Age-related decrement in hearing for speech. Sampling and longitudinal studies.
A 10-year study was conducted in which 282 adults in age decades of 20 through 80 were tested in a comprehensive battery of tasks requiring the perception of speech under a variety of conditions in which the speech signal was degraded. The original results were plotted to reveal the differences in performance of the population samples of each decade. In follow-up studies, after 3 years and again after 7 years, samples of the original subject population were retested. The results of the first, stratified sampling and of the longitudinal studies are compared. The two most apparent trends are: (1) the perception of degraded (distorted and competed) speech undergoes a noticeable decline beginning with the 5th decade of life, and (2) the decline is sharply steeper in the 7th decade.


The ClpP protease is required for the stress tolerance and biofilm formation in Actinobacillus pleuropneumoniae.
In the respiratory tract and lung tissue, a balanced physiological response is essential for Actinobacillus pleuropneumoniae to survive various types of challenges. ClpP, the catalytic core of the Clp proteolytic complex, is involved in various stresses response and regulation of biofilm formation in many pathogenic bacteria. To investigate the role of ClpP in the virulence of A. pleuropneumoniae, the clpP gene was deleted by homologous recombination, resulting in the mutant strain S8ΔclpP. The reduced growth of S8ΔclpP mutant at high temperatures and under several other stress conditions suggests that the ClpP protein is required for the stress tolerance of A. pleuropneumoniae. Interestingly, we observed that the S8ΔclpP mutant exhibited an increased ability to take up iron in vitro compared to the wild-type strain. We also found that the cells without ClpP displayed rough and irregular surfaces and increased cell volume relative to the wild-type strain using scanning electron microscopy (SEM). Confocal laser scanning microscopy (CLSM) revealed that the S8ΔclpP mutant showed decreased biofilm formation compared to the wild-type strain. We examined the transcriptional profiles of the wild type S8 and the S8ΔclpP mutant strains of A. pleuropneumoniae using RNA sequencing. Our analysis revealed that the expression of 16 genes was changed by the deletion of the clpP gene. The data presented in this study illustrate the important role of ClpP protease in the stress response, iron acquisition, cell morphology and biofilm formation related to A. pleuropneumoniae and further suggest a putative role of ClpP protease in virulence regulation.


No Mediation Effect of Telomere Length or Mitochondrial DNA Copy Number on the Association Between Adverse Childhood Experiences (ACEs) and Central Arterial Stiffness.
Background Adverse childhood experiences (ACEs) have been linked to increased cardiovascular disease (CVD) risk. Previous reports have suggested that accelerated biological aging-indexed by telomere length (TL) and mitochondrial DNA copy number (mtDNAcn)-may contribute to associations between ACEs and cardiovascular health outcomes. Here, we examine the potential mediating effects of TL and mtDNAcn on the association between ACEs and central arterial stiffness-an intermediate cardiovascular health outcome-as a novel pathway linking ACEs to CVD risk among young adults. Methods and Results One hundred and eighty-five (n=102 women; mean age, 22.5±1.5 years) individuals provided information on ACEs. TL (kb per diploid cell) and mtDNAcn (copies per diploid cell) were quantified using quantitative polymerase chain reaction techniques. Central arterial stiffness was measured as carotid-femoral pulse wave velocity (cfPWV; m/s). Multiple linear regression analyses were used to examine the associations between ACEs, TL, mtDNAcn, and cfPWV. ACEs were positively associated with cfPWV (β=0.147, P=0.035). TL (β=-0.170, P=0.011) and mtDNAcn (β=-0.159, P=0.019) were inversely associated with cfPWV. Neither TL (β=-0.027, P=0.726) nor mtDNAcn (β=0.038, P=0.620) was associated with ACEs. Neither marker mediated the association between ACEs and cfPWV. Conclusions An increasing number of ACEs were associated with a faster cfPWV and thus, a greater degree of central arterial stiffness. ACEs were not associated with either TL or mtDNAcn, suggesting that these markers do not represent a mediating pathway linking ACEs to central arterial stiffness.


Effects of dialyzable leukocyte extracts with transfer factor activity on leukocyte migration in vitro. V. Antigen-specific lymphocyte responsiveness can be initiated by two structurally distinct polyribonucleopeptides.
Human transfer factors (TF) active in specifically inducing responsiveness in human thymus-derived (T) lymphocytes previously nonresponsive to purified protein derivative from Myobacterium tuberculosis (PPD) or to Coccidioides immites (Cocci) in vitro were isolated from the dialyzable portion of extracts of immune leukocytes (DLE). Each TF segregated into two active fractions after high-pressure reverse-phase liquid chromatography (HPLC), suggesting the presence of two TF components in DLE for each antigen specificity. Determination of the structures of both TF components specific for PPD was accomplished by evaluating their activity after incubation with various endonucleases, exonucleases, phosphatases, peptidases and a protease. The results indicated that both PPD-specific TF components are oligoribonucleopeptides but that they are structurally distinct. Simplest-case molecular models were constructed on the basis of the data obtained.


Finding potential inhibitors against RNA-dependent RNA polymerase (RdRp) of bovine ephemeral fever virus (BEFV): an in-silico study.
The bovine ephemeral fever virus (BEFV) is an enzootic agent that affects millions of bovines and causes major economic losses. Though the virus is seasonally reported with a very high morbidity rate (80-100%) from African, Australian, and Asiatic continents, it remains a neglected pathogen in many of its endemic areas, with no proper therapeutic drugs or vaccines presently available for treatment. The RNA-dependent RNA polymerase (RdRp) catalyzes the viral RNA synthesis and is an appropriate candidate for antiviral drug developments. We utilized integrated computational tools to build the 3D model of BEFV-RdRp and then predicted its probable active binding sites. The virtual screening and optimization against these active sites, using several small-molecule inhibitors from a different category of Life Chemical database and FDA-approved drugs from the ZINC database, was performed. We found nine molecules that have docking scores varying between -6.84 to -10.43 kcal/mol. Furthermore, these complexes were analyzed for their conformational dynamics and thermodynamic stability using molecular dynamics simulations in conjunction with the molecular mechanics generalized Born surface area (MM-GBSA) scheme. The binding free energy calculations depict that the electrostatic interactions play a dominant role in the RdRp-inhibitor binding. The hot spot residues, such as Arg565, Asp631, Glu633, Asp740, and Glu707, were found to control the RdRp-inhibitor interaction. The ADMET analysis strongly suggests favorable pharmacokinetics of these compounds that may prove useful for treating the BEFV ailment. Overall, we anticipate that these findings would help explore and develop a wide range of anti-BEFV therapy.Communicated by Ramaswamy H. Sarma.


Dose level of occupational exposure in China.
This paper discusses the dose level of Chinese occupational exposures during 1986-2000. Data on occupational exposures from the main categories in nuclear fuel cycle (uranium enrichment and conversion, fuel fabrication, reactor operation, waste management and research activity, except for uranium mining and milling because of the lack of data), medical uses of radiation (diagnostic radiation, nuclear medicine and radiotherapy) and industrial uses of radiation (industrial radiography and radioisotope production) are presented and summarised in detail. These are the main components of occupational exposures in China. In general, the average annual effective doses show a steady decreasing trend over periods: from 2.16 to 1.16 mSv in medical uses of radiation during 1990-2000; from 1.92 to 1.18 mSv in industrial radiography during 1990-2000; from 8.79 to 2.05 mSv in radioisotope production during the period 1980-2000. Almost all the average annual effective doses in discussed occupations were lower than 5 mSv in recent years (except for well-logging: 6.86 mSv in 1999) and no monitored workers were found to have received the occupational exposure exceeding 50 mSv in a single year or 100 mSv in a five-year period. So the Chinese protection status of occupation exposure has been improved in recent years. However, the average annual effective doses in some occupations, such as diagnostic radiology and coal mining, were still much higher than that of the whole world. There are still needs for further improvement and careful monitoring of occupational exposure to protect every worker from excessive occupational exposure, especially for the workers who were neglected before.


Serum biomarkers can predict a change in liver fibrosis 1 year after lifestyle intervention for biopsy-proven NASH.
The dynamic response of serum fibrosis biomarkers to histological changes within the liver following lifestyle intervention (LI) is unknown. We explored relationships between changes in serum biomarkers and liver fibrosis in NASH patients undergoing LI. Paired liver biopsies were performed in 261 NASH patients to assess fibrosis change after 1 year of LI. We explored the utility of serum fibrosis markers to predict changes in hepatic fibrosis and developed and internally validated a model for predicting fibrosis improvement in patients with baseline fibrosis. Regression, stabilization and worsening of fibrosis occurred in 51 (20%), 165 (63%) and 45 (17%) patients respectively. By multivariable analysis, change in HbA1c (OR, 0.39, P<.01), platelets (OR, 1.22, P<.01) and NFS (OR, 0.27, P<.01), as well as ALT normalization (OR, 9.7, P<.01) were independently associated with fibrosis improvement, whereas change in platelets (OR, 0.96, P<.01), and NFS (OR, 1.8, P<.01) as well as ALT normalization (OR, 0.21, P<.01) were linked to fibrosis progression. A model, including change in HbA1c, platelet and ALT normalization, was significantly more accurate (AUC of 0.96, 95% CI, l0.94-0.99) than NFS, FIB-4 and APRI for predicting fibrosis improvement. Using a threshold of ≥0.497, positive and negative predictive values were 94% (95% CI, 84-98) and 91% (95% CI, 81-96) respectively. Change in NFS, platelets and ALT normalization are associated with change in liver fibrosis after 1 year of LI. A model including change in HbA1c, platelet and ALT normalization discriminated patients with fibrosis improvement significantly better than other biomarkers.


Severity in irritable bowel syndrome: a Rome Foundation Working Team report.
The concept of severity in irritable bowel syndrome (IBS) is clinically recognized and operative in diagnostic decision making and treatment planning. Yet, there is no consensus on its definition, and there are limited data on the prevalence of severity subgroups, its medical and psychosocial determinants, and its association with other health status measures. The aims of the Rome Foundation Working Team Committee were to summarize current research, to develop a consensus of understanding on this concept, and to make recommendations for its use in research and clinical care. In 2006, a multinational committee of clinical investigators with expertise in IBS and/or psychometric research methods undertook a systematic review of the literature relating to severity in IBS. Owing to limited data, the Foundation commissioned three clinical studies to better characterize the concept of severity in IBS, and summary information and recommendations for future research and clinical care were developed. The main findings were: (i) severity in IBS is defined as a biopsychosocial composite of patient-reported gastrointestinal and extraintestinal symptoms, degree of disability, and illness-related perceptions and behaviors; (ii) both visceral and central nervous system physiological factors affect severity; as severity increases, the central nervous system provides a greater contribution; (iii) severity is related to and influences health-related quality of life and health behaviors and also guides diagnostic and therapeutic clinical decision making; (iv) severity can be subcategorized into clinically meaningful subgroups as mild (∼40%), moderate (∼35%), and severe (∼25%), and this provides a working model for use in future research and clinical care. Future work is required to understand more precisely the factors contributing to severity and to develop a valid patient-reported instrument to measure severity in IBS.


The effects of fracture permeability on acoustic wave propagation in the porous media: A microscopic perspective.
An illustrative theory is developed to analyze the acoustic wave propagation characteristics in the porous media with anisotropic permeability. We focus here on the role of fracture permeability in the unconsolidated porous media, looking in particular at the compressional P-wave phase velocity and attenuation. Two fluid pressure equilibration characteristic time factors are defined, which are corresponding to crack-pore system and crack-crack system, respectively. The theoretical results show that the dispersion and attenuation characteristics of acoustic wave are affected by porous matrix and fracture permeability simultaneously. Due to the fluid exchange that takes place between fractures and pores dominantly, the influence of the fracture connectivity on the wave propagation is very weak when the permeability of background medium is relatively high. However, correlation between wave propagation and fracture permeability is significant when the matrix permeability at a low level. A second attenuation peak occurs for the fluid flow within fractures in high-frequency region for more and more higher fracture permeability. The exact analytical solutions that are compared to numerical forward modeling of wave propagation in fractured media allow us to verify the correctness of the new model. If there exists another approach for obtaining the connectivity information of background media, we can use this model to analyze qualitatively the permeability of fractures or afford an indicator of in-situ permeability changes in a oil reservoir, for example, fracturing operations.


Association between tooth loss and frailty among Chinese older adults: the mediating role of dietary diversity.
This study aimed to examine the association between tooth loss and frailty among Chinese older adults and the mediating role of dietary diversity in this association. Data from five waves of the Chinese Longitudinal Healthy Longevity Survey conducted between 2005 and 2018 were used. Path analyses were employed to assess both concurrent and cross-lagged relationships between tooth loss and frailty index while accounting for intrapersonal correlation. Furthermore, the mediation effect of dietary diversity was also examined. In concurrent models, severe tooth loss was associated with frailty after adjusting for demographic characteristics (odds ratio [OR] = 1.82, p < 0.001). The OR of frailty for severe tooth loss was only slightly decreased to 1.74 (p < 0.001) when dietary diversity was added to the model and to 1.64 (p < 0.001) when socioeconomic status, family support, and healthy lifestyles were further adjusted. In the cross-lag or longitudinal models, the ORs were mildly or moderately reduced to 1.29, 1.27, and 1.23, respectively, yet remained statistically significant (p < 0.001 or p < 0.01). The mediation analyses showed that dietary diversity had some small yet significant effects on the relationship between tooth loss and frailty in both concurrent and longitudinal settings. This study improves current knowledge regarding the impact of tooth loss on frailty among Chinese older adults. Future intervention strategies designed to improve healthy diets may have preventive effects against the risk of frailty among Chinese older adults with severe tooth loss.


Breast cancer genetics: unsolved questions and open perspectives in an expanding clinical practice.
Breast cancer is the most common cause of cancer death in the United Kingdom, with a lifetime risk of one in nine in women. Only 5-10% of all cancers is thought to be due to strongly penetrant inherited predisposing genes, such as BRCA1 and BRCA2. However, other less penetrant genes, including some autosomal recessive genes, are likely to be of etiological importance in other families. This review addresses the current knowledge of breast cancer susceptibility genes and explores the possibilities for future developments. Features of tumor pathology, prognosis, and the scope for targeted treatments in mutation carriers are discussed, and the management of known carriers and those at increased risk for developing breast cancer are evaluated. Genetic testing for cancer susceptibility may become widely available in the future, and has important ethical and management implications.


Phase II trial of taxol in patients with metastatic renal cell carcinoma.
Based on results of previous Phase I studies, 18 patients with documented metastatic renal cell carcinoma received Taxol 250 mg/m2 as a 24-h infusion, repeated every 21 days in this Phase II study. All patients received premedication with dexamethasone, diphenhydramine, and cimetidine. There were no responses in the 18 patients treated.


CDKN2B Methylation Correlates with Survival in AML Patients.
Aberrant DNA methylation has been reported as an important phenotype in acute myeloid leukemia. However the clinical significance of methylation changes has not been clear yet. In this study methylation Specific Melting Curve Analysis (MS-MCA) and real time PCR was used to assess the CDKN2B promoter hyper-methylation and gene expression in 59 Iranian acute myeloid leukemia (AML) patients. The incidence of aberrant hyper methylation of CDKN2B gene and cytogenetic abnormalities were 37.3% (22 of 59 patients) and 35.6% (21 of 59) respectively in our patients. We observed that CDKN2B expression level was lower than normal mesenchymal stem cells. Our data revealed significant correlation between methylated CDKN2B promoter region and mRNA gene expression (P= 0.007). Also, our data indicated that AML patients with aberrant methylation of CDKN2B gene had a lower survival rates (P=0.043). In addition, they had a higher proportion of leukemic blast cells (P=0.022) and higher white blood cell count in peripheral blood (P=0.0123). Aberrant methylation of CDKN2B was observed to higher in M2 subtype and lower in M3 and M4 subtypes. Although, we observed a significant correlation between Methylation and survival, there was no significant correlation between CDKN2B methylation and treatment outcome of AML patients (P=0.187). Furthermore, our data didn't illustrated a significant correlation between CDKN2B expression and survival (P=0.93). In conclusion our study showed that the aberrant methylation is one of molecular mechanisms involved in CDKN2B gene expression, moreover we can consider the CDKN2B methylation, as a prognostic marker in predict AML patients' survival.


[Effect of Yishenqinghuo compound on biological characteristics of rat bone marrow stromal cells].
To evaluate the effect of Yishenqinghuo recipe on biological characteristic of rat bone marrow stromal cells (BMSCs) and search for the function and mechanism of this recipe in treatment of periodontitis. 12- to 15-month-old SD rats were allocated into 5 groups. Group A: control group (with no periodontitis model, fed with the same dosage of saline as Group D); Group B: model group (with periodontitis model, fed with the same dosage of saline as Group D); Group C: high dosage group (with periodontitis model, fed with a high dosage of medicine); Group D: middle dosage group (with periodontitis model, fed with a middle dosage of medicine); and Group E: low dosage group (with periodontitis model, fed with a low dosage of medicine). Ten days later, serums were collected from all the five groups for in vitro cultivation of BMSCs. There was displayed a similarity in effect between the serum collected from Group C1 (serum collected 0.5 h after the last gavage of Group C) and that from Group A after the last gavage, the effect being the best in terms of proliferation of BMSCs. A comparison with the other groups had revealed a striking difference (P < 0.01), with Group B having turned out to be the worst. The serum from Group C2 (serum collected 1 h after the last gavage of Group C) after the last gavage could best enhance the generation and activity of ALP, having demonstrated a significant difference (P < 0.01) in comparison with the other groups. Yishenqinghuo recipe can improve the proliferation of BMSCs and facilitate the differentiation to osteoblast.


Requirements for immunoglobulin synthesis in leukocyte cultures exposed to human cytomegalovirus.
T cell-depleted leukocytes from normal healthy donors lacking antibody to cytomegalovirus (CMV) were induced to secrete immunoglobulin (Ig) by exposure to inactivated CMV. The responses to two virus strains were compared. One strain had been reported to require specific T cell help to induce Ig synthesis, and the other had been reported to induce Ig synthesis in the presence of only very few cells. Both viruses induced T cell-depleted leukocytes from one group of seronegative donors to secrete Ig. However, both viruses failed to induce leukocytes from a second group of donors to secrete Ig unless B cell growth factor was added as a source of T cell help. These findings suggest that certain individuals are hyperresponsive to CMV and raise the possibility that this group may be most likely to develop mononucleosis after primary infection with CMV.


Lipopolysaccharide diversity evolving in Helicobacter pylori communities through genetic modifications in fucosyltransferases.
Helicobacter pylori persistently colonizes the gastric mucosa of half the human population. It is one of the most genetically diverse bacterial organisms and subvariants are continuously emerging within an H. pylori population. In this study we characterized a number of single-colony isolates from H. pylori communities in various environmental settings, namely persistent human gastric infection, in vitro bacterial subcultures on agar medium, and experimental in vivo infection in mice. The lipopolysaccharide (LPS) O-antigen chain revealed considerable phenotypic diversity between individual cells in the studied bacterial communities, as demonstrated by size variable O-antigen chains and different levels of Lewis glycosylation. Absence of high-molecular-weight O-antigen chains was notable in a number of experimentally passaged isolates in vitro and in vivo. This phenotype was not evident in bacteria obtained from a human gastric biopsy, where all cells expressed high-molecular-weight O-antigen chains, which thus may be the preferred phenotype for H. pylori colonizing human gastric mucosa. Genotypic variability was monitored in the two genes encoding alpha1,3-fucosyltransferases, futA and futB, that are involved in Lewis antigen expression. Genetic modifications that could be attributable to recombination events within and between the two genes were commonly detected and created a diversity, which together with phase variation, contributed to divergent LPS expression. Our data suggest that the surrounding environment imposes a selective pressure on H. pylori to express certain LPS phenotypes. Thus, the milieu in a host will select for bacterial variants with particular characteristics that facilitate adaptation and survival in the gastric mucosa of that individual, and will shape the bacterial community structure.


Effects of desmopressin acetate (DDAVP) and dextran on hemostatic and thromboprophylactic mechanisms.
The effects on hemostatic and thromboprophylactic mechanisms of intravenous desmopressin (DDAVP, 0.3 micrograms/kg) and dextran 40 and 70 given both separately and in various combinations were evaluated in five male volunteers. Dextran did not inhibit the DDAVP-induced hemostatic changes. The dextran-induced decrease in platelet adhesiveness and the prolonged bleeding time were totally reversed by DDAVP. Hematocrit decrease was seen after both drugs, lasting longer when they were combined. We conclude that DDAVP and dextran may be used concomitantly, each with maintained beneficial properties. DDAVP will still act hemostatically by increasing platelet adhesiveness, factor VIII and von Willebrand factor and by shortening the dextran-induced prolongation of bleeding time. Dextran and DDAVP may even have additive antithrombotic effects due to the DDAVP-induced stimulation of the fibrinolytic activity, which is not inhibited by dextran, and to rheologic changes such as hematocrit decrease induced by both drugs.


A novel connection between the yeast Cdc42 GTPase and the Slt2-mediated cell integrity pathway identified through the effect of secreted Salmonella GTPase modulators.
Modulation of host cellular GTPases through the injection of the effector proteins SopE2 and SptP is essential for Salmonella typhimurium to enter into non-phagocytic cells. Here we show that expression of the guanine nucleotide exchange factor for Cdc42 SopE2 in Saccharomyces cerevisiae leads to the activation of Fus3 and Kss1 MAPKs, which operate in the mating and filamentation pathways, causing filamentous growth in haploid yeast cells. Furthermore, it promotes the activation of the cell integrity MAPK Slt2. Cdc42 activation by removal of its putative intrinsic GTPase-activating proteins (GAPs), Rga1, Rga2, and Bem3, also results in the phosphorylation of Kss1, Fus3, and Slt2 MAPKs. These data support the role of these GAP proteins as negative regulators of Cdc42, confirm the modulating effect of this GTPase on the filamentation and mating pathways and point to a novel connection between Cdc42 and the cell integrity pathway. Cdc42-induced activation of Slt2 occurs in a mating and filamentation pathway-dependent manner, but it does not require the function of Rho1, which is the GTPase that operates in the cell integrity pathway. Moreover, we report that Salmonella SptP can act as a GAP for Cdc42 in S. cerevisiae, down-regulating MAPK-mediated signaling. Thus, yeast provides a useful system to study the interaction of bacterial pathogenic proteins with eukaryotic signaling pathways. Furthermore, these proteins can be used as a tool to gain insight into the mechanisms that regulate MAPK-mediated signaling in eukaryotes.


Degradation of C-terminal tag sequences on domain antibodies purified from E. coli supernatant.
Expression of recombinant proteins often takes advantage of peptide tags expressed in fusion to allow easy detection and purification of the expressed proteins. However, as the fusion peptides most often are flexible appendages at the N- or C-terminal, proteolytic cleavage may result in removal of the tag sequence. Here, we evaluated the functionality and stability of 14 different combinations of commonly used tags for purification and detection of recombinant antibody fragments. The tag sequences were inserted in fusion with the c-terminal end of a domain antibody based on the HEL4 scaffold in a phagemid vector. This particular antibody fragment was able to refold on the membrane after blotting, allowing us to detect c-terminal tag breakdown by use of protein A in combination with detection of the tags in the specific constructs. The degradation of the c-terminal tags suggested specific sites to be particularly prone to proteolytic cleavage, leaving some of the tag combinations partially or completely degraded. This specific work illustrates the importance of tag design with regard to recombinant antibody expression in E. coli, but also aids the more general understanding of protein expression.


[Renal damage in a chronic active hepatitis C patient receiving interferon-alpha therapy].
A 68-year-old male patient with chronic active hepatitis C was treated with interferon-alpha (IFN-alpha) for a period of 5 months. The patient responded well to the IFN therapy showing substantial improvement in liver function and disappearance of HCV-RNA. However, one year after the treatment he was found to have developed proteinuria and showed a reduction in Ccr. Renal biopsy findings were as follows: Light microscopy showed diffuse expansion of mesangial cells with a focal/local increase in cellularity accompanied by capillary loop thickening. Splitting of the basement membrane was also present. An immunofluorescent study showed that IgA was localized predominantly in the peripheral capillary wall. Electron microscopy showed that there was mesangial cell interposition between the peripheral capillary wall and endothelial cells. Furthermore, endothelial cells were expanded and numerous platelets were seen in the capillary lumen. These findings were compatible with focal MPGN accompanied by activation of endothelial cells. These histological data suggest two clinical disease entities: late-onset renal damage induced by IFN-alpha alone, and HCV-induced renal damage possibly modified by the direct effect of IFN-alpha on the endothelium. The present case suggests that IFN therapy for HCV may produce a particular type of renal damage, under the influence of either IFN or HCV infection, and/or both.


Comparison of antileukotrienes and antihistamines in the treatment of allergic rhinitis.
The aim of this study was to compare the effect of antileukotriene (anti-LT), antihistamine, and a combination of anti-LT and antihistamine on the symptoms and nasal resistance in allergic rhinitis patients. We performed a placebo-controlled study, with 120 persistent, moderate to severe allergic rhinitis patients randomly selected to receive the different treatments for 4 weeks: no treatment, 10 mg of cetirizine once per day, 20 mg of zafirlukast once per day, 20 mg of cafirlukast twice per day, a combination of 20 mg of zafirlukast and 10 mg of cetirizine once per day, or a combination of 20 mg of zafirlukast twice per day and 10 mg cetirizine once per day. The nasal secretion nitric oxide (NO) concentration, nasal symptom score, and nasal resistance were measured before and after treatment. Total symptom scores improved in each treated group compared with the control group (p < 0.05). Nasal obstruction significantly improved in the anti-LT-treated groups (p < 0.05). High-dose anti-LT or the combination of low-dose anti-LT and antihistamine significantly improved allergy symptoms compared with no treatment, low-dose anti-LT, or antihistamine alone (p < 0.05). Furthermore, anti-LT decreased NO concentration in nasal secretions (p < 0.05), regardless of the dose administered. These results suggest that high-dose anti-LT alone or the combination of low-dose anti-LY and antihistamine can effectively treat allergic rhinitis.


Function of the duct-ligated canine pancreatic allograft.
Heterotopic transplantation of a duct-ligated canine pancreas was performed in 20 previously pancreatectomized, non-related recipient dogs. A technical procedure was elaborated for this grafting. It was found that early, fatal postoperative bleeding in the recipient could be avoided when the interval between pancreatectomy and transplantation was reduced from 7 to 2-4 days. The early endocrine function was studied in 15 surviving animals by determination of blood glucose and serum insulin during fasting and during glucose load. 24 h after transplantation the blood glucose values were normal and 4-8 days after transplantation the glucose tolerance was within normal limits. The serum insulin was on a supranormal level, also during glucose load. The early endocrine capacity of the transplanted duct-ligated pancreas after transplantation was found to be satisfactory, restoring the blood glucose in the pancreatectomized recipients to normal levels.


[Commentary on the history of forensic medicine in Venezuela].
The author explains definitions and fields of forensic medicine. Three periods are described: 1) Since colonial times to the foundation of the Caracas forensic medicine (1937); 2) From 1937 to the foundation of the Technical Judiciary Police (1958); 3) From 1958 until now; this period includes the process called "Nationalization of forensic medicine". Then there are remarks, within the historical context, on forensic medicine and teaching, the importance of the Forensic Medicine Society and the importance of postgraduate courses.


Interim therapeutic restoration approach versus treatment under general anaesthesia approach.
Although dental treatment under general anaesthesia (GA) remains the long-established approach for treating anxious children, treatment under GA presents with increased risks, costs and parental acceptability issues. Interim therapeutic restoration (ITR) has been proposed as an alternative approach. To compare the incidence and types of failures between children managed with the ITR approach and those managed under GA within 12 months of treatment completion. A retrospective cohort study of children who received dental treatment utilizing the ITR approach was compared to children treated under GA. Age, gender and dental disease matching was done. Statistical analyses were carried out with Independent t-test and chi-square analyses. A total of 132 children (GA = 66, ITR = 66) were included, and the groups did not differ in terms of initial age, sex, dmft and initial behaviour score. ITR group had a significantly higher rate (P < 0.001; 95% CI: [0.21 to 0.97]) of restorative failure and visits required when compared to the GA group. There were no difference for incidence of pain (P = 0.55; 95% CI: [-0.074 to 0.10]) and behaviour scores (P = 0.46) between the two groups at the 12-month visit. ITR approach may be a viable alternative to the GA approach when treating paediatric dental patients.


[Tachicardia-induced cardiomyopathy. Case report].
The tachycardia-induced cardiomyopathy is a rare case of reversible heart failure and left ventricle disfunction. The diagnostic approach and treatment strategy are described in this article. Also the clinical case of heart failure compensation in the patient with left ventricle dilatation and atrial flutter after the reverse to sinus rhythm is after catheter ablation presented.


Aggression during early years - infancy and preschool.
This review explores the meaning and origins of aggression in early years. Eight pathways to aggression with origins in early childhood are suggested. These include: the contribution of individual factors; the effects of disturbed family dynamics; parental characteristics and parenting practices; the impact of exposure to violence and the influence of attachment relationships. Other influences such as: aggression relating to psychiatric/medical syndromes; the influence of neurodevelopment pathways and psychodynamic explanations, such as aggressive behavior in relation to mothers' reflective capacity are also discussed. While several routes to aggression have been proposed, no single factor is sufficient to explain the development of aggressive behavior. Longitudinal studies are sorely needed to observe aggressive behavior in children and to monitor their developmental trajectories.


External Validation of aMAP Hepatocellular Carcinoma Risk Score in Patients With Chronic Hepatitis B-Related Cirrhosis Receiving ETV or TDF Therapy.
Background and Aim: A prediction model of hepatocellular carcinoma (HCC) risk in patients with chronic liver diseases, based on age, male sex, albumin-bilirubin, and platelets (aMAP), has been previously reported. We validated the aMAP score and compared its performance to those of other risk scores in an independent at-risk cohort. Methods: Treatment-naïve patients with chronic hepatitis B-related compensated cirrhosis who received entecavir or tenofovir monotherapy for at least 12 months were enrolled in this study. The performances of the aMAP and other HCC risk scores were assessed using Harrell's c-index, and predefined cut-off values were evaluated using survival analysis. Results: Of the 1,042 patients, 131 (12.6%) developed HCC during a median follow-up of 41 months. The aMAP score provided the highest Harrell's c-index (0.724), followed by CAMD (0.719), mPAGE-B (0.719), and PAGE-B (0.695). The 5-year cumulative HCC probabilities were 2.9% for patients with a low aMAP score (<50), 11.2% for patients with an intermediate aMAP score (50-60), and 27.9% for patients with a high aMAP score (>60). Using both aMAP and mPAGE-B, 11.6% of patients were identified as low risk with a negative predictive value of 98.2% for not developing HCC within 5 years. Patients with aMAP >60 and diabetes exhibited an extremely high risk of HCC, with a cumulative incidence of 49.3% at 5 years. The predictive performance of aMAP with a reassessment at 1 year after the initiation of antiviral therapy outperformed the predictive performance of aMAP at enrollment. Conclusions: The aMAP score accurately predicted the risk of HCC in at-risk patients with compensated cirrhosis undergoing antiviral therapy. A combination of the aMAP score and diabetes status could further stratify the risk of HCC.


Group-velocity-locked vector soliton molecules in fiber lasers.
Physics phenomena of multi-soliton complexes have enriched the life of dissipative solitons in fiber lasers. By developing a birefringence-enhanced fiber laser, we report the first experimental observation of group-velocity-locked vector soliton (GVLVS) molecules. The birefringence-enhanced fiber laser facilitates the generation of GVLVSs, where the two orthogonally polarized components are coupled together to form a multi-soliton complex. Moreover, the interaction of repulsive and attractive forces between multiple pulses binds the particle-like GVLVSs together in time domain to further form compound multi-soliton complexes, namely GVLVS molecules. By adopting the polarization-resolved measurement, we show that the two orthogonally polarized components of the GVLVS molecules are both soliton molecules supported by the strongly modulated spectral fringes and the double-humped intensity profiles. Additionally, GVLVS molecules with various soliton separations are also observed by adjusting the pump power and the polarization controller.


Cyclic AMP-protein kinase A and Snf1 signaling mechanisms underlie the superior potency of sucrose for induction of filamentation in Saccharomyces cerevisiae.
Under specific environmental conditions, the yeast Saccharomyces cerevisiae can undergo a morphological switch to a pseudohyphal growth pattern. Pseudohyphal differentiation is generally studied upon induction by nitrogen limitation in the presence of glucose. It is known to be controlled by several signaling pathways, including mitogen-activated protein kinase, cyclic AMP-protein kinase A (cAMP-PKA), and Snf1 kinase pathways. We show that the alpha-glucoside sugars maltose and maltotriose, and especially sucrose, are more potent inducers of filamentation than glucose. Sucrose even induces filamentation in nitrogen-rich media and in the mep2Delta/mep2Delta ammonium permease mutant on ammonium-limiting medium. We demonstrate that glucose also inhibits filamentation by means of a pathway parallel to the cAMP-PKA pathway. Deletion of HXK2 shifted the pseudohyphal growth pattern on glucose to that of sucrose, while deletion of SNF4 abrogated filamentation on both sugars, indicating a negative role of glucose repression and a positive role for Snf1 activity in the control of filamentation. In all strains and in all media, sucrose induction of filamentation is greatly diminished by deletion of the sucrose/glucose-sensing G-protein-coupled receptor Gpr1, whereas it has no effect on induction by maltose and maltotriose. The competence of alpha-glucoside sugars to induce filamentation is reflected in the increased expression of the cell surface flocculin gene FLO11. In addition, sucrose is the only alpha-glucoside sugar capable of rapidly inducing FLO11 expression in a Gpr1-dependent manner, reflecting the sensitivity of Gpr1 for this sugar and its involvement in rapid sucrose signaling. Our study identifies sucrose as the most potent nutrient inducer of pseudohyphal growth and shows that glucose inactivation of Snf1 kinase signaling is responsible for the lower potency of glucose.


Restriction analysis of an amplified rodA gene fragment to distinguish Aspergillus fumigatus var. ellipticus from Aspergillus fumigatus var. fumigatus.
A previous multidisciplinary study indicated that gliotoxin-producing Aspergillus fumigatus Fresen. isolates from silage commodities mostly belonged to its variant A. fumigatus var. ellipticus Raper & Fennell. Sequence analysis revealed the presence of a single nucleotide polymorphism at five positions in a fragment of the rodA gene (coding for a hydrophobin rodletA protein) between Aspergillus fumigatus var. fumigatus and Aspergillus fumigatus var. ellipticus. A method was developed to distinguish these two types of isolates based on restriction analysis of this rodA gene fragment using the HinfI restriction enzyme. In addition, in silico analysis of 113 rodA gene fragments retrieved from GenBank was performed and confirmed the suitability of this method. In conclusion, the method developed in this study allows easy distinction between A. fumigatus var. fumigatus and its variant ellipticus. In combination with the earlier developed PCR-restriction fragment length polymorphism method of Staab et al. (2009, J Clin Microbiol 47: 2079), this method is part of a sequencing-independent identification scheme that allows for rapid distinction between similar species/variants within Aspergillus section Fumigati, specifically A. fumigatus, A. fumigatus var. ellipticus, Aspergillus lentulus Balajee & K.A. Marr, Neosartorya pseudofischeri S.W. Peterson and Neosartorya udagawae Y. Horie, Miyaji & Nishim.


Effect of cumulus maturity on sperm penetration in the golden hamster.
The influence of the cumulus on gamete interaction was investigated in naturally and precociously ovulated eggs from superstimulated (eCG) hamsters. Inseminations were performed in which the absolute gamete ratio (sperm/egg) was held constant, but the relative gamete ratio (sperm x egg-1 x ml-1) was varied 10-fold. Sperm penetration to the perivitelline space was significantly higher at the higher relative gamete ratio, indicating that there is no chemoattractant in the cumulus and that gamete interaction in cumulus-intact eggs is a function of collision frequency, which varies according to the relative gamete ratio. The level of successful gamete interaction as a function of the relative gamete ratio was determined for naturally and precociously ovulated eggs. The level of sperm penetration reached saturation at a relative gamete ratio of 10(3.3) for naturally ovulated eggs and 10(4.0) sperm x egg-1 x ml-1 for precociously ovulated eggs. At suboptimal relative gamete ratios, there was no difference in the level of penetration between partially and fully capacitated sperm. These results indicate that the larger, more mature cumulus of naturally ovulated eggs is successfully penetrated at lower collision frequencies than the denser, less mature cumulus of precociously ovulated eggs. To determine whether the maturity of the cumulus affects the timing of sperm penetration, cumulus-free and cumulus-intact eggs were inseminated at their optimal relative gamete ratios. The rate of sperm penetration of partially capacitated sperm was not different between cumulus-free and cumulus-intact eggs, regardless of ovulation method. However, the period of time between insemination and when half the eggs were penetrated (T50) was longer in cumulus-intact eggs.(ABSTRACT TRUNCATED AT 250 WORDS)


Targeting of a plasma cell line with a conjugate containing xanthine oxidase and the monoclonal antibody 62B1.
We report on the preparation of an antibody-conjugated enzyme consisting of xanthine oxidase, a free-radical-producing enzyme, linked to the 62B1 monoclonal antibody, which recognizes the last steps of differentiation of B cell lineage (plasma cell and hairy cells). The conjugate specifically kills target cells, retaining both enzymic and immunological properties, without any damage to normal myeloid clonogenic efficiency. The model is suitable for ex vivo bone marrow purging in multiple myeloma patients.


Low reoperation rate following 336 multilevel lumbar laminectomies with noninstrumented fusions.
Few reoperations are required in older patients undergoing multilevel lumbar laminectomy with noninstrumented fusions for spinal stenosis with/without spondylolisthesis/instability, and they rarely require instrumentation. We reviewed 336 patients averaging 66.5 years of age undergoing initial average 4.7 level lumbar laminectomies with average 1.4 level noninstrumented fusions over an average 7.1-year period (range 2.0-16.5 years). Patients uniformly exhibited spinal stenosis, instability (Grade I [195 patients] or Grade II spondylolisthesis [67 patients]), disc herniations (154 patients), and/or synovial cysts (66 patients). Reoperations, including for adjacent segment disease (ASD), addressed new/recurrent pathology. Nine (2.7%) of 336 patients required reoperations, including for ASD, an average of 6.3 years (range 2-15 years) following initial 4.7 level laminectomies with 1.4 level noninstrumented fusions. Second operations warranted average 4.8 level (range 3-6) laminectomies and average 1.1 level non instrumented fusions addressing stenosis with instability (Grade I [7 patients] or Grade II [1 patient] spondylolisthesis), new disc herniations (2 patients), and/or a synovial cyst (1 patient). Only 9 (2.7%) of 336 patients required reoperations (including for ASD) consisting of multilevel laminectomies with noninstrumented fusions for recurrent/new stenosis even with instability; these older patients were not typically unstable, or were likely already fused, and did not require instrumentation. Alternatively, reoperation rates following instrumented fusions in other series approached 80% at 5 postoperative years. Therefore, we as spinal surgeons should realize that older patients even with instability rarely require instrumentation and that the practice of performing instrumented fusions in everyone, irrespective of age, needs to stop.


[Neuroimaging in Lyme disease].
Imaging techniques are commonly used in the diagnostics of the central nervous system disorders. Abnormalities found using MRI and MRS in neuroborreliosis patients are described.


The making of a professional digital caregiver: personalisation and friendliness as practices of humanisation.
The aim of this paper is to explore how a digital caregiver, developed within a Swedish interdisciplinary research project, is humanised through health-enhancing practices of personalisation and friendliness. The digital caregiver is developed for being used in older patients' homes to enhance their health. The paper explores how the participants (researchers and user study participants) of the research project navigate through the humanisation of technology in relation to practices of personalisation and friendliness. The participants were involved in a balancing act between making the digital caregiver person-like and friend-like enough to ensure the health of the patient. Simultaneously, trying to make the patients feel like as if they were interacting with someone rather than something-while at the same time not making the digital caregiver seem like a real person or a real friend. This illustrates the participants' discursive negotiations of the degree of humanisation the digital caregiver needs in order to promote the health of the patient. A discursive conflict was identified between a patient discourse of self-determination versus a healthcare professional discourse of authority and medical responsibility: whether the digital caregiver should follow the patient's health-related preferences or follow the healthcare professionals' health rules. Hence, a possible conflict between the patient and the digital caregiver might arise due to different understandings of friendliness and health; between friendliness (humanisation) as a health-enhancing practice governed by the patient or by the healthcare professionals (healthcare professionalism).


Outcomes with Finerenone in Participants with Stage 4 CKD and Type 2 Diabetes: A FIDELITY Subgroup Analysis.
Background Patients with stage 4 chronic kidney disease (CKD) and type 2 diabetes have limited treatment options to reduce their persistent cardiovascular and kidney risk. In FIDELITY, a prespecified pooled analysis of FIDELIO-DKD and FIGARO-DKD, finerenone improved heart-kidney outcomes in participants with CKD and type 2 diabetes. Methods This FIDELITY subgroup analysis investigated the effects of finerenone in participants with stage 4 CKD (estimated glomerular filtration rate [eGFR] <30 ml/min/1.73 m2). Efficacy outcomes included a cardiovascular composite (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and a kidney composite (kidney failure, sustained ≥57% decrease in eGFR from baseline, or kidney disease death). Results Of 13,023 participants, 890 (7%) had stage 4 CKD. The hazard ratio for risk of cardiovascular composite outcome with finerenone versus placebo was 0.78 (95% confidence interval 0.57-1.07). The kidney composite outcome proportional hazards assumption was not met for the overall study period, with a protective effect only shown up to 2 years, after which the direction of association was inconsistent and an observed loss of precision over time incurred on finerenone versus placebo risk differences. Nonetheless, albuminuria and rate of eGFR decline were consistently reduced with finerenone versus placebo. Adverse events were balanced between treatment arms. Hyperkalemia was the most common AE reported (stage 4 CKD: 26% and 13% for finerenone versus placebo, respectively) however, the incidence of hyperkalemia leading to permanent discontinuation was low (stage 4 CKD: 3% and 2% for finerenone versus placebo, respectively). Conclusions The cardiovascular benefits and safety profile of finerenone in participants with stage 4 CKD were consistent with the overall FIDELITY population; this was also the case for albuminuria and the rate of eGFR decline. The effects on the composite kidney outcome were not consistent over time.


Real-world clinical, psychosocial and economic burden of atopic dermatitis: Results from a multicountry study.
Atopic dermatitis (AD), a relapsing, inflammatory skin disease, is associated with pruritus that can negatively affect patients' quality of life. Understanding the burden of AD is critical for informing and tailoring treatment and disease management to improve patient outcomes. This study characterized global treatment patterns and the clinical, psychosocial and economic burden of moderate-to-severe AD. MEASURE-AD was a cross-sectional 28-country study in patients with physician-confirmed moderate-to-severe AD who were either receiving or eligible for systemic therapy for AD. Patients ≥12 years were enrolled between December 2019 and December 2020 while attending routine office or clinic visit. Primary outcomes included Worst Pruritus Numeric Rating Scale (WP-NRS; range: 0-10) and Dermatology Life Quality Index (DLQI; range: 0-30) and Children's DLQI (CDLQI; range: 0-30). Secondary outcomes included physician- and patient-reported clinical, psychosocial and economic burden. Of the 1591 patients enrolled, 1558 (1434 adults and 124 adolescents) fulfilled all patient selection criteria and were included in this analysis. Almost all patients (98.4%) in the total population were using AD medications and more than half (56%) were receiving systemic medication (15% systemic monotherapy). The most used systemic therapies were dupilumab (56.3%), systemic glucocorticoids (18.1%) and methotrexate (16.2%). Mean WP-NRS was 5.3 in the total population, and most patients (≥55%) reported moderate-to-severe pruritus (WP-NRS ≥4). Mean DLQI was 10.8 and mean CDLQI was 9.6. Secondary endpoints demonstrated substantial clinical, psychosocial, and economic burden of disease. Subgroup analysis demonstrated that patients receiving systemic therapy had lower disease burden than those not taking systemic medications. While systemic therapy lowers overall disease burden, patients with moderate-to-severe AD continue to have substantial multidimensional disease burden and uncontrolled disease. Overall, there is a need for effective disease management, including effective treatments that improve patients' psychosocial outcomes and reduce the economic burden of AD.


A correlation study affecting survival in patients after radical colon cancer surgery: A retrospective study.
The objective of this study was to explore the relevant factors affecting the 5-year survival rate of patients after radical colon cancer surgery, and to provide some basis for improving the quality of life and prognosis of colon cancer patients. The clinical data of 116 colon cancer patients who underwent treatment in our hospital from January 2017 to December 2017 were retrospectively selected. Using the date of performing surgical treatment as the starting point and the completion of 5 years after surgery or patient death as the end point, all patients were followed up by telephone to count the 5-year survival rate and analyze the influence of each factor with the prognosis of colon cancer patients. Of the 116 patients, 14 patients were lost to follow-up. Of the 102 patients with complete follow-up, 33 patients were died, with an overall 5-year survival rate of 67.6%. After univariate analysis, it was found that distant metastasis (χ2 = 10.493, P = .001), lymph node metastasis (χ2 = 25.145, P < .001), depth of muscle infiltration (χ2 = 14.929, P < .001), alcohol consumption (χ2 = 15.263, P < .001), and preoperative obstruction (χ2 = 9.555, P = .002) were significantly associated with the prognosis of colon cancer patients. Multivariate logistic analysis showed that distant metastasis (odds ratio [OR]: 1.932, 95% confidence intervals [CI]: 1.272-2.934, P = .002), lymph node metastasis (OR: 1.219, 95% CI: 1.091-1.362, P < .001), and obstruction (OR: 1.970, 95% CI: 1.300-2.990, P < .001) were significant independent risk factors affecting the prognosis in patients after radical colon cancer surgery. In summary, preoperative obstruction, lymph node metastasis, and distant metastasis are independent factors influencing 5-year survival rate after radical colon cancer surgery. Patients with risk factors should be followed up more closely and reasonable postoperative adjuvant chemotherapy regimens should be used to improve long-term survival.


Highly chemoselective and efficient production of 2,6-difluorobenzamide using Rhodococcus ruber CGMCC3090 resting cells.
Chemoselective biocatalytic hydrolysis of nitriles is a valuable alternative to chemical hydrolysis that operates under harsh conditions. 2,6-Difluorobenzamide (DFBAM) is an essential intermediate derived from synthesis of benzoyl urea insecticide from 2,6-difluorobenzonitrile (DFBN). High yield of DFBAM was achieved, and the method using resting cells of Rhodococcus ruber CGMCC3090 exhibited excellent product specificity. The reaction parameters for DFBAM biosynthesis were also investigated. The resting cells effectively converted DFBN at high concentrations of up to 3.5 mol L-1 without forming acids or other by-products. Therefore, biological production of DFBAM features high yield, chemoselectivity, low cost, and environment friendliness and is more suitable to the industry than chemical synthesis techniques.


Effects of participation in the WIC program on birthweight: evidence from the National Longitudinal Survey of Youth. Special Supplemental Nutrition Program for Women, Infants, and Children.
This study sought to estimate the impact on birthweight of maternal participation in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). WIC estimates were based on sibling models incorporating data on children born between 1990 and 1996 to women taking part in the National Longitudinal Survey of Youth. Fixed-effects estimates indicated that prenatal WIC participation was associated with a 0.075 unit difference (95% confidence interval [CI] = -0.007, 0.157) in siblings' logged birthweight. At the 88-oz (2464-g) low-birthweight cutoff, this difference translated into an estimated impact of 6.6 oz (184.8 g). Earlier WIC impact estimates may have been biased by unmeasured characteristics affecting both program participation and birth outcomes. Our approach controlled for such biases and revealed a significant positive association between WIC participation and birthweight.


Serological studies of an enterically transmitted non-A, non-B hepatitis in Somalia.
An outbreak of an acute sporadic viral hepatitis occurring at three villages in the lower Shebli region of southern Somalia was studied. Sera were examined for antibodies to hepatitis E virus (HEV) antigen by a recently developed enzyme-linked immunosorbent assay. The prevalence of anti-HEV ranged from 77.8% to 94.0% among the three villages. Anti-HEV prevalence did not differ significantly with age or sex. HEV infections were widely distributed among all age groups, without a preponderance in any specific age category. Overall, 97.6% of afflicted patients who were examined 6-10 days after onset of jaundice developed either IgM or IgG anti-HEV.


Primary screening of relatively less allergenic wheat varieties.
Since the number of wheat-allergic patients has been increasing in recent years, less allergenic wheat varieties are socially demanded. The aim of this study was to primarily screen 324 varieties of wheat picked up from various parts of the world. Prior to the screening, the inhibition ELISA (enzyme-linked immunosorbent assay) was examined with major wheat allergens (glutenin, gliadin and alpha-amylase inhibitor). As a result, the patient's IgE antibodies used in this assay reacted to these three allergens, and thereby turned out to be suitable for the primary screening for the less allergenic wheat varieties. Thus, the allergenicity of each wheat sample was measured by direct ELISA using the sole patient's serum as an IgE source and 'Aoba Komugi' as a control (a value of 1.0). The mean +/- SD of all kinds was 1.14 +/- 0.37. Among them, 'CM32859' (Mexico) gave the lowest value (0.38). Several other varieties, such as 'Einkorn' (Unknown), 'Iliniaza' (Ecuador), 'Hsin Mai 2' (China), 'Italy 1' (Italy) and so on, also serve as candidates for the less allergenic varieties. More detailed secondary screening will lead to a finding of the less allergenic wheat varieties for wheat-allergic patients, because these varieties are expected to become mother plants for breeding.


The occurrence of the third trochanter and its correlation to certain anthropometric parameters of the human femur.
The purpose of the study was to analyse the occurrence of the third trochanter and its correlation with the morphology of the human femur. The third trochanter was found in 38 of 622 (6.2%) human femora taken from 3 excavation sites. 36 of these were included in the study and were compared to the femora without the third trochanter. The bones with the third trochanter were characterised by a greater superior sagittal diameter and diaphysis platymetry index as well as a larger greater trochanter. These results suggest that the third trochanter is not a progressive morphological feature of the skeleton. Rather it is connected with an altered gluteal muscle function.


SELECTION FOR HEAT-SHOCK RESISTANCE IN LARVAL AND IN ADULT DROSOPHILA BUZZATII: COMPARING DIRECT AND INDIRECT RESPONSES.
Direct and correlated responses in selection for heat-shock resistance in adult and in larval Drosophila buzzatii were studied. Two lines were artificially selected for higher survival to heat stress as adults, and two other lines were reared under a fluctuating thermal environment as larvae, 35°C for 6 h and 25°C for 18 h, to "naturally" select for higher resistance as larvae. The latter two lines were duplicated after nine generations to yield additional lines to be "naturally" selected as larvae at a higher temperature, 38.2°C for 6 h. Control lines were maintained separately for the adult and larval selection lines. A significant direct response to selection was found for the adult selection lines. However, larvae of these adult selection lines were no more heat resistant than were larvae of the control lines. One of the two larval selection lines increased significantly in heat resistance as larvae. However, adult heat resistance was similar for lines selected as larvae and the corresponding control lines maintained at 25°C. Changes in developmental time accompanied changes in survival after stress in both sets of lines selected for increased heat resistance.


Understanding the interactions of neptunium and plutonium ions with graphene oxide: scalar-relativistic DFT investigations.
Due to the vast application potential of graphene oxide (GO)-based materials in nuclear waste processing, it is of pivotal importance to investigate the interaction mechanisms between actinide cations such as Np(V) and Pu(IV, VI) ions and GO. In this work, we have considered four types of GOs modified by hydroxyl, carboxyl, and carbonyl groups at the edge and epoxy group on the surface, respectively. The structures, bonding nature, and binding energies of Np(V) and Pu(IV, VI) complexes with GOs have been investigated systematically using scalar-relativistic density functional theory (DFT). Geometries and harmonic frequencies suggest that Pu(IV) ions coordinate more easily with GOs compared to Np(V) and Pu(VI) ions. NBO and electron density analyses reveal that the coordination bond between Pu(IV) ions and GO possesses more covalency, whereas for Np(V) and Pu(VI) ions electrostatic interaction dominates the An-OG bond. The binding energies in aqueous solution reveal that the adsorption abilities of all GOs for actinide ions follow the order of Pu(IV) > Pu(VI) > Np(V), which is in excellent agreement with experimental observations. It is expected that this study can provide useful information for developing more efficient GO-based materials for radioactive wastewater treatment.


A comprehensive review of erectile dysfunction in men with diabetes.
Erectile dysfunction (ED) is more common in men with diabetes (DM). Dependent on the selected population, age, DM type and duration, the prevalence of diabetic ED (DED) varies from 32 to 90%. In 12-30% of men ED is the first sign of diabetes, diagnosed later. Today men with diabetes live longer than ever, and develop more late diabetic complications. Having in mind also the global ageing of the world population all this data suggests an increasing number of men with DED in the future. The main factors playing in the complex pathogenesis of DED are diabetic neuropathy (oxidative stress, polyol pathway, advanced glycation end-products, nerve growth factor deficiency, dysfunction of protein kinase C, tissue remodeling, etc.), macrovascular arterial disease (endothelial dysfunction, abnormal collagen deposition and smooth muscle degeneration, dyslipidemia, arterial hypertension, veno-occlusive dysfunction, etc.), hypogonadism, structural remodeling of the corporeal tissue, psychogenic components and adverse drug reactions. The diagnostic process is based on the results of questionnaires, neurological, vascular (Doppler) and other more rarely used investigations.Because of the complex pathogenesis of DED diabetic men represent a "difficult" treatment group. The difficulties are from the "beginning", because patients do not talk about their problem spontaneously, and doctors do not ask about it. The treatment of DED should be team work, preferably including also specialists in sexual medicine. Psychological support and counseling of the couple is necessary in most cases. The general measures include implementation of a healthier lifestyle, improved glycemic-, lipids-, and arterial pressure control, and careful re-evaluation of the concomitant medications. The specific treatment includes as first line therapy the inhibitors of phosphodiesterase type 5 (PDE-5) with lesser effectiveness compared to non-DM men. There are rare studies with selected diabetic populations and even less with head-to-head comparisons between the PDE-5 inhibitors. Men with DM have a higher prevalence of hypogonadism. Testosterone replacement therapy should be started in symptomatic men with proven hypogonadism and no contraindications. Vacuum constriction devices and intracavernous or intraurethral applications of vasoactive drugs are the second line therapy. Vascular surgery rarely comes into consideration. The penile implant is the last and effective option in men with severe DED.


Governing the oxidative addition of iodine to gold(I) complexes by ligand tuning.
While several gold(I) complexes of the type (L)AuX (X = Cl, Br) are known to undergo oxidative addition of elemental chlorine and bromine (X2), respectively, to give the corresponding gold(III) complexes (L)AuX3, the addition of iodine to (iodo)gold(I) compounds is strongly ligand-dependent, suggesting a crucial threshold in the oxidation potentials. A systematic investigation of this particular oxidative addition of iodine using a large series of tertiary phosphines as ligands L has shown that both electronic and steric effects influence the course of the reaction. The reactions were followed by 31P NMR spectroscopy and the products crystallized from dichloromethane-pentane solutions. Complexes with small triakylphosphines (PMe3, PEt3) are readily oxidized, while those with more bulky ligands (PiPr3, PtBu3) are not. With L taken from the triarylphosphine series [PPh3, P(2-Tol)3, P(3-Tol3), P(4-Tol)3] no oxidation takes place at all, but mixed alkyl/aryl-phosphines [PMenPh(3-n)] induce oxidation for n = 3 and 2, but not for n = 1 and 0. However, in cases where no oxidation of the gold atoms is observed, the synthons may crystallize as adducts with molecular iodine of the polyiodide type instead, which have an iodine rich stoichiometry. This fact explains inconsistent reports in the literature. The metal atoms in (L)AuI coordination compounds with L representing a tri(heteroaryl)phosphine [P(2-C4H3E)3, E = O, S], a phosphite [P(OR)3] or a trialkenylphosphine [PVi3] are all not subject to oxidative addition of iodine. The dinuclear complex of the ditertiary phosphine Ph2PCH2PPh2, (dppm)(AuI)2, gives an iodine adduct (without oxidation of the metal atoms), but with 1,2-Ph2P(C6H4)PPh2(dppbe) an ionic complex [(dppbe)AuI2]+I3- with a chelated gold(III) centre is obtained. The gold(I) bromide complexes with tertiary phosphines are readily oxidized by bromine to give the corresponding gold(III) tribromide complexes, as demonstrated for (BzMePhP)AuBr and (Ph3P)AuBr. With (dppm)(AuBr)2 the primary product with mixed oxidation states was also isolated: (dppm)AuBr(AuBr3). The crystal structures of the following representative examples and reference compounds have been determined: (Me3P)AuI3, (Me2PhP)AuI3, (iPr3P)AuI.1.5I2, (Ph3P)AuI.I2, [[(2-Tol)3P]AuI]2.I2, [(2-Tol)3P]AuI, (dppm)(AuX)2 (with X = Br, I), (dppm)AuBr(AuBr3) and [(dppbe)AuI2]+I3-. The structures are discussed focusing on the steric effects. It appears that e.g. the reluctance of (Ph3P)AuI to add I2 is an electronic effect, while that of (iPr3P)AuI has its origin in the steric influence of the ligand.


Clinical severity and molecular characteristics of circulating and emerging rotaviruses in young children attending hospital emergency departments in France.
Group A rotavirus (RVA) is the leading cause of acute gastroenteritis in young children worldwide. A prospective surveillance network has been set up to investigate the virological and clinical features of RVA infections and to detect the emergence of potentially epidemic strains in France. From 2009 to 2014, RVA-positive stool samples were collected from 4800 children <5 years old attending the paediatric emergency units of 16 large hospitals. Rotaviruses were then genotyped by RT-PCR with regard to their outer capsid proteins VP4 and VP7. Genotyping of 4708 RVA showed that G1P[8] strains (62.2%) were predominant. The incidence of G9P[8] (11.5%), G3P[8] (10.4%) and G2P[4] (6.6%) strains varied considerably, whereas G4P[8] (2.7%) strains were circulating mostly locally. Of note, G12P[8] (1.6%) strains emerged during the seasons 2011-12 and 2012-13 with 4.1% and 3.0% prevalence, respectively. Overall, 40 possible zoonotic reassortants, such as G6 (33.3%) and G8 (15.4%) strains, were detected, and were mostly associated with P[6] (67.5%). Analysis of clinical records of 624 hospitalized children and severity scores from 282 of them showed no difference in clinical manifestations or severity in relation to the genotype. The relative stability of RVA genotypes currently co-circulating and the large predominance of P[8] type strains may ensure vaccine effectiveness in France. The surveillance will continue to monitor the emergence of new reassortants that might not respond to current vaccines, all the more so as all genotypes can cause severe infections in infants.


Cigarette Smoking Among Urban American Indian Adults - Hennepin and Ramsey Counties, Minnesota, 2011.
In 2013, it was estimated that the prevalence of cigarette smoking among American Indians was 36.5%, the highest of all racial/ethnic groups in the continental United States (1). Among American Indians, considerable cultural and geographic variation in cigarette smoking exists. Smoking prevalence among American Indians is lowest in the Southwest and highest in the Upper Midwest/Northern Plains (2). Little information is available about tobacco use among urban American Indians, who might not have ever lived on a reservation or be enrolled in or affiliated with a tribe. In Minnesota, a significant proportion of American Indians reside in urban areas. Among Minnesota's residents who identify as American Indian alone or in combination with another race, 30% live in Hennepin County and Ramsey County, which encompass Minneapolis and St. Paul, respectively (collectively known as the Twin Cities). The predominant tribes (Ojibwe [Chippewa] and Dakota/Lakota/Nakota [Sioux]) traditionally have used locally grown tobacco (Nicotiana rustica), red willow, and other plants for religious ceremonies, although nonceremonial tobacco is often substituted for traditional plants. To assess prevalence of cigarette smoking among this population, it is important to distinguish ceremonial tobacco use (smoked or used in other ways) from nonceremonial tobacco use. To obtain estimates of cigarette smoking prevalence among American Indians in Hennepin and Ramsey counties, the American Indian Adult Tobacco Survey was administered to 964 American Indian residents in 2011, using respondent-driven sampling. Among all participants, 59% were current smokers, 19% were former smokers, and 22% had never smoked. Approximately 40% of employed participants reported that someone smoked in their workplace area during the preceding week. High prevalences of cigarette smoking and secondhand smoke exposure among urban American Indians in Minnesota underscores the need for a comprehensive and culturally appropriate approach to reducing nonceremonial tobacco use.


Information in feedback ratchets.
Feedback control uses the state information of the system to actuate on it. The information used implies an effective entropy reduction of the controlled system, potentially increasing its performance. How to compute this entropy reduction has been formally shown for a general system and has been explicitly computed for spatially discrete systems. Here, we address a relevant example of how to compute the entropy reduction by information in a spatially continuous feedback-controlled system. Specifically, we consider a feedback flashing ratchet, which constitutes a paradigmatic example for the role of information and feedback in the dynamics and thermodynamics of transport induced by the rectification of Brownian motion. A Brownian particle moves in a periodic potential that is switched on and off by a controller. The controller measures the position of the particle at regular intervals and performs the switching depending on the result of the measurement. This system reaches a long-time dynamical regime with a nonzero mean particle velocity, even for a symmetric potential. Here, we calculate the efficiency at maximum power in this long-time regime, computing all the required contributions. We show how the entropy reduction can be evaluated from the entropy of the non-Markovian sequence of control actions, and we also discuss the required sampling effort for its accurate computation. Moreover, the output power developed by the particle against an external force is investigated, which-for some values of the system parameters-is shown to become larger than the input power provided by the switching of the potential. The apparent efficiency of the ratchet thus becomes higher than one, if the entropy reduction contribution is not considered. This result highlights the relevance of including the entropy reduction by information in the thermodynamic balance of feedback-controlled devices, specifically when writing the second principle. The inclusion of the entropy reduction by information leads to a well-behaved efficiency over all the range of parameters investigated.


Effects of stimulated adrenocortical activity on the concentration of thyroxine and triiodothyronine in blood serum of piglets.
The effects of elevated adrenocortical activity, induced by cold exposure, weaning or starvation, or exogenous adrenocorticotrophin (ACTH) on the concentrations of thyroxine (T4) and triiodothyronine (T3) in blood serum were investigated in 99 sucking piglets and weaners, divided into five experiments. No changes in concentrations of circulating iodothyronines were recorded during a 3-hour exposure of 3- to 4-day-old piglets to ambient temperature of 8-12 degrees C. Two days after weaning of 4-week-old piglets the concentration of T4 increased. At the same time a decrease of the concentration of T3 was observed in their starving littermates. Two hours after the administration of ACTH, the concentration of both iodothyronines decreased, that of T4 nonsignificantly. 17 hours after the administration of the second of two doses of ACTH, i.e. at the time when the concentration of corticosteroids approached initial values, the blood concentration of iodothyronines both in sucking piglets and in weaners was elevated, that of T4 nonsignificantly. We suggest that for the changes of T4 and T3 concentrations in blood sera of stressed animals both specific stressor effects and circulating corticosteroids are responsible. The suppressive action of corticosteroids seems to be limited to the period of adrenocortical stimulation only.


Fermentation products of solvent tolerant marine bacterium Moraxella spp. MB1 and its biotechnological applications in salicylic acid bioconversion.
As part of a proactive approach to environmental protection, emerging issues with potential impact on the environment is the subject of ongoing investigation. One emerging area of environmental research concerns pharmaceuticals like salicylic acid, which is the main metabolite of various analgesics including aspirin. It is a common component of sewage effluent and also an intermediate in the degradation pathway of various aromatic compounds which are introduced in the marine environment as pollutants. In this study, biotransformation products of salicylic acid by seaweed, Bryopsis plumosa, associated marine bacterium, Moraxella spp. MB1, have been investigated. Phenol, conjugates of phenol and hydroxy cinnamic acid derivatives (coumaroyl, caffeoyl, feruloyl and trihydroxy cinnamyl) with salicylic acid (3-8) were identified as the bioconversion products by electrospray ionization mass spectrometry. These results show that the microorganism do not degrade phenolic acid but catalyses oxygen dependent transformations without ring cleavage. The degradation of salicylic acid is known to proceed either via gentisic acid pathway or catechol pathway but this is the first report of biotransformation of salicylic acid into cinnamates, without ring cleavage. Besides cinnamic acid derivatives (9-12), metabolites produced by the bacterium include antimicrobial indole (13) and β-carbolines, norharman (14), harman (15) and methyl derivative (16), which are beneficial to the host and the environment.


Intramolecular Chirality Transfer [2 + 2] Cycloadditions of Allenoates and Alkenes.
Intramolecular chirality transfer [2 + 2] cycloaddition of enantiomerically enriched allenoates and alkenes is presented. The use of a chiral catalyst was found to be critical to achieve high levels of diastereoselectivity compared to use of an achiral catalyst. The method developed leads to highly substituted cyclobutanes that would be difficult to prepare by alternative methods.


An internal control for the detection of Onchocerca volvulus DNA by PCR-ELISA and rapid detection of specific PCR products by DNA Detection Test Strips.
We developed a polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA) for the detection of Onchocerca volvulus DNA. To standardize the PCR and to avoid false-negative results, an internal control DNA was co-amplified by the same set of primers. We differentiated the wild-type PCR product of the O-150 DNA sequence from the internal control by specific DNA probes. Detection of biotinylated PCR products by DNA probes was performed by ELISA to quantify the PCR product or by DNA Detection Test Strips as a rapid field technique. The methods were evaluated on skin biopsies from individuals living in an area endemic for O. volvulus in Uganda, but with low microfilaria densities because of ivermectin treatment. Microfilaria density was assessed by a single skin snip and a second skin snip was examined by PCR. Among 69 samples from microfilaria carriers, 47 (68%) were positive by ELISA and 55 (80%) by test strip detection of PCR products. When 39 samples of microfilaria-negative individuals from the same area were tested, 10 (27%) were positive by ELISA and 12 (31%) by test strips. None of the 19 samples obtained from persons living in an area not endemic for O. volvulus but endemic for Mansonella streptocerca was positive in either test. Although the ELISA is theoretically more sensitive than the test strips for the detection of PCR products, examination of field samples revealed that the test strip method had a higher operational sensitivity and was more convenient to perform. Thus, the DNA Detection Test Strips are a rapid and low-tech tool for identification of PCR products in laboratories of countries endemic for onchocerciasis.


Several hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus 5 E1B 55-kD protein.
The p53 tumor suppressor gene product is a transcriptional activator that may be associated with its ability to suppress tumor cell growth. The acidic amino terminus of the p53 protein has been shown to contain this trans-activation activity as well as the domains for mdm-2 and adenovirus 5 E1B 55-kD protein binding. An extensive genetic analysis of this amino-terminal p53 domain has been undertaken using site-specific mutagenesis. The results demonstrate that the acidic residues in the amino terminus of p53 may contribute to, but are not critical for, this trans-activation activity. Rather, the hydrophobic amino acid residues Leu-22 and Trp-23 of human p53 are both required for trans-activation activity, binding to the adenovirus E1B 55-kD protein and the human mdm-2-p53 protein in vitro. In addition, hydrophobic residues Leu-14 and Phe-19 are crucial for the interactions between p53 and human mdm-2 (hdm-2). Hydrophobic residues Trp-23 and Pro-27 are also important for binding to the adenovirus 5 (Ad5) E1B 55-kD protein in vitro. These mutations have no impact on the ability of the p53 protein to bind to a p53-specific DNA element. These results suggest that 2-4 critical hydrophobic residues in the amino-terminal domain of the p53 protein interact with the transcriptional machinery of the cell resulting in transcriptional activation. These very same hydrophobic residues contact the hdm-2 and Ad5 E1B 55-kD oncogene products.


A new subtype classification of ischemic stroke based on treatment and etiologic mechanism.
A new subtype classification of ischemic stroke was developed to reflect recent therapeutic strategies as well as evolving concepts of stroke definitions and mechanisms. In 200 consecutive patients with acute ischemic stroke, the inter-rater reliability and proportion of subtypes of the new classification system were assessed and compared with those of the Trial of ORG 10172 in the Acute Stroke Treatment (TOAST) classification. The most frequent subtype of the new classification was atherothrombosis (n = 80, 40%), followed by stroke of undetermined etiology (n = 54, 27%), small artery disease (n = 33, 16.5%), cardioembolism (n = 26, 13%), and stroke of other determined etiology (n = 7, 3.5%). Three raters agreed to the stroke subtype diagnosis in 165 out of 200 cases and the overall kappa value was excellent (kappa = 0.82). The new classification system for brain infarction was easy to use and had high inter-rater reliability.


[Ecological quality of Beijing urban area from 1996 to 2005].
From the aspects of four ecological themes, i.e., ecological element, ecological process, ecological function and ecological destruction, an indicator framework including 16 indicators was developed to make an integrated assessment on the ecological quality of Beijing urban area. The weights of the indicators were determined by the methods of entropy weight, optimal state weight, and worst state weight, and the ecological element index (EEI), ecological process index (EPI), ecological function index (EFI), ecological destruction index (EDI), and composite ecological index (CEI) were computed by a weighted sum method and served as effective tools for analyzing the evolvement of the ecological quality of Beijing urban area from 1996 to 2005. The results showed that during the period of 1996-2005, the EEI of Beijing urban area did not display visible improvement and maintained a low level, far from the ideal state. The EPI and EFI increased dramatically, and approached to the ideal state in 2005. The EDI fluctuated within a low level, far from ideal state, and did not show an evolutionary trend. The CEI improved year after year, but was still low and did not reach the ideal state. The EPI, EFI, and CEI increased rapidly with economic development when the GDP per capita was less than US $ 3,000, but the decrease was decelerated after the GDP exceeded US $ 3,000. The EEI and EDI were less affected by economic development, but mainly restrained by the natural conditions and global and regional eco-environmental evolvement.


[A case of ureteral malignant lymphoma with concentric thickening of the ureteral wall].
A 59-year-old man was referred to our hospital with right hydronephrosis, which was diagnosed from a medical examination. On imaging studies, he had concentric thickness of the right ureteral wall, and retroperitoneal and mesenteric lymphadenopathy. Urine cytology was negative, and an ureteroscopic biopsy showed no malignancy. We performed laparoscopic biopsy of the retroperitoneal lymphadenopathy, and the histopathological diagnosis was B-cell follicular lymphoma. The patient received four cycles of RCVP (rituximab, cyclophosphamide, vincristine, prednisolone) chemotherapy and four cycles of rituximab monotherapy and then he obtained complete remission. If concentric thickness of the ureteral wall is found, physicians should be aware of the possibility of malignant lymphoma and should consider laparoscopic biopsy for diagnosis.


Computed tomography of the coelomic cavity in healthy veiled chameleons (Chamaeleo calyptratus) and panther chameleons (Furcifer pardalis).
Veiled chameleon (Chamaeleo calyptratus) and panther chameleon (Furcifer pardalis) are two of the most popular pet chameleons, and consequently, these species are frequently evaluated in veterinary practices. According to our review of the literature, normal computed tomography (CT) anatomy of these lizards has not been previously described. The purposes of this prospective study were to describe the normal CT anatomy of the coelomic organs in healthy patients and to provide normal reference values in these species. Seventeen clinically healthy veiled chameleons and 15 clinically healthy panther chameleons were included. All CT studies were performed with the chameleons under light anesthesia and positioned in sternal recumbency. Studies were performed with a 16-slice helical CT scanner with a slice thickness of 0.625 mm. The authors recorded qualitative and quantitative CT characteristics of the coelomic structures. Macroscopic cross-sectional anatomy was performed for comparison of the CT findings. Heart, lungs, liver, including caudal vena cava, hepatic vessels, gallbladder, esophagus, stomach, intestines, gonads, fat bodies, kidneys, and urinary bladder could be visualized with CT. The spleen, pancreas, and adrenal glands could not be identified. This study provides a guide to the normal cross-sectional and computed tomographic anatomy of the coelomic cavity in veiled and panther chameleons. Our results could be used as a reference for future research studies or comparison of clinically ill patients.


Calculating the dose of subcutaneous immunoglobulin for primary immunodeficiency disease in patients switched from intravenous to subcutaneous immunoglobulin without the use of a dose-adjustment coefficient.
Primary immunodeficiency disease (PIDD) is an inherited disorder characterized by an inadequate immune system. The most common type of PIDD is antibody deficiency. Patients with this disorder lack the ability to make functional immunoglobulin G (IgG) and require lifelong IgG replacement therapy to prevent serious bacterial infections. The current standard therapy for PIDD is intravenous immunoglobulin (IVIG) infusions, but IVIG might not be appropriate for all patients. For this reason, subcutaneous immunoglobulin (SCIG) has emerged as an alternative to IVIG. A concern for physicians is the precise SCIG dose that should be prescribed, because there are pharmacokinetic differences between IVIG and SCIG. Manufacturers of SCIG 10% and 20% liquid (immune globulin subcutaneous [human]) recommend a dose-adjustment coefficient (DAC). Both strengths are currently approved by the FDA. This DAC is to be used when patients are switched from IVIG to SCIG. In this article, we propose another dosing method that uses a higher ratio of IVIG to SCIG and an incremental adjustment based on clinical status, body weight, and the presence of concurrent diseases.


Anisotropic layered Bi2Te3-In2Te3 composites: control of interface density for tuning of thermoelectric properties.
Layered (Bi1-xInx)2Te3-In2Te3 (x = 0.075) composites of pronounced anisotropy in structure and thermoelectric properties were produced by zone melting and subsequent coherent precipitation of In2Te3 from a (Bi1-xInx)2Te3 (x > 0.075) matrix. Employing solid state phase transformation, the Bi2Te3/In2Te3 interface density was tuned by modifying the driving force for In2Te3 precipitation. The structure-property relationship in this strongly anisotropic material is characterized thoroughly and systematically for the first time. Unexpectedly, with increasing Bi2Te3/In2Te3 interface density, an increase in electrical conductivity and a decrease in the absolute Seebeck coefficient were found. This is likely to be due to electron accumulation layers at the Bi2Te3/In2Te3 interfaces and the interplay of bipolar transport in Bi2Te3. Significantly improved thermoelectric properties of Bi2Te3-In2Te3 composites as compared to the single phase (Bi1-xInx)2Te3 solid solution are obtained.


An investigation of satiety in ageing, dementia, and hyperphagia.
To investigate satiety in young, middle-aged, and elderly healthy adults, and in nonhyperphagic and hyperphagic elderly people with dementia. Previous work suggested hyperphagia in dementia was due to increased hunger and absence of satiation. The primary measure of satiety was the amount of food eaten in an ad libitum meal, given 1 hr after a fixed preload. Three types of preload were used, high- and low-energy milkshakes and water. The effect of age was investigated by comparing the three groups of healthy adults. The effect of dementia was investigated by comparing the two demented groups with healthy elderly. Measurements suggested that accuracy of compensation for preload energy differences decreased with age and was absent in people with dementia. Lack of compensatory response in the elderly, particularly those with dementia, indicates the need for monitoring food intake to prevent over- or undereating.


Cross-talk between Wnt and bone morphogenetic protein 2 (BMP-2) signaling in differentiation pathway of C2C12 myoblasts.
Loss of function of the Wnt co-receptor, lipoprotein receptor-related protein 5, decreases bone formation, and a point mutation in this gene results in high bone mass, indicating the importance of this signaling pathway in bone formation. However, the exact mechanism is currently unknown. We examined a potential role for Wnt signaling and functional cross-talk of bone morphogenetic protein 2 (BMP-2) in osteoblast differentiation. To assess the contribution of Wnt, we generated C2C12 cells over-expressing Wnt3a or Wnt5a and treated these with BMP-2. We showed that expression of matrix extracellular phosphoglycoprotein was induced by BMP-2 in Wnt3a over-expressing C2C12 cells but not in Wnt5a over-expressing C2C12 cells. Over-expression of Wnt3a blocked BMP-2-induced inhibition of myotube formation in C2C12 cells when switched to low mitogen medium. In these cultures, expression of inhibitor of DNA binding/differentiation (Id) 1, a helix-loop-helix protein induced by BMP-2, decreased in stable Wnt3a- but not in Wnt5a-expressing cells. This suppression is mediated by a GC-rich region of the BMP-2-responsive element of the Id1 gene promoter, and interaction between Smad1/4 and beta-catenin is crucial for Wnt-mediated suppression of the BMP-2 response in C2C12 cells. Over-expression of the inhibitor of canonical Wnt signaling, Dickkopf, inhibits this suppression. In contrast, BMP-2 or Smad1/4 up-regulated Wnt3a or activated beta-catenin-induced lymphoid-enhancing factor 1/T cell factor-dependent transcriptional activity. These findings identify functional cross-talk of Id1 expression between Wnt and BMP signaling and demonstrate a novel mechanism for Wnt regulation of the BMP-2 response, linking Id1 expression to Wnt/beta-catenin signaling.


Cytotoxic effects of a chimeric protein consisting of tetanus toxin light chain and anthrax toxin lethal factor in non-neuronal cells.
The light chain of tetanus toxin is a zinc endoprotease that inhibits neurotransmitter release by selective proteolysis of the synaptic vesicle-associated protein synaptobrevin/vesicle-associated membrane protein. Cellubrevin is a homologue of synaptobrevin that is found in most cell types and is also a substrate for tetanus toxin. The lack of receptors for tetanus toxin on most cell types has made studies of tetanus toxin action in non-neuronal cells difficult. To characterize tetanus toxin effects in non-neuronal cells, a fusion protein consisting of the 254 amino-terminal amino acids of lethal factor (LF) of anthrax toxin and tetanus toxin light chain (LC) was prepared. This protein (LF-LC) inhibited evoked glycine release from primary spinal cord neurons at concentrations between 1.0 and 100 ng/ml. LF-LC was cytotoxic to RAW 264.7, ANA-1 cells (mouse macrophage cell lines), and Chinese hamster ovary cells in a dose-dependent manner. These effects required the presence of protective antigen, the receptor binding component of anthrax toxin. In contrast, LF-LC was not cytotoxic to RBL-2H3, Vero, or mouse hybridoma cell lines. Mutagenesis of conserved amino acids (His237 and Glu234) in the zinc-binding motif of LC resulted in fusion proteins having no biological activity. LF-LC did not inhibit regulated secretion of serotonin in RBL-2H3 cells or constitutive secretion in any non-neuronal cell lines as measured in several different assays. We suggest that the cytotoxic effects of LF-LC result from inhibition of a specific intracellular membrane fusion event mediated by cellubrevin.


A systematic review of ultrasound-mediated drug delivery to the eye and critical insights to facilitate a timely path to the clinic.
Ultrasound has long been identified as a promising, non-invasive modality for improving ocular drug delivery across a range of indications. Yet, with 20 years of learnings behind us, clinical translation remains limited. To help address this, and in accordance with PRISMA guidelines, the various mechanisms of ultrasound-mediated ocular drug delivery have been appraised, ranging from first principles to emergent applications spanning both ex vivo and in vivo models. The heterogeneity of study methods precluded meta-analysis, however an extensive characterisation of the included studies allowed for semi-quantitative and qualitative assessments. Methods: In this review, we reflected on study quality of reporting, and risk of bias (RoB) using the latest Animal Research: Reporting of In Vivo Experiments (ARRIVE 2.0) guidelines, alongside the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) RoB tools. Literature studies from 2002 to 2022 were initially characterised according to methods of ultrasound application, ultrasound parameters applied, animal models employed, as well as safety and efficacy assessments. This exercise contributed to developing a comprehensive understanding of the current state of play within ultrasound-mediated ocular drug delivery. The results were then synthesised and processed into a guide to aid future study design, with the goal of improving the reliability of data, and to support efficient and timely translation to the clinic. Results: Key attributes identified as hindering translation included: poor reporting quality and high RoB, skewed use of animals unrepresentative of the human eye, and the over reliance of reductionist safety assessments. Ex vivo modelling studies were often unable to have comprehensive safety assessments performed on them, which are imperative to determining treatment safety, and represent a pre-requisite for clinical translation. Conclusion: With the use of our synthesised guide, and a thorough understanding of the underlying physicochemical interactions between ultrasound and ocular biology provided herein, this review offers a firm foundation on which future studies should ideally be built, such that ultrasound-mediated ocular drug delivery can be translated from concept to the coalface where it can provide immense clinical benefit.


Controlled synthesis of photoresponsive bismuthinite (Bi2S3) nanostructures mediated through a new 1D bismuth-pyrimidylthiolate coordination polymer as a molecular precursor.
Bismuthinite (Bi2S3) nanostructures have garnered significant interest due to their appealing photoresponsivity which has positioned them as an attractive choice for energy conversion applications. However, to utilize their full potential, a simple and economically viable method of preparation is highly desirable. Herein, we present the synthesis and characterization including structural elucidation of a new air- and moisture-stable bismuth-pyrimidylthiolate complex. This complex serves as an efficient single-source molecular precursor for the facile preparation of phase-pure Bi2S3 nanostructures. Powder X-ray diffraction (PXRD), Raman spectroscopy, electron dispersive spectroscopy (EDS) and electron microscopy techniques were used to assess the crystal structure, phase purity, elemental composition and morphology of the as-prepared nanostructures. This study also revealed the profound effects of temperature and growth duration on the crystallinity, phase formation and morphology of nanostructures. The optical band gap of the nanostructures was tuned within the range of 1.9-2.3 eV, which is blue shifted with respect to the bulk bandgap and suitable for photovoltaic applications. Liquid junction photo-electrochemical cells fabricated from the as-prepared Bi2S3 nanostructure exhibit efficient photoresponsivity and good photo-stability, which project them as promising candidates for alternative low-cost photon absorber materials.


Participation in a diabetes education and care program: experience from the diabetes care for older adults project.
There is very little reported information concerning the participation of older adults in diabetes education and care programs, factors related to their attendance, and the influence of attendance on program outcomes. In this study, which was part of a larger study of insulin therapy, subjects (> or = 65 years old) assigned to the intensive management group (n = 53) were provided with educational sessions during the 18-month study period. Data for this group were examined to determine factors that influenced enrollment and attendance. Attendance rates for individual participants averaged 72% during the first 6 months and 68% during the subsequent 12 months. Demographic factors, baseline knowledge test scores, and baseline glycosylated hemoglobin levels did not significantly influence participation. Greater distance from the clinic and shorter time using insulin were significantly related (P = .05) to attendance. Perceived benefits of the program included diabetes education (45%), glucose control (23%), and interacting with others who have diabetes (23%).