetric instrument to avoid false identifications. Since measurements can be conducted in the reflection mode they can be nonintrusive.


Hypothermia blocks beta-catenin degradation after focal ischemia in rats.
Dephosphorylated and activated glycogen synthase kinase (GSK) 3beta hyperphosphorylates beta-catenin, leading to its ubiquitin-proteosome-mediated degradation. beta-catenin-knockdown increases while beta-catenin overexpression prevents neuronal death in vitro; in addition, protein levels of beta-catenin are reduced in the brain of Alzheimer's patients. However, whether beta-catenin degradation is involved in stroke-induced brain injury is unknown. Here we studied activities of GSK 3beta and beta-catenin, and the protective effect of moderate hypothermia (30 degrees C) on these activities after focal ischemia in rats. The results of Western blot showed that GSK 3beta was dephosphorylated at 5 and 24 h after stroke in the normothermic (37 degrees C) brain; hypothermia augmented GSK 3beta dephosphorylation. Because hypothermia reduces infarction, these results contradict with previous studies showing that GSK 3beta dephosphorylation worsens neuronal death. Nevertheless, hypothermia blocked degradation of total GSK 3beta protein. Corresponding to GSK 3beta activity in normothermic rats, beta-catenin phosphorylation transiently increased at 5 h in both the ischemic penumbra and core, and the total protein level of beta-catenin degraded after normothermic stroke. Hypothermia did not inhibit beta-catenin phosphorylation, but it blocked beta-catenin degradation in the ischemic penumbra. In conclusion, moderate hypothermia can stabilize beta-catenin, which may contribute to the protective effect of moderate hypothermia.


Captopril inhibits the pulmonary toxicity of paraquat in rats.
Paraquat (PQ) is a herbicide that is very toxic to all living organisms. It generates free radicals and leads to acute or chronic lung injury. Free radicals are often associated with fibrogenesis, which occurs in various disease states. The purpose of this study was to determine whether captopril prevents paraquat toxicity in lung tissue. Paraquat alone increased the level of lipid peroxidation (LPO) and the activity of superoxide dismutase (SOD) after 4, 12, 24 and 72 h of administration. Also, the level of hydroxyproline showed an increase after 24 h of paraquat administration. However, paraquat also decreased the level of glutathione (GSH) and the activity of glutathione peroxidase (GSH-Px). Captopril (50 mg/kg i.p.) and paraquat were simultaneously injected (40 mg/kg i.p.), and the captopril injection 1 h after paraquat ameliorated the biochemical toxicity induced by paraquat. This was evidenced by a significant reduction in LPO and balancing the endogenous antioxidant capacity by normalizing the activities of SOD and GSH-Px and the GSH content in the lung tissue. Moreover, captopril injection prevented the increase of hydroxyproline content as an index of lung fibrosis. From these results, the beneficial effects of captopril on paraquat toxicity appear to be through enhancement of the endogenous antioxidant system preventing the lung fibrosis.


Preparation and characterization of nuclear-envelope vesicles from rat liver nuclei.
We describe a procedure for the preparation of sealed nuclear-envelope vesicles from rat liver nuclei. These vesicles are strikingly similar in their polypeptide composition when compared with those of nuclear envelopes prepared conventionally using deoxyribonuclease I. Subfractionation analysis by means of extraction with high salt and urea show that the components of the nuclear envelope, e.g. the pore-complex/lamina fraction, are present. The residual DNA content is only 1.5%, and typical preparations consist of about 80% vesicles, with the vesicular character of these envelopes shown by microscopic and biochemical studies. The vesicles can be obtained in high yield, are tight and stable for at least two days and are enriched in a nucleoside triphosphatase thought to be involved in nucleocytoplasmic transport processes. Because the vesicles are largely free of components of the nuclear interior, but retain properties of intact nuclei, we believe that they are a valuable model system to study nucleocytoplasmic transport. Although in transport studies with isolated nuclei interference from intranuclear events has to be considered, the nuclear-envelope vesicles provide the possibility of studying translocation alone. Furthermore, the less complex nature of these vesicles compared with whole nuclei should facilitate investigation of the components involved in the regulation of nuclear transport processes.


A case with multiple accessory foramina of mandible in a fetus.
It is aimed to better recognize the mandibular variations by understanding the diversity and positions of accessory foramina better. Accessory formations on a full-term fetal mandible dissected for a mandibular study were examined under a microscope. To observe these formations more clearly, they were photographed with the help of a camera and microscope. In one of the mandibles dissected for a fetal mandibular study, a lateral accessory foramen (LAF1) was detected in the right half just near the mental foramen, and also a medial accessory foramen (MAF1) was detected over the mandibular foramen. In the left half, on the lateral surface relative to the mental foramen, one in the medial (LAF3) and one just above it (LAF2), and last one is near to the ramus of mandible (LAF4), three lateral accessory foramina, were detected. Again, a medial accessory foramen just above the left mandibular foramen (MAF3), and another foramen is near to mandibular symphysis (MAF2), also two medial accessory foramina on the lateral surface were detected. Detection and recognition of such variations are quite important for clinicians in the diagnostic methods and prevention of possible surgical complications.


The dental manifestations of the Morquio syndrome (mucopolysaccharidosis type IV). A diagnostic aid.
This study describes in detail the enamel defects in a patient in whom the diagnosis of Morquio syndrome (muchopolysaccharidosis IV) has been supported both biochemically and roentgenographically. These defects are an apparently constant feature of the Morquio syndrome, and are therefore important aids to its differential diagnosis. The defects consist of abnormally thin enamel that is rough because of the numerous minute pits on its surface. The thinness of the enamel results in altered shape and discoloration of the teeth and in their being spaced. Apart from these defects, the enamel is histologically normal and is of normal hardness and radiodensity.


Aging and vestibular system: specific tests and role of melatonin in cognitive involvement.
Balance disorders are frequent with aging. They are particularly important because they decrease social autonomy of the aged subjects and they often provoke falls. The cause is always multifactorial. There is evidence that aging affects multiple sensory inputs, as well as the muscoloskeletal system and central nervous system ability to perform sensorimotor integration. For the evaluation of decreased balance skills in elderly, a specific questionnaire has been prepared, in order to identify high risk of falling called falling risk inventory (FRI) questionnaire, and a complex psycho-sensory-motor test has been studied by means of posturography, in order to detect specific vestibular impairment. Regarding ethiopathogenesis of balance disorders in aged subjects, because the decline of behavioral and cognitive performances are due also to decline of biological rhythm control, the role of melatonin (the hormone regulating circadian rhythms, being strictly connected with cerebellar function, and it is well known that cerebellum acts in elderly both at motor and cognitive regulation. The goals of the present paper are: (i) To present a self-administered FRI questionnaire aimed at identifying possible causes of falls and quantifying falling risk in aged. (ii) To validate posturography as a specific test to investigate vestibular involvement in elderly in correlation with FRI. (iii) To present a complex behavioral test (NT) aimed at evaluating both spatial orientation and spatial memory in elderly, factors involved into the genesis of complex dizziness and unsteadiness. (iv) To evaluate the role of melatonin in cognitive involvement in dizzy, old subjects due to the functional correlations between circadian rhythms, cerebellum balance disturbances and cognitive disorders. General conclusions are: FRI correlates with falling risk. Posturography identifies specific vestibular impairments correlated to balance disorders and elderly falls. Spatial orientation is altered in about 40% of dizzy patients but no significant differences are revealed in melatonin rhythm. Spatial memory is highly altered only in subjects with inversion of circadian melatonin rhythm it is possible to hypothesize that the alteration of the normal circadian melatonin rhythm plays some role in the genesis of dizziness in a subpopulation of patients.


Phage typing of the Mycobacterium avium-intracellulare-scrofulaceum complex. A study of strains of diverse geographic and host origin.
A total of 339 strains of the Mycobacterium avium-intracellulare-scrofulaceum complex were phage typed using our previously described technique and 11 typing phages. These included 235 strains of human origin obtained from state health laboratories in Virginia, Georgia, Florida, and Arkansas, 26 strains isolated from persons with AIDS, 38 strains isolated from animals, and 40 environmental isolates. A phage-typing scheme was developed that denotes sensitivity to 8 primary typing phages: the JF group (JF1, JF2, JF3, and JF4), phage D302, and the AN group (AN3, AN9, and AN1-8). The 3 auxiliary phages (VC3, VA6, and D32) define subgroups of the strains sensitive to the AN phages. A total of 99 strains were sensitive to at least 1 phage. Of 31 serotype 1 or 2 strains from animals, 13 were sensitive to AN phages but resistant to JF phages. In contrast, 7/33 serotype 4 or 8 strains from animals or from persons with AIDS were sensitive to JF phages but not to the AN phages. Of the clinical isolates not associated with AIDS, 78/235 were phage sensitive. These strains could be divided roughly into 4 groups: sensitive to AN phages, sensitive to JF phages, sensitive to phage D302, and sensitive to multiple phages. Only 1 of the environmental isolates was phage sensitive. The results indicate that phage typing can subdivide this heterogeneous group of organisms and is a useful tool for epidemiological studies.


Aortic intimal tears: detection with spiral computed tomography.
To determine the frequency, locations, and sizes of aortic intimal tears detected using spiral computed tomography (CT). CT scans (26 single detector and 26 multidetector studies) from 52 patients with an unoperated aortic dissection and a patent false lumen were evaluated on a workstation. The number, location, and size of aortic tears were recorded and compared between the following groups: acute and chronic dissection, type A and type B, and single detector and multidetector studies. In 52 patients, 129 tears were identified (mean 2.48 per patient, median 2, range 1-7). There were no significant differences in the number or size of tears between the acute and chronic, the type A and type B, or the single detector and multidetector groups (p>0.05). The most common locations for tears were the descending aorta (57, 44%) and the juxtarenal region (26, 20%). Within the type B category, there was no significant difference in tear locations between the acute and chronic groups (p>0.05). The majority of tears (88, 68%) were < or =1 cm in each dimension. Tears in the thoracic aorta were significantly larger than abdominal aortic tears (p<0.05). All patients with an aortic dissection and a patent false lumen demonstrated one or more aortic intimal tears using spiral CT. Although most tears were small (</=1 cm), they were usually easily visualized.


[Nephrogenic adenoma. Report of 4 new cases].
Four additional cases of nephrogenic adenoma are described. The clinical records of patients with nephrogenic adenoma that had been diagnosed at our hospital from 1994 to 1999 were reviewed. The most frequent localization was the urinary bladder and it was more prevalent in middle-aged men. This condition usually presented as a histological finding in the course of follow-up or treatment of other bladder conditions by TUR or cystectomy. Biopsy is fundamental for diagnosis. Nephrogenic adenoma is a rare benign metaplastic lesion of the urinary tract that appears to result from chronic irritative stimulus to the urothelium. The treatment of choice is by transurethral resection. Although no case of progression to malignancy have been detected, long-term follow-up by endoscopy and ultrasound is advocated due to its predispositon to recurrence.


[The study on health promoting lifestyle of the elderly women].
This study was undertaken in order to determine factors affecting health promoting lifestyle of elderly women. The subjects were 299 elderly community residing women over the age 65 living in 2 large cities. The instruments used for this study were a survey of general characteristics, health promoting lifestyle(47 items), perceived health status(6 items), self-efficacy(17 items), and social support(18 items). The data was analyzed using descriptive statistics, t-test, ANOVA, Pearson correlation coefficients, and Stepwise Multiple Regression. The result of the study are as follows : The average item score for the health promoting lifestyle was 2.46, the highest score on the subscale was interpersonal support(M=2.83). A significant difference between age, education level, income, experience of smoking, alcohol, exercise, and health promoting lifestyle were found. Stepwise multiple regression analysis revealed that the most powerful predictor of health promoting lifestyle was social support(55%). Social support accounted for 54% of the variance in health promoting lifestyle in the elderly women. Therefore, health promoting programs that increase social support should be developed to promote a healthy lifestyle of the elderly women.


Enhancing or Quenching of a Mitochondria-Targeted AIEgens-Floxuridine Sensor by the Regulation of pH-Dependent Self-assembly, Efficient Recognition of Hg2+, and Stimulated Response of GSH.
Biocompatible fluorescent probes have emerged as essential tools in life sciences for visualizing subcellular structures and detecting specific analytes. Herein, we report the synthesis and characterization of a novel fluorescent probe (TPE-FdU), incorporated with hydrophilic 2'-fluoro-substituted deoxyuridine and hydrophobic ethynyl tetraphenylethene moieties, which possessed typical aggregation-induced emission (AIE) behavior. In comparison to the TPE-FdU (pKa 7.68) treated in neutral conditions, it performed well at pH 4, exhibiting an enhanced 450 nm emission signal of approximately four times stronger. As the pH value was increased to 10, the fluorescence intensity was completely quenched. The TEM images of TPE-FdU in an acidic environment (nanospherical morphology, AIE enhance, pH = 4) and in a basic environment (microrods, fluorescence quenching, pH = 9) revealed that it was a pH-dependent self-assembled probe, which was also illustrated by the interpretation of the NMR spectrum. Furthermore, the TPE-FdU probe exhibited a specific response to trace Hg2+ ions. Interestingly, the quenched fluorescence of the TPE-FdU probe caused by Hg2+ can be recovered by the addition of GSH due to the formation of the Hg-S bond being released away. MTT assay and CLSM images demonstrated that TPE-FdU was nontoxic and selectively visualized in the intracellular mitochondria. These results contributed to the development of advanced fluorescent probes with diverse applications in cell imaging, environment protection, and biomedical research.


Preoperative duplex ultrasonography evaluation for deep vein thrombosis in hip and knee arthroplasty patients.
We performed preoperative and postoperative duplex ultrasonography examinations on both lower extremities in 128 patients undergoing 146 hip and knee reconstructive procedures. The results of the examinations were reviewed by an independent radiologist who specializes in these studies. Three of the 128 patients (146 procedures; 2.1%) had evidence of a deep venous thrombosis or other venous abnormality before surgery. Three additional patients developed a deep venous thrombosis after surgery, despite mechanical and pharmacologic prophylaxis. We have discontinued performing preoperative duplex ultrasonography prior to primary, uncomplicated total joint replacement of the lower extremities. We continue to perform duplex ultrasonography before surgery in patients at high risk, with a history of deep venous thrombosis or phlebitic syndrome, and in those who have previously had major surgery on the lower extremities.


Back pain in in-vitro fertilized and spontaneous pregnancies.
The influence of ovarian stimulation in in-vitro fertilization (IVF) on the prevalence of back pain with onset during pregnancy was studied in 31 women who became pregnant after IVF treatment and compared with that of 200 spontaneously pregnant women. A two times higher prevalence rate of sacral pain in late pregnancy was reported among IVF pregnant women (P < 0.0001), as well as a significantly higher prevalence rate of positive results of pelvic pain provocation tests performed in late pregnancy (0.0001 < or = P < or = 0.015), as compared with that of the spontaneously pregnant women. Among the IVF pregnant women, there was a significant positive correlation between relaxin concentrations in early pregnancy and the outcome of pelvic pain provocation tests (0.44 < or = r < or = 0.51, P < 0.05). In addition, the serum relaxin concentration was the factor that best explained differences in sacral pain prevalence. When the influence of serum relaxin concentration on back pain prevalence was taken into account, women carrying multiple pregnancies had no more pain than women carrying singletons, and IVF pregnant women had no more pain than spontaneously pregnant women. These results support the hypothesis that relaxin is involved in the generation of pelvic pain in pregnant women.


Nuclear receptors in abdominal aortic aneurysms.
Abdominal aortic aneurysms (AAA) pose a considerable health burden and at present are only managed surgically since there is no proven pharmacotherapy that will retard their expansion or reduce the incidence of fatal rupture. This pathology shares several pathophysiological mechanisms with atherosclerosis, such as macrophage infiltration, inflammation, and degradation of extracellular matrix. Therefore, therapeutic targets proven effective in the treatment of atherosclerosis could also be considered for treatment of AAA. Different members of the nuclear receptor (NR) superfamily have been extensively studied as potential targets in the treatment of cardiovascular disease (CVD) and therefore might also be suited for AAA treatment. In this context, this review summarizes the role of different NRs in CVD, mostly atherosclerosis, and discusses in detail the current knowledge of their implications in AAA. From this overview it becomes apparent that NRs that were attributed a beneficial or adverse role in CVD have similar roles in AAA. Together, this overview provides compelling evidence to consider several NRs as attractive targets for future treatment of AAA.


Modulation of Macrophage Polarization and HMGB1-TLR2/TLR4 Cascade Plays a Crucial Role for Cardiac Remodeling in Senescence-Accelerated Prone Mice.
The aim of this study was to investigate the role of macrophage polarization in aging heart. Macrophage differentiation is pathogenically linked to many inflammatory and immune disorders. It is often preceded by myocardial inflammation, which is characterized by increased cardiac damage and pro-inflammatory cytokine levels. Therefore, we investigated the hypothesis that senescence accelerated-prone (SAMP8) mice cardiac tissue would develop macrophage polarization compared with senescence-resistant control (SAMR1) mice. Both SAMP8 and SAMR1 mice were sacrificed when they became six month old. We evaluated, histo-pathological changes and modifications in protein expression by Western blotting and immuno-histochemical staining for M1 and M2 macrophage markers, high mobility group protein (HMG)B1 and its cascade proteins, pro-inflammatory factors and inflammatory cytokines in cardiac tissue. We observed significant upregulation of HMGB1, toll-like receptor (TLR)2, TLR4, nuclear factor (NF)κB p65, tumor necrosis factor (TNF)α, cyclooxygenase (COX)2, interferon (IFN)γ, interleukin (IL)-1β, IL-6 and M1 like macrophage specific marker cluster of differentiation (CD)68 expressions in SAMP8 heart. In contrast, M2 macrophage specific marker CD36, and IL-10 expressions were down-regulated in SAMP8 mice. The results from the study demonstrated that, HMGB1-TLR2/TLR4 signaling cascade and induction of phenotypic switching to M1 macrophage polarization in SAMP8 mice heart would be one of the possible reasons behind the cardiac dysfunction and thus it could become an important therapeutic target to improve the age related cardiac dysfunction.


Genome-wide identification of ABCC gene family and their expression analysis in pigment deposition of fiber in brown cotton (Gossypium hirsutum).
ABC (ATP-binding cassette) transporters are a class of superfamily transmembrane proteins that are commonly observed in natural organisms. The ABCC (ATP-binding cassette C subfamily) protein belongs to a subfamily of the ABC protein family and is a multidrug resistance-associated transporter that localizes to the tonoplast and plays a significant role in pathogenic microbial responses, heavy metal regulation, secondary metabolite transport, and plant growth. Recent studies have shown that the ABCC protein is also involved in the transport of anthocyanins/proanthocyanidins (PAs). To clarify the types and numbers of ABCC genes involved in PA transport in Gossypium hirsutum, the phylogenetic evolution, physical location, and structure of ABCC genes were classified by bioinformatic methods in the upland cotton genome, and the expression levels of these genes were analyzed at different developmental stages of the cotton fiber. The results showed that 42 ABCC genes were initially identified in the whole genome of upland cotton; they were designated GhABCC1-42. The gene structure and phylogenetic analysis showed that the closely related ABCC genes were structurally identical. The analysis of chromosomal localization demonstrated that there were no ABCC genes on the chromosomes of AD/At2, AD/At5, AD/At6, AD/At10, AD/At12, AD/At13, AD/Dt2, AD/Dt6, AD/Dt10, and AD/Dt13. Outside the genes, there were ABCC genes on other chromosomes, and gene clusters appeared on the two chromosomes AD/At11 and AD/Dt8. Phylogenetic tree analysis showed that some ABCC proteins in G. hirsutum were clustered with those of Arabidopsis thaliana, Vitis vinifera and Zea mays, which are known to function in anthocyanin/PA transport. The protein structure prediction indicated that the GhABCC protein structure is similar to the AtABCC protein in A. thaliana, and most of these proteins have a transmembrane domain. At the same time, a quantitative RT-PCR analysis of 42 ABCC genes at different developmental stages of brown cotton fiber showed that the relative expression levels of GhABCC24, GhABCC27, GhABCC28, GhABCC29 and GhABCC33 were consistent with the trend of PA accumulation, which may play a role in PA transport. These results provide a theoretical basis for further analysis of the function of the cotton ABCC genes and their role in the transport of PA.