Oligosaccharides derived by keratanase II digestion of bovine articular cartilage keratan sulphates.
Alkaline borohydride-reduced keratan sulphate chains from bovine articular cartilage (6-8-year-old animals) were subjected to a limit digest with the enzyme keratanase II. Using 1H-NMR spectroscopy, 25 reduced oligosaccharides deriving from keratan sulphate were shown to have the following structures [GlcNAc(6S)-ol represents N-acetylglucosaminitol 6-O-sulphate]: Gal beta 1-4-GlcNAc(6S)-ol, Gal beta 1-4GlcNAc(6S)beta 1-3Gal beta 1-4GlcNAc(6S)-ol, Gal(6S)beta 1-4GlcNAc(6S)-ol, Gal-(6S)beta 1-4GlcNAc(6S) beta 1-3Gal beta 1-4GlcNAc(6S)-ol, Gal beta 1-4GlcNAc(6S)beta 1-3Gal(6S)beta 1-4GlcNAc(6S)-ol, Gal(6S)beta 1-4GlcNAc(6S)beta 1-3Gal(6S)1-4GlcNAc(6S)-ol, Gal beta 1-4(Fuc alpha 1-3)GlcNAc(6S)-ol, Gal beta 1-4-(Fuc alpha 1-3)GlcNAc(6S)beta1-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc(6S)-ol, Gal beta 1-4GlcNAc(6S)beta 1-3Gal beta 1-4(Fuc alpha 1-3)-GlcNAc(6S)-ol, Gal beta 1-4(Fuc alpha 1-3)GlcNAc(6S)beta 1-3Gal beta 1-4GlcNAc(6S)-ol, Gal(6S) beta 1-4GlcNAc-(6S)beta 1-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc(6S)-ol, Gal beta 1-4(Fuc alpha 1-3)GlcNAc(6S)beta 1-3Gal(6S)1-4GlcNAc(6S)-ol, Gal beta 1-4GlcNAc(6S)beta 1-6(Gal beta 1-3)GalNAc-ol, Gal beta 1-4GlcNAc(6S) beta1-6(NeuAc2-3Gal beta 1-3)Gal-NAc-ol, Gal beta 1-4GlcNAc(6S)beta 1-3Gal beta 1-4GlcNAc(6S)beta 1-6(Gal beta 1-3) GalNAc-ol, Gal(6S)beta 1-4GlcNAc-(6S)beta 1-6(Gal beta 1-3)GalNAc-ol, Gal beta 1-4GlcNAc(6S)beta 1-3Gal beta 1-4GlcNAc(6S)beta 1-6(NeuAc2-3Gal beta 1-3)-GalNAc-ol, Gal(6S)beta 1-4GlcNAc(6S)beta 1-6(NeuAc alpha 2-3Gal beta 1-3)GalNAc-ol, Gal(6S) beta 1-4GlcNAc-(6S)beta 1-3Gal beta 1-4GlcNAc(6S)beta 1-6(Gal beta 1-3)GalNAc- ol, Gal(6S)beta 1-4GlcNAc(6S)beta 1-3Gal beta 1-4GlcNAc-(6S)beta 1-6(NeuAc alpha 2-3Gal beta 1-3)GalNAc-ol, NeuAc alpha 2-6Gal beta 1-4GlcNAc(6S)beta 1-3Gal beta 1-4GlcNAc(6S)-ol, NeuAc alpha 2-3Gal beta 1-4GlcNAc(6S)beta 1-3Gal beta 1-4GlcNAc(6S)-ol, NeuAc alpha 2-6Gal beta 1-4GlcNAc(6S)beta 1-3Gal-(6S)beta 1-4GlcNAc(6S)-ol, NeuAc alpha 2-3Gal beta 1-4GlcNAc(6S)beta 1-3Gal(6S)beta 1-4GlcNAc(6S)-ol and Neu-Ac alpha 2-3Gal(6S)beta 1-4GlcNAc(6S)beta 1-3Gal(6S beta)1-4GlcNAc(6S)-ol. Proton chemical shifts for these oligosaccharides were assigned using one- and two-dimensional NMR spectroscopic methods. These results confirm the findings of Nakazawa et al. [Nakazawa, K., Ito, M., Yamagata, T. and Suzuki, S. (1989) in Keratan sulphate: chemistry, biology and chemical pathology (Greiling, H. and Scott, J.E., eds) pp. 99-110, The Biochemical Society, London], namely that keratanase II cleaves the O-glycosidic bond of a beta(1-3)-linked 6-O-sulphated N-acetylglucosamine.(ABSTRACT TRUNCATED AT 400 WORDS)


Variation of wheat root exudates under aluminum stress.
The wheat (Triticum aestivum L.) cultivar Yangzhou 158 was used as a reference. The wheat root exudates were collected using a hydroponic mode. The changes of the electrolytes, H+, sugar, organic acids, amino acids, and secondary metabolites in wheat root exudates induced by aluminum (Al) were studied. The research results show that Al stress affects wheat root exudation. The secreted electrolytes and sugar increase with the increasing of the external Al3+ concentration. The total amount of secreted amino acids has a specific correlation with the external Al3+ concentration. At first, the amino acids secrete normally, but when Al3+ concentration is over 10 mg.L-1, the amino acid constitution varies obviously. Under Al stress, some original secondary metabolites disappear gradually, and other new secondary metabolites release simultaneously. Increasing the external Al3+ concentration gradually stimulates the exudation of organic acids. The organic acid levels in the wheat root zone increase in response to Al treatments. Active Al ions are accumulated in wheat roots. This Al-dependent variation in wheat root exudates suggests a specific Al-induced response of the wheat.


Disseminated Scedosporium prolificans (S. inflatum) infection after single-lung transplantation.
This report concerns the first case of disseminated infection with Scedosporium prolificans (S. inflatum) that occurred in a patient who had received an organ transplant and was verified at autopsy. The patient underwent single (right)-lung transplantation and subsequently died on the 33rd postoperative day in a context of septic shock. S. prolificans was isolated from various specimens, including two cultured blood samples. The organism was associated with Candida albicans in some of these specimens. Autopsy revealed the presence of numerous nodular abscesses in the lungs, myocardium, kidneys, spleen, and gall bladder. These abscesses contained mycelial filaments and numerous oval conidia suggestive of Scedosporium species but no yeasts. MIC studies demonstrated the resistance of the S. prolificans isolate to amphotericin B, fluctyosine, miconazole, ketoconazole, and itraconazole, whereas the isolate of C. albicans was susceptible to amphotericin B, flucytosine, miconazole, and ketoconazole. From the data from our case and six published reports of cases of disseminated S. prolificans infection, it can be concluded that this filamentous fungus is a new agent responsible for the most serious mycoses in both neutropenic patients and patients who have undergone organ transplantation.


An inhibitory insulin-like growth factor binding protein (In-IGFBP) from human prostatic cell conditioned medium reveals N-terminal sequence identity with bone derived In-IGFBP.
Insulin-like growth factor binding proteins (IGFBPs), are produced by several cell types, are present in biological fluids, and may function in modulating insulin-like growth factor (IGF) biological activities. Recently the presence of multiple IGFBPs was reported in seminal fluid, suggesting that IGFBPs are produced by prostatic epithelium. We have found that human prostatic tumor cells of the PC3 cell line produce an IGFBP. PC3-IGFBP was purified to homogeneity using sequential IGF I affinity and HPLC C4 reverse phase chromatographies. Chemical cross-linking of PC3-IGFBP to 125I-IGF I revealed a molecular weight of 25 kDa. Its N-terminal sequence and amino-acid composition were highly homologous to that of a recently described 25 kDa inhibitory IGFBP (In-IGFBP), produced by osteoblasts in vitro. PC3-IGFBP inhibited basal and IGF II-stimulated bone cell DNA synthesis. We conclude that the PC3-IGFBP is very similar, if not identical to the osteoblast-derived In-IGFBP. Expression of PC3-IGFBP by metastatic human prostate tumor cells thus might affect the osteoblast proliferation that is induced by metastatic prostatic carcinoma. The PC3-IGFBP may be similar to a 24 kDa IGFBP described in seminal fluid and thus may be important in the regulation of cell proliferation in the male reproductive tract.


Which patients with moderate hypoxemia benefit from long-term oxygen therapy? Ways forward.
Long-term oxygen therapy (LTOT) improves prognosis in patients with COPD and chronic severe hypoxemia. The efficacy in moderate hypoxemia (tension of arterial oxygen; on air, 7.4-8.0 kPa) was questioned by a recent large trial. We reviewed the evidence to date (five randomized trials; 1,191 participants, all with COPD). Based on the current evidence, the survival time may be improved in patients with moderate hypoxemia with secondary polycythemia or right-sided heart failure, but not in the absence of these signs. Clinically, LTOT is not indicated in moderate hypoxemia except in the few patients with polycythemia or signs of right-sided heart failure, which may reflect more chronic and severe hypoxemia.


Ultrasonography in predicting and screening liver cirrhosis in children: a preliminary study.
To evaluate the value of ultrasonography in predicting and screening liver cirrhosis in children. Twenty-eight children with liver cirrhosis of various etiologies were examined by routine ultrasonography. A percutaneous liver biopsy guided by ultrasound was also performed on each patient, and the results of liver biopsy and ultrasonography were compared. When compared with the biopsy results, ultrasonography in combination of clinical and laboratory findings gave accurate diagnoses of children liver cirrhosis. Although ultrasound imaging of children with liver cirrhosis revealed abnormal characteristics, these images were not specific to this disease, thus reinforcing the necessity of ultrasound-guided liver biopsy in the diagnosis of children liver cirrhosis. Ultrasonography is reliable in the diagnosis of children liver cirrhosis, and its usefulness should be stressed in the screening and follow-up of high-risk pediatric patients.


Biliary tract complications in laparoscopic cholecystectomy. A multicenter study of 148 biliary tract injuries in 26,440 operations.
The higher risk of biliary tract injury is considered the most significant disadvantage of laparoscopic cholecystectomy. A national multicenter retrospective study was performed to determine the frequency, etiology, and treatment of biliary tract injuries between January 1, 1991, and December 31, 1994. Follow-up was by questionnaire. Some 148 biliary tract complications were observed during 26,440 laparoscopic cholecystectomies. There was no significant correlation found between the number of LCs performed in one institute and the incidence of biliary tract injuries and postoperative bile leakage, but in the 2nd year of practice, the incidence of both complications decreased. In institutes with more conversions, more cases of bile leakage were also observed. A significant positive relationship was found between biliary tract injuries and postoperative bile leaks. There was no significant relationship between usage of intravenous and intraoperative cholangiography and ERCP. In univariant analysis of the type of injury, the primary treatment modality did not affect the outcome of injury or entail the necessity of reoperation. Obscure anatomy leads to significantly more main bile duct injuries. According to multivariant analysis, the outcome is significantly influenced unfavorably by the necessity of repeated interventions and advanced age. The definitely higher risk of bile duct injury mentioned in early studies was not confirmed.


Decline in Clinical Efficacy of Oral Miltefosine in Treatment of Post Kala-azar Dermal Leishmaniasis (PKDL) in India.
Recent studies have shown significant decline in the final cure rate after miltefosine treatment in visceral leishmaniasis. This study evaluates the efficacy of miltefosine in the treatment of post kala-azar dermal leishmaniasis (PKDL) patients recruited over a period of 5 years with 18 months of follow-up. In this study 86 confirmed cases of PKDL were treated with two different dosage regimens of miltefosine (Regimen I- 50mg twice daily for 90 days and Regimen II- 50 mg thrice for 60 days) and the clinical outcome assessed monthly. Cure/relapse was ascertained by clinical and histopathological examination, and measuring parasite burden by quantitative real-time PCR. In vitro susceptibility of parasites towards miltefosine was estimated at both promastigote and amastigote stages. Seventy three of eighty six patients completed the treatment and achieved clinical cure. Approximately 4% (3/73) patients relapsed by the end of 12 months follow-up, while a total of 15% (11/73) relapsed by the end of 18 months. Relapse rate was significantly higher in regimen II (31%) compared to regimen I (10.5%)(P<0.005). Parasite load at the pre-treatment stage was significantly higher (P<0.005) in cases that relapsed compared to the cases that remained cured. In vitro susceptibility towards miltefosine of parasites isolated after relapse was significantly lower (>2 fold) in comparison with the pre-treatment isolates (P<0.005). Relapse rate in PKDL following miltefosine treatment has increased substantially, indicating the need of introducing alternate drugs/ combination therapy with miltefosine.


Multiscale Hierarchical Architecture-Based Bioactive Scaffolds for Versatile Tissue Engineering.
Artificial construction from tendon to bone remains a formidable challenge in tissue engineering owing to their structural complexity. In this work, bioinspired calcium silicate nanowires and alginate composite hydrogels are utilized as building blocks to construct multiscale hierarchical bioactive scaffolds for versatile tissue engineering from tendon to bone. By integrating 3D printing technology and mechanical stretch post-treatment in a confined condition, the obtained composite hydrogels possess bioinspired reinforcement architectures from nano- to submicron- to microscale with significantly enhanced mechanical properties. The biochemical and topographical cues of the composite hydrogel scaffolds provide much more efficient microenvironment to the rabbit bone mesenchymal stem cells and rabbit tendon stem cells, leading to ordered alignment and improved differentiation. The composite hydrogels markedly promote in vivo tissue regeneration from bone to tendon, especially fibrocartilage transitional tissue. Therefore, such calcium silicate nanowires/alginate composite hydrogels with multiscale hierarchical structures have potential application for tissue regeneration from tendon to bone. This work provides an innovative strategy to construct multiscale hierarchical architecture-based scaffolds for tendon/bone engineering.


Early pulmonary compliance increase during cardiac surgery predicted post-operative lung dysfunction.
Lung dysfunction following cardiac surgery is currently viewed as the consequence of atelectasis and lung injury. While the mechanism of atelectasis has been largely detailed, the pathogenesis of lung injury after cardiopulmonary bypass is still unclear. Based upon clinical and experimental studies, we hypothesized that lungs could be injured through a mechanical phenomenon. We recorded pulmonary compliance at six key moments of a heart operation in 62 adult patients undergoing elective cardiac surgery. We focused on the period lasting from anesthetic induction to aorta unclamping. We calculated the variation of static and dynamic pulmonary compliance caused by thorax opening; ΔCstat1 and ΔCdyn1 and that caused by cardiopulmonary bypass, ΔCstat2 and ΔCdyn2. Blood gases were performed under standardized ventilation after anesthetic induction and after surgical closure. The PaO2/FiO2 ratio was calculated. ∆PaO2/FiO2 was the criterion for lung dysfunction. We compared ΔCstat1 and ΔCdyn1 with both ∆PaO2/FiO2 and, respectively, ΔCstat2 and ΔCdyn2. Static and dynamic compliance increased with the opening of the thorax and decreased with the start of cardiopulmonary bypass. The PaO2/FiO2 ratio diminished after surgery. ΔCstat1 and ΔCdyn1 were negatively correlated with both ∆PaO2/FiO2 (r=-0.42; p<0.001 and r=-0.44; p<0.001) and, respectively, with ΔCstat2 and ΔCdyn2 (r=-0.59; p<0.001 and r=-0.53; p<0.001). Increased pulmonary compliance induced by the opening of the thorax is correlated with worsened intrapulmonary shunt after cardiopulmonary bypass. A mechanical phenomenon could be partly responsible for post-operative hypoxemia.


An embryonic source of Ly1 but not conventional B cells.
Ly1+ B cells differ from conventional B cells with respect to their anatomical localization, cell surface marker expression, and antibody repertoire suggesting that they may constitute a functionally distinct subset of B cells. To determine whether Ly1+ B cells also have a developmentally distinct site of origin we grafted various fetal primordia into adult severe combined immunodeficient (scid) mice and analyzed their potential to give rise to T and B cells. We demonstrated that fetal omentum, but not spleen or thymus grafts, reconstituted exclusively Ly1 B cells (including the Ly1 sister population) as well as a population of IgM and IgA producing plasma cells in the spleen and gut, respectively. Although thymus grafts regularly reconstituted T cells, thymus plus fetal omentum cografts gave rise to a population of Ly1+ B cells as well as T cells which were also derived from omentum. However, in neither omentum nor omentum plus thymus cografts were conventional B cells detected. These results provide the first evidence that Ly1 B cells but not conventional B cells are generated from the fetal omentum.


Classification of Resistance to Permeation Caused by Fouling during Ultrafiltration of Whey and Skim Milk.
To identify the cause of fouling of the membrane surface and pores during the ultrafiltration of whey or skim milk, these liquids were filtered through a membrane, allowed to adsorb to it, or both. Measurements of flux were made before and after gentle hand cleaning with a soft sponge, and resistance to permeation because of fouling was calculated and classified into four kinds: by adsorption to the surface, by adsorption in side the pores, because of filtration on the surface, and because of filtration in the pores. In the ultrafiltration of whey, resistance caused by fouling on the surface by filtration was great, and that caused by fouling in the pores by filtration was slight. In the ultrafiltration of skim milk, resistance caused by fouling by adsorption was great, and that caused by fouling on the surface by filtration was slight, probably because the casein micells in skim milk scrape fouling materials off the surface.


Cyclooxygenase-2 upregulates vascular endothelial growth factor expression and angiogenesis in human gastric carcinoma.
Although gastric cancer with cyclooxygenase (COX)-2 overexpression is associated with poor prognosis, the mechanistic pathway remains unknown. We examined the associations between expressions of COX-2 and vascular endothelial growth factor (VEGF) in both gastric cancer cells and in human gastric cancer. The gastric cell line, Kato III, was transiently transfected with cox-2 expressing vector. The levels of COX-2, prostaglandin (PG) E2 and VEGF expression were measured post-transfection. Additionally, expressions of COX-2 and VEGF in human gastric cancer were determined by immunohistochemistry in archive gastrectomy specimens. Tumor angiogenesis was assessed by the microvessel density (MVD), which was determined by anti-CD34 immunostaining. Transient transfection of Kato III with cox-2 was associated with increased COX-2 expression, higher PGE2 production and upregulated VEGF expressions. Treatment with NS398, a specific COX-2 inhibitor, reduced VEGF expression in COX-2 expressing Kato III cells by 25%. Among the 67 gastric cancers examined, COX-2 overexpression was found in 45 (67%) cases whereas increased VEGF expression was detected in 46 (69%) cases. There was a significant association between COX-2 and VEGF expressions in gastric cancer (r=0.25, p=0.041). Additionally, tumor MVD was associated with both COX-2 (r=0.32, p=0.008) and VEGF (r=0.39, p=0.001) expressions. Our results showed that overexpression of COX-2 in both gastric cells and primary gastric cancer is associated with upregulation of VEGF and angiogenesis. Future studies should evaluate the potential anti-angiogenic effect of COX-2 inhibitors on human gastric cancer.


Understanding and Controlling the Emission Brightness and Color of Molecular Cerium Luminophores.
Molecular cerium complexes are a new class of tunable and energy-efficient visible- and UV-luminophores. Understanding and controlling the emission brightness and color are important for tailoring them for new and specialized applications. Herein, we describe the experimental and computational analyses for series of tris(guanidinate) (1-8, Ce{(R2N)C(N iPr)2}3, R = alkyl, silyl, or phenyl groups), guanidinate-amide [GA, A = N(SiMe3)2, G = (Me3Si)2NC(N iPr)2], and guanidinate-aryloxide (GOAr, OAr = 2,6-di- tert-butylphenoxide) cerium(III) complexes to understand and develop predictive capabilities for their optical properties. Structural studies performed on complexes 1-8 revealed marked differences in the steric encumbrance around the cerium center induced by various guanidinate ligand backbone substituents, a property that was correlated to photoluminescent quantum yield. Computational studies revealed that consecutive replacements of the amide and aryloxide ligands by guanidinate ligand led to less nonradiative relaxation of bright excited states and smaller Stokes shifts. The results establish a comprehensive structure-luminescence model for molecular cerium(III) luminophores in terms of both quantum yields and colors. The results provide a clear basis for the design of tunable, molecular, cerium-based, luminescent materials.


Microbial Communities in Gynecological Cancers and Their Association with Tumor Somatic Variation.
There are strong correlations between the microbiome and human disease, including cancer. However, very little is known about potential mechanisms associated with malignant transformation in microbiome-associated gynecological cancer, except for HPV-induced cervical cancer. Our hypothesis is that differences in bacterial communities in upper genital tract epithelium may lead to selection of specific genomic variation at the cellular level of these tissues that may predispose to their malignant transformation. We first assessed differences in the taxonomic composition of microbial communities and genomic variation between gynecologic cancers and normal samples. Then, we performed a correlation analysis to assess whether differences in microbial communities selected for specific single nucleotide variation (SNV) between normal and gynecological cancers. We validated these results in independent datasets. This is a retrospective nested case-control study that used clinical and genomic information to perform all analyses. Our present study confirms a changing landscape in microbial communities as we progress into the upper genital tract, with more diversity in lower levels of the tract. Some of the different genomic variations between cancer and controls strongly correlated with the changing microbial communities. Pathway analyses including these correlated genes may help understand the basis for how changing bacterial landscapes may lead to these cancers. However, one of the most important implications of our findings is the possibility of cancer prevention in women at risk by detecting altered bacterial communities in the upper genital tract epithelium.


A survey of anthelmintic resistance on ten sheep farms in Mashonaland East Province, Zimbabwe.
A survey to detect anthelmintic resistance in nematode parasites of sheep was conducted on 10 randomly-distributed farms in the Chivhu District, Mashonaland East Province, Zimbabwe. Before the survey, a questionnaire was circulated to the farmers concerning nematode parasite control. Results showed that parasite control using anthelmintic treatment was the only method practised and that the benzimidazoles were the most frequently used anthelmintic drugs. The faecal egg count reduction test was used to detect resistance. The anthelmintic groups tested were benzimidazoles, levamisole and ivermectin. Resistance to benzimidazoles was detected on 6 of 10 farms and levamisole resistance on 2 of 3 farms. Ivermectin resistance was not observed on the farms surveyed. Post-treatment larval cultures indicated that Haemonchus contortus survived administration of fenbendazole, albendazole, oxfendazole and levamisole. A Cooperia sp. strain resistant to albendazole was detected and this is the first report in Zimbabwe of a resistant parasite in this genus.


Method of constructing a dose-response curve for normal cells in situ.
A method is presented for planning experiments and analysing data with a view to determining in detail the shape of a single-dose survival curve for normal cells exposed in situ to relatively low doses of radiation. Applying this method to data published on the responses of gastric mucosal and colonic stem cells showed that the single-dose survival curves for these cells were linear up to about 250 rads, after which they bent downwards. Some applications of this method are discussed.


Evidence for the structural heterogeneity of the polysaccharide component of Coxiella burnetii strain Nine Mile lipopolysaccharide.
Highly purified lipopolysaccharide (LPS) preparation obtained from Coxiella burnetii strain Nine Mile in phase I was used to determine the structure and monosaccharide composition of the polysaccharide component. The procedure included sodium dodecyl sulphate-polyacrylamide gel electrophoresis followed by silver staining and gel chromatographic fractionation of acetic acid-hydrolyzed LPS. Five fractions (A-E) were analysed by GLC-mass spectrometry. D-Mannose and D-glycero-D-mannoheptose were present in an appreciable amount in all polysaccharide fractions (A-D), whereas the virenose and dihydrohydroxystreptose contents varied. The highest content of both rhamnose and ribose was found in the low-molecular weight polysaccharide fraction D. The former sugar is being reported for the first time to be a LPS constituent. D-Xylose and D-glucose content varied considerably in the individual fractions and was the highest in fraction A. Glucosamine and galactosaminuronic acid were present in all polysaccharide fractions and, surprisingly, L-glycero-D-mannoheptose was also found, but its presence was limited within the certain degree of polymerisation of the polysaccharide chains. Mild acid hydrolysis of LPS resulted in a partial release of dihydrohydroxystreptose and virenose residues, which were collected and identified in fraction E. The data presented indicate a strong microheterogenity within the individual polysaccharide chains with respect to their sugar composition, size, and shape. Thus, the chemical structure of Coxiella LPS appears to represent a significant departure from the structures described for enteric LPSs.


[Distribution Characteristics and Health Risk Assessment of Metal Elements in Groundwater of Longzici Spring Area].
Longzici Spring is an important water source for industry, agriculture, and urban life in Linfen City. With the improvements in public environmental health awareness, it is particularly necessary to study the health risk of posed by metal elements in groundwater. In this study, 43 groundwater samples from Longzici Spring area were analyzed for ten metal elements (As, Cd, Hg, Al, Pb, Co, Mn, Fe, Cu, and Ni). The distribution and health risk of these metal elements in the groundwater were studied using multivariate statistical analysis and a health risk assessment model. The results show that metal elements can be ranked, from high to low, by their average concentrations in groundwater in the following order: Fe, Al, Mn, Ni, As, Cu, Co, Pb, Hg, and Cd. The concentration of Al, Mn, Fe, and As exceed the limit for class Ⅲ water, as defined in the quality standard for groundwater (GB/T 14848-2017). Different types of groundwater in the spring area showed different metal contents. The quality of karst spring water was good, reaching the standard for drinking water, while mine drainage water exceeded the standard for drinking water, with the highest metal concentration (60%) and the worst water quality. Multivariate statistical results show that Pb, Ni, Co, Cd, Mn, and Cu concentrations were mainly affected by the geochemical background, while Al, Fe, Hg, and As concentrations were closely related to human mining activities under the unique geological background of Shanxi Province. The health risk assessment showed that the different types of groundwater could be ranked by the annual total health risks, posed by metal elements to adults and children through drinking water and skin infiltration, as follows: karst well > non-karst spring > non-karst well > karst spring. The health risks mainly came from drinking water, while health risks through skin infiltration would not cause obvious harm to the human body. The metal element causing the greatest health risk in spring groundwater was As, which should therefore be controlled in the utilization of water resources, especially in children's drinking water.


Predictors of olfactory dysfunction in patients with chronic rhinosinusitis.
To measure the prevalence of and identify clinical characteristics associated with poor olfactory function in a large cohort of patients with chronic rhinosinusitis (CRS). Multi-institutional, cross sectional analysis. An objective measure of olfactory dysfunction, the Smell Identification Test, demographic data, clinical factors, and comorbidity data were collected from a cohort of 367 patients who presented with CRS at three tertiary care centers. Data were analyzed using univariate and multivariate analyses. Sixty-four percent of men and women aged 18 to 64 had olfactory dysfunction whereas 95% of patients older than or equal to 65 years had olfactory dysfunction (P < .001); no significant difference was noted by gender. By multivariate logistic regression analysis, patients with nasal polyposis [Odds ratio (OR) 2.4, 95% confidence interval (CI) 1.3-4.2, P = .003] and patients older than or equal to 65 years (OR 10.0, 95% CI 2.3-43.7, P = .002) were at increased risk of hyposmia. Patients with nasal polyposis (OR 13.2, 95% CI 5.7-30.7, P < .001), asthma (OR 4.2, 95% CI 1.8-9.8, P = .001), older than or equal to 65 years (OR 15.6, 95% CI 2.3-104.9, P = .005), and smokers (OR 7.6, 95% CI 1.8-31.6, P = .005) were at increased risk of anosmia. Poor olfactory function is common in patients with CRS. Age, nasal polyposis, smoking, and asthma were significantly associated with olfactory dysfunction in patients with CRS. Neither prior endoscopic sinus surgery nor a history of allergic rhinitis was associated with olfactory dysfunction. Septal deviation and inferior turbinate hypertrophy were associated with normal olfactory function.


Regulation of spine density and morphology by IQGAP1 protein domains.
IQGAP1 is a scaffolding protein that regulates spine number. We now show a differential role for IQGAP1 domains in spine morphogenesis, in which a region of the N-terminus that promotes Arp2/3-mediated actin polymerization and branching stimulates spine head formation while a region that binds to Cdc42 and Rac is required for stalk extension. Conversely, IQGAP1 rescues spine deficiency induced by expression of dominant negative Cdc42 by stimulating formation of stubby spines. Together, our observations place IQGAP1 as a crucial regulator of spine number and shape acting through the N-Wasp Arp2/3 complex, as well as upstream and downstream of Cdc42.


Highly sensitive detection of gene expression of an intronless gene: amplification of mRNA, but not genomic DNA by nucleic acid sequence based amplification (NASBA).
NASBA is an isothermal nucleic acid amplification reaction that amplifies mRNA in a dsDNA background. Although similar to the sensitive reverse transcription/polymerase chain reaction (RT-PCR) in mRNA detection, NASBA is not prone to give false positive results caused by genomic dsDNA. Therefore, NASBA is unique for sensitive detection of transcription of intronless genes, which preclude strategies such as intron spanning primer pairs to control false positive results in RT-PCR. Using NASBA, mRNA of the intronless human interferon-beta gene was demonstrated with a sensitivity of 10 copies, whereas 100 ng genomic DNA gave a negative result.


Listeria endocarditis: current management and patient outcome--world literature review.
This is believed to be the 58th reported case of Listeria monocytogenes infective endocarditis. Published reports worldwide were reviewed as to treatment, outcome, and prognostic features. There is controversy over whether all patients with this condition should have surgery. Moreover the best antibiotic treatment is not known, which accounts for the heterogeneity of regimens used. Listeria endocarditis has a high mortality rate (37%). This was higher in men (41% v 32%) and in patients with valve prostheses (41% v 31%), though neither observation reached statistical significance. There was no significant difference in mortality between surgical and non-surgical treatment, but untreated listeria endocarditis proved universally fatal. From the data, treatment with ampicillin is recommended, with resort to surgery in cases where the infection cannot be eradicated or where haemodynamic compromise has occurred.


Polycyclic aromatic hydrocarbons (PAHs) and putative PAH-degrading bacteria in Galveston Bay, TX (USA), following Hurricane Harvey (2017).
Hurricane Harvey was the wettest hurricane in US history bringing record rainfall and widespread flooding in Houston, TX. The resulting storm- and floodwaters largely emptied into the Galveston Bay. Surface water was collected from 10 stations during five cruises to investigate the concentrations and sources of 16 priority polycyclic aromatic hydrocarbons (PAHs), and relative abundances of PAH-degrading bacteria. Highest PAH levels (102-167 ng/L) were detected during the first sampling event, decreasing to 36-69 ng/L within a week. Four sites had elevated concentrations of carcinogenic benzo[a]pyrene that exceeded the Texas Standard for Surface Water threshold. The highest relative abundances of known PAH-degrading bacteria Burkholderiaceae, Comamonadaceae, and Sphingomonadales were detected during the first and second sampling events. PAH origins were about 60% pyrogenic, 2% petrogenic, and the remainder of mixed sources. This study improves our understanding on the fate, source, and distributions of PAHs in Galveston Bay after an extreme flooding event.


Effects of occlusive and conventional gauze dressings on incisional healing after abdominal operations.
To compare the effect of occlusive (Comfeel) and conventional (Mepore) dressings on the healing of incisional wounds after abdominal operations. Prospective randomised study. Laboratory and teaching hospital, Denmark. 73 patients who underwent clean operations requiring incisions longer than 5 cm between August 1993 and August 1995 were randomised to have their wounds dressed with either Comfeel or Mepore. Comfeel was left on until the sutures were removed, and Mepore was removed 2 days postoperatively. Infection, adherence, leakage, and cosmetic appearance three months later. 36 patients were randomised to have Comfeel and 37 to have Mepore. 29 patients were withdrawn from the study (20 having Mepore and 9 having Comfeel) leaving 26, and 17 for analysis, respectively. Wound infections developed in 1 patient in the Comfeel group and 5 in the Mepores group (p = 0.2). There were no differences between the groups regarding the need for dressings to be changed, the incidence of leakage, or loosening of the dressing from the skin. Comfeel adhered securely to the skin and remained more or less transparent until sutures were removed. It remained totally transparent in 23 (64%), and no dressing became totally opaque. There were no differences in cosmetic appearance after three months. We had the impression that patients who had Comfeel were more comfortable and found it easier to mobilise and carry out their daily activities. Occlusive dressings stay in place and stay transparent, and do not increase the risk of wound infection. They may even be more comfortable. they are a reasonable alternative to conventional dressings.


A different wax sculpture technique for implant-retained auricular prosthesis.
Replacement of missing ears is a challenging task in which extensive array of materials and techniques have been employed. This article describes a different and simplified procedure for fabricating auricular prostheses very similar to the intact left ear of the patient. A 65-year-old male patient was referred to the Department of Prosthodontics with the loss of the right ear. In this case, the impression was made using hydrocolloid material (alginate) from the both defected and the opposite side. After hardening of the stone casts, a custom-made transparent splint plate was designed for the left auricular side. The splint was reversed and a cast model of the right auricular side was obtained as pouring the dental stone into transparent orthodontic splint. After getting the impression from cast model, conventional wax pattern and try on process was done. Finally, silicone elastomer was polymerized and the retention of the prosthesis acquired with the magnetic attachments. The technique described is economical, conventional, and time-saving. Furthermore, the prosthesis imitates the patient's intact auricular tissue.


Inhalable polymer nanoparticles for versatile mRNA delivery and mucosal vaccination.
An inhalable platform for mRNA therapeutics would enable minimally invasive and lung targeted delivery for a host of pulmonary diseases. Development of lung targeted mRNA therapeutics has been limited by poor transfection efficiency and risk of vehicle-induced pathology. Here we report an inhalable polymer-based vehicle for delivery of therapeutic mRNAs to the lung. We optimized biodegradable poly(amine-co-ester) polyplexes for mRNA delivery using end group modifications and polyethylene glycol. Our polyplexes achieved high transfection of mRNA throughout the lung, particularly in epithelial and antigen-presenting cells. We applied this technology to develop a mucosal vaccine for SARS-CoV-2. Intranasal vaccination with spike protein mRNA polyplexes induced potent cellular and humoral adaptive immunity and protected K18-hACE2 mice from lethal viral challenge. Inhaled polymer nanoparticles (NPs) achieve high mRNA expression in the lung and induce protective immunity against SARS-CoV-2.


Chloride permeability regulation via a cyclic AMP pathway in cultured human sweat duct cells.
1. Isolated coiled reabsorptive sweat ducts from normal subjects and patients with cystic fibrosis (CF) were cultured in vitro. Cells were harvested and plated onto permeable supports to form confluent cell sheets. The Ussing chamber technique was used to study pharmacological regulation of the transepithelial ion transport in these membranes. 2. Addition of a stable cyclic AMP analogue, 8-Br-cyclic AMP, to normal cell cultures resulted in a decrease of the transepithelial potential difference (PD). 3. Forskolin exposure resulted in a similar PD decrease, which was augmented by the phosphodiesterase inhibitor, isobutylmethylxanthine (IBMX). 4. Exposure to isoprenaline, prostaglandin E2 (PGE2), and phenylephrine resulted in a response mimicking the forskolin-induced response, that was also amplified by IBMX. 5. Pre-incubation with cholera toxin abolished the isoprenaline response and reduced the control resistance. 6. Propranolol abolished the responses induced by isoprenaline and phenylephrine, whereas phentolamine had no effect. PGE2-induced responses were inert to both types of blockers. 7. Indomethazine addition to an unstimulated membrane resulted in a weak PD increase, i.e. a response opposite to that induced by isoprenaline. 8. IBMX addition to an unstimulated membrane resulted in a weak isoprenaline-like response. When the cells were pre-treated with indomethazine this IBMX response was absent. 9. Unidirectional Cl- isotope flux studies demonstrated a large increase of net Cl- reabsorption in response to isoprenaline and PGE2. 10. Mannitol isotope flux studies revealed that the paracellular permeability was unaffected by isoprenaline exposure. 11. Membranes derived from CF patients did not respond similarly to any of these agents. However, a weak spike, occasionally followed by a gradual increase of the short-circuit current (Iscc), was observed in both normal subjects and CF patients. 12. It is concluded that the primary effect on ion transport of factors increasing the cyclic AMP in normal cultured sweat duct cells is an activation of a transcellular Cl- permeability. This effect was missing in cells derived from CF patients.


Screening sweetcorn for enhanced zeaxanthin concentration.
New varieties of fruits and vegetables, with higher carotenoid levels, are being developed to improve the potential health benefits to consumers. To assist the development of a new variety of high zeaxanthin sweetcorn, an analytical screening method was developed, including chromameter measurement of hue angle and optimized extraction for HPLC, and applied to 385 lines of a breeding population and six commercial varieties. Saponification had no effect on carotenoid extraction. In the breeding population, carotenoid levels had a wide range with the highest levels of zeaxanthin being 11.9 mg kg(-1) fresh weight, which was at least six times greater than the tested commercial varieties. The regression of hue angle versus zeaxanthin was described by the equation, hue angle = 76.16 + 4.50 x exp(-0.24 x zeaxanthin) + 11.73 x exp(-0.24 x zeaxanthin), r(2) of 0.59. The top 6% of lines, with regards to zeaxanthin (zeaxanthin + beta-cryptoxanthin + beta-carotene) and total carotenoids, all had hue angles <or=84.1 degrees. The use of a hue angle of 85 degrees as a maximum cut-off for liquid extraction will allow for much increased efficiency in screening further germplasm for high zeaxanthin lines. There appears to be significant opportunity to further increase the zeaxanthin concentration by selecting for lines which preferentially channel carotenoid synthesis towards zeaxanthin.


Atrial fibrillation incrementally increases dementia risk across all CHADS2 and CHA2DS2VASc strata in patients receiving long-term warfarin.
Patients with atrial fibrillation (AF) are at higher risk for developing dementia. Warfarin is a common therapy for the prevention of thromboembolism in AF, valve replacement, and thrombosis patients. The extent to which AF itself increases dementia risk remains unknown. A total 6030 patients with no history of dementia and chronically anticoagulated with warfarin were studied. Warfarin management was provided through a Clinical Pharmacy Anticoagulation Service. Patients were stratified by warfarin indication of AF (n=3015) and non-AF (n=3015) and matched by propensity score (±0.01). Patients were stratified by the congestive heart failure, hypertension, age >75 years, diabetes, stroke (CHADS2) score calculated at the time of warfarin initiation and followed for incident dementia. The average age of the AF cohort was 69.3±11.2 years, and 52.7% were male; average age of non-AF cohort was 69.3±10.9 years, and 51.5% were male. Increasing CHADS2 score was associated with increased dementia incidence, P trend=.004. When stratified by warfarin indication, AF patients had an increased risk of dementia incidence. After multivariable adjustment, AF patients continued to display a significantly increased risk of dementia when compared with non-AF patients across all CHADS2 scores strata. In patients receiving long-term warfarin therapy, dementia risk increased with increasing CHADS2 scores. However, the presence of AF was associated with higher rates of dementia across all CHADS2 score strata. These data suggest that AF contributes to the risk of dementia and that this risk is not solely attributable to anticoagulant use. Dementia may be an end manifestation of a systemic disease state, and AF likely contributes to its progression.


Effects of lipoprotein lipase and statins on cholesterol uptake into heart and skeletal muscle.
Regulation of cholesterol metabolism in cultured cells and in the liver is dependent on actions of the LDL receptor. However, nonhepatic tissues have multiple pathways of cholesterol uptake. One possible pathway is mediated by LPL, an enzyme that primarily hydrolyzes plasma triglyceride into fatty acids. In this study, LDL uptake and tissue cholesterol levels in heart and skeletal muscle of wild-type and transgenic mice with alterations in LPL expression were assessed. Overexpression of a myocyte-anchored form of LPL in heart muscle led to increased uptake of LDL and greater heart cholesterol levels. Loss of LDL receptors did not alter LDL uptake into heart or skeletal muscle. To induce LDL receptors, mice were treated with simvastatin. Statin treatment increased LDL receptor expression and LDL uptake by liver and skeletal muscle but not heart muscle. Plasma creatinine phosphokinase as well as muscle mitochondria, cholesterol, and lipid droplet levels were increased in statin-treated mice overexpressing LPL in skeletal muscle. Thus, pathways affecting cholesterol balance in heart and skeletal muscle differ.


[[Natalizumab therapy, 2013].
Multiple sclerosis (MS) is the most common chronic disease of the central nervous system in young adults. No curative therapy is known. Currently, six drugs are available that can reduce the activity of MS. The first-line drugs can completely reduce the activity of the disease in nearly two-thirds of the patients. In the remainder, who suffer from breakthrough disease, the condition of the patient worsens, and second-line therapies must be used. The second-line drug natalizumab exhibits almost double efficacy of the first-line drugs, but also have less favourable adverse effects. As a severe side-effect for instance, natalizumab carries the risk of the development of progressive multifocal leucoencephalopathy (PML), caused by a polyoma virus, the JC virus. There are three major risk factors for PML: an anti-JCV antibody status, a long duration of natalizumab treatment and prior immunosuppressant therapy. The lowest-risk group (1:14,286) comprises of patients who are anti-JCV antibody-negative, in whom the prior immunosuppressant use and duration of natalizumab therapy do not influence the risk of PML. With no prior immunosuppressant treatment, the incidence of PML increases to 1 in 192 patients after 2 years among those who are anti-JCV antibody-positive. These data may lead the physician to decide to discontinue natalizumab treatment. The half-life of natalizumab is three months; during this time other therapies can not be administered and the patients encounter the rebound effect: as the patients receiving natalizumab therapy displayed a high disease activity before treatment, the rebound effect can lead to relapses. After the termination of natalizumab second-line disease-modifying therapy with fingolimod may be introduced; no PML cases occur in response to fingolimod treatment. In the large majority of patients taking natalizumab who do not develop PML, this drug is highly effective and can prevent the progression of MS. The benefit of therapy and the risk of PML must be considered on an individual basis, with regard to the disease activity, the progression and the MRI activity, before natalizumab therapy is implemented.


16-channel tunable and 25-Gb/s EAM-integrated DBR-LD for WDM-based mobile front-haul networks.
We report a tunable distributed Bragg reflector-laser diode (DBR-LD) integrated with an electro-absorption-modulator (EAM) at an operating wavelength of 1.3 µm. This LD consists of gain, phase control (PC), DBR, and EAM sections, realized by using a butt-coupling technique in monolithically integrating the multiple quantum wells (MQWs) with the passive core and by applying an etched-mesa buried hetero-structure (EMBH) to the resonance cavity (i.e., gain to DBR section) and a deep-ridge type to the EAM section in fabricating the waveguide structure. Wavelength tuning of the LD is achieved by both applying a voltage to the heater metal of DBR section (coarse tuning) and injecting a current to the ohmic metal of PC section (fine tuning). From the work, the fabricated chips show a threshold current of about 13 mA, a side mode suppression ratio (SMSR) of more than 35 dB, and a tuning range of 15 nm within a heater voltage of 2 V. Dynamic tests for the EAM-integrated LD show the 3 dB bandwidth of more than 20 GHz and clear 25 Gb/s eye openings with a dynamic extinction ratio (DER) of over 7 dB for 16 channels spaced at the wavelength interval of 0.55 nm. Based on these results, we conclude that the EAM-integrated DBR-LD is capable of providing 16 channel operation at a data rate of 25 Gb/s and can be used as an effective light source for WDM-based mobile front-haul networks.


Effects of amusing memes on concern for unappealing species.
There is limited knowledge of the mechanisms that can inspire people's concern and engagement in the protection of unpopular and unappealing species. We analyzed Polish people's interest in themed internet memes featuring the proboscis monkey (Nasalis larvatus) and the consequences of this interest for conservation marketing. We examined Google Trends data, used Google Search, and searched popular media materials to estimate interest in the proboscis monkey in Poland. Photos of the proboscis monkey when presented with humor in internet memes attracted as much interest as usually more popular species (e.g., koala, panda, and orangutan) used in marketing by nongovernmental organizations. Amusing internet memes spread by social media positively correlated with increasing interest in the unappealing species, such as proboscis monkey. Interest in amusing internet memes positively correlated with individuals' decisions to donate to 6 crowdfunding actions. Thus, conservation marketing that includes amusing memes and social media may provide a worthwhile complement to traditional campaigns and are likely to influence individuals who are unaffected by the usual means.


Rationale for the use of statins in liver disease.
The evolution of chronic liver injuries from benign and manageable dysfunction to life threatening end-stage liver disease with severe complications renders chronic liver disease a global health burden. Because of the lack of effective medication, transplantation remains the only and final curative option for end-stage liver disease. Since the demand for organ transplants by far exceeds the supply, other treatment options are urgently required to prevent progression and improve end-stage liver disease. Statins are primarily cholesterol-lowering drugs used for primary or secondary prevention of cardiovascular diseases. In addition to the primary effect, statins act beneficially through different pleiotropic mechanisms on inflammation, fibrosis, endothelial function, thrombosis, and coagulation to improve chronic liver diseases. However, concerns remain about the efficacy and safety of statin treatment because of their potential hepatotoxic risks, and as of now, these risks impede broader use of statins in the treatment of chronic liver diseases. The aim of this review is to comprehensively describe the mechanisms by which statins improve prospects for different chronic liver diseases with special focus on the pathophysiological rationale and the clinical experience of statin use in the treatment of liver diseases.


Students' perception of anatomy education at a Korean medical college with respect to time and contents.
Among medical education institutions worldwide, the time allotted for anatomy instruction has decreased without any reasonable time optimization suggestions. In addition, the utility of cadaver dissection has long been debated. Herein, we surveyed students' perceptions of anatomy education with respect to time and hands-on cadaver dissection, at Seoul National University College of Medicine. With the help of a questionnaire, we surveyed third- and fourth-year students at our institute who had completed the anatomy module as freshmen as well as their clinical clerkship. At our institute, students complete 50 hours of anatomy lectures and 120 hours of dissection laboratory during their first year. According to the survey responses, they generally considered these durations to be adequate for achieving their anatomy education goals. Almost all the students regarded the dissection laboratory as an essential and most helpful modality. Thus, we suggest that these ranges of time along with cadaver dissection could be useful guidelines for optimized anatomy education. The survey data also indicated that a more clinically oriented anatomy education could improve students' results.


Gold(I)-catalyzed 1,4- and/or 1,5-heteroaryl migration reactions through regiocontrolled cyclizations.
Gold(I)-catalyzed regioselective cycloisomerizations of furan-ynes have been described. The reaction provides a concise access to stereodefined trisubstituted alkenes by endo cyclization with concomitant 1,5-migration of the furanyl group in the presence of unactivated 3 Å molecular sieves. In the absence of molecular sieves, indene products are generated by exo cyclization, followed by 1,4-furanyl migration/cyclization. The scope for 1,5-migrations can be extended to other heterocycles, such as benzofurans, thiophenes, and pyrroles.


Trophoblastic and mesenchymal structures in rat yolk sac carcinoma.
The presence of trophoblastic and mesenchymal structures in primary as well as in transplanted rat yolk sac carcinomas (YSC) is described. These structures were only recorded in rat yolk sac carcinomas derived from displaced yolk sac but never in embryo-derived yolk sac carcinomas. It is suggested that the endodermal carcinoma cells displaying either a parietal or a visceral yolk sac pattern as well as the mesenchymal and trophoblastic structures may have a common cell ancestor.


Patient-reported quality of life in multiple sclerosis differs between cultures and countries: a cross-sectional Austrian-German-Polish study.
Patient-reported quality of life (QOL) is an outcome measure in clinical trials in multiple sclerosis (MS), but translated QOL instruments may affect the actual comparability of data. We aimed to investigate possible differences in QOL in MS between cultures and countries. We employed the Functional Assessment of Multiple Sclerosis (FAMS) Version 4 questionnaire, which is a state-of-the-art QOL instrument. Some 484 MS patients from Austria (145), Germany (144), and Poland (195) aged 20-60 years, and stratified for sex and disease severity as measured by the Expanded Disability Status Scale (EDSS) score completed the respective FAMS translation and a socio-demographic questionnaire. Analysis of variance and post-hoc Scheffé-test showed that 64% of the FAMS items were answered significantly differently (p < 0.001) between the three countries. A multivariate regression analysis including all the available disease-related and socio-demographic variables revealed the factors age, EDSS score, employment, social contacts, MS course, and country to be significant predictors of both the total FAMS score and the score for items answered differently between the three countries. Differences exist in the QOL of MS patients from Austria, Germany, and Poland which seem to lie beyond the impact of disease severity. They appear to be related to culture or other country-specific factors, as country was an independent predictor of differently answered items of the FAMS and thus also of the whole FAMS. QOL instruments should consider this aspect to faithfully reflect subjective information such as patient-reported benefit of treatment in multinational clinical trials.


Multimodal approach for the management of Hunan hand syndrome: a case report.
Hunan hand syndrome, a form of painful contact dermatitis, is a rare case finding. It is usually seen in people with continuous and prolonged exposure to chili peppers. The main ingredient in chili peppers is capsaicin that leads to the clinical condition, Hunan hand syndrome. This is paradoxical to the use of capsaicin as local application for relief of pain in various clinical situations, such as diabetic neuropathy and postherpetic neuralgia. We report a case of Hunan hand syndrome, managed successfully by using a multimodal approach comprised of a continuous stellate ganglion block, gabapentin, local ice water, and fluocinonide application.


Difficult diagnosis of atypical kawasaki disease in an infant younger than six months: a case report.
Kawasaki disease (KD) is an acute inflammatory vasculitis of unknown origin. We report the case of a 5-month-old child with an atypical form of KD, characterized by undulating symptoms, who developed an aneurysm of the right coronary artery and an ectasia of the left anterior descending coronary artery. This case report underlines the difficulties in recognizing incomplete forms of the illness in young infants, who are at higher risk of cardiac complications.


Detection of microRNA by Electrocatalytic Amplification: A General Approach for Single-Particle Biosensing.
Here we report a sensing scheme for detection of microRNA (miRNA) using electrocatalytic amplification (ECA). ECA is a method in which nanoparticles (NPs) that are catalytic for a specific electrochemical reaction collide with an inert electrode surface. Each collision results in a detectable current transient. In the present article, we show that this general approach can be extended to detection of miRNA. Specifically, PtNPs are modified with a single-strand DNA (ssDNA) shell that is complementary to the miRNA target. Next, the ssDNA:miRNA conjugate is formed, which passivates the PtNP surface. In the presence of an enzyme called duplex specific nuclease (DSN), however, a fraction of the surface-bound DNA is removed thereby exposing some of the PtNP surface. In other words, the electrocatalytic properties of the PtNPs are reactivated only if miRNA complementary to ssDNA is present. This methodology resolves a number of problems that have rendered ECA ineffective for biosensing applications. Moreover, the results suggest that the underlying chemistry is broadly applicable to nucleic acid sensing.


Epigenetic interventions for epileptogenesis: A new frontier for curing epilepsy.
This article highlights the emerging therapeutic potential of specific epigenetic modulators as promising antiepileptogenic or disease-modifying agents for curing epilepsy. Currently, there is an unmet need for antiepileptogenic agents that truly prevent the development of epilepsy in people at risk. There is strong evidence that epigenetic signaling, which exerts high fidelity regulation of gene expression, plays a crucial role in the pathophysiology of epileptogenesis and chronic epilepsy. These modifications are not hard-wired into the genome and are constantly reprogrammed by environmental influences. The potential epigenetic mechanisms, including histone modifications, DNA methylation, microRNA-based transcriptional control, and bromodomain reading activity, can drastically alter the neuronal gene expression profile by exerting their summative effects in a coordinated fashion. Such an epigenetic intervention appears more rational strategy for preventing epilepsy because it targets the primary pathway that initially triggers the numerous downstream cellular and molecular events mediating epileptogenesis. Among currently approved epigenetic drugs, the majority are anticancer drugs with well-established profiles in clinical trials and practice. Evidence from preclinical studies supports the premise that these drugs may be applied to a wide range of brain disorders. Targeting histone deacetylation by inhibiting histone deacetylase enzymes appears to be one promising epigenetic therapy since certain inhibitors have been shown to prevent epileptogenesis in animal models. However, developing neuronal specific epigenetic modulators requires rational, pathophysiology-based optimization to efficiently intercept the upstream pathways in epileptogenesis. Overall, epigenetic agents have been well positioned as new frontier tools towards the national goal of curing epilepsy.


Moral injury in the wake of coronavirus: Attending to the psychological impact of the pandemic.
Moral injury is a helpful lens through which we can better understand and prepare for the downstream psychosocial impact faced by health care providers during the coronavirus pandemic. Moral injury is psychological weight caused by a transgression of one's own or shared morals and values and can manifest as guilt, shame, inability to self-forgive, demoralization, and, in the worst case, self-harming behaviors. Given the morally challenging and life-threatening decisions our health care workers need to make daily in the face of consistent and ongoing death and loss, it is important to prepare for moral injury and the psychological toll by offering psychological support early and as often as needed at both the personal and institutional level. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Predictors of outcome in children with otitis media with effusion.
Otitis media with effusion (OME) is the commonest cause of hearing impairment in young children. The fluctuating nature of the condition makes identification of those with persistent disease difficult without subjecting each child to a period of 'watchful waiting'. The aim of this study was to determine if the outcome of this observation period could in any way be predicted. The study involved the retrospective analysis of 517 children, aged 3-15 years (mean 5 years and 4 months) in whom the diagnosis of OME had been established. All children had been subjected to an observation period before a decision on surgery was taken. There was a significant correlation between the degree of hearing loss at presentation and after the period of observation. Sex was not a reliable predictor of outcome, but age less than 4 years and presentation in autumn or winter were associated with a poor audiometric outcome. This study identifies a predictive influence on the resolution of OME for these three factors and points the way for future research aimed at identifying the subgroup of children with OME who would benefit from early surgical intervention.


A Potential Off-Target Effect of the Wnt/β-Catenin Inhibitor KYA1797K: PD-L1 Binding and Checkpoint Inhibition.
The quest for small molecule inhibitors of the PD-1/PD-L1 checkpoint continues in parallel to the extensive development of monoclonal antibodies directed against this immune checkpoint. Drug screening strategies are being set up to identify novel PD-L1 inhibitors. A virtual screening based on molecular docking with the PD-L1 protein dimer has been performed to identify a new binder. Binding of the identified ligand to PD-L1 has been validated experimentally using a microscale thermophoresis (MST) assay. The cellular effect of the compound was evidenced using a fluorescence resonance energy transfer (FRET) assay based on activation of tyrosine phosphatase SHP-2. We have identified the potent Wnt/β-catenin inhibitor KYA1797K as a weak PD-L1 binder. Molecular docking suggested that the compound can bind to the interface of a PD-L1 dimer, with a geometry superimposable to that of the reference PD-L1 inhibitor BMS-202. The atypical 2-thioxo-4-thiazolidinone motif of KYA1797K, derived from the natural product rhodanine, plays a major role in the interaction with PD-L1. Binding of KYA1797K to recombinant hPD-L1 was validated experimentally, using MST. The drug was found to bind modestly but effectively to hPD-L1. The FRET assay confirmed the weak capacity of KYA1797K to interfere with the activation of SHP-2 upon its interaction with human PD-1. Collectively, the data show that KYA1797K could function as a weak modulator of the PD-1/PD-L1 checkpoint. This effect may contribute, at least partially, to the reported capacity of the β-catenin inhibitor to downregulate PD-L1 in cancer cells. The work also underlines the interest to further consider the rhodanine moiety as a chemical motif for the design of new PD-L1 binders.


Autochthonous dengue outbreak in Italy 2020: clinical, virological and entomological findings.
In August 2020, in the context of COVID-19 pandemics, an autochthonous dengue outbreak was identified for the first time in Italy. Following the reporting of the index case of autochthonous dengue, epidemiological investigation, vector control and substances of human origin safety measures were immediately activated, according to the national arbovirus surveillance plan. Dengue cases were followed-up with weekly visits and laboratory tests until recovery and clearance of viral RNA from blood. The primary dengue case was identified in a young woman, who developed fever after returning from Indonesia to northern Italy, on 27 July 2020. She spent the mandatory quarantine for COVID-19 at home with relatives, six of whom developed dengue within two weeks. Epidemiological investigation identified further five autochthonous dengue cases among people who lived or stayed near the residence of the primary case. The last case of the outbreak developed fever on 29 September 2020. Dengue cases had a mild febrile illness, except one with persistent asthenia and myalgia. DENV-1 RNA was detected in blood and/or urine in all autochthonous cases, up to 35 days after fever onset. All cases developed IgM and IgG antibodies which cross-reacted with West Nile virus (WNV) and other flaviviruses. Sequencing of the full viral genome from blood samples showed over 99% nucleotide identity with DENV-1 strains isolated in China in 2014-2015; phylogenetic analysis classified the virus within Genotype I. Entomological site inspection identified a high density of Aedes albopictus mosquitoes, which conceivably sustained local DENV-1 transmission. Aedes koreicus mosquitoes were also collected in the site. Areas in Europe with high density of Aedes mosquitoes should be considered at risk for dengue transmission. The presence of endemic flaviviruses, such as WNV, might pose problems in the laboratory diagnosis.


Learning Curve Assessment for Percutaneous Left Atrial Appendage Closure With the WATCHMAN Occluder.
We sought to evaluate the effect of increasing experience with left atrial appendage (LAA) closure on short-term outcome. Data regarding the impact of the learning curve of LAA closure-particularly regarding technical aspects of the procedure-are lacking. The present analysis represents first data from a single-center all-comer registry. The population was divided into 3 groups according to treatment time (group 1: patients 1-30; group 2: patients 31-60; group 3: patients 61-90). The mean age of the population was 77 years. Median CHA2 DS2 VASC Score and HAS-BLED were 5 (IQR 3-5) and 3 (IQR 3-4), respectively. Implantation success was 90% with a slight but not statistically significant increase during the course of the registry. Procedure time (75 [62-108] vs. 50 [43-66] vs. 47 [41-61] minutes; P < 0.0001), fluoroscopy time (20 [15-30] vs. 11 [8-19] vs. 11 [9-18] minutes; P = 0.002), and contrast volume (105 [70-170] vs. 60 [50-75] vs. 50 [50-73] ml; P < 0.0001) were reduced across the 3 groups. In-hospital complications decreased significantly (20 vs. 7% vs. 0%; P = 0.021). The compression grade of the occluder was chosen higher with increasing learning curve (15 [11-25] vs. 25 [17-29] vs. 21 [14-26] %; P = 0.05). With increasing operator experience the performance and safety of percutaneous LAA closure improved continuously.


Environmental influences on family similarity in afternoon cortisol levels: twin and parent-offspring designs.
Modest genetic effects on morning, but not late-day, cortisol levels have been established. Environmental demands may influence basal cortisol levels later in the day. Thus, we anticipated that individuals in the same family would have similar afternoon cortisol levels to the extent that they share aspects of their environment. We examined afternoon basal cortisol levels measured across 3 consecutive days in mothers and fathers and in multiple offspring in two separate large and longitudinal studies. Study I involved 321 families with singletons while study II involved 233 families with twins. Modest family similarity was apparent for afternoon basal cortisol levels in both studies. Spouses' cortisol levels were also correlated. Data from study II demonstrated that family resemblance in afternoon cortisol was accounted for by underlying shared environmental factors, but not underlying genetic factors. Shared environment accounted for 62% of the variation in twin afternoon basal cortisol levels and 14% of the variation in parent afternoon basal cortisol levels. We used pooled data from the two studies to examine whether parental depression, socioeconomic status (SES), and offspring sex and age impacted cortisol levels. Female offspring had higher cortisol levels than males, and cortisol decreased with age until about 9 years of age, after which cortisol increased with age. Family similarity persisted after accounting for parental depression, SES, time of day, and offspring sex and age, which suggests that the shared family environment influences parent and offspring stress hormone levels throughout the childhood years.


Limits on the axial coupling constant of new light bosons.
We report on a neutron particle physics experiment, which provides for the first time an upper limit on the strength of an axial coupling constant for a new light spin 1 boson in the millimeter range. Such a new boson would mediate a new force between ordinary fermions, like neutrons and protons. The experiment was set up at the cold neutron reflectometer Narziss at the Paul Scherrer Institute and uses Ramsey's technique of separated oscillating fields to search for a pseudomagnetic neutron spin precession induced by this new interaction. For the axial coupling constant g(A)(2), an upper limit of 6×10(-13) (95% C.L.) was determined for an interaction range of 1 mm.


A newly recognised cause of vertigo: horizontal canal variant of benign positional vertigo.
To describe the presentation, causes, treatment, and outcomes of patients presenting with the newly recognised horizontal canal variant of benign positional vertigo (BPV); and to emphasise the importance of performing a positional test on all patients being assessed for vertigo. The records on 400 patients presenting with BPV were analysed. Two detailed patient histories from 2004 are included. Forty-nine patients (12%) had horizontal canal BPV. The median presentation age was 59 years. In 17 patients, it presented de novo during repositioning treatment for 'classical' posterior canal BPV. Repositioning is in the horizontal plane, with the direction depending on whether the mechanism is canalithiasis or cupulolithiasis. Horizontal canal BPV explains nearly all variations on 'classical' (posterior canal) BPV. It accounts for at least 10% of BPV and has been frequently misdiagnosed. Repositioning is usually curative if the symptomatic ear is correctly identified.


Effects of fatiguing tone frequency on temporary threshold shift in bottlenose dolphins (Tursiops truncatus).
Temporary threshold shift (TTS) was measured in two bottlenose dolphins (Tursiops truncatus) after exposure to 16-s tones between 3 and 80 kHz to examine the effects of exposure frequency on the onset, growth, and recovery of TTS. Hearing thresholds were measured approximately one-half octave above the exposure frequency using a behavioral response paradigm featuring an adaptive staircase procedure. Results show frequency-specific differences in TTS onset and growth, and suggest increased susceptibility to auditory fatigue for frequencies between approximately 10 and 30 kHz. Between 3 and 56 kHz, the relationship between exposure frequency and the exposure level required to induce 6 dB of TTS, measured 4 min post-exposure, agrees closely with an auditory weighting function for bottlenose dolphins developed from equal loudness contours [Finneran and Schlundt. (2011). J. Acoust. Soc. Am. 130, 3124-3136].


Selective and sensitive determination of protoberberines by capillary electrophoresis coupled with molecularly imprinted microextraction.
In this work, we developed a novel molecularly imprinted solid-phase microextraction with capillary electrophoresis method for the selective extraction and determination of protoberberines in complicated samples. The imprinted monolith was prepared in a micropipette tip-based device by using acrylamide as the functional monomer, ethyleneglyoldimethacrylate as the cross-linker and dimethylsulfoxide as the porogen, and exhibited an imprinting factor of 2.41 to berberine, 2.36 to palmatine and 2.38 to jatrorrhizine. Good capillary electrophoresis separation was achieved by using 20 mM phosphate buffer at pH 7 as running buffer with the addition of organic modifier of 10% methanol. Parameters such as sample pH value, sample flow rate and sample volume were investigated for imprinted monolith-based solid-phase microextraction. An imprinted solid-phase microextraction with capillary electrophoresis method was developed, the method showed a wide linear range (0.3-50 μg/mL), good linearity (R2 ≥ 0.9947) and good reproducibility (relative standard deviations ≤ 0.73%), the limit of detection was as low as 0.1 μg/mL, which was lower than some reported methods based on capillary electrophoresis for protoberberines. The method has been applied for determination of three common protoberberines in Cortex Phellodendri Chinensis, by using a molecularly imprinted monolith as the selective sorbent, most of the matrices in the Cortex Phellodendri Chinensis sample were removed and three protoberberines were selectively enriched and well determined.


Arabidopsis lipins, PDAT1 acyltransferase, and SDP1 triacylglycerol lipase synergistically direct fatty acids toward β-oxidation, thereby maintaining membrane lipid homeostasis.
Triacylglycerol (TAG) metabolism is a key aspect of intracellular lipid homeostasis in yeast and mammals, but its role in vegetative tissues of plants remains poorly defined. We previously reported that PHOSPHOLIPID:DIACYLGLYCEROL ACYLTRANSFERASE1 (PDAT1) is crucial for diverting fatty acids (FAs) from membrane lipid synthesis to TAG and thereby protecting against FA-induced cell death in leaves. Here, we show that overexpression of PDAT1 enhances the turnover of FAs in leaf lipids. Using the trigalactosyldiacylglycerol1-1 (tgd1-1) mutant, which displays substantially enhanced PDAT1-mediated TAG synthesis, we demonstrate that disruption of SUGAR-DEPENDENT1 (SDP1) TAG lipase or PEROXISOMAL TRANSPORTER1 (PXA1) severely decreases FA turnover, leading to increases in leaf TAG accumulation, to 9% of dry weight, and in total leaf lipid, by 3-fold. The membrane lipid composition of tgd1-1 sdp1-4 and tgd1-1 pxa1-2 double mutants is altered, and their growth and development are compromised. We also show that two Arabidopsis thaliana lipin homologs provide most of the diacylglycerol for TAG synthesis and that loss of their functions markedly reduces TAG content, but with only minor impact on eukaryotic galactolipid synthesis. Collectively, these results show that Arabidopsis lipins, along with PDAT1 and SDP1, function synergistically in directing FAs toward peroxisomal β-oxidation via TAG intermediates, thereby maintaining membrane lipid homeostasis in leaves.


Tungsten Carbide Nanolayer Formation by Ion Beam Mixing with Argon and Xenon Ions for Applications as Protective Coatings.
A novel nanolayer is formed by means of ion irradiation applicable as protective coating. Tungsten carbide (WC)-rich nanolayers were produced at room temperature by applying ion beam mixing of various carbon/tungsten (C/W) multilayer structures using argon and xenon ions with energy in the range of 40-120 keV and fluences between 0.25 and 3 × 1016 ions/cm2. The hardness of the nanolayers was estimated by means of standard scratch test applying an atomic force microscope equipped with a diamond-coated tip (radius < 10 nm); the applied load was 2 μN. The irradiation-induced hardness of the nanolayers correlated with the areal density of the WC; with the increasing amount of WC, the hardness of the nanolayer increased. The produced layers had an order of magnitude better corrosion resistance than a commercially available WC cermet circular saw. If the WC amount was high enough, the hardness of the layer became higher than that of the investigated WC cermet. These findings allow us to tune and design the mechanical and chemical properties of the WC protective coatings.


Non-cancer effects of exposure to A-bomb radiation.
A slight rearrangement of the data included in a recent report from the Radiation Effects Research Foundation (RERF) has shown differences between cardiovascular and other non-malignant diseases of A-bomb survivors which probably result from two factors: selection effects of early infection deaths and residual effects of marrow damage. Both effects were dose related but neither was obvious becasue one reduced the risk of later infection deaths and the other increased the risk. Allowance for these factors is bound to alter present RERF estimates for cancer effects of radiation and the change will probably be in an upward direction, thus bringing these estimates closer to ones based on radiation workers.


Prognostic value and staging classification of retropharyngeal lymph node metastasis in nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy.
The development of intensity-modulated radiotherapy (IMRT) has revolutionized the management of nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the prognostic value and classification of TNM stage system for retropharyngeal lymph node (RLN) metastasis in NPC in the IMRT era. We retrospectively reviewed data from 749 patients with biopsy-proven, non-metastatic NPC. All patients received IMRT as the primary treatment. Chemotherapy was administered to 86.2% (424/492) of the patients with stage III or IV disease. The incidence of RLN metastasis was 64.2% (481/749). Significant differences were observed in the 5-year disease-free survival (DFS; 70.6% vs. 85.4%, P<0.001) and distant metastasis-free survival (DMFS; 79.2% vs. 90.1%, P<0.001) rates of patients with and without RLN metastasis. In multivariate analysis, RLN metastasis was an independent prognostic factor for disease failure and distant failure (P = 0.005 and P = 0.026, respectively), but not for locoregional recurrence. Necrotic RLN metastases have a negative effect on disease failure, distant failure and locoregional recurrence in NPC with RLN metastasis (P = 0.003, P = 0.018 and P = 0.005, respectively). Survival curves demonstrated a significant difference in DFS between patients with N0 disease and N1 disease with only RLN metastasis (P = 0.020), and marginally statistically significant differences in DMFS and DFS between N1 disease with only RLN metastasis and other N1 disease (P = 0.058 and P = 0.091, respectively). In N1 disease, no significant differences in DFS were observed between unilateral and bilateral RLN metastasis (P = 0.994). In the IMRT era, RLN metastasis remains an independent prognostic factor for DFS and DMFS in NPC. It is still reasonable for RLN metastasis to be classified in the N1 disease, regardless of laterality. However, there is a need to investigate the feasibility of classifying RLN metastasis as N1a disease in future by a larger cohort study.


Evolution of Cerebral Ischemia Assessed by Amide Proton Transfer-Weighted MRI.
Amide proton transfer-weighted (APTW) magnetic resonance imaging (MRI) has recently become a potentially important tool for evaluating acidosis in ischemic stroke. The purpose of this study was to evaluate the dynamic pH-related changes in the lesions in patients with ischemia. Thirty-nine patients with ischemic stroke (symptom onset to imaging time ranging 2 h-7 days) were examined with a 3.0-T MRI system. Patients were divided into four groups: at the hyperacute stage (onset time ≤ 6 h), at the acute stage (6 h < onset time ≤ 48 h), at the early subacute stage (48 h < onset time ≤ 96 h), and at the late subacute stage (96 h < onset time ≤ 168 h). The APTW signal intensities were quantitatively measured in multiple ischemic regions for each patient. Compared with the contralateral normal white matter, APTW signals were significantly lower in ischemic tissue for all four stages (P < 0.05). The APTW signal intensities (APTWave and APTWmin) increased consistently with onset time (R2 = 0.11, P = 0.040; R2 = 0.13, P = 0.022, respectively). APTWmax-min showed a continued reduction with onset time (R2 = 0.44, P < 0.001). Our results suggest that persistent tissue acidification could occur after ischemia, and as the time from stroke onset increases, the acidotic environment would alleviate. APTW signal intensities could reflect pH-weighted properties in ischemic tissue at different stages and time points.


Identification of Two New Phenanthrenes from Dendrobii Herba and Their Cytotoxicity towards Human Hypopharynx Squamous Carcinoma Cell (FaDu).
Two new phenanthrenes, (1R,2R)-1,7-hydroxy-2,8-methoxy-2,3-dihydrophenanthrene-4(1H)-one (1) and 2,7-dihydroxy-phenanthrene-1,4-dione (2), were isolated from the ethyl acetate-soluble fraction of Dendrobii Herba, together with seven known phenanthrenes (3-9), two bibenzyls (10-12), and a lignan (13). Structures of 1 and 2 were elucidated by analyzing one-dimensional (1D) and two-dimensional (2D)-NMR and High-resolution electrospray ionization mass spectra (HR-ESI-MS) data. The absolute configuration of compound 1 was confirmed by the circular dichroism (CD) spectroscopic method. In cytotoxicity assay using FaDu human hypopharynx squamous carcinoma cell line, compounds 3-6, 8, 10, and 12 showed activities, with IC50 values that ranged from 2.55 to 17.70 μM.


Understanding those who self-mutilate.
Self-mutilating behavior is a symptom seen in both men and women with various psychiatric disorders, but the majority of those who self-mutilate are women with borderline personality disorder. This complex, maladaptive behavior is used by clients as a means of self-preservation and emotion regulation, and is often associated with childhood trauma. Clients who self-mutilate perceive they receive poor care in hospital emergency departments and are retraumatized by these experiences. Clinicians who understand the complexity and purposes of self-mutilating behavior are better able to provide clients with supportive, empathetic care.


Eosinophilic gastroenteritis: A state-of-the-art review.
Eosinophilic gastrointestinal disorders are a series of diseases that include eosinophilic esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilic enteritis, and eosinophilic colitis. Among these disorders, eosinophilic gastroenteritis is an uncommon and heterogeneous disease characterized by eosinophilic infiltration of the gastrointestinal tract in the absence of secondary causes, presenting with a variety of gastrointestinal manifestations. Up to now, epidemiology and pathophysiology of eosinophilic gastroenteritis are still unclear. Based on clinical manifestations and depth of eosinophilic infiltration into the gastrointestinal tract wall, eosinophilic gastroenteritis is classified into three different patterns including predominantly mucosal pattern, predominantly muscular pattern, and predominantly serosal pattern. For diagnosing eosinophilic gastroenteritis, it is necessary for clinicians to have a high degree of clinical suspicion. In addition to the gastrointestinal symptoms, other evidences such as laboratory results, radiological findings and endoscopy can also provide important diagnostic evidences for eosinophilic gastroenteritis. And these indirect pieces of information together with histological results will lead to a definitive diagnosis of eosinophilic gastroenteritis. To avoid specific allergen, dietary treatments can be considered as initial treatment strategy before drug treatment. Corticosteroids are the main medication for eosinophilic gastroenteritis and have a dramatic therapeutic efficacy. Yet other medications need to further verify their effects in clinical practice, and surgery should be avoided as far as possible.


A cross-sectional and longitudinal magnetic resonance imaging study of cingulate gyrus gray matter volume abnormalities in first-episode schizophrenia and first-episode affective psychosis.
Previous magnetic resonance imaging (MRI) findings have demonstrated psychopathological symptom-related smaller gray matter volumes in various cingulate gyrus subregions in schizophrenia and bipolar disorder. However, it is unclear whether these gray matter abnormalities show a subregional specificity to either disorder and whether they show postonset progression. To determine whether there are initial and progressive gray matter volume deficits in cingulate gyrus subregions in patients with first-episode schizophrenia (FESZ) and patients with first-episode affective psychosis (FEAFF, mainly manic) and their specificity to FESZ or FEAFF. A naturalistic cross-sectional study at first hospitalization for psychosis and a longitudinal follow-up approximately 1(1/2) years later. Patients were from a private psychiatric hospital. Thirty-nine patients with FESZ and 41 with FEAFF at first hospitalization for psychosis and 40 healthy control subjects (HCs) recruited from the community underwent high-spatial-resolution MRI, with follow-up scans in 17 FESZ patients, 18 FEAFF patients, and 18 HCs. Individual subjects were matched for age, sex, parental socioeconomic status, and handedness. Cingulate gyrus gray matter volumes in 3 anterior subregions (subgenual, affective, and cognitive) and 1 posterior subregion, and whether there was a paracingulate sulcus. At first hospitalization, patients with FESZ showed significantly smaller left subgenual (P = .03), left (P = .03) and right (P = .005) affective, right cognitive (P = .04), and right posterior (P = .003) cingulate gyrus gray matter subregions compared with HCs. Moreover, at the 1(1/2)-year follow-up, patients with FESZ showed progressive gray matter volume decreases in the subgenual (P = .002), affective (P < .001), cognitive (P < .001), and posterior (P = .02) cingulate subregions compared with HCs. In contrast, patients with FEAFF showed only initial (left, P < .001; right, P = .002) and progressive subgenual subregion abnormalities (P < .001). Finally, patients with FESZ showed a less asymmetric paracingulate pattern than HCs (P = .02). Patients with FEAFF and FESZ showed differences in initial gray matter volumes and in their progression. Initial and progressive changes in patients with FEAFF were confined to the subgenual cingulate, a region strongly associated with affective disorder, whereas patients with FESZ evinced widespread initial and progressively smaller volumes.


Wingate Test as a Strong Predictor of 1500-m Performance in Elite Speed Skaters.
Wingate test scores are strongly associated with anaerobic capacity in athletes involved in speed-endurance sports. In speed skating Wingate results are known to predict performance cross-sectionally but have not been investigated relative to their ability to predict performance longitudinally. To investigate whether Wingate tests performed during summer training are predictive of 1500-m speed-skating performance the subsequent winter in elite speed skaters. Wingate test results from the summer training periods and 1500-m performances during the subsequent winter were analyzed over a 3-y period in 5 female and 8 male elite (Olympic, World Championship, and World Cup medalists) speed skaters. Regression analyses using generalized estimating equations (GEE) were used to estimate the relationship between Wingate test variables and 1500-m speed-skating performance. Wingate peak power (PP) and mean power (MP) were used to predict 1500-m time and 400-m lap times. Improvements of 1 W/kg on PP and MP in women predict improvements of -0.75 s and -2.05 s, respectively, on 1500-m time (World Record 110.85 s). In men, improvements in PP and MP were associated with performance improvements of -0.92 s and -2.32 s on 1500-m time per 1 W/kg (World Record 101.04 s). Wingate test results achieved during the summer training period are a good predictor of improvements in 1500-m speed-skating performance during the subsequent winter. For the smallest worthwhile improvement in 1500-m performance, a gain in PP and MP of 2.1% and 1.4% (0.38 and 0.14 W/kg) for females and 1.2% and 0.9% (0.29 and 0.12 W/kg) for males is needed.


[The interaction of pathogenic microorganisms with the sorbent polymethylsiloxane].
The method of electron microscopy has been used to study adhesion of the microbic cells of standard strains of Staphylococcus aureus, Escherichia coli and fungi of genus Candida on the organosilicon sorbent polymethylsiloxane (PMS) and medicamentous complex containing it. This complex contains furazolidone and metronidazole immobilized on silver ions-modified PMS. It is shown that the adhesion of microorganisms is accompanied by their destruction whose rate on pure PMS and medicamentous complex is different. Using experimental data the assumptions are advanced concerning the mechanism of the PMS interaction with Gram-positive and Gram-negative microorganisms as well as with fungi of genus Candida.


Ras effector-homologue region on Rac regulates protein associations in the neutrophil respiratory burst oxidase complex.
Rac, a small molecular weight GTPase in the Ras superfamily, participates in the activation of the multicomponent superoxide-generating NADPH oxidase of human neutrophils. Rac is 30% identical to Ras overall, but is 75% identical within the sequence corresponding to the effector region of Ras, which regulates mitogenesis through interactions with the protein kinase Raf1. We investigated the role of this region in Rac1 using site-directed mutagenesis. In a cell-free semirecombinant NADPH oxidase system, mutants in the 26, 33, 38, and 45 amino acids showed 20-110-fold reduced binding to the oxidase complex as judged by EC50 values and reduced (44-80%) maximal activities in superoxide generation. Only the GTP gamma S-bound form associated, since the GDP-bound form of Rac neither activated alone nor competed with GTP gamma S-Rac. EC50 values for neither p47-phox nor p67-phox were affected when mutant Racs were used in place of Rac. Data indicate direct binding of the Rac effector region to one or more components of the respiratory burst oxidase. Results indicate a general role for conserved effector-equivalent regions in small GTPases in the regulation of protein-protein interactions.


Dynamics of flexible filaments in oscillatory shear flows.
The fluid-structure interactions between flexible fibers and viscous flows play an essential role in various biological phenomena, medical problems, and industrial processes. Of particular interest is the case of particles freely transported in time-dependent flows. This work elucidates the dynamics and morphologies of actin filaments under oscillatory shear flows by combining microfluidic experiments, numerical simulations, and theoretical modeling. Our work reveals that, in contrast to steady shear flows, in which small orientational fluctuations from a flow-aligned state initiate tumbling and deformations, the periodic flow reversal allows the filament to explore many different configurations at the beginning of each cycle. Investigation of filament motion during half time periods of oscillation highlights the critical role of the initial filament orientation on the emergent dynamics. This strong coupling between orientation and deformation results in new deformation regimes and novel higher-order buckling modes absent in steady shear flows. The primary outcome of our analysis is the possibility of suppression of buckling instabilities for certain combinations of the oscillation frequency and initial filament orientation, even in very strong flows. We explain this unusual behavior through a weakly nonlinear Landau theory of buckling, in which we treat the filaments as inextensible Brownian Euler-Bernoulli rods whose hydrodynamics are described by local slender-body theory.


Anomalous Origin of Right Coronary Artery Originating from the Pulmonary Trunk (ARCAPA): an Incidental Finding in a Patient Presenting with Chest Pain.
Anomalous origin of the right coronary artery originating from the pulmonary trunk (ARCAPA) is a rare congenital coronary anomaly with an estimated prevalence of 0.002%. Most patients are asymptomatic and the anomaly is detected incidentally during evaluation for other problems. Occasionally, ARCAPA may lead to myocardial ischemia and/or sudden cardiac arrest. We present a case of a 55-year-old female with a history of hypertension who presented to the emergency department with intermittent chest discomfort for three days. Laboratory results showed an elevated troponin of 0.18 ng/ml and subsequently increased to 0.39 ng/ml. The initial electrocardiogram study demonstrated sinus tachycardia with no acute changes. The patient was diagnosed with non-ST-segment elevation myocardial infarction. She underwent cardiac catheterization that showed 90% stenosis of the left main/left anterior descending artery. Reflux of contrast from the right coronary artery (RCA) ostium to the pulmonary artery was seen along with left to right collaterals with retrograde filling of the RCA. There was no significant obstruction of the RCA when viewed via left to right collaterals. Right heart catheterization and pulmonary angiography were performed which confirmed the origin of the RCA from the pulmonary trunk. The patient was referred for surgery and ligation of the aberrant RCA originating from the pulmonary artery was performed along with coronary artery bypass grafting x 2, left internal mammary artery to left anterior descending artery (LAD) and saphenous vein graft to the proximal posterior descending artery. The patient was discharged home with marked improvement of her symptoms. Origin of the RCA from the pulmonary artery (ARCAPA) is a rare congenital malformation with a potentially malignant outcome for the patient. The majority of patients with ARCAPA remain asymptomatic. In this case report, the chest discomfort was due to occlusion of the LAD and was probably unrelated to the coronary malformation. However, sudden cardiac death has been linked to ARCAPA and therefore a corrective operation is recommended even for asymptomatic patients. Of the surgical techniques available, which include: simple ligation of the RCA, ligation of the RCA with saphenous vein bypass grafting and re-implantation of the RCA into the aorta, the last method is believed to be superior for the restoration of myocardial blood supply. However, its long-term benefits have not been conclusively demonstrated. Therefore, in our patient, ligation of RCA with saphenous vein bypass grafting was done as it is recognized as a less traumatic surgical alternative to RCA implantation into the aorta.


The use of monofilament suture in vascular surgery.
The blood lost through the suture line holes of vessels closed with braided polyester sutures is compared with that lost when a monofilament polypropylene suture is employed. In a retrospective analysis of blood replacement during saphenous vein aortorenal bypasses, twice as much blood replacement was required when the braided polyester suture was used. Further, ten dogs had one femoral artery reanastomosed with braided polyester suture and the other with monofilament polypropylene. Bleeding was three times greater and lasted six times longer when the braided polyester suture material was utilized.


13C NMR spectroscopy study of cortical nerve cell cultures exposed to hypoxia.
Primary cultures of cerebral cortical GABA-ergic neurons growing on top of a preformed layer of astrocytes (co-cultures) were incubated with [1-13C]glucose and exposed to a low oxygen atmosphere (2% O2) for 17 hr. 13C, 1H, and 31P nuclear magnetic resonance (NMR) spectroscopy was performed on perchloric acid (PCA) extracts of cells and of media collected from these cultures. In the control groups incorporation of 13C label into glutamine, citrate, and lactate could be demonstrated in both cell extracts and culture media. Labeled GABA and glutamate were only observed in cell extracts. During hypoxia high energy phosphates decreased but lactate production and glucose consumption increased. There was a decreased amount of citrate and glutamine in cell extracts and media of the hypoxic co-cultures. There was a change in distribution of the 13C label within the GABA molecule, with an increase of labeling in the C-2 position. This change in 13C distribution was not found in glutamine present in the media where it is a precursor for GABA in neurons. Instead a decrease in the corresponding C-4 position was observed. These results suggest that energy depletion during hypoxia leads to reduced export from the astrocytic tricarboxylic acid (TCA) cycle as demonstrated by a decreased amount of citrate and changed distribution of 13C in glutamine. The change in the distribution of label in GABA from cell extracts as compared to glutamine in the medium may indicate that neurons are synthesizing GABA using precursors supplied from their own TCA cycle and not from precursors supplied by astrocytes.


Immunoenzymometric assay of creatine kinase with monoclonal antibodies to the MB isoenzyme compared with electrophoresis.
We compare a "second-generation" immunoenzymometric assay (Tandem-E CKMB II) for creatine kinase (EC 126.96.36.199) MB with its electrophoretic (Beckman Paragon system) determination. In the former, two monoclonal antibodies are directed against the B and M subunits. We evaluated 502 samples from 253 patients. Precision, linearity, and analytical recovery for both assays were excellent. The two methods correlated well (r = 0.936). The reference interval for individuals with no suspected cardiac disorder was 0-6.0 micrograms/L; that for non-infarct patients was 0-18.0 micrograms/L. Peak CK-MB values determined by the two assays agreed for 95% of the patients, in terms of exceeding the normal reference interval or not. Diagnostic efficiencies were 86% (Tandem) and 88% (electrophoresis). The immunoenzymometric assay showed no cross reaction with other CK isoenzymes. Both assay methods performed well in detecting CK-MB, although there were some false positives by both methods, as judged from electrocardiographic results. When total CK for the Tandem assay exceeds 2000 U/L, we recommend calculation of a ratio (CK-MB, micrograms/L:total CK, U/L).