Metabolism of trans-stilbene in rabbits and rats.
The biotransformation of intramuscularly administered 14C-labeled trans-stilbene was investigated in both rabbits and rats. In rabbits radioactivity was excreted (78.8% in 17 days) almost exclusively in the urine. In rats, feces accounted for more than half of the total excretion (80.3% in 19 days). Hydroxylated metabolites in urine and feces were identified by thin-layer chromatography and quantitated by liquid scintillation counting. They were 4-hydroxy and 4,4'-dihydroxystilbene, and the two monomethyl ethers of 3,4-dihydroxystilbene and 4,4'-dihydroxybibenzyl. In addition, four polyhydroxylated metabolites of stilbene and bibenzyl were identified in rat urine by comparison of gas-liquid chromatography retention times of their silyl derivatives with synthetic reference compounds. They were 3,4,4'-trihydroxystilbene, and 3,4-dihydroxy-, 3,4,4'=trihydroxy-, and 3,4,3',4'-tetrahydroxybibenzyl. Oxidative cleavage of trans-stilbene to benzoic acid and 4-hydroxy- and 3,4-dihydroxybenzoic acid was established by the presence of both the free acids and conjugates of these compounds in both rabbit and rat urine. Their glycine conjugates were identified by thin-layer chromatography and quantitated by reverse isotope dilution procedures from unhydrolyzed rabbit and rat urine. Percentages obtained indicate that cleavage of trans-stilbene is more extensive in rabbits (9.5%) than in rats (2.7%).


A sialidase mutant displaying trans-sialidase activity.
Trypanosoma cruzi, the agent of Chagas disease, expresses a modified sialidase, the trans-sialidase, which transfers sialic acid from host glycoconjugates to beta-galactose present in parasite mucins. Another American trypanosome, Trypanosoma rangeli, expresses a homologous protein that has sialidase activity but is devoid of transglycosidase activity. Based on the recently determined structures of T.rangeli sialidase (TrSA) and T.cruzi trans-sialidase (TcTS), we have now constructed mutants of TrSA with the aim of studying the relevant residues in transfer activity. Five mutations, Met96-Val, Ala98-Pro, Ser120-Tyr, Gly249-Tyr and Gln284-Pro, were enough to obtain a sialidase mutant (TrSA(5mut)) with trans-sialidase activity; and a sixth mutation increased the activity to about 10% that of wild-type TcTS. The crystal structure of TrSA(5mut) revealed the formation of a trans-sialidase-like binding site for the acceptor galactose, primarily defined by the phenol group of Tyr120 and the indole ring of Trp313, which adopts a new conformation, similar to that in TcTS, induced by the Gln284-Pro mutation. The transition state analogue 2,3-didehydro-2-deoxy-N-acetylneuraminic acid (DANA), which inhibits sialidases but is a poor inhibitor of trans-sialidase, was used to probe the active site conformation of mutant enzymes. The results show that the presence of a sugar acceptor binding-site, the fine-tuning of protein-substrate interactions and the flexibility of crucial active site residues are all important to achieve transglycosidase activity from the TrSA sialidase scaffold.


Sex, weight status, and chronic kidney disease among African Americans: the Jackson Heart Study.
Obesity has been shown to have implications for chronic kidney disease (CKD); however, it has received minimal attention from scientists studying CKD among African Americans. The purpose of this study was to examine the manner in which weight status has implications for CKD among this group through analysis of data drawn from the Jackson Heart Study (JHS). Cross-sectional analysis of a single-site longitudinal population-based cohort. The data for this study were drawn from the baseline examination of the Jackson Heart Study (JHS). The analytic cohort consisted of 3430 African American men and women (21-84 years of age) living in the tricounty area of the Jackson, Mississippi metropolitan areas with complete data to determine CKD status. The primary dependent variable was CKD (defined as the presence of albuminuria or reduced estimated glomerular filtration rate <60 mL/min per 1.73 m(2)). Weight status, the primary predictor, was a 4-category measure based on body mass index. Associations were explored through bivariable analyses and multivariable logistic regression analyses adjusting for CKD, weight status, diabetes, hypertension, and cardiovascular disease risk factors as well as demographic factors. The prevalence of CKD in the JHS was 20%. The proportion of overweight, class I, and class II obese individuals was 32.5%, 26.9%, and 26.2% respectively. In the pooled model, weight status was not found to be associated with CKD; however, subgroup analysis revealed that class II obesity was associated with CKD among men (odds ratio, 2.37; confidence interval, 1.34-4.19) but not among women (odds ratio, 1.32; confidence interval, 0.88-1.98). The relationship between CKD prevalence and diabetes and CKD prevalence and hypertension varied by sex and differed across weight categories. Weight status has implications for CKD among the JHS participants, and this study underscores the need for additional research investigating the relationship between weight status, sex, and CKD among African Americans.


Insulin-like growth factors and aging.
Since its proposal three decades ago, the evidence in favor of the somatomedin hypothesis has been compelling. It is clear that somatotrophic actions of growth hormone are mediated through generation of insulin-like peptides and interaction of these peptides with plasma membrane receptors on sensitive cells. It is possible that such actions result from effects of circulating insulin-like peptides and/or insulin-like peptides generated in proximity to their sites of action (autocrine or paracrine effects). Most or all of circulating somatomedin activity in humans can be accounted for by insulin-like growth factors I and II (IFGs I and II). These peptides have considerable structural homology with insulin but, unlike insulin, they circulate in tight, noncovalent association with specific carrier protein. Levels of circulating IGF I and IGF II are affected by growth hormone, but the former peptide is the more sensitive to growth hormone. Levels of circulating IGF I in humans are low at birth, rise progressively during childhood, and peak during midadolescence. The increase in stature that occurs normally during adolescence probably results from this increase in circulating IGF I. Following adolescence, levels of circulating IGF I fall progressively as a function of age. There is good evidence that the reduction in levels of circulating IGF I is related to decreased secretion of growth hormone that accompanies aging. Although it has been suggested that decreased function of the growth hormone-somatomedin axis may cause changes in anabolic indices that accompany the aging process, definitive proof for this hypothesis is lacking. In contrast to IGF I, circulating IGF II reaches "adult" levels early in childhood, and changes are relatively small as a function of increasing age. Counterparts of IGF I and IGF II are present in rats. Dynamics of the growth hormone-somatomedin axis are similar in rats and humans for IGF I. In contrast, levels of IGF II in rat fall precipitously following birth, suggesting a role for rat IGF II in fetal growth and development. The rat has been used as an experimental animal to define the role of the growth hormone-somatomedin axis in aging. As in human studies, no firm relationship between somatomedins and aging has been established in the rat.


[Radiometabolic therapy for metastatic thyroid carcinoma: overview of the literature and rational bases for the use of recombinant human TSH].
The established treatment for differentiated thyroid carcinoma (DTC) is founded on total thyroidectomy and subsequent administration of radioiodine (131I) to ablate the thyroid remnant and to treat the metastatic disease. In the case of metastatic or recurrent disease, further cycles of 131I therapy are often necessary. The condition for maximizing the effectiveness of the treatment is to have an adequate stimulation from TSH, which must be >25-30 mIU/L. This elevation is achieved either discontinuing the hormone suppression therapy for an appropriate period, or administering recombinant human TSH (rhTSH). The latter has shown good clinical efficacy in patients with residual thyroid gland and is nowadays commonly employed since it is easy to use and allows to avoid the side effects of hypothyroidism. It thus represents a good alternative to thyroid hormone withdrawal for the remnant ablation, while is still open the question if its efficacy on the management of metastatic disease is superimposable to thyroid hormone withdrawal. To this purpose, a Panel of expert reviewed the literature, assessing the advantages and disadvantages for the patient, as well as the impact in terms of cost and benefit to the National Health Service. The work of the Panel concluded with a proposal for the use of rhTSH in selected patients with metastatic DTC, in which is considered the efficacy and safety of the product and is examined its use in terms of costs; this proposal was accepted by the Italian Drug Agency resulting in an update of the indications for rhTSH.


Flow-diverting device versus coil embolization for unruptured intracranial aneurysm: A meta-analysis.
Both coil embolization (CE) and flow-diverting device (FDD) placement are widely used for treatment of intracranial aneurysms (IAs). The aim of this meta-analysis is to compare the relative clinical safety and efficacy of FDD and CE for the treatment of unruptured IAs. The PubMed, Embase, and Cochrane Library databases were searched for relevant studies from the date of inception through April 2020. The primary endpoint for this meta-analysis was the 6-month rate of complete occlusion, while secondary endpoints included rates of retreatment, complications, and parental arterial patency. This meta-analysis includes 8 studies, which included 839 total patients that underwent FDD and 2734 that underwent CE. FDD group exhibited a significantly higher pooled 6-month complete occlusion rate (P = .02). The subgroup analysis demonstrated that FDD treatment was associated with significantly higher pooled 6-month complete occlusion rates in patients with large or giant IAs (P < .00001), whereas no differences in 6-month complete occlusion rates were observed between the FDD and CE groups of patients with non-large/giant IAs (P = .83). The pooled retreatment (P = .16) and complication (P = .15) rates were comparable between 2 groups. The CE group exhibited significantly higher pooled parent artery patency rate (P = .01). The funnel plots did not reveal any evidence of publication bias. FDDs can be used to effectively and safely treat large and giant IAs, achieving higher rates of complete occlusion than CE treatment. For non-large/giant IAs, we observed comparable efficacy between FDD and CE treatments.


Mo-Terminated Edge Reconstructions in Nanoporous Molybdenum Disulfide Film.
The catalytic and magnetic properties of molybdenum disulfide (MoS2) are significantly enhanced by the presence of edge sites. One way to obtain a high density of edge sites in a two-dimensional (2D) film is by introducing porosity. However, the large-scale bottom-up synthesis of a porous 2D MoS2 film remains challenging and the correlation of growth conditions to the atomic structures of the edges is not well understood. Here, using molecular beam epitaxy, we prepare wafer-scale nanoporous MoS2 films under conditions of high Mo flux and study their catalytic and magnetic properties. Atomic-resolution electron microscopy imaging of the pores reveals two new types of reconstructed Mo-terminated edges, namely, a distorted 1T (DT) edge and the Mo-Klein edge. Nanoporous MoS2 films are magnetic up to 400 K, which is attributed to the presence of Mo-terminated edges with unpaired electrons, as confirmed by density functional theory calculation. The small hydrogen adsorption free energy at these Mo-terminated edges leads to excellent activity for the hydrogen evolution reaction.


Immunocytochemical localization of band 3 protein in the rat collecting duct.
Band 3 protein is the major anion transport protein of the erythrocyte cell membrane where it catalyzes the exchange of HCO3- for Cl-. There is evidence that band 3 protein is present in the collecting duct of both the rat and rabbit kidney. We used colloidal-gold immunocytochemistry to determine the ultrastructural location of band 3 protein in the rat cortical (CCD) and outer medullary collecting ducts (OMCD). Kidneys of normal Sprague-Dawley rats were fixed by intravascular perfusion with 1% glutaraldehyde and embedded in Lowicryl K4M. Two polyclonal antibodies raised in rabbits were used as the primary antibody in separate experiments, one against the 43-kDa fragment of the cytoplasmic domain of human erythrocyte band 3 protein and the other against rat erythrocyte band 3 protein. This was followed by exposure to gold-conjugated goat anti-rabbit immunoglobulin G. Transmission electron microscopy revealed gold particles along the basal and lateral plasma membranes of all intercalated cells of the OMCD. In the CCD, the basal and lateral plasma membranes of the type A intercalated cells only were labeled with gold particles. The type B intercalated cells and principal cells were devoid of gold particles, as were all cells of the proximal tubule, the distal convoluted tubule, and the thick ascending limb of the loop of Henle. We conclude that a Cl(-)-HCO3- transporter is present in the basal and lateral plasma membranes of the intercalated cells in the OMCD and the type A intercalated cells in the CCD. These findings provide further evidence that these intercalated cells are involved in H+ secretion in the OMCD and CCD of the rat. We have no evidence for the presence of band 3 protein in the type B intercalated cells of the CCD, which supports the hypothesis that type B cells are functionally and structurally distinct from type A cells.


Effect of alpha-interferon and alpha-tocopherol in reversing hepatic cirrhosis in rats.
The aim of this study was to assess the effects of alpha-interferon and alpha-tocopherol (vitamin E), or a combination of both, in reversing hepatic fibrosis following the induction of cirrhosis using thioacetamide by histological and biochemical analysis. Fifty male Wistar rats were used in this study. The animals were divided equally into five groups. Animals in group I were used as controls. The remaining animals (groups II-V) were provided with 0.5 g/L of thioacetamide in order to induce liver cirrhosis. Group II animals were used as the cirrhotic control. Animals of groups III, IV and V were given alpha-interferon, alpha-tocopherol and interferon together with alpha-tocopherol, respectively, for 30 days. After 30 days the animals were killed and following gross morphological examination of the liver, the hepatic tissues were processed for histological analysis and the serum was used for liver function tests. Morphological analysis showed a decrease in the number of nodules on the surface of the liver in both interferon- as well as vitamin E-treated cirrhotic rats. Histopathological analysis showed that the abnormalities of the cirrhotic liver were partially reversed and liver function tests showed an overall improvement following treatment of animals of groups III, IV and V. Combination therapy using both interferon and alpha-tocopherol did not have any substantial effect on the rats compared with that when they were given separately. These findings suggest that alpha-interferon and alpha-tocopherol may have therapeutic value in reversing liver cirrhosis.


Glutamatergic neural transmission in the nucleus tractus solitarius: N-methyl-D-aspartate receptors.
1. The nucleus tractus solitarius (NTS) is the first central site where the reflex control of autonomic, including baroreceptor, reflex function is coordinated. Autonomic signals are transmitted from the first-order visceral afferent fibres to second-order NTS neurons by L-glutamate. It is well established that activation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) receptors, which mediate the fast component of L-glutamate signalling, is required for generating changes in membrane potentials of the second-order NTS neurons. The contribution of the slower-developing, longer-lasting N-methyl-D-aspartate (NMDA) receptor-mediated component of glutamate signalling to synaptic transmission at these synapses is less well understood. 2. The aim of this work is to highlight evidence that functional NMDA receptors exist on second-order NTS neurons in autonomic, including baroreceptor, afferent pathways by determining whether NMDA receptors can be activated by: (i) exogenous application of NMDA; and (ii) endogenous release of L-glutamate from autonomic afferent fibres. Studies were performed on second-order neurons in transverse and horizontal brainstem slices containing the intermediate NTS and the tractus solitarius. Second-order NTS neurons were identified by electrophysiological criteria or by attached fluorescent-labelled aortic depressor nerve (ADN) boutons. 3. N-Methyl-D-aspartate (50 nmol(-2) micromol) dose-dependently evoked excitatory post-synaptic currents in second-order NTS neurons (P = 0.004; n = 4). The NMDA receptor-mediated currents were also synaptically evoked by low-frequency stimulation of the autonomic afferent fibres in the tractus solitarius. The NMDA receptor-mediated currents were blocked by the NMDA receptor antagonist AP5 (n = 7; P = 0.027). 4. The findings suggest that functional NMDA receptors exist on second-order NTS neurons. While the NMDA receptor- mediated currents may not be required for signal transmission when the second-order neurons are at resting membrane potential, their activation may help to modulate autonomic signal transmission in the NTS under conditions in which the membrane is depolarized by high frequency or convergent inputs.


Parent-adolescent relationships, religiosity, and the social adjustment of Indonesian Muslim adolescents.
Parent-adolescent relationships invariably occur within a complex cultural context that in some populations include strong religious influences. Using data from multiple sources that were analyzed using structural equation modeling, we found that parental warmth and parental religiosity predicted adolescent religiosity in a sample of 296 Indonesian 15-year-old adolescents. The significant interaction of parental warmth and parent religiosity indicated that parental warmth moderated the relation between parent religiosity and adolescent religiosity. We expanded this model to predict externalizing and prosocial behavior where direct paths from adolescent religiosity to outcomes were significant for prosocial but not antisocial behavior; parental warmth, parent religiosity, and their interaction did not predict either outcome. Adolescent religiosity was found to be a mediator of these relations between predictor and outcomes for prosocial but not antisocial behavior. These results suggest that, in Indonesia and perhaps other highly religious cultures, parent-adolescent relationships and social competence may be interconnected with religion.


Prediction and attenuation of seasonal spillover of parasites between wild and domestic ungulates in an arid mixed-use system.
Transmission of parasites between host species affects host population dynamics, interspecific competition, and ecosystem structure and function. In areas where wild and domestic herbivores share grazing land, management of parasites in livestock may affect or be affected by sympatric wildlife due to cross-species transmission.We develop a novel method for simulating transmission potential based on both biotic and abiotic factors in a semi-arid system in Botswana. Optimal timing of antiparasitic treatment in livestock is then compared under a variety of alternative host scenarios, including seasonally migrating wild hosts.In this region, rainfall is the primary driver of seasonality of transmission, but wildlife migration leads to spatial differences in the effectiveness of treatment in domestic animals. Additionally, competent migratory wildlife hosts move parasites across the landscape.Simulated transmission potential matches observed patterns of clinical disease in livestock in the study area. Increased wildlife contact is correlated with a decrease in disease, suggesting that non-competent wild hosts may attenuate transmission by removing infective parasite larvae from livestock pasture.Optimising the timing of treatment according to within-year rainfall patterns was considerably more effective than treating at a standard time of year. By targeting treatment in this way, efficient control can be achieved, mitigating parasite spillover from wildlife where it does occur. Synthesis and applications. This model of parasite transmission potential enables evidence-based management of parasite spillover between wild and domestic species in a spatio-temporally dynamic system. It can be applied in other mixed-use systems to mitigate parasite transmission under altered climate scenarios or changes in host ranges.


Kaempferol Induces G2/M Cell Cycle Arrest via Checkpoint Kinase 2 and Promotes Apoptosis via Death Receptors in Human Ovarian Carcinoma A2780/CP70 Cells.
Kaempferol is a widely distributed dietary flavonoid. Epidemiological studies have demonstrated kaempferol consumption lowers the risk of ovarian cancer. Our previous research proved that kaempferol suppresses human ovarian cancer cells by inhibiting tumor angiogenesis. However, the effects of kaempferol on the cell cycle and extrinsic apoptosis of ovarian cancer cells have not yet been studied. In the present study, we demonstrated that kaempferol induced G2/M cell cycle arrest via the Chk2/Cdc25C/Cdc2 pathway and Chk2/p21/Cdc2 pathway in human ovarian cancer A2780/CP70 cells. Chk2 was not responsible for kaempferol-induced apoptosis and up-regulation of p53. Kaempferol stimulated extrinsic apoptosis via death receptors/FADD/Caspase-8 pathway. Our study suggested that Chk2 and death receptors played important roles in the anticancer activity of kaempferol in A2780/CP70 cells. These findings provide more evidence of the anti-ovarian cancer properties of kaempferol and suggest that kaempferol could be a potential candidate for ovarian cancer adjuvant therapy.


Tumor necrosis factor-alpha polymorphism, bone strength phenotypes, and the risk of fracture in older women.
TNFalpha is a proinflammatory cytokine that promotes osteoclastic bone resorption. We evaluated the association between a G-308A polymorphism (rs1800629) at the TNFA locus and osteoporosis phenotypes in 4306 older women participating in the Study of Osteoporotic Fractures. Femoral neck bone mineral density (BMD) and structural geometry were measured using dual-energy x-ray absorptiometry and hip structural analysis. Incident fractures were confirmed by physician adjudication of radiology reports. Despite similar femoral neck BMD, women with the A/A genotype had greater subperiosteal width (P = 0.01) and endocortical diameter (P = 0.03) than those with the G/G genotype. The net result of these structural differences was that there was a greater distribution of bone mass away from the neutral axis of the femoral neck in women with the A/A genotype, resulting in greater indices of bone bending strength (cross-sectional moment of inertia: P = 0.004; section modulus: P = 0.003). Among 376 incident hip fractures during 12.1 yr of follow-up, a 22% decrease in the risk of hip fracture was seen per copy of the A allele (relative risk 0.78; 95% confidence interval 0.63, 0.96), which was not influenced by adjustments for potential confounding factors, BMD, or bone strength indices. The G-308A polymorphism was not associated with a reduced risk of other fractures. These results suggest a potential role of genetic variation in TNFalpha in the etiology of osteoporosis.


Socioeconomic factors analysis for COVID-19 US reopening sentiment with Twitter and census data.
Investigating and classifying sentiments of social media users (e.g., positive, negative) towards an item, situation, and system are very popular among researchers. However, they rarely discuss the underlying socioeconomic factor associations for such sentiments. This study attempts to explore the factors associated with positive and negative sentiments of the people about reopening the economy, in the United States (US) amidst the COVID-19 global crisis. It takes into consideration the situational uncertainties (i.e., changes in work and travel patterns due to lockdown policies), economic downturn and associated trauma, and emotional factors such as depression. To understand the sentiment of the people about the reopening economy, Twitter data was collected, representing the 50 States of the US and Washington D.C, the capital city of the US. State-wide socioeconomic characteristics of the people (e.g., education, income, family size, and employment status), built environment data (e.g., population density), and the number of COVID-19 related cases were collected and integrated with Twitter data to perform the analysis. A binary logit model was used to identify the factors that influence people toward a positive or negative sentiment. The results from the logit model demonstrate that family households, people with low education levels, people in the labor force, low-income people, and people with higher house rent are more interested in reopening the economy. In contrast, households with a high number of family members and high income are less interested in reopening the economy. The accuracy of the model is reasonable (i.e., the model can correctly classify 56.18% of the sentiments). The Pearson chi-squared test indicates that this model has high goodness-of-fit. This study provides clear insights for public and corporate policymakers on potential areas to allocate resources, and directional guidance on potential policy options they can undertake to improve socioeconomic conditions, to mitigate the impact of pandemic in the current situation, and in the future as well.


[The first-choice technic for assessing myocardial viability. Stress echocardiography].
Myocardial viability can be studied by different techniques. Although PET is considered to be the technique of choice, both isotopes and stress echocardiography have demonstrated their usefulness in clinical practice. While the former has high sensitivity, the latter has better specificity. The differences in results between these two techniques may be due to the fact that they each evaluate different aspects: isotopes detect the presence of viable cells, whereas echocardiography assesses the contractility reserve of hibernating myocardium. If by viability we mean improvement in contractility, stress echocardiography should be considered the technique of choice. Although this technique is considered to be partially limited by image quality and inter-observer variability, recent technological advances should overcome these problems. Availability, cost and access to information are also important advantages of stress echocardiography.


Two processing pathways for the MHC class II-restricted presentation of exogenous influenza virus antigen.
The natural Ag influenza virus A was used to test the requirements for the HLA-DR1-restricted presentation of the epitopes 18-29 in the matrix protein and 307-318 in the hemagglutinin protein. CD4+ cytotoxic T cell clones of similar efficiency were used to detect presentation of these two epitopes. Presentation of the matrix epitope by APC pulsed with either inactivated virus particles or purified soluble protein followed the classical pathway in that 1) it required invariant chain expression, 2) it was blocked by inhibition of protein synthesis, and 3) it was dependent on a function(s) encoded in the MHC class II region. These characteristics suggest that peptides corresponding to the matrix epitope can only load onto newly synthesized class II molecules that were targeted to a processing compartment by the invariant chain. In contrast, presentation of the hemagglutinin epitope processed from virus particles followed a different pathway. First, presentation of hemagglutinin was independent of invariant chain expression. Second, a human B lymphoblastoid cell line in which protein synthesis was inhibited for 9 h was still able to present hemagglutinin even at very low doses of Ag. Third, a DR1-transfected mutant B cell line missing the MHC class II region was able to present hemagglutinin. Thus, mature class II alpha beta molecules can acquire immunogenic peptides derived from intact natural Ags for presentation to CD4+ T cells. This pathway may be useful for the binding of peptides derived from Ags that are rapidly degraded upon uptake into APC.


Downregulation of OSR1 Promotes Colon Adenocarcinoma Progression via FAK-Mediated Akt and MAPK Signaling.
Odd-skipped related transcription factor 1 (OSR1) is a newly identified tumor suppressor in many tumor types. However, the role and mechanism of OSR1 in colon adenocarcinoma (COAD) remain unknown. OSR1 expression was detected in COAD tissues and cells. COAD cells with OSR1 overexpression or knockdown were analyzed by in vitro CCK-8, transwell and flow cytometry assays, and by in vivo xenograft model. OSR1 expression was downregulated in COAD and low expression level of OSR1 was positively correlated with tumor stage and lymph node metastasis. Furthermore, low OSR1 expression was significantly associated with poor overall survival (OS) and distant metastasis-free survival (DMFS). Lentivirus-mediated restoration of OSR1 expression-inhibited proliferation, invasion and migration while induced cell cycle arrest and apoptosis in COAD cells in vitro, and inhibited tumor growth in vivo. In contrast, OSR1 knockdown promoted proliferation, invasion and migration in COAD cells in vitro. Mechanistically, OSR1 exerted anticancer effects by inhibiting FAK-mediated activation of Akt and MAPK pathways. Our findings suggest that OSR1 functions as a tumor suppressor in COAD by suppressing FAK-mediated activation of Akt and MAPK pathways.


Orchestrating privacy-protected big data analyses of data from different resources with R and DataSHIELD.
Combined analysis of multiple, large datasets is a common objective in the health- and biosciences. Existing methods tend to require researchers to physically bring data together in one place or follow an analysis plan and share results. Developed over the last 10 years, the DataSHIELD platform is a collection of R packages that reduce the challenges of these methods. These include ethico-legal constraints which limit researchers' ability to physically bring data together and the analytical inflexibility associated with conventional approaches to sharing results. The key feature of DataSHIELD is that data from research studies stay on a server at each of the institutions that are responsible for the data. Each institution has control over who can access their data. The platform allows an analyst to pass commands to each server and the analyst receives results that do not disclose the individual-level data of any study participants. DataSHIELD uses Opal which is a data integration system used by epidemiological studies and developed by the OBiBa open source project in the domain of bioinformatics. However, until now the analysis of big data with DataSHIELD has been limited by the storage formats available in Opal and the analysis capabilities available in the DataSHIELD R packages. We present a new architecture ("resources") for DataSHIELD and Opal to allow large, complex datasets to be used at their original location, in their original format and with external computing facilities. We provide some real big data analysis examples in genomics and geospatial projects. For genomic data analyses, we also illustrate how to extend the resources concept to address specific big data infrastructures such as GA4GH or EGA, and make use of shell commands. Our new infrastructure will help researchers to perform data analyses in a privacy-protected way from existing data sharing initiatives or projects. To help researchers use this framework, we describe selected packages and present an online book (https://isglobal-brge.github.io/resource_bookdown).


Immunochemical identification and preliminary characterization of a nonfimbrial hemagglutinating adhesin of Bacteroides gingivalis.
A cell-bound hemagglutinating adhesin (HA-Ag2) of Bacteroides gingivalis was identified by crossed immunoaffinity electrophoresis as one of the common antigens of the species. A polyclonal antiserum with a restricted specificity for HA-Ag2 was produced by immunizing with the relevant immunoprecipitate excised from crossed-immunoelectrophoresis gels. The immunoglobulin G fraction of this monospecific antiserum inhibited hemagglutination. The antiserum was used against a cell surface extract of B. gingivalis in immunoblotting experiments, and we detected two antigens with apparent molecular masses of 33 and 38 kilodaltons in B. gingivalis ATCC 33277 and W83. Monoclonal antibody, C1.17, produced in another laboratory against B. gingivalis 381 and characterized as showing reactivity with a hemagglutinin of this strain (Y. Naito, K. Okuda, T. Kato, and I. Takazoe, Infect. Immun. 50:231-235, 1985), was also used to produce immunoblots of extracts of strains ATCC 33277 and W83. The apparent molecular masses of the major polypeptides recognized by monoclonal C1.17 in the immunoblots were the same as those detected by the polyclonal monospecific antiserum, i.e., 33 and 38 kilodaltons. Significantly, none of the polypeptides identified in this study corresponded to the polypeptide appearing in the 41- to 43-kilodalton region and identified by Yoshimura and co-workers (F. Yoshimura, K. Takahashi, N. Yoshinobu, and T. Suzuki, J. Bacteriol. 160:949-957, 1984) as the fimbrial protein characteristic of the species. Enzyme-linked immunosorbent assay inhibition experiments with the monospecific antiserum indicated that the cell surface extracts from strains ATCC 33277 and W83 were strong inhibitors, whereas the fimbria-enriched preparations from both strains failed to inhibit binding of antibodies to the cell surface antigens. As a whole, our study indicates that a nonfimbrial surface protein complex demonstrating erythrocyte-binding capacity, HA-Ag2, is common to three strains of B. gingivalis and is composed of at least two associated polypeptides with apparent molecular masses of 33 and 38 kilodaltons which share at least one antigenic determinant.


Function and prognostic value of basement membrane -related genes in lung adenocarcinoma.
Background: Lung adenocarcinoma (LUAD) has become a common cause of cancer-related death. Many studies have shown that the basement membrane (BM) is associated with the development of cancer. However, BM-related gene expression and its relationship to LUAD prognosis remains unclear. Methods: BM-related genes from previous studies were used. Clinical and mRNA expression information were obtained from TCGA database. Cox, minimum absolute contraction, and selection operator regression were applied to analyze the selected genes affecting LUAD prognosis. A prognostic-risk model was then established. Furthermore, this study applied Kaplan-Meier analysis to assess the outcomes of high- and low-risk groups, then explored their differences in drug sensitivity. The DSigDB database was used to screen for therapeutic small-molecule drugs. Results: Fourteen prognostic models based on BM-related genes were successfully constructed and validated in patients with LUAD. We also found that independence was a prognostic factor in all 14 BM-based models. Functional analysis showed that the enrichment of BM-related genes mainly originated from signaling pathways related to cancer. The BM-based model also suggested that immune cell infiltration is associated with checkpoints. The low-risk patients may benefit from cyclopamine and docetaxel treatments. Conclusion: This study identified a reliable biomarker to predict survival in patients with LUAD and offered new insights into the function of BM-related genes in LUAD.


Quantifying the Effects of Hip Surgery on the Sphericity of the Femoral Head in Patients with Mucopolysaccharidosis Type I.
The introduction of stem cell transplantation has improved life expectancy and cognitive outcome in patients with mucopolysaccharidosis I, but this condition remains associated with substantial residual disease in several parts of the body. Many patients have hip dysplasia with progressive medial flattening of the femoral head. Quantitative evidence on the effect of surgery on remodeling to sphericity of flattened femoral heads is lacking. In the present study, we used statistical shape modeling to quantify the effect of hip surgery on the sphericity of the femoral head in patients with mucopolysaccharidosis I. We performed a retrospective case control study involving a series of 23 patients with hip dysplasia due to mucopolysaccharidosis I. Surgery was not offered to the first 11 children (control group). Following a change in treatment protocol, the next 12 children underwent bilateral proximal femoral varus derotation osteotomy and Pemberton osteotomy for the treatment of acetabular dysplasia with progressive femoral head flattening (surgery group). The surgery and control groups were compared with a reference group of patients with normal hips. Statistical shape modeling was used to quantify the shape of the femoral head (i.e., flattening and/or roundness of the epiphysis). The mean age at the time of stem cell transplantation in the surgery and control groups was comparable (1.2 years). The mean age at the time of surgical intervention was 5.5 years, and mean duration of postoperative follow-up was 3.3 years. Statistical shape modeling showed variations within the total group in terms of medial indentation, width, height, and sphericity of the femoral heads. In contrast to the progressive femoral head flattening in the control group, the surgery group showed improvement of the sphericity of the femoral head after surgery. The overall shape characteristics of the femoral head in the surgery group were similar to those of the reference group of patients with normal hips. To our knowledge, this is the first study in patients with mucopolysaccharidosis I that has shown quantitative remodeling of the dysplastic, flattened femoral head to normal sphericity after increasing containment of the femoral head. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Understanding Resilience and Mental Well-Being in Southwest Indigenous Nations and the Impact of COVID-19: Protocol for a Multimethods Study.
Despite experiencing many adversities, American Indian and Alaska Native populations have demonstrated tremendous resilience during the COVID-19 pandemic, drawing upon Indigenous determinants of health (IDOH) and Indigenous Nation Building. Our multidisciplinary team undertook this study to achieve two aims: (1) to determine the role of IDOH in tribal government policy and action that supports Indigenous mental health and well-being and, in turn, resilience during the COVID-19 crisis and (2) to document the impact of IDOH on Indigenous mental health, well-being, and resilience of 4 community groups, specifically first responders, educators, traditional knowledge holders and practitioners, and members of the substance use recovery community, working in or near 3 Native nations in Arizona. To guide this study, we developed a conceptual framework based on IDOH, Indigenous Nation Building, and concepts of Indigenous mental well-being and resilience. The research process was guided by the Collective benefit, Authority to control, Responsibility, Ethics (CARE) principles for Indigenous Data Governance to honor tribal and data sovereignty. Data were collected through a multimethods research design, including interviews, talking circles, asset mapping, and coding of executive orders. Special attention was placed on the assets and culturally, socially, and geographically distinct features of each Native nation and the communities within them. Our study was unique in that our research team consisted predominantly of Indigenous scholars and community researchers representing at least 8 tribal communities and nations in the United States. The members of the team, regardless of whether they identified themselves as Indigenous or non-Indigenous, have many collective years of experience working with Indigenous Peoples, which ensures that the approach is culturally respectful and appropriate. The number of participants enrolled in this study was 105 adults, with 92 individuals interviewed and 13 individuals engaged in 4 talking circles. Because of time constraints, the team elected to host talking circles with only 1 nation, with participants ranging from 2 to 6 in each group. Currently, we are in the process of conducting a qualitative analysis of the transcribed narratives from interviews, talking circles, and executive orders. These processes and outcomes will be described in future studies. This community-engaged study lays the groundwork for future studies addressing Indigenous mental health, well-being, and resilience. Findings from this study will be shared through presentations and publications with larger Indigenous and non-Indigenous audiences, including local recovery groups, treatment centers, and individuals in recovery; K-12 and higher education educators and administrators; directors of first responder agencies; traditional medicine practitioners; and elected community leaders. The findings will also be used to produce well-being and resilience education materials, in-service training sessions, and future recommendations for stakeholder organizations. DERR1-10.2196/44727.


Loss of STK11 expression is an early event in prostate carcinogenesis and predicts therapeutic response to targeted therapy against MAPK/p38.
Prostate cancer (PCa) is the second leading cause of cancer-related death in men; however, the molecular mechanisms leading to its development and progression are not yet fully elucidated. Of note, it has been recently shown that conditional stk11 knockout mice develop atypical hyperplasia and prostate intraepithelial neoplasia (PIN). We recently reported an inverse correlation between the activity of the STK11/AMPK pathway and the MAPK/p38 cascade in HIF1A-dependent malignancies. Furthermore, MAPK/p38 overactivation was detected in benign prostate hyperplasia, PIN and PCa in mice and humans. Here we report that STK11 expression is significantly decreased in PCa compared to normal tissues. Moreover, STK11 protein levels decreased throughout prostate carcinogenesis. To gain insight into the role of STK11-MAPK/p38 activity balance in PCa, we treated PCa cell lines and primary biopsies with a well-established MAPK14-MAPK11 inhibitor (SB202190), which has been extensively used in vitro and in vivo. Our results indicate that inhibition of MAPK/p38 significantly affects PCa cell survival in an STK11-dependent manner. Indeed, we found that pharmacologic inactivation of MAPK/p38 does not affect viability of STK11-proficient PCa cells due to the triggering of the AMPK-dependent autophagic pathway, while it induces apoptosis in STK11-deficient cells irrespective of androgen receptor (AR) status. Of note, AMPK inactivation or autophagy inhibition in STK11-proficient cells sensitize SB202190-treated PCa cells to apoptosis. On the other end, reconstitution of functional STK11 in STK11-deficient PCa cells abrogates apoptosis. Collectively, our data show that STK11 is a key factor involved in the early phases of prostate carcinogenesis, and suggest that it might be used as a predictive marker of therapeutic response to MAPK/p38 inhibitors in PCa patients.


Variation in Antithrombotic Therapy and Clinical Outcomes in Patients With Preexisting Atrial Fibrillation Undergoing Transcatheter Aortic Valve Replacement: Insights From the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry.
Optimal antithrombotic management of patients with preexisting atrial fibrillation undergoing transcatheter aortic valve replacement is challenging given the need to balance the risk of bleeding and thromboembolism. We aimed to examine variation in care and association of antithrombotic therapies with 1-year outcomes of stroke, bleeding, and mortality in patients undergoing transcatheter aortic valve replacement with concomitant atrial fibrillation in the United States. Patients who underwent transcatheter aortic valve replacement with preexisting atrial fibrillation from November 2011 through September 2015 in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy registry linked to the Medicare database were examined according to receipt of oral anticoagulants (OACs) or antiplatelet therapies (APTs) or a combination of these (OAC+APT) at discharge. To assess the associations of antithrombotic therapies with 1-year outcomes of stroke, bleeding, and mortality, we utilized inverse probability weighting for antithrombotic therapies and multivariable regression modeling to adjust for patient- and hospital-level variables. In the 11 382 patients included in our study, 5833 (51.2%) were discharged on OAC+APT, 4786 (42.0%) on APT alone, and 763 (6.7%) on OAC alone. There was significant variability in discharge medication patterns, including 42% of patients discharged without OAC therapy. In adjusted analyses, the risk for all-cause mortality and stroke was not significantly different when comparing the 3 different antithrombotic strategies. Risk of bleeding was higher with OAC+APT compared with APT alone (hazard ratio, 1.16 [95% CI, 1.05–1.27]) and similar compared with OAC alone (hazard ratio, 1.17 [95% CI, 0.93–1.47]). There was significant variability in discharge medication patterns across US sites in patients with atrial fibrillation undergoing transcatheter aortic valve replacement, including significant underuse of OAC in this high-risk cohort. The use of OAC+APT (versus OAC alone or APT alone) was not associated with a lower risk of stroke or mortality but was associated with increased risk of bleeding complications at 1 year compared with APT alone.


[Assessment of the demand for and use of health services by rural population of the Province of Salamanca. Survey by personal interviews].
This study falls within the framework of the Community epidemiological studies and has the aim of ascertaining the demand for and use of health care services on the part of the rural population in Salamanca through the use of a Health Survey taken on a representative sample thereof. Surveys based on personal interviews are a useful method for obtaining data in epidemiological research and are a fast way of obtaining direct, up-to-date health data, making it possible to ascertain data such as demand for and use of services without excluding that sector of the population not normally making use of the health care services (the underprivileged). Herein, we provide a description of the data which, when analyzed, can aid us in defining some of the needs and problems to be given priority and to be solved by the Health Care System and in rationally forecasting the future demand for health care services, which is the essence of Health Care Planning. According to the results obtained, the greatest demand is for primary care, falling within the 71% percentile, with the main reason for seeking medical advice being the request for prescriptions. Only 7% of the demand at the level of primary care reach the hospital level, which gives one an idea of the functional importance of Primary Care in our Health Care Systems.


A population-based examination of cigarette smoking and mental illness in Black Americans.
This study examines the relation between tobacco use and cessation with lifetime and past year mental illness in a nationally representative sample of Blacks. This cross-sectional study analyzed nationally representative data from 3,411 adult Blacks participating in the 2001-2003 National Survey of American Life. Smoking prevalence and quit rates according to lifetime and past year Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition mental disorders were assessed by a modified version of the Composite International Diagnostic Interview. Compared with those without mental illness, respondents with a lifetime, past year, or past month mental illness had a higher smoking prevalence (20.6%, 35.6%, 36.0%, and 45.4%, respectively) and lower quit rate (40.5%, 31.2%, and 26.2%, respectively). The odds of being a current smoker among Blacks with mental illness in their lifetime, past year, and past month, after adjusting for age, gender, education, poverty, and marital status were 1.76 (95% CI = 1.39-2.22), 1.57 (95% CI = 1.22-2.03), and 2.20 (95% CI = 1.56-3.12), respectively. Mental illness also was associated with heavier smoking. Blacks with past year mental illness represented 18.1% of the sample, yet consumed 23.9% of cigarettes smoked by Black smokers. Past year (odds ratio [OR] = 0.72, 95% CI = 0.53-0.97) and past month (OR = 0.54, 95% CI = 0.29-0.98) mental illness were associated with a lower odds of quitting for at least 1 year. Findings indicate that mental illness is significantly associated with tobacco use in Blacks. Tobacco cessation interventions that address mental illness as a barrier to cessation are needed.


Grading quality of evidence and strength of recommendations in clinical practice guidelines: Part 2 of 3. The GRADE approach to grading quality of evidence about diagnostic tests and strategies.
The GRADE approach to grading the quality of evidence and strength of recommendations provides a comprehensive and transparent approach for developing clinical recommendations about using diagnostic tests or diagnostic strategies. Although grading the quality of evidence and strength of recommendations about using tests shares the logic of grading recommendations for treatment, it presents unique challenges. Guideline panels and clinicians should be alert to these special challenges when using the evidence about the accuracy of tests as the basis for clinical decisions. In the GRADE system, valid diagnostic accuracy studies can provide high quality evidence of test accuracy. However, such studies often provide only low quality evidence for the development of recommendations about diagnostic testing, as test accuracy is a surrogate for patient-important outcomes at best. Inferring from data on accuracy that using a test improves outcomes that are important to patients requires availability of an effective treatment, improved patients' wellbeing through prognostic information, or - by excluding an ominous diagnosis - reduction of anxiety and the opportunity for earlier search for an alternative diagnosis for which beneficial treatment can be available. Assessing the directness of evidence supporting the use of a diagnostic test requires judgments about the relationship between test results and patient-important consequences. Well-designed and conducted studies of allergy tests in parallel with efforts to evaluate allergy treatments critically will encourage improved guideline development for allergic diseases.


Airborne Pseudomonas species in Healthcare Facilities in a Tropical Setting.
Pseudomonas species are nosocomial pathogens that are capable of colonising moist surfaces. Little is known whether they get airborne. The study was undertaken to 1) characterise Gram-negative bacteria in indoor air of different hospitals; 2) characterise Pseudomonas sp. by phenotypic and genotypic methods; 3) determine homology of study environmental Pseudomonas isolates and correlate with established pathogenic strains' sequences. Samples were collected (duplicates) at the time of peak activity, by exposing media-containing plates (blood agar and MacConkey agar) for 30 minutes. Plates were incubated aerobically at 37°C for 24-48 h. Microorganisms were identified by standard microbiological procedures. Polymerase chain reaction targeting Pseudomonas specific 16S-rDNA was performed to obtain 618 bp amplicons. Representative strains were sequenced and compared with established sequences of pathogenic Pseudomonas strains from existing database for evolutionary details. A total of six hospitals comprising 13 wards, 7 intensive care units (ICUs) and 8 operating rooms (ORs) were sampled over one-year period. A variety of Gram-negative bacilli were isolated, of which Pseudomonas sp. was predominant. Indoor air of 10 wards (77%), 5 ICUs (71%), 4 ORs (50%) harboured Pseudomonas. Similar strains of Pseudomonas stutzeri were isolated from indoor air of different hospitals. Phylogenetic analysis showed these environmental strains to be closely related to the pathogenic Pseudomonas stutzeri strain from the GenBank database. Isolation of airborne Pseudomonas stutzeri from different hospitals suggests a possible new reservoir in the hospital environment, indicating the need for appropriate engineering control measures to contain the spread of these nosocomial agents.


[Clinical aspects of anatomy of the nervous apparatus of the pharyngoesophageal junction].
By examining extraorgan innervation of the pharyngeal-esophageal junction of adult cadavers, it was found that the risk of injury of the superior laryngeal nerve and its branches was very high during larynx resection and extirpation, lateral pharyngotomy, thyroid gland resection according to the method of A.V. Martynov, and Crile's operation. Esophageal branches of the recurrent laryngeal nerve or the inferior laryngeal nerve can be damaged during larynx extirpation or strumectomy according to the method of O. V. Nikolaev. The nervous apparatus of the pharyngeal-esophageal junction consists of nerve bundles located in the adventitia, muscular layer, and submucous base.


Increasing thyroid cancer incidence in Queensland, Australia 1982-2008 - true increase or overdiagnosis?
Thyroid cancer incidence has been increasing worldwide. Some suggest greater ascertainment of indolent tumours is the only driver, but others suggest there has been a true increase. Increases in Australia appear to have been among the largest in the world, so we investigated incidence trends in the Australian state of Queensland to help understand reasons for the rise. Thyroid cancers diagnoses in Queensland 1982-2008 were ascertained from the Queensland Cancer Registry. We calculated age-standardized incidence rates (ASR) and used Poisson regression to estimate annual percentage change (APC) in thyroid cancer incidence by socio-demographic and tumour-related factors. Thyroid cancer ASR in Queensland increased from 2·2 to 10·6/100 000 between 1982 and 2008 equating to an APC of 5·5% [95% confidence interval (CI) 4·7-6·4] in men and 6·1% (95% CI 5·5-6·6) in women. The rise was evident, and did not significantly differ, across socio-economic and remoteness-of-residence categories. The largest increase seen was in the papillary subtype in women (APC 7·9%, 95% CI 7·3-8·5). Incidence of localized and more advanced-stage cancers rose over time although the increase was greater for early-stage cancers. There has been a marked increase in thyroid cancer incidence in Queensland. The increase is evident in men and women across all adult age groups, socio-economic strata and remoteness-of-residence categories as well as in localized and more advanced-stage cancers. Our results suggest 'overdiagnosis' may not entirely explain rising incidence. Contemporary aetiological data and individual-level information about diagnostic circumstances are required to further understand reasons for rising thyroid cancer incidence.


Cellular barcoding tool for clonal analysis in the hematopoietic system.
Clonal analysis is important for many areas of hematopoietic stem cell research, including in vitro cell expansion, gene therapy, and cancer progression and treatment. A common approach to measure clonality of retrovirally transduced cells is to perform integration site analysis using Southern blotting or polymerase chain reaction-based methods. Although these methods are useful in principle, they generally provide a low-resolution, biased, and incomplete assessment of clonality. To overcome those limitations, we labeled retroviral vectors with random sequence tags or "barcodes." On integration, each vector introduces a unique, identifiable, and heritable mark into the host cell genome, allowing the clonal progeny of each cell to be tracked over time. By coupling the barcoding method to a sequencing-based detection system, we could identify major and minor clones in 2 distinct cell culture systems in vitro and in a long-term transplantation setting. In addition, we demonstrate how clonal analysis can be complemented with transgene expression and integration site analysis. This cellular barcoding tool permits a simple, sensitive assessment of clonality and holds great promise for future gene therapy protocols in humans, and any other applications when clonal tracking is important.


Regulation of 3-hydroxybutyrate formation and secretion of very-low-density-lipoprotein triacylglycerol by perfused livers from fed and starved rats.
Acetoacetate was the sole ketone body formed when livers from starved rats were perfused with minimal concentrations of non-esterified fatty acid. Absence of 3-hydroxybutyrate was related to a low substrate potential, which caused a more oxidized redox state and a decreased [ATP]/[ADP] ratio. Only under conditions of comparable non-esterified fatty acid uptake was lipoprotein triacylglycerol production inversely related to ketogenesis.


Parenting styles as a tobacco-use protective factor among Brazilian adolescents.
The objective was to evaluate the relationship between tobacco use (previous month and frequent use), parenting styles and parental smoking behavior in a sample of high school students. Participants were recruited from public and private high schools from 27 Brazilian state capitals (N = 17,246). The overall prevalence of tobacco use in life was 25.2%; 15.3% in the previous year; 8.6% in the previous month; and 3.2% for frequent use. Tobacco use by the parents was reported by 28.6% of the students. Regarding parenting styles, 39.2% were classified as negligent, 33.3% authoritative, 15.6% as indulgent and 11.9% authoritarian. Compared to adolescents with authoritative parents, those with negligent or indulgent parents were more prone to report tobacco use during the last month or frequent use. This study showed an association between parenting styles and tobacco use by high school students. Authoritative parents were associated with protection from frequent and previous month tobacco use among adolescents.


Trichothecene Genotype of Fusarium graminearum Isolates from Soybean (Glycine max) Seedling and Root Diseases in the United States.
Fusarium graminearum is an economically important pathogen that causes Fusarium head blight of wheat, barley, and oat, and Gibberella ear and stalk rot of maize. More recently, F. graminearum was reported as a soybean seedling and root pathogen in North America (1,5), causing seed decay, damping-off, and brown to reddish-brown root rot symptoms. Type B trichothecene mycotoxins are commonly produced by F. graminearum, which can be categorized into three trichothecene genotypes; those that produce 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), or nivalenol (NIV). The 15-ADON genotype is dominant in populations from small grains and maize in North America (4), but the 3-ADON genotype has recently been found (4). F. graminearum was known as a pathogen of wheat and maize in North America for over a century before it was reported as a soybean pathogen. Therefore, we hypothesized that recent reports on soybean could be associated with the appearance of the 3-ADON genotype. The objective of this research was to determine the trichothecene genotype of F. graminearum isolates from soybean in the United States. Thirty-eight isolates from soybean were evaluated. Twenty-seven isolates came from a 3-year survey for Fusarium root rot from 2007 to 2009 in Iowa. Other isolates (Ahmad Fakhoury, Southern Illinois University, Carbondale) were collected from soybean seedlings during a multi-state survey in 2012, and included three isolates from Illinois, three from Indiana, and five from Nebraska. Species identification and lineage of F. graminearum were confirmed by sequencing the translation elongation factor gene (EF1-α) using EF-1H and EF-2T primers. A maximum likelihood analysis of the EF1-α, including voucher strains from nine lineages of F. graminearum (2), placed all 38 isolates into lineage 7, F. graminearum sensu stricto (representative GenBank accessions KJ415349 to KJ415352). To determine the trichothecene genotype of each isolate we used three multiplex PCR assays. The first two assays targeted a portion of trichothecene biosynthesis genes Tri3 and Tri12 (4), while the third assay targeted portions of the Tri3, Tri5, and Tri7 genes (3). The PCR for the first two assays was conducted as described by Ward et al. (4) using four sets of primers: 3CON, 3NA, 3D15A, and 3D3A; and 12CON, 12NF, 12-15F, and 12-3F for the Tri3 and Tri12 genes, respectively. The PCR for the third assay was conducted as described by Quarta et al. (3) using the following primers: Tri3F971, Tri3F1325, Tri3R1679, Tri7F340, Tri7R965, 3551H, and 4056H. The amplification products were analyzed by gel electrophoresis. All 38 isolates produced amplicons consistent with the 15-ADON genotype; ~610 and 670 bp for the Tri3 and Tri12 genes, respectively (4), and two amplicons of ~708 and 525 bp for the Tri3/Tri5 genes (3). Our results indicated that the dominant trichothecene genotype among isolates of F. graminearum from soybean is 15-ADON, and the introduction of 3-ADON isolates does not explain the recent host shift of F. graminearum to soybean in North America. To our knowledge, this is the first assessment of trichothecene genotypes in F. graminearum populations from soybean from the United States. References: (1) K. E. Broders et al. Plant Dis. 91:1155, 2007. (2) K. O'Donnell et al. Fungal Gen. Biol. 41:600, 2004. (3) A. Quarta et al. FEMS Microbiol. Lett. 259:7, 2006. (4) T. D. Ward et al. Fungal Gen. Biol. 45:473, 2008. (5) A. G. Zue et al. Can. J. Plant Pathol. 29:35, 2007.


Photosensitive site in lettuce seeds.
Red light is effective only in promoting germination of Grand Rapids lettuce seeds, and far-red light is effective only in inhibiting it, when the hypocotyl half of the seed is exposed to the light. It is concluded that the photoreceptor is probably located in the tip of the hypocotyl.


Blood flow distribution within the airway wall.
Altered perfusion of the bronchial mucosal plexus relative to the adventitial plexus may contribute to geometric changes in the airway wall and lumen. We studied bronchial perfusion distribution in sheep by using fluorescent microspheres at baseline and during intrabronchial artery challenge with methacholine chloride (MCh; n = 7). Additionally, we measured airway resistance (Raw) during MCh with control or increased perfusion (n = 9). Raw with MCh was significantly greater for high than control flow. Microspheres in histological sections lodged predominantly in the mucosa (60%), and this was not altered by MCh. However, more microspheres lodged in airways >1-mm in diameter during MCh and increased perfusion than MCh and control flow. In airways < or =1 mm in diameter, fewer microspheres lodged during control than increased flow. If the number of microspheres represents regional agonist access to airway smooth muscle, then the differences observed in Raw can be explained by the distribution of agonist. During challenge, there was greater MCh delivery to larger airways during increased flow and less delivery to smaller airways during control flow. The results demonstrate the effects of axial perfusion distribution on Raw.


[Bio-Resources and Database for Preemptive Medicine.]
Establishing a primary defense for the improvement of individual quality of life by epidemiology and various clinical studies applying bio-resources/database analysis is very important. Furthermore, recent studies on understanding the epigenetic regulatory mechanisms of developmental origins of health and diseases are attracting increasing interest. Therefore, the storing of not only bio-fluid (i.e., blood, urine) but also certain tissues (i.e., placenta, cord) is very important for research. The Resource Center for Health Science (RECHS) and Bio-databases Institute of Reproductive and Developmental Medicine (BIRD) have estab- lished Bio-bank and initiated a project based on the development and utilization of bio-resources/database, comprising personal health records (PHR), such as health/medical records including individual records of daily diet and exercise, physically consolidated with bio-resources, taken from the same individuals. These Bio-Resources/Database projects are very important for the establishment of preemptive medicine and un- derstanding the mechanisms of the developmental origins of health and diseases.


[Pediatric soft tissue sarcomas: analysis of non rhabdomyosarcoma group].
We evaluated 29 patients with non rhabdomyosarcoma soft tissue sarcomas treated with surgery between 2000 and 2010; we analyzed overall survival and which factors affect the prognosis. The mean age was 11.6 years (range 3 months-17 years); 16 patients were males and the median follow-up was 56 months (8 to 132 months). Eight different histological malignant tumors were identified, being synovial sarcoma the most prevalent one (14 patients). Twenty-eight patients were treated with limb salvage surgery and in 26 cases, adjuvant therapy was used. Five years overall survival was 72%. Nine of the 29 patients presented a local recurrence. The presence of metastases (p <0.0001) and local recurrence (p <0.007) were negative prognostic factors for overall survival.


Localization and development of nerve growth factor-sensitive rat basal forebrain neurons and their afferent projections to hippocampus and neocortex.
In order to understand further the role of NGF in the development of NGF-sensitive basal forebrain neurons and their afferent connections to the hippocampus and neocortex, we have used monoclonal antibody 192 IgG to detect and localize NGF receptors immunocytochemically in the developing rat brain. NGF receptor immunoreactivity (NGF-RI) is first visible at embryonic day 13 (E 13) in the ventrolateral telencephalic wall and follows a caudal-to-rostral gradient in its initial appearance. NGF-RI neuronal number and neuropil staining undergo substantial increases before birth, and extensive dendritic growth and increases in perikaryal size continue during the first 3 weeks of postnatal life. This growth and cellular differentiation, however, is followed in the fourth postnatal week and later by an apparent decrease in dendritic arborization and 50% shrinkage in the size of perikarya. Initial NGF-RI fiber outgrowth from immature basal forebrain neurons directed toward appropriate target fields is observed as early as E 15. The formation of a laminar pattern by septal axons in the hippocampal terminal fields and invasion of NB afferents into the cortex occur postnatally over a protracted time. In the hippocampus, NGF-RI is initially diffusely distributed, and wide bands of immature granule and pyramidal cells are almost devoid of immunoreactive fibers; however, with maturity, septal axon terminals become concentrated in narrow zones closely associated with the cellular layers. In the neocortex, early-arriving basal forebrain afferents accumulate in the intermediate zone underneath the darkly immunoreactive subplate before they enter The cortex. Dense subplate and transiently present, radially aligned fiber staining completely disappear in later postnatal week and are gradually replaced by specific axonal and terminal staining associated with NB afferents. The expression of NGF receptor in the subplate zone at the time afferents arrive and its subsequent disappearance with the specific terminal formation suggest that NGF receptor and concomitant accumulation of NGF in the subplate may act as a temporary target for the early-arriving basal forebrain afferents; ingrowing afferents may then be guided by radially oriented NGF-RI fibers to proper synaptic sites.


A Risk-adapted Approach to Follow-up in Differentiated Thyroid Cancer.
The last 10 years have seen a renewed interest in a risk-adapted approach to the management of differentiated thyroid cancer. This review outlines a state-of-the-art approach to individualized management in which the original follow-up plan that was developed based on initial risk stratification is modified over time as new data become available. This risk-adapted follow-up approach allows clinicians to determine the intensity of follow-up and management recommendations in response to real-time dynamic risk assessments which may change over time.


Murine marrow cellularity and the concept of stem cell competition: geographic and quantitative determinants in stem cell biology.
In unperturbed mice, the marrow cell numbers correlate with the stem cell numbers. High levels of long-term marrow engraftment are obtained with infusion of high levels of marrow cells in untreated mice. To address the issue of stem cell competition vs 'opening space', knowledge of total murine marrow cellularity and distribution of stem and progenitor cells are necessary. We determined these parameters in different mouse strains. Total cellularity in BALB/c mice was 530+/-20 million cells; stable from 8 weeks to 1 year of age. C57BL/6J mice had 466+/-48 million marrow cells. Using these data, theoretical models of infused marrow (40 million cells) replacing or adding to host marrow give chimerism values of 7.5 and 7.0%, respectively; the observed 8-week engraftment of 40 million male BALB/c marrow cells into female hosts (72 mice) gave a value of 6.91+/-0.4%. This indicates that syngeneic engraftment is determined by stem cell competition. Our studies demonstrate that most marrow cells, progenitors and engraftable stem cells are in the spine. There was increased concentration of progenitors in the spine. Total marrow harvest for stem cell purification and other experimental purposes was both mouse and cost efficient with over a four-fold decrease in animal use and a financial saving.


[Combined use of glucose and rest period between noise exposure to reduce noise--induced hearing loss].
This paper reports the way which protects hearing from harmful effects of noise. 67 guinea pigs were divided into four groups, 8-9 guinea pigs in each group. The total time of noise exposure at 125 dB SPL white noise in each group was one hour. The control was exposed continuously for 1 hour. Group I was exposed to noise for 30 minutes after intraperitoneal injection of glucose at 2 mg/g body wt., then rest for 30 minutes and exposed for 30 minutes again. Group II was exposed continuously to noise for 1 hour after intraperitoneal injection of glucose at 2 mg and 4 mg/g body wt. Group III was exposed to noise for 30 minutes, rested for 30 minutes and exposed for 30 minutes again without glucose injection. The auditory brain stem response (ABR) was measured before, immediately, 3 days, and 7 days after noise exposure. The effect on hearing conservation was evaluated according to ABR threshold. We observed that the auditory threshold in group I was significantly lower than that of the control in the given time after noise exposure (P less than 0.05), but not so in group II and III. Combined use of glucose and rest period between noise exposure was able to decrease the threshold shift by 15 dB and 10 dB immediately and 7 days after noise exposure respectively.


Analysis of the major patterns of B cell gene expression changes in response to short-term stimulation with 33 single ligands.
We examined the major patterns of changes in gene expression in mouse splenic B cells in response to stimulation with 33 single ligands for 0.5, 1, 2, and 4 h. We found that ligands known to directly induce or costimulate proliferation, namely, anti-IgM (anti-Ig), anti-CD40 (CD40L), LPS, and, to a lesser extent, IL-4 and CpG-oligodeoxynucleotide (CpG), induced significant expression changes in a large number of genes. The remaining 28 single ligands produced changes in relatively few genes, even though they elicited measurable elevations in intracellular Ca(2+) and cAMP concentration and/or protein phosphorylation, including cytokines, chemokines, and other ligands that interact with G protein-coupled receptors. A detailed comparison of gene expression responses to anti-Ig, CD40L, LPS, IL-4, and CpG indicates that while many genes had similar temporal patterns of change in expression in response to these ligands, subsets of genes showed unique expression patterns in response to IL-4, anti-Ig, and CD40L.


Use of spatiotemporal response information from sorption-based sensor arrays to identify and quantify the composition of analyte mixtures.
Linear sensor arrays made from small molecule/carbon black composite chemiresistors placed in a low-headspace volume chamber, with vapor delivered at low flow rates, allowed for the extraction of new chemical information that significantly increased the ability of the sensor arrays to identify vapor mixture components and to quantify their concentrations. Each sensor sorbed vapors from the gas stream and, thereby, as in gas chromatography, separated species having high vapor pressures from species having low vapor pressures. Instead of producing only equilibrium-based sensor responses that were representative of the thermodynamic equilibrium partitioning of analyte between each sensor and the initial vapor phase, the sensor responses varied depending on the position of the sensor in the chamber and the time since the beginning of the analyte exposure. The concomitant spatiotemporal (ST) sensor array response therefore provided information that was a function of time, as well as of the position of the sensor in the chamber. The responses to pure analytes and to multicomponent analyte mixtures comprised of hexane, decane, ethyl acetate, chlorobenzene, ethanol, and/or butanol were recorded along each of the sensor arrays. Use of a non-negative least-squares (NNLS) method for analysis of the ST data enabled the correct identification and quantification of the composition of two-, three-, four-, and five-component mixtures from arrays using only four chemically different sorbent films. In contrast, when traditional time- and position-independent sensor response information was used, these same mixtures could not be identified or quantified robustly. The work has also demonstrated that, for ST data, NNLS yielded significantly better results than analyses using extended disjoint principal components modeling. The ability to correctly identify and quantify constituent components of vapor mixtures through the use of such ST information significantly expands the capabilities of such broadly cross-reactive arrays of sensors.


Evaluation of cases of concussion and subluxation in the permanent dentition: a retrospective study.
Objectives This study evaluated the evolution of cases of concussion and subluxation through a retrospective study of 20 years. Material and Methods Were examined clinical and radiographic records of 1,309 patients who underwent treatment of dentoalveolar trauma in the discipline of Integrated Clinic of the School of Dentistry of Araçatuba, UNESP, of which we selected 137 whose patients had concussion and subluxation injuries, with average age of 23.3 (SD - 10.96). The variables collected were: gender, age, history of previous and actual trauma, treatments performed, the presence of necrotic pulp, and time elapsed until the same trauma. The concussion and subluxation groups were subjected to statistical analyses using the SPSS 16.0 version software (α=0.05), Chi-square, and t-tests. Results Of the 301 teeth involved, 49 (16.3%) suffered concussion and 252 (83.7%), subluxation, being the upper anterior teeth the most affected (75.1%) for both conditions. Subluxation and concussion traumas were more prevalent in men aged 10 to 20 years, most caused by cycling accidents (36.2%). There was a concomitant presence of crown fracture in 21% of cases of concussion and 34.7% of subluxation. Pulp necrosis was detected in 16.3% (concussion) and 27.1% (subluxation) (p=0.12), and most occurred within 6 months after the trauma (p=0.29). The pulp necrosis shows a positive correlation with motorcycle accidents (p=0.01), direct impact (p≤0.0001), crown fracture with pulp exposure (p≤0.0001), darkening of the crown (p=0.004) and spontaneous pain (p≤0.0001); and negative correlation with indirect impact (p≤0.0001). Conclusions Although concussion and subluxation traumas are considered of minor degrees, they must be monitored, since the possibility of pulp necrosis exists, and its early treatment favors a good prognosis.


A bicistronic expression strategy for large scale expression and purification of full-length recombinant human parathyroid hormone for osteoporosis therapy.
Parathyroid hormone (PTH) contributes to the increase of trabecular connectivity and is a candidate medication for effective treating osteoporosis. PTH is a protein of 84 amino acids and some studies have suggested that the active site lies within the range from amino acid (aa) 1 to 34. However, a few reports have indicated a causal relationship between PTH (aa 1-34) and osteogenic sarcoma in rats, while some less obvious but important roles of the carboxyl-terminus of PTH were also found. Unfortunately, it is difficult to obtain the active integrated PTH (1-84) in vitro, due to the instability of both the protein and its mRNA. Because an alternative translation start site is located at +25 nucleotides downstream of the true start site, a truncated PTH can be translated. We constructed a rhPTH bicistronic expression plasmid (pTrepth) that could highly express non-fusion soluble rhPTH proteins in Escherichia coli. The BL-21(DE3) containing pTrepth was cultured on a small scale until satisfactory expression and purification results were obtained. We then amplified the transformed cells in a 15-L fermentor and harvested 27g/L cells (wet weight). Extensive rhPTH purification was achieved by a three step chromatography process. Activity tests demonstrated that our purified protein could dramatically increase cAMP in osteosarcoma cells in vitro.


Utilizing Indocyanine Green Dye Angiography to Detect Simulated Flap Venous Congestion in a Novel Experimental Rat Model.
Venous congestion is a leading cause for free flap failure and still relies on clinical observation as the diagnostic gold standard. We sought to characterize blood flow in a variable venous congestion murine hind limb model using indocyanine green (ICG, SPY Pack, LifeCell, Branchburg, NJ) angiography. Male Sprague-Dawley rats (Charles River, Hudson, NY) underwent bilateral partial amputation at the inguinal ligament, leaving only the femoral vessels and femur intact. Complete unilateral venous occlusion was achieved via suture ligation, while partial occlusion was achieved by surrounding the femoral vein with a synthetic microtube to achieve 25, 75, 85, or 92% occlusion. Relative blood flow of occluded and control limbs was tracked with ICG angiography throughout a 90-minute time course. ICG angiography detected statistically significant (p < 0.05) reductions in limb blood flow 1 and 2 minutes following ICG injection in the 100, 92, and 85% occluded limbs when compared with contralateral control limbs. Dynamic tracking using the slope of ICG inflow for 45 seconds postinjection reflected this same significant difference. No statistically significant change in limb blood flow or dye influx rate was observed in the 25 and 75% occlusion groups. ICG angiography can detect venous congestion in a rat lower extremity model reliably at occlusion rates ≥ 85%. This method may offer surgeons an intraoperative diagnostic tool to identify venous congestion at extremely early time points, allowing for immediate intervention. Further investigation and characterization is warranted in a larger animal model before clinical adaptation.


Chemistry-dependent X-ray-induced surface charging.
Materials science in general, and surface/interface science in particular, have greatly benefited from the development of high energy synchrotron radiation facilities. Irradiation with intense ionizing beams can however influence relevant sample properties. Permanent radiation damage and irradiation-induced sample modifications have been investigated in detail during the last decades. Conversely, reversible sample alterations taking place only during irradiation are still lacking comprehensive in situ characterization. Irradiation-induced surface charging phenomena are particularly relevant for a wide range of interface science investigations, in particular those involving surfaces of solid substrates in contact with gaseous or liquid phases. Here, we demonstrate partially reversible radiation-induced surface charging phenomena, which extend far beyond the spatial dimensions of the X-ray beam mainly as a consequence of the interaction between the surface and ionized ambient molecules. The charging magnitude and sign are found to be surface chemistry specific and dependent on the substrates' bulk conductivity and grounding conditions. These results are obtained by combining a scanning Kelvin probe with a synchrotron surface diffractometer to allow simultaneous in situ work function measurements during precisely controlled hard X-ray micro-beam irradiation.


Brain imaging in AIDS.
Although central nervous system (CNS) involvement is common in the population with acquired immunodeficiency syndrome, the presenting neurologic signs and symptoms are often vague and nonfocal. This represents a significant diagnostic challenge for the primary care physician. Cross-sectional imaging now plays an important role in the diagnosis of pathologic processes involving the brain in HIV-infected patients. Involvement of the brain with atypical viruses, parasites, fungi, and neoplasms is more prevalent in AIDS patients. On identification of a brain lesion, it is the role of the imager to characterize it in an attempt to provide a limited differential diagnosis. We review the imaging findings of the pathogens that most commonly affect the brain in AIDS patients.


[Experimental data on the biological effect of nickel and lead contained in the drinking water acting in combination].
During one year toxicological experiment on white male rats, receiving simultaneously per os nickel in doses 0.005 mg/kg and lead in doses 0.0025 mg/kg, equivalent respectively to the recommended by CMEA norms for nickel and hygienic norm for lead in potable waters, as well as nickel and lead in doses 0.015 and 0.01 mg/kg. 0.15 and 0.1 mg/kg, surpassing 3 and 4 times and 30 and 40 times the norms or only nickel in doses 0.015 mg/kg, are studied for some sides of their biological effect. The following indices are examined: blood sugar lactatedehydrogenase, sodium, and potassium in the serum; haemoglobin, erythrocytes, reticulocytes and deltaaminlevulinatdehydrase activity in blood; glycoso-6-phosphatdehydrogenase in heart. It is already established, that in chronic combined oral influence with nickel and lead respectively in doses 0.15 and 0.1 mg/kg and 0.015 and 0.01 mg/kg is disturbed the carbohydrate metabolism, the electrolyte balance and the hemapoiesis, and in doses 0.005 and 0.0025 mg/kg no changes are established according to all examined indices. The nickel in doses 0.015 mg/kg at independent effect also leads to disturbance of the electrolyte, reticulocytic and erythrocytic metabolism.


Retinal changes in sarcoidosis.
In this series, ten patients with systemic sarcoidosis presented with retinal changes as the initial manifestation of the disease. The diagnosis was suspected on the basis of the retinal findings, and subsequently substantiated by medical evaluation. Anterior uveitis, the best-known finding in ocular sarcoidosis, was overshadowed by the retinal changes. The retinal findings in this condition are characteristic and should alert the ophthalmologist to evaluate the patient for systemic sarcoidosis.


[Cerebrovascular emergencies: difficulties and errors in diagnosing various stroke types].
The frequency of and reasons for errors in diagnosing various types of cerebrovascular disease at the emergency room of National Cheng Kung University Hospital were analyzed in 548 consecutive patients from January to December 1990. Each patient was evaluated by neurological residents and a bedside diagnosis was made on the basis of history-taking, physical examination, and diagnostic reasoning. The emergency diagnosis was made after finishing the radiological and/or laboratory investigations. The tentative emergency diagnosis of each patient was judged as correct or not by comparison with the final diagnosis, which was based on either the results of specific investigation or on the typical cerebrovascular syndrome ascertained by the attending physicians if the specific investigation was not helpful. If the tentative emergency diagnosis had been judged to be wrong, the cause for the misdiagnosis was determined by reviewing the records of the entire diagnostic process. The diagnosis in the emergency setting was erroneous in 131 (24%) patients. Primary intraventricular hemorrhage, cerebral venous thrombosis and subarachnoid hemorrhage were frequently misdiagnosed as compared with other types of stroke. The explored reasons for diagnostic inaccuracy were: inadequate basic data (46%), reasoning errors (38%), and lack of fundamental knowledge (16%). These results implied that the education and training for diagnosis of subarachnoid hemorrhage in emergency should be enhanced. Deeply comatose states caused diagnostic difficulties in data collection. Diagnostic errors were frequently encountered in unusual stroke or stroke with atypical presentations. To increase diagnostic ability in cerebrovascular emergencies, residents should strive to improve interview and examination skills and reasoning discipline. Modern technology is not a panacea for diagnostic difficulties.(ABSTRACT TRUNCATED AT 250 WORDS)


Expectable diversity patterns in wine yeast communities.
Wine fermentations are dominated by Saccharomyces yeast. However, dozens of non-Saccharomyces yeast genera can be found in grape musts and in the early and intermediate stages of wine fermentation, where they co-exist with S. cerevisiae. The diversity of non-Saccharomyces species is determinant for the sensorial attributes of the resulting wines, both directly (by producing aroma impact compounds) and indirectly (modulating the performance of Saccharomyces). Many research groups worldwide are exploring the great diversity of wine yeasts to exploit their metabolic potential to improve wine flavor or to prevent wine spoilage. In this work, we share a new data set from a wide ITS amplicon survey of 272 wine samples, and we perform a preliminary exploration to build a catalogue of 242 fungal and yeast genera detectable in wine samples, estimating global figures of their prevalence and relative abundance patterns across wine samples. Thus, our mycobiome survey provides a broad measure of the yeast diversity potentially found in wine fermentations; we hope that the wine yeast research community finds it useful, and we also want to encourage further discussion on the advantages and limitations that meta-taxonomic studies may have in wine research and industry.


Pathophysiology of Parkinson's disease: from clinical neurology to basic neuroscience and back.
Parkinson's disease (PD) is characterized by motor and nonmotor (cognitive and limbic) deficits. The motor signs of PD include hypokinetic signs such as akinesia/bradykinesia, rigidity and loss of normal postural reflexes, and hyperkinetic signs such as tremor. Dopamine depletion in the striatum is the hallmark of PD and of its animal models, still the pathophysiology of the parkinsonian symptoms and especially of parkinsonian tremor are under debate. The most extreme hypotheses argue about peripheral versus central nervous system origin, intrinsic cellular oscillator versus network oscillators, and basal ganglia-based pathophysiology versus cerebellar-thalamic based pathophysiology. Recent studies support the view that parkinsonian symptoms are most likely due to abnormal synchronous oscillating neuronal activity within the basal ganglia. Peripheral factors do only play a minor role for the generation, maintenance, and modulation of PD tremor and other signs. The most likely candidates producing these neuronal oscillations are the weakly coupled neural networks of the basal ganglia-thalamo-cortical loops. However, the present evidence supports the view that the basal ganglia loops are influenced by other neuronal structures and systems and that the tuning of these loops by cerebello-thalamic mechanisms and by other modulator neurotransmitter systems entrain the abnormal synchronized oscillations. Neurosurgical procedures, such as lesions or high-frequency stimulation of different parts of the loop, might resume the normal unsynchronized activity of the basal ganglia circuitry, and, therefore, ameliorate the clinical symptoms of Parkinson's disease.


Cytogenetic and array-CGH characterization of a complex de novo rearrangement involving duplication and deletion of 9p and clinical findings in a 4-month-old female.
Approximately 15 patients with partial trisomy 9p involving de novo duplications have been previously described. Here, we present clinical, cytogenetic, FISH and aCGH findings in a patient with a de novo complex rearrangement in the short arm of chromosome 9 involving an inverted duplication at 9p24-->p21.3 and a deletion at 9pter-->p24.2. FISH probes generated from BACs selected from the UCSC genome browser were utilized to verify this rearrangement. It is likely that some previously described duplications of 9p may also be products of complex chromosomal aberrations. This report in which FISH and aCGH were used to more comprehensively characterize the genomic rearrangement in a patient with clinical manifestations of 9p duplication syndrome underscores the importance of further characterizing cytogenetically detected rearrangements.


The Relationship Between Speech Perception, Speech Production, and Vocabulary Abilities in Children: Insights From By-Group and Continuous Analyses.
The purpose of this study was to explore the relationship between speech perception, speech production, and vocabulary abilities in children with and without speech sound disorders (SSDs), analyzing the data both by group and continuously. Sixty-one Australian English-speaking children aged 48-69 months participated in this study. Children's speech production abilities ranged along the continuum from SSDs through to typical speech. Their vocabulary abilities ranged along the continuum from typical to above average ("lexically precocious"). Children completed routine speech and language assessments in addition to an experimental Australian English lexical and phonetic judgment task. When analyzing data by group, there was no significant difference between the speech perception ability of children with SSDs and that of children without SSDs. Children with above-average vocabularies had significantly better speech perception ability than children with average vocabularies. When analyzing data continuously, speech production and vocabulary were both significant positive predictors of variance in speech perception ability, both individually in simple linear regression and when combined in multiple linear regression. There was also a significant positive correlation between perception and production of two of the four target phonemes tested (i.e., /k/ and /ʃ/) among children in the SSD group. Results from this study provide further insight into the complex relationship between speech perception, speech production, and vocabulary abilities in children. While there is a clinical and important need for categorical distinctions between SSDs and typically developing speech, findings further highlight the value of investigating speech production and vocabulary abilities continuously and categorically. By capturing the heterogeneity among children's speech production and vocabulary abilities, we can advance our understanding of SSDs in children. https://doi.org/10.23641/asha.22229674.


Effect of extracellular calcium on myocardial mechanical function in the neonatal rabbit.
The effects of extracellular calcium ([Ca2+]0) and barium ([Ba2+]0) on myocardia mechanical function were studied in the isolated arterially perfused neonatal and adult rabbit heart. The force of cardiac contraction per gram tissue in the newborn was approximately one third that in the adult for [Ca]0 of 1.5 mM. One half maximal values of developed tension (DT) and maximal tension first derivative [+dT/dt (max)] in the newborn were observed at [Ca2+]0 that were significantly higher than those in the adult. The maximal inotropic effect of calcium was observed at [Ca2+]0 of 10 mM in the adult and 30 mM in the newborn. Calcium binding to the isolated sarcolemma in the newborn and adult were identical. Cellular calcium in the newborn was significantly less than that in the adult. Barium infusion caused equal contracture in the newborn and adult, and the time to half maximal contracture was not different in the two age groups. These data indicate that (1) sarcolemmal permeability to divalent cations is similar in the newborn and adult rabbit, and (2) although calcium influx is similar in the two age groups, the amount of contractile calcium in the newborn is less than that in the adult for all [Ca]0.


Potential pathways to restore β-cell mass: pluripotent stem cells, reprogramming, and endogenous regeneration.
Currently available β-cell replacement therapies for patients with diabetes, including islet and pancreas transplantation, are largely successful in restoring normal glucose metabolism, but the scarcity of organ donors restricts their more widespread use. To solve this supply problem, several different strategies for achieving β-cell mass restoration are being pursued. These include the generation of β cells from stem cells and their subsequent transplantation, or regeneration-type approaches, such as stimulating endogenous regenerative mechanisms or inducing reprogramming of non-β cells into β cells. Because these strategies would ultimately generate allogeneic or syngeneic β cells in humans, the control of alloimmunity and/or autoimmunity in addition to replacing lost β cells will be of utmost importance. We briefly review the recent literature on these three promising strategies toward β-cell replacement or restoration and point out the major issues impacting their translation to treating human diabetes.


Intravitreal bevacizumab for the treatment of feeder vessel of subfoveal choroidal neovascularization.
To report in a single case the effectiveness of bevacizumab in the treatment of feeder vessels (FVs) of subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). One patient received intravitreal bevacizumab (Avastin) (1.25 mg) which was repeated 4 weeks after the first intravitreal injection. Fluorescein angiography and optical coherence tomography (OCT) were performed. Visual acuity (VA) was also checked. Occlusion of the FVs was observed 4 weeks after starting treatment. During the follow-up period and in the final examination 13 months after the first injection, the FVs remained occluded. Complete resolution of macular edema and improvement of the VA were noticed after the second bevacizumab intravitreal injection. This report documents the successful occlusion of FVs of subfoveal neovascularization after two intravitreal bevacizumab injections in a patient who was followed up for 1 year after the occlusion. Further long-term investigation is warranted given the promising 12-month results.


Current Concepts of Neurodegenerative Mechanisms in Alzheimer's Disease.
Neurodegenerative diseases are hereditary or sporadic conditions that result in the progressive loss of the structure and function of neurons as well as neuronal death. Although a range of diseases lie under this umbrella term, Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases that affect a large population around the globe. Alzheimer's disease is characterized by the abnormal accumulation of extracellular amyloid-β plaques and intraneuronal neurofibrillary tangles in brain regions and manifests as a type of dementia in aged individuals that results in memory loss, multiple cognitive abnormalities, and intellectual disabilities that interfere with quality of life. Since the discovery of AD, a wealth of new information has emerged that delineates the causes, mechanisms of disease, and potential therapeutic agents, but an effective remedy to cure the diseases has not been identified yet. This could be because of the complexity of the disease process, as it involves various contributing factors that include environmental factors and genetic predispositions. This review summarizes the current understanding on neurodegenerative mechanisms that lead to the emergence of the pathology of AD.