Zero-magnetic-field hall effect in broken-mirror-symmetry conductors under illumination.
A novel effect is predicted for conductors with a broken mirror symmetry [e.g., polar metals and asymmetrical quantum well (QW) structures]: if such a conductor is under the direct current J approximately E(d), the circular polarized infrared radiation should induce an additional transverse current JH approximately E(d)xc, where E(d) is the driving electric field and c is a vector directed either along the polar axis or perpendicular to a QW. The sign of the current JH can be reversed by switching the helicity of the light from right to left-handed. Thus the phenomenon is, in fact, something like the Hall effect in which light acts as an external magnetic field.


[Nitric oxide in respiratory diseases].
Recent reports have described a pathogenic role of nitric oxide in several respiratory disease. It is specially useful in the adult respiratory distress syndrome, where it acts as a selective vasodilator and improves gas exchange, decreasing pulmonary shunting. Although it has a proven bronchodilator effect, its therapeutic role in diseases such as asthma and chronic limitation of airway flow is not well defined. This article review the metabolism, mechanisms of action, potential uses and adverse effects of nitric oxide in respiratory disease.


The invisible community: undocumented Polish workers in Athens.
"This article describes the development of an economic migration from Poland to Greece and the creation of a migrant community in Athens. It presents the development of a new migration route by political immigrants. It then describes how the Polish political emigrants heading for Greece in the mid-1980s established the pillar institutions which were inherited by the Polish undocumented workers who have followed, and which have served the latter well. The article proceeds to highlight the work milieu of the Polish undocumented workers in Athens, and discusses the role played by the ¿Polish church', i.e., the Roman Catholic church to which Poles were given access. It concludes by considering the future prospects of this migration and of the Polish migrant community in Greece."


Beating the biological clock: the compressed family life cycle of young women with BRCA gene alterations.
Empirical and clinical literature suggests a temporal thread running through family narratives of hereditary disease, linking past experiences to current beliefs about risk. This study asked young women with elevated risk of developing hereditary breast or ovarian cancer (HBOC) how their family histories with cancer and their gene status inform meaning construction around cancer risk and family development. Twenty-three women aged 22-35 who carry a BRCA gene alteration completed illness genograms and open-ended, narrative interviews. Transcripts were analyzed using the Listening Guide, a narrative tool that emphasizes key themes, meanings, and relational structures. Data analysis revealed distinct priorities for (1) single versus partnered women and (2) women who wished to have children versus those who had completed childbearing or were not intending to have children. Findings suggest single women experience increased urgency at finding a life partner capable of handling the emotional strain of the cancer world and open to pursuing multiple paths toward parenthood. Further, participants' family experiences shaped beliefs about perceived time to achieve desired family goals, specifically having biological children, before a cancer diagnosis or the need for preventive surgery. Clinical practice and research implications are discussed.


Mechanisms of action of and resistance to ciprofloxacin.
Ciprofloxacin and other newer quinolone antimicrobial agents exhibit increased potency and decreased frequency of spontaneous bacterial resistance in comparison with older analogues such as nalidixic acid. New and published observations on the mechanisms of action of and resistance to ciprofloxacin in Escherichia coli are presented and discussed. Genetic and biochemical studies have identified the A subunit of the essential bacterial enzyme DNA gyrase as a target of ciprofloxacin and other quinolones. For a series of quinolones, inhibition of purified DNA gyrase correlated with antibacterial activity. The bactericidal activity of ciprofloxacin and ofloxacin is, in contrast to that of certain other quinolones, somewhat less affected by rifampin and cell starvation, suggesting the existence of a site of drug action in addition to DNA gyrase. The frequency of selection of spontaneous single-step resistance mutants of E. coli was more than 100-fold lower with ciprofloxacin than with nalidixic acid. Strains highly resistant to ciprofloxacin could, nevertheless, be selected by serial passage on drug-containing agar. Two mutations contributing to this high level of resistance were analyzed. One, designated cfxA, conferred a 16-fold increase in drug resistance and mapped in a location consistent with a gyrA mutation; similar increases in resistance to ciprofloxacin were seen with gyrA mutations selected for resistance to other quinolones. The other mutation, cfxB, conferred pleiotropic resistance to ciprofloxacin, tetracycline, and chloramphenicol and appeared to be an allele of the multiple antibiotic resistance gene marA. The mutation cfxB was associated with a decreased amount of porin outer membrane protein OmpF, suggesting that drug permeation may occur in part through this channel. In summary, the A subunit of DNA gyrase is a target of ciprofloxacin and other quinolones. Ciprofloxacin resistance appears to occur both by mutation in this target and by alteration of drug permeation through the outer membrane of the cell.


Effect of trichosanthin an anti-leukemia protein on normal mouse spleen cells.
Trichosanthin, from Trichosanthes kirilowii is a member of the Cucurbitaceae family. It has been reported to have anti-cancer activity. The effects of Trichosanthin peptides (15 amino acids in length) on ConA stimulated incorporation of 3[H] thymidine into cultured, primary mouse spleen cells and L1210 cells were determined. Both spleen cells and L1210 cells were plated at 7.5 x 10(5) cells/ml in a microtiter plate. Different concentrations of the peptide (0.5, 5, 25, and 50 micrograms/ml) and ConA (1 microgram/ml) were added with serum free media, and half of the samples were labeled with 1 microCi/well of 3[H] thymidine. The additional half of the cell samples were used to determine cell number and % viability. After 24 hours incubation, the N-terminal peptides (amino acid residues #1-15 and 16-30) caused increases in ConA stimulated incorporation of 3[H] thymidine into normal spleen cells at low concentrations of the peptides (5 micrograms/ml). The viability of spleen cells and L1210 cells were not affected by these peptides at 5 micrograms/ml. These N-terminal peptides (#1-15 and 16-30) were tested for in vivo anti-tumor activity. There was a delay of tumor formation in the treated vs control group. The results suggest that N-terminal sequences of trichosanthin have anti-tumor activity.


Extracorporeal membrane oxygenation to cardiopulmonary bypass with a single circuit exposure.
Due to the short supply of donor organs available, many patients decompensate or die while waiting for transplantation. Options for mechanical support for infants and pediatrics with congenital heart disease are limited because of the patient's size and device availability. Extracorporeal membrane oxygenation (ECMO) is the most common means of cardiac and respiratory support for these patients. One of the many indications for ECMO use in cardiac patients is as a bridge to transplantation, with patients being transported to the operating room (OR) on ECMO support. Converting the ECMO circuit to an open cardiopulmonary bypass system in the OR minimizes the patient's exposure to new circuitry, decreases further donor exposures and provides continuous support for patients in cardiac and/or respiratory failure. In addition, the ability to use modified ultrafiltration post-bypass aids in reducing extracellular fluid, increasing the hematocrit and improving hemodynamic stability following an extended duration of ECMO and bypass support. The integrity of the ECMO circuit is maintained and can be converted back to ECMO for support postoperatively if needed.


Planar Chiral 1,3-Disubstituted Ferrocenyl Phosphine Gold(I) Catalysts.
Planar chiral monodentate 1,3-disubstituted ferrocene phosphines inspired on JohnPhos-type ligands have been synthesized and applied to the enantioselective gold(I) catalyzed [4 + 2] cycloaddition of 1,6-arylenynes. Computational studies rationalized the working mode of the catalyst on the folding of the substrate in the chiral environment of the ligand involving attractive noncovalent interactions.


Improved radiolabeling of DOTATOC with trivalent radiometals for clinical application by addition of ethanol.
Typically, metal-based radiopharmaceuticals are synthesized in aqueous solutions with no or low ethanol content. Labeling yields are defined by temperature, period of labeling, amount of precursor, pH etc. As recently observed, radiolabeling yields (RCY) seem to increase in the presence of non-aqueous solvents. Consequently, this effect was investigated systematically using ethanol as non-aqueous solvent (n-as), which is widely utilized in medicine, and DOTATOC as model compound. To determine the impact of ethanol on the radiolabeling efficacy, "standard" labeling conditions of 68Ga-DOTATOC (95-100 °C, 10-15 min, 20-50 μg DOTATOC, aqueous solution), i.e. 10 nmol (2.9 μM, 14.2 μg), were modified in terms of lower temperature (70 °C) to achieve lower RCY (<75 %). From those lower RCY, positive effects of increasing amounts of ethanol (0-40 vol%) could directly be observed. Labeling parameters were finally evaluated in terms of shorter reaction time and lower amount of precursor. To investigate whether the effects observed are also true for other trivalent radiometals, labeling was also performed with 44Sc. For increasing amounts of ethanol, 68Ga-DOTATOC RCY at 70 °C improved significantly. RCY of ~95 % can be achieved within 10 min using 30 vol% ethanol compared to 46 % in the pure aqueous system. If "standard" temperatures of 95 °C are applied, high RCY of 89 % can be achieved within 5 min with much lower amounts of precursor, i.e. even at 0.93 nmol (0.3 μM, 1.3 μg). This also represents significantly increased specific activities. Similar behavior was observed for 44Sc where RCY increase successively with increasing amounts of ethanol. There is clear experimental evidence, that adding more than 20 vol% ethanol to the reaction mixtures significantly improve labeling efficacies. This could be demonstrated for 68Ga-DOTATOC and 44Sc-DOTATOC in terms of temperature, time and concentration of required precursor. Whether this is a principal phenomenon with practical impact on the radiopharmaceutical chemistry of trivalent metals and whether this applies to other non-aqueous solvents as well - and what the physico-chemical reasons are, remains to be studied in more detail. Nevertheless, the effect observed here will improve 68Ga-DOTATOC labeling and may save at least half of the usually applied amount of precursor.


Screening for depression in women with metastatic breast cancer: a comparison of the Beck Depression Inventory Short Form and the Hospital Anxiety and Depression Scale.
To compare two self-report questionnaires for identifying possible depression in women with metastatic breast cancer. We conducted structured psychiatric interviews and administered the Beck Depression Inventory Short Form (BDI-SF) and Hospital Anxiety and Depression Scale (HADS) to 227 women with stage IV breast cancer. The accuracy for identifying DSM-IV-defined major and minor depression was examined. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated and receiver operating characteristic curves plotted. Seventy-four (32.6%) patients satisfied DSM-IV criteria for a depressive disorder. With a cut-off of 4, the BDI-SF had a sensitivity of 0.84, specificity of 0.63, and PPV of 0.52. A cut-off of 11 on the HADS-Depression scale (HADS-D) resulted in sensitivity, specificity, and PPV of 0.16, 0.97, and 0.75, respectively. For major depression alone, the BDI-SF with a cut-off of 5 had excellent sensitivity but poor PPV; the HADS, with a cut-off of 7, had weak sensitivity and PPV. Overall, the two scales perform similarly in identifying major depression, while the BDI-SF is the more useful in screening for DSM-IV major or minor depression categories in this clinical group.


Photochemical Formation of Nitrite and Nitrous Acid (HONO) upon Irradiation of Nitrophenols in Aqueous Solution and in Viscous Secondary Organic Aerosol Proxy.
Irradiated nitrophenols can produce nitrite and nitrous acid (HONO) in bulk aqueous solutions and in viscous aqueous films, simulating the conditions of a high-solute-strength aqueous aerosol, with comparable quantum yields in solution and viscous films (10-5-10-4 in the case of 4-nitrophenol) and overall reaction yields up to 0.3 in solution. The process is particularly important for the para-nitrophenols, possibly because their less sterically hindered nitro groups can be released more easily as nitrite and HONO. The nitrophenols giving the highest photoproduction rates of nitrite and HONO (most notably, 4-nitrophenol and 2-methyl-4-nitrophenol) could significantly contribute to the occurrence of nitrite in aqueous phases in contact with the atmosphere. Interestingly, dew-water evaporation has shown potential to contribute to the gas-phase HONO levels during the morning, which accounts for the possible importance of the studied process.


Acrylamide levels in selected Colombian foods.
Acrylamide (AA) levels in conventional (n = 112) and traditional (n = 43) Colombian foods were analysed by gas chromatography with mass spectrometry (GC/MS) detection. Samples included: infant powdered formula, coffee and chocolate powders, corn snacks, bakery products and tuber-, meat- and vegetable-based foods. There was a wide variability in AA levels among different foods and within different brands of the same food, especially for coffee powder, breakfast cereals biscuits and French fries samples. Among the conventional foods tested, the highest mean AA value was found in bakery products, such as biscuit (1104 µg kg(-1)) and wafer (1449 µg kg(-1)), followed by potato chips (916 µg kg(-1)). On the other hand, among the traditional foods, higher AA amounts were detected in fried platano (2813 µg kg(-1)) and yuca (3755 µg kg(-1)) compared to other products. Interestingly, the arepa, a traditional Colombian bakery product made with corn flour, showed a lower AA content (< 75 µg kg(-1)) when compared with similar bakery products tested, such as soft bread (102-594 µg kg(-1)), which is a made with wheat flour.


Regularized quantile regression for SNP marker estimation of pig growth curves.
Genomic growth curves are generally defined only in terms of population mean; an alternative approach that has not yet been exploited in genomic analyses of growth curves is the Quantile Regression (QR). This methodology allows for the estimation of marker effects at different levels of the variable of interest. We aimed to propose and evaluate a regularized quantile regression for SNP marker effect estimation of pig growth curves, as well as to identify the chromosome regions of the most relevant markers and to estimate the genetic individual weight trajectory over time (genomic growth curve) under different quantiles (levels). The regularized quantile regression (RQR) enabled the discovery, at different levels of interest (quantiles), of the most relevant markers allowing for the identification of QTL regions. We found the same relevant markers simultaneously affecting different growth curve parameters (mature weight and maturity rate): two (ALGA0096701 and ALGA0029483) for RQR(0.2), one (ALGA0096701) for RQR(0.5), and one (ALGA0003761) for RQR(0.8). Three average genomic growth curves were obtained and the behavior was explained by the curve in quantile 0.2, which differed from the others. RQR allowed for the construction of genomic growth curves, which is the key to identifying and selecting the most desirable animals for breeding purposes. Furthermore, the proposed model enabled us to find, at different levels of interest (quantiles), the most relevant markers for each trait (growth curve parameter estimates) and their respective chromosomal positions (identification of new QTL regions for growth curves in pigs). These markers can be exploited under the context of marker assisted selection while aiming to change the shape of pig growth curves.


Intensifying approach to the therapy of patients with constellation of the diseases: chronic obstructive pulmonary disease and osteoarthritis.
Chronic obstructive pulmonary disease (COPD) is one of 21st century. About 210 million people all over the world are suffering with COPD, and annually 3 million people die of it. Under the influence of different factors, such as smoking, air prolusion, evaporation of chemicals, poisoning effect of chemical firings, inflammation processes take place in lungs, and if it is prolonged and take place simultaneously with morphological changes in the lungs, it it provide the de4velopment of the systemic inflammation process. At present systemic inflammation is regarded to be an essential component of COPD pathogeneses capable to become risk factor in developing and progressing multiple complications of the disease. The development of osteoporoses as the basis for the development of osteoarthritis (OA) is often considered one of a great amount of COPD complications and systemic effects. In the course of complex approach to treating patients for COPD, especially in the case when it is accompanied with OA, resolving therapy is more and more often referred to nowadays, namely, to the use of fenspirid hydrochloride. The aim of the article is to depict the results of the study of the effectiveness of fenspirid hydrochloride (EurespalR, ≪Servier≫ France) included in complex therapy in treating patients for COPD accompanied with OA. Hospitalized in the Pulmonology Department of Poltava regional clinical hospital named after N.V. Sklifosovsky served as the bases for the research, the investigation being carried out in the Institute of genetic and immune studies of development of pathology and pharmocogenetics of Ukrainian Higher State Educational Establishment "Ukrainian Medical Stomatological Academy of Poltava". Under investigation there were 33 patients (the average age of them was 54.4±3.1) suffering from exacerbation of COPD (clinic group B-GOPDII), accompanied with OA - basic group. Patients of the basic group were divided into two representative subgroups - A and B. The patients of A subgroup were restricted to basic therapy COPD according to the running protocol, while in B subgroup the basic therapy was accompanied with fenspirid hydrochloride hydrochloride per 80 mg twice a day 12 days running. Check group included 25 practically healthy people of the identical age. Results obtained showed that regress of the illness (cough decreasing) among the patients of the subgroup with COPD accompanied with OA, who were given fenspirid hydrochloride together with the basic therapy, 2.9±0.4 days earlier, dyspnoea 2.3±0.33 comparing to another subgroup ( p<0.05), the quality of the patients' life was getting better, the ability to endue more physical assignment increased. By the end of the treatment the sharpened forced exhalation FEV1level within the A subgroup patients equaled 57.1 ±4.2% (before the treatment it was 53.4±3.9 %), while within the B subgroup patients it became 59.9 ±3.9 (before the treatment it was 53.9±4.0 %). Repayments of bronchial obstruction in both groups became a bit higher- in A subgroup by 3.2±0.7%, and in B subgroup - by 3.6±0.5%. Concentration of IL-1β in blood serum of basic group patients was 14.6 times higher than that of practically healthy people. After the therapy the level of IL-1β within the A subgroup patients became 1.7 times lower (p < 0.01). After the basic therapy being accompanied with fenspirid hydrochloride to B subgroup patients the level of lowering was more vivid, and equelled 2.8 times ( p < 0.001). Decrease of the concentration of other mediators of inflammatory process under the influence of fenspirid hydrochloride was evident in other researches as well. Strong negative correlation ( r = -0.812; p < 0.05) between the level of IL-1β in blood serum of basic group patients and their sharpened forced inhalation/exhalation. Forced expiratory volume (FEV)1 level before the treatment became moderately negative within the patients of A subgroup ( r= - 0.681; p < 0.05) and week within the patients of B subgroup ( r= -0.475; p <0.05). The term of treatment of A subgroup patients was 14.3 ± 0.4 days, and that of B subgroup patients it was a bit less, namely, 12.9 ± 0.5 days. An important result of the therapy with additional use of fenspirid hydrochloride was determining the periods between the case when next COPD exacerbation occurs because it is the frequency of the disease exacerbation that predicts the disease. Within A subgroup this time was 10.3±0.9 months, and within B subgroup it was 15.7±1.1 months. All this made it possible to draw the conclusion that usage of fenspirid hydrochloride hydrochloride in addition to complex therapy essentially reduces the level of IL-1β in blood serum in compereson to the cases when only basic remedy was used, favours reduction of cases and intensity of systemic inflammations associated with increasing the duration of remission within this type/constellation of patients.


Assessment of Gold Nanoparticle-Mediated-Enhanced Hyperthermia Using MR-Guided High-Intensity Focused Ultrasound Ablation Procedure.
High-intensity focused ultrasound (HIFU) has gained increasing popularity as a noninvasive therapeutic procedure to treat solid tumors. However, collateral damage due to the use of high acoustic powers during HIFU procedures remains a challenge. The objective of this study is to assess the utility of using gold nanoparticles (gNPs) during HIFU procedures to locally enhance heating at low powers, thereby reducing the likelihood of collateral damage. Phantoms containing tissue-mimicking material (TMM) and physiologically relevant concentrations (0%, 0.0625%, and 0.125%) of gNPs were fabricated. Sonications at acoustic powers of 10, 15, and 20 W were performed for a duration of 16 s using an MR-HIFU system. Temperature rises and lesion volumes were calculated and compared for phantoms with and without gNPs. For an acoustic power of 10 W, the maximum temperature rise increased by 32% and 43% for gNPs concentrations of 0.0625% and 0.125%, respectively, when compared to the 0% gNPs concentration. For the power of 15 W, a lesion volume of 0, 44.5 ± 7, and 63.4 ± 32 mm3 was calculated for the gNPs concentration of 0%, 0.0625%, and 0.125%, respectively. For a power of 20 W, it was found that the lesion volume doubled and tripled for concentrations of 0.0625% and 0.125% gNPs, respectively, when compared to the concentration of 0% gNPs. We conclude that gNPs have the potential to locally enhance the heating and reduce damage to healthy tissue during tumor ablation using HIFU.


Judgments of idiom familiarity and transparency: a comparison of children and adolescents.
Idioms (e.g., go by the book, keep a straight face) are figurative expressions that frequently occur in the English language. Given the pervasiveness of these expressions, it is important that young people can understand their meanings. Developmental studies have shown that idioms that are higher in familiarity and transparency (e.g., blow off some steam) are generally easier for children and adolescents to understand than those that are less familiar and more opaque (e.g., pull up one's socks). In those studies, judgments of idiom familiarity and transparency were based on the perceptions of individuals who were older than the study participants. In the present study, 11-year-old children (n = 50) and 16-year-old adolescents (n = 50) were asked to judge the familiarity and transparency of a set of 20 idioms. Their comprehension of the same expressions was also examined. The results indicated that the children were less familiar with the idioms and had greater difficulty comprehending them than did the adolescents. However, the children's transparency judgments did not differ from those of the adolescents. For the children, the easiest idioms were also more familiar and transparent than the most difficult expressions. For the adolescents, the easiest idioms were more transparent than the most difficult ones, but the two types did not differ in familiarity. Suggestions are offered for conducting future studies of the development of idiom understanding in youth.


Feasibility of Routine Assessment of Exercise Knowledge and Safety in Youth With Type 1 Diabetes.
This pilot study assessed the feasibility and satisfaction of an electronic clinical tool to survey management of exercise in youth with type 1 diabetes (T1DM) for use in an outpatient diabetes clinic setting. Fifty youth with T1DM were recruited (ages, 10-18 years; mean ± SD, 14.8 ± 2.4) and 11 diabetes providers. Prior to a clinic visit and with an electronic tablet, participants completed the Type 1 Diabetes Report of Exercise Practices Survey, which included 9 primary exercise management guidelines. Responses were flagged if contrary to guidelines, and automated individualized reports with personalized evidence-based recommendations were produced for providers prior to seeing the patient. Postclinic assessment surveys were completed by patients and providers. Out of the 9 guidelines, a mean of 4 ± 0.9 responses per patient were flagged as potentially unsafe. Ninety-one percent of providers took <10 minutes to review and discuss the report with their patients. Ninety-one percent of providers rated the tool as highly useful in facilitating patient education regarding exercise guidelines at that clinic visit. Fifty-six percent of youth rated the tool highly when asked whether its use altered their planned behavior around exercise. When participants were asked if such a tool should be used routinely in diabetes clinic, 64% of provider responses and 60% of patient responses were highly positive. This electronic tool identified deficits in exercise management in youth with T1DM and improved education in the clinic visit regarding exercise, and a majority felt it feasible and desirable to include in routine outpatient diabetes care.


Determinants of peritoneal solute transport rates in newly started nondiabetic peritoneal dialysis patients.
An overrepresentation of a fast peritoneal transport status in new peritoneal dialysis (PD) patients with extensive comorbidity has been reported in some studies. High mass transfer area coefficients (MTACs) of low MW solutes suggest the presence of a large effective peritoneal surface area. The mechanism is unknown. It might include comorbidity, chronic inflammation, or an effect of mesothelial cell mass on peritoneal transport by the production of vasoactive substances. To investigate their relative importance in early PD, peritoneal permeability characteristics in incident PD patients were analyzed for relationships with comorbidity, serum concentrations of inflammatory markers, and products of the mesothelial cells that can be detected in dialysate. A cross-sectional study. A university hospital. 46 patients who fulfilled the following inclusion criteria were analyzed: a standard peritoneal permeability analysis (SPA) within 6 months after the start of PD, no peritonitis prior to the SPA, older than 18 years, and without diabetes mellitus as a primary renal disease. The patients were divided into tertiles based on the MTAC creatinine: slow, medium, and fast transport groups. The Davies comorbidity score was used to assess comorbidity. Serum and dialysate samples obtained during the SPA were used to determine hyaluronan, interleukin (IL)-6, vascular endothelial growth factor (VEGF), and cancer antigen 125 (CA125). The dialysate concentrations of these substances were expressed as their dialysate appearance rates. No significant differences were present in the three transport groups for comorbidity, serum concentrations of inflammatory markers, or serum VEGF. Interleukin-6 and VEGF concentration attributed to local VEGF production were not different between the tertiles. Levels of VEGF were higher in the medium transport group compared to the slow transport group (p = 0.02); CA125 was higher in the fast transport group compared to the medium transport group (p= 0.01). When analyzed as continuous variables, MTAC creatinine was related to VEGF (r= 0.33, p < 0.05) and CA125 (r= 0.41, p = 0.03). In linear regression analysis, VEGF influenced the association between CA125 and MTAC creatinine; IL-6 weakened this association only marginally. A fast peritoneal transport status in incident nondiabetic PD patients was not related to comorbidity. The relationships found between VEGF, CA125, and MTAC creatinine may suggest a role of VEGF in the regulation of the vascular peritoneal surface area, possibly already before structural abnormalities have developed. Our analyses are consistent with the hypothesis that mesothelial cell mass is an important determinant of the peritoneal transport status in incident nondiabetic PD patients without previous peritonitis. Of the many potential mediators produced by mesothelial cells, VEGF was more important than the inflammation marker IL-6.


Evaluation of Clonorchis sinensis recombinant 7-kilodalton antigen for serodiagnosis of clonorchiasis.
The diagnostic applicability of the Clonorchis sinensis recombinant 7-kDa protein was evaluated. In enzyme-linked immunosorbent assays and immunoblots, the protein showed high sensitivities (81.3 and 71.9%, respectively) and specificities (92.6 and 89.7%, respectively) for sera obtained from various helminthic infections. Some paragonimiasis sera showed cross-reactions. The antigen might be valuable in the serodiagnosis of human clonorchiasis.


Extrarenal angiomyolipoma with melanocytic and hibernoma-like features.
Angiomyolipoma is a tumor commonly occurring in the kidney, but occasionally found in extrarenal sites. Retroperitoneal angiomyolipoma with unusual features presenting in a 39 year old woman with hypertension is reported in this paper. Tumor fat was inconspicuous, and present largely as hibernoma-like microvesicular lipid. Tumor cells also demonstrated positivity for HMB-45 and S-100 protein, and by electron microscopy showed occasional cytoplasmic striated granules indistinguishable from stage II premelanosomes. However, electron microscopy and immunocytochemistry also confirmed the presence of a substantial myogenous component in the tumor, establishing the diagnosis of angiomyolipoma. The implications of these findings, and the role of immunocytochemistry and electron microscopy in the diagnosis of this tumor are discussed.


[Tumor lysis syndrome after transarterial embolization for hepatocellular carcinoma].
A man in his 70's was admitted to our hospital for treatment of a huge hepatocellular carcinoma (HCC) by transcatheter hepatic arterial embolization (TAE). After treatment, anuria occurred, and laboratory examinations revealed a diagnosis of tumor lysis syndrome (TLS). He underwent conservative therapy including hemodialysis, resulting in complete remission of TLS. On the other hand, poor hepatic functional reserve was seen temporarily. After conservative therapy, biochemical markers returned dramatically. TLS is a group of metabolic complications in cancer therapy. It may occur in highly sensitive tumors, resulting from a rapid release of cytoplasmic degradation products of malignant cells. Generally it is rare in the treatment of solid tumors. In the case of TAE for huge HCC, we should keep the possibility of TLS in mind.


Relative tolerance of an enzymatic molten globule and its thermostable counterpart to point mutation.
Enzyme structures reflect the complex interplay between the free energy of unfolding (DeltaG) and catalytic efficiency. Consequently, the effects of point mutations on structure, stability, and function are difficult to predict. It has been proposed that the mutational robustness of homologous enzymes correlates with a higher initial DeltaG. To examine this issue, we compared the tolerance of a natural thermostable chorismate mutase and an engineered molten globular variant to targeted mutation. These mutases possess similar sequence, structure, and catalytic efficiency but dramatically different DeltaG values. We find that analogous point mutations can have widely divergent effects on catalytic activity in these scaffolds. In a set of five rationally designed single-amino acid changes, the thermostable scaffold suffers activity losses ranging from 50-fold smaller, for an aspartate-to-glycine substitution at the active site, to 2-fold greater, for a phenylalanine-to-tryptophan substitution in the hydrophobic core, versus that of the molten globular scaffold. However, biophysical characterization indicates that the variations in catalytic efficiency are not caused by losses of either secondary structural integrity or thermodynamic stability. Rather, the activity differences between variant pairs are very much context-dependent and likely stem from subtle changes in the fine structure of the active site. Thus, in many cases, it may be more productive to focus on changes in local conformation than on global stability when attempting to understand and predict how enzymes respond to point mutations.


Transumbilical Single-Site Multiport Laparoscopic Pyeloplasty for Children with Ureteropelvic Junction Obstruction in China: A Multicenter Study.
Transumbilical single-site multiport laparoscopic pyeloplasty (TSMLP) for children with ureteropelvic junction obstruction (UPJO) has become feasible and popular recently. The purpose of this study was to evaluate the safety and efficacy of TSMLP for pediatric UPJO in a large multicenter series. Medical records of consecutive patients who underwent TSMLP for pediatric UPJO in six academic institutions between June 2010 and May 2015 were retrospectively analyzed. The data of ultrasound, magnetic resonance urography, and diuretic renogram using 99Tc-diethylene triamine pentaacetic acid scan were collected during preoperative and postoperative periods. A total of 704 patients (750 kidneys) with UPJO who underwent TSMLP were recruited for this study. Of these patients, there were no significant differences in demographics and clinical presentation of the patients among the six centers. The operative time of all patients decreased significantly with time. The earlier the beginning of the operation, such as cohort A, B, and C, the longer the learning curve has been. Of these 704 patients, there were 60 (8.11%) postoperative minor complications during the postoperative hospitalization period, and all minor postoperative complications were cured by observation or drugs. There were 14 (1.99%) major postoperative complications, and all major complications were cured by minimally invasive surgery. No additional complications were encountered during the follow-up of 2.1 years (mean, ranged 1 year to 4 years). Success rate of TSMLP are more than 95% among six centers. We reported a multi-institutional series of TSMLP in children with UPJO. Our findings suggest that TSMLP represents a feasible treatment option for UPJO by offering reliable outcomes, low postoperative complications and high success rates.


Fc- and non-Fc-mediated phagocytosis of Borrelia burgdorferi by macrophages.
The Fc receptor (FcR) for immunoglobulin has been assigned a major role in the ingestion of Borrelia burgdorferi, the Lyme disease spirochete, by macrophages. Yet macrophages readily take up and kill B. burgdorferi that have not been opsonized. By use of doubly-labeled macrophages infected with spirochetes and analyzed by confocal fluorescence microscopy, simultaneous localization of both FcR and spirochetes (opsonized and unopsonized) was quantified. After infection with unopsonized spirochetes, bacterial surface antigen and the FcR remained distinct, confirming the expectation that unopsonized uptake of B. burgdorferi is largely independent of the FcR. A similar lack of colocalization was seen when opsonized spirochetes were ingested by macrophages whose FcRs were sequestered by an immune complex-coated substrate. Furthermore, comparable efficiency of uptake was observed whether or not the FcR was engaged.


Differences in the phosphate oxygen requirements for self-cleavage by the extended and prototypical hammerhead forms.
The hammerhead self-cleaving motif occurs in a variety of RNAs that infect plants and consists of three non-conserved helices connected by a highly conserved central core. A variant hammerhead, called the extended hammerhead, is found in satellite 2 transcripts from a variety of caudate amphibians. The extended hammerhead has the same core as the prototypical hammerhead, but has unusually conserved sequence and structural elements in its peripheral helices. Here we present the results of a thiophosphate substitution interference analysis of the pro-Rp phosphate oxygen requirements in the two hammerhead forms. Five pro-Rp phosphate oxygens, all in the central core, were found to be important for self-cleavage by the prototypical hammerhead. A similar set of core positions were important for self-cleavage by the extended hammerhead, but five non-core positions were also found to be important. Thiosubstitution at one of these positions had the most severe effect on self-cleavage observed in this analysis. Mn2+ did not alleviate this negative effect, indicating that this position was not part of a divalent cation binding site. We propose that novel tertiary interactions in the extended hammerhead help form the same catalytic core structure as that used by the prototypical plant virus hammerhead.


Modeling linear and cyclic PKS intermediates through atom replacement.
The mechanistic details of many polyketide synthases (PKSs) remain elusive due to the instability of transient intermediates that are not accessible via conventional methods. Here we report an atom replacement strategy that enables the rapid preparation of polyketone surrogates by selective atom replacement, thereby providing key substrate mimetics for detailed mechanistic evaluations. Polyketone mimetics are positioned on the actinorhodin acyl carrier protein (actACP) to probe the underpinnings of substrate association upon nascent chain elongation and processivity. Protein NMR is used to visualize substrate interaction with the actACP, where a tetraketide substrate is shown not to bind within the protein, while heptaketide and octaketide substrates show strong association between helix II and IV. To examine the later cyclization stages, we extended this strategy to prepare stabilized cyclic intermediates and evaluate their binding by the actACP. Elongated monocyclic mimics show much longer residence time within actACP than shortened analogs. Taken together, these observations suggest ACP-substrate association occurs both before and after ketoreductase action upon the fully elongated polyketone, indicating a key role played by the ACP within PKS timing and processivity. These atom replacement mimetics offer new tools to study protein and substrate interactions and are applicable to a wide variety of PKSs.


Optimal inventory policy within hospital space constraints.
The materials management group at any hospital is responsible for ensuring that their inventory policies provide a good service in delivering products. The group also needs to be aware of their own costs for distribution, in terms of the frequency of delivery. With future changes to the hospital's infrastructure, function and size, the group require that these policies are reviewed and prepared for the changes taking place. For this, inventory policy models need to be built and used to anticipate the effect of these changes. Due to the importance of many products, high service levels are essential, yet there are often space and delivery constraints, limiting the amount of stock which can be held and delivered at each location. We present in this paper a new constraint-based model for determining optimal stock levels for all products at a storage location, with restrictions on space, delivery and criticality of items taken into account. We validate this model on sterile and bulk items in a real-life setting of an intensive care unit within Cork University Hospital, Ireland.


Hyperinflammation and derangement of renin-angiotensin-aldosterone system in COVID-19: A novel hypothesis for clinically suspected hypercoagulopathy and microvascular immunothrombosis.
Early clinical evidence suggests that severe cases of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are frequently characterized by hyperinflammation, imbalance of renin-angiotensin-aldosterone system, and a particular form of vasculopathy, thrombotic microangiopathy, and intravascular coagulopathy. In this paper, we present an immunothrombosis model of COVID-19. We discuss the underlying pathogenesis and the interaction between multiple systems, resulting in propagation of immunothrombosis, which through investigation in the coming weeks, may lead to both an improved understanding of COVID-19 pathophysiology and identification of innovative and efficient therapeutic targets to reverse the otherwise unfavorable clinical outcome of many of these patients.


Endoscopic Endonasal Approach for Tuberculum Sellae Meningioma: 2-Dimensional Operative Video.
Ideal indications for tuberculum sellae meningiomas (TSM) removal through endoscopic endonasal approach (EEA) are midline tumors (<3.5 cm), possibly with no optic canal invasion and no vessels encasement. The EEA is favored by a wide tuberculm sellae (TS) angle and a deep sella at the sphenoid sinus (SS). 1 Adequate removal of paranasal structures provides a wider surgical corridor ensuring exposure at the suprasellar area and safe instruments manuevrability. 2. The endoscopic transtuberculum transplanum approach allows for wide suprasellar intradural exposure. 3 Removal of the supraoptic recess (SOR) provides further lateral extension over the planum sphenoidale (PS) and proper management of dural involvement at the optic canal. 4. The patients have consented to the procedure. Bone removal starts at the upper sella and TS and is extended anteriorly over the PS and laterally, upon needs, at the SORs. On dural opening, tumor devascularization, dedressing, debulking, and dissection are run. Skull base reconstruction is performed using the 3F technique. 5. In those cases with vessel encasement, possibility of achieving total resection has to be balanced with risk of vascular injury. 6 Optic canal dural invasion precludes tumor total removal; however, bony decompression is maximal using the EEA. Concerning postoperative cerebrospinal fluid fistula, nowadays the rates have dropped to <2%. A wider skull base osteodural opening allows for the removal of selected meningiomas extending to the PS and cribriform plate.


On the flow dependency of the electrical conductivity of blood.
Experiments presented in the literature show that the electrical conductivity of flowing blood depends on flow velocity. The aim of this study is to extend the Maxwell-Fricke theory, developed for a dilute suspension of ellipsoidal particles in an electrolyte, to explain this flow dependency of the conductivity of blood for stationary laminar flow in a rigid cylindrical tube. Furthermore, these theoretical results are compared to earlier published measurement results. To develop the theory, we assumed that blood is a Newtonian fluid and that red blood cells can be represented by oblate ellipsoids. If blood flows through a cylindrical tube, shear stresses will deform and align the red blood cells with one of their long axes aligned parallel to the stream lines. The pathway of a low-frequency (< 1 MHz) alternating electrical current will be altered by this orientation and deformation of the red blood cells. Consequently, the electrical conductivity in the flow direction of blood increases. The theoretically predicted flow dependency of the conductivity of blood corresponds well with experimental results. This theoretical study shows that red blood cell orientation and deformation can explain quantitatively the flow dependency of blood conductivity.


Global overexpression of divalent metal transporter 1 delays crocidolite-induced mesothelial carcinogenesis in male mice.
Exposure to asbestos fiber is central to mesothelial carcinogenesis, for which iron overload in or near mesothelial cells is a key pathogenic mechanism. Alternatively, iron chelation therapy with deferasirox or regular phlebotomy was significantly preventive against crocidolite-induced mesothelial carcinogenesis in rats. However, the role of iron transporters during asbestos-induced carcinogenesis remains elusive. Here, we studied the role of divalent metal transporter 1 (DMT1; Slc11a2), which is a Fe(II) transporter, that is present not only on the apical plasma membrane of duodenal cells but also on the lysosomal membrane of every cell, in crocidolite-induced mesothelial carcinogenesis using DMT1 transgenic (DMT1Tg) mice. DMT1Tg mice show mucosal block of iron absorption without cancer susceptibility under normal diet. We unexpectedly found that superoxide production was significantly decreased upon stimulation with crocidolite both in neutrophils and macrophages of DMT1Tg mice, and the macrophage surface revealed higher iron content 1 h after contact with crocidolite. Intraperitoneal injection of 3 mg crocidolite ultimately induced malignant mesothelioma in ∼50% of both wild-type and DMT1Tg mice (23/47 and 14/28, respectively); this effect was marginally (p = 0.069) delayed in DMT1Tg mice, promoting survival. The promotional effect of nitrilotriacetic acid was limited, and the liver showed significantly higher iron content both in DMT1Tg mice and after crocidolite exposure. The results indicate that global DMT1 overexpression causes decreased superoxide generation upon stimulation in inflammatory cells, which presumably delayed the promotional stage of crocidolite-induced mesothelial carcinogenesis. DMT1Tg mice with low-stamina inflammatory cells may be helpful to evaluate the involvement of inflammation in various pathologies.


Thrombin stimulates dissociation and induction of HSP27 via p38 MAPK in vascular smooth muscle cells.
We investigated the effects of thrombin on the induction of heat shock proteins (HSP) 70 and 27, and the mechanism behind the induction in aortic smooth muscle A10 cells. Thrombin increased the level of HSP27 but had little effect on the level of HSP70. Thrombin stimulated the accumulation of HSP27 dose dependently between 0.01 and 1 U/ml and cycloheximide reduced the accumulation. Thrombin stimulated an increase in the level of HSP27 mRNA and actinomycin D suppressed the thrombin-increased mRNA level. Thrombin induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK). The HSP27 accumulation by thrombin was reduced by SB-203580 and PD-169316 but not by SB-202474. SB-203580 and PD-169316 suppressed the thrombin-induced phosphorylation of p38 MAPK. SB-203580 reduced the thrombin-increased level of HSP27 mRNA. Dissociation of the aggregated HSP27 to the dissociated HSP27 was induced by thrombin. Dissociation was inhibited by SB-203580. Thrombin induced the phosphorylation of HSP27 and the phosphorylation was suppressed by SB-203580. These results indicate that thrombin stimulates not only the dissociation of HSP27 but also the induction of HSP27 via p38 MAPK activation in aortic smooth muscle cells.


Nucleotide sequence and transcription start point of the phosphoglycerate transporter gene of Salmonella typhimurium.
We identified the phosphoglycerate transporter gene of Salmonella typhimurium and its polypeptide product and determined the nucleotide sequence of the gene. The predicted translation product was a protein of 406 amino acid residues and was extremely hydrophobic, a feature that is consistent with its role in membrane transport. Hydropathy analysis suggested that there are eight transmembrane segments of at least 20 amino acid residues for the protein. The transcription start point was mapped to lie at position -44 relative to the putative translational initiation start point. Comparison of PgtP with UhpT and GlpT, the membrane-bound proteins involved in the transport of hexose-6-phosphate and glycerol-3-phosphate, respectively, revealed a very high degree of amino acid sequence similarity among them, reflecting not only similar structures and functions among these polypeptides but also a common evolutionary origin for them.


Molecular mechanisms underlying hypothermia-induced neuroprotection.
Stroke is a dynamic event in the brain involving heterogeneous cells. There is now compelling clinical evidence that prolonged, moderate cerebral hypothermia initiated within a few hours after severe ischemia can reduce subsequent neuronal death and improve behavioral recovery. The neuroprotective role of hypothermia is also well established in experimental animals. However, the mechanism of hypothermic neuroprotection remains unclear, although, presumably involves the ability of hypothermia to suppress a broad range of injurious factors. In this paper, we addressed this issue by utilizing comprehensive gene and protein expression analyses of ischemic rat brains. To predict precise target molecules, we took advantage of the therapeutic time window and duration of hypothermia necessary to exert neuroprotective effects. We proposed that hypothermia contributes to protect neuroinflammation, and identified candidate molecules such as MIP-3α and Hsp70 that warrant further investigation as targets for therapeutic drugs acting as "hypothermia-like neuroprotectants."


The economic burden of rotavirus infection in South Korea from 2009 to 2012.
Rotavirus is a common cause of diarrhea worldwide, and vaccination prevents rotaviral gastroenteritis. Since the rotavirus vaccine was introduced in Korea in 2007, the prevalence of rotaviral gastroenteritis has decreased. However, little is known on the economic burden of rotavirus infection and its variations in Korea. Here, we estimated the economic costs of rotavirus infection from 2009 to 2012 using nationwide data from the National Health Insurance Service (NHIS) claims. Socioeconomic costs were subdivided into direct and indirect and measured with a prevalence-based approach. Costs were converted from Won to United States dollars (US$). The number of children <5 years old infected with rotavirus decreased from 21,437 to 10,295 during the study period, representing a decrease in prevalence from 947 to 443 per 100,000. The sum of direct and indirect costs also decreased, from $17.3 million to $9.6 million, and the days of admission decreased from 76,000 to 38,000. However, per capita expenditures slightly increased, from $809 to $934. Thus, the economic burden of rotavirus infection decreased after implementation of rotavirus vaccination. Including the vaccine as part of the national essential vaccination program could reduce the prevalence of and economic loss from rotavirus infection in Korea.


Inhaled corticosteroids and the increased risk of pneumonia.
Recently it has been suggested that there is a causal association between the use of inhaled corticosteroids (ICSs) and the risk of developing pneumonia in patients with chronic obstructive pulmonary disease (COPD). An increased risk of pneumonia associated with ICS use has been seen in trials with different design, different study populations and with evidence of a dose-response relationship. However, as none of these clinical trials were originally designed to assess pneumonia risk, radiographic confirmation of pneumonia was not always obtained. The extent to which pneumonia events have been confounded with acute exacerbations of COPD is unclear. As increased pneumonia events were not associated with increased mortality it remains unclear what the clinical significance of these findings are. Further complicating the association between ICSs and pneumonia is that meta-analyses restricted to budesonide trials have not shown an increased risk of pneumonia, and no association has been seen in patients with asthma. A number of mechanisms by which ICSs could increase the risk of pneumonia have been proposed, principally related to their immunosuppressive effect. Well-designed clinical trials with predefined endpoints and objective pneumonia definitions are needed before the real risk of pneumonia conferred by ICSs can be established. In the meantime, it seems reasonable to reduce ICSs given to COPD patients to the lowest effective doses, reduce the risk in individual patients by ensuring appropriate vaccination and to be vigilant for the possibility of pneumonia in patients with COPD on ICSs as they largely overlap with those of an acute exacerbation.


Neural Axis Abnormalities in Patients With Adolescent Idiopathic Scoliosis: Is Routine Magnetic Resonance Imaging Indicated Irrespective of Curve Severity?
Magnetic resonance imaging (MRI)-verified neural axis abnormalities (NAAs) have been described in adolescent idiopathic scoliosis (AIS), and several risk factors have been associated with the presence of NAAs in AIS patients. However, the clinical significance of these findings is unclear. The purpose of the present study was to determine the prevalence of NAAs in a large consecutive cohort of AIS patients and to evaluate the clinical significance of previously proposed risk factors. We prospectively included AIS patients referred to a tertiary facility for evaluation. Full-spine MRI scans were performed on all included patients irrespective of curve magnitude or proposed treatment modality. MRI scans were prospectively analyzed by a neuroradiologist and the pathologic findings were confirmed by a second independent radiologist. NAA was observed in 34 of the 381 patients (8.9%): 32 patients had a syrinx, 1 patient had an arachnoid cyst, and 1 patient had a Chiari malformation. Four patients were referred for a neurosurgical evaluation but none received any neurosurgical treatment. No statistically significant difference was observed between the NAA and non-NAA groups in terms of sex, major curve size, thoracic kyphosis, left thoracic curve, curve convexity, curve progression, or level of pain (p>0.05). In this prospective study examining the risk factors for NAA in AIS patients, we found that previously proposed risk factors could not predict the MRI outcomes. The finding of an NAA had no clinical implications and we do not support MRI scans as a routine diagnostic modality in all AIS patients.


Capillary isoelectric focusing with laser-induced fluorescence whole column imaging detection as a tool to monitor reactions of proteins.
Capillary isoelectric focusing (CIEF) with laser-induced fluorescence (LIF) whole column imaging detection (WCID) has the characteristics of high resolution, high speed and high sensitivity for separation of amphoteric biomolecules. These features enable a CIEF-LIF-WCID system to monitor the dynamic process of a protein reaction. The reaction can be a physical change or a chemical reaction, provided that the kinetics of the reaction is slower than the focusing speed or that the intermediates involved have long enough life-span compared to the analysis time. The processes of denaturation (a physical reaction), reduction and carbamylation (both chemical reactions) were dynamically monitored. The CIEF profiles at successive reaction times clearly displayed the formation of different products at different stages. At incomplete denaturation, intermediates with higher apparent pI values relative to the products at complete denaturation were detected. Carbamylation products of a protein were detected when the protein reacted with a urea solution that had prepared three months earlier, exhibiting gradually decreased pI values. Mechanisms involved in these reactions were rationalized. A combined mechanism of denaturation and reduction was suggested to explain the denaturing process under high concentrations of urea. Potential applications and critical factors to manipulate these reactions were also discussed.


Bacteria-Activated Theranostic Nanoprobes against Methicillin-Resistant Staphylococcus aureus Infection.
Despite numerous advanced imaging and sterilization techniques available nowadays, the sensitive in vivo diagnosis and complete elimination of drug-resistant bacterial infections remain big challenges. Here we report a strategy to design activatable theranostic nanoprobes against methicillin-resistant Staphylococcus aureus (MRSA) infections. This probe is based on silica nanoparticles coated with vancomycin-modified polyelectrolyte-cypate complexes (SiO2-Cy-Van), which is activated by an interesting phenomenon of bacteria-responsive dissociation of the polyelectrolyte from silica nanoparticles. Due to the aggregation of hydrophobic cypate fluorophores on silica nanoparticles to induce ground-state quenching, the SiO2-Cy-Van nanoprobes are nonfluorescent in aqueous environments. We demonstrate that MRSA can effectively pull out the vancomycin-modified polyelectrolyte-cypate complexes from silica nanoparticles and draw them onto their own surface, changing the state of cypate from off (aggregation) to on (disaggregation) and leading to in vitro MRSA-activated near-infrared fluorescence (NIRF) and photothermal elimination involving bacterial cell wall and membrane disruption. In vivo experiments show that this de novo-designed nanoprobe can selectively enable rapid (4 h postinjection) NIRF imaging with high sensitivity (105 colony-forming units) and efficient photothermal therapy (PTT) of MRSA infections in mice. Remarkably, the SiO2-Cy-Van nanoprobes can also afford a long-term tracking (16 days) of the development of MRSA infections, allowing real-time estimation of bacterial load in infected tissues and further providing a possible way to monitor the efficacy of antimicrobial treatment. The strategy of bacteria-activated polyelectrolyte dissociation from nanoparticles proposed in this work could also be used as a general method for the design and fabrication of bacteria-responsive functional nanomaterials that offer possibilities to combat drug-resistant bacterial infections.


Design, Characterization and Antimicrobial Activity of Novel Antimicrobial Peptides from Temporin-Pta.
A new approach is applied to the design and study of the antibacterial activity of novel Temporin-Pta peptides. Using Temporin-Pta as a template, together with spiral structure domain breaking and amino acid residue substitution principles, antibacterial peptides are reformed to create new antibacterial peptides. The broth dilution analysis method was used to determine the bacteriostatic effect of the new Temporin-Pta structures, and the hemolytic effect and protease stability of the new peptides were studied. Results showed that the modified antibacterial peptide HX-12A has higher inhibitory effects of active protease stability on E. coli and other bacteria and the hemolytic ability is below 5%, thus achieving successful new Temporin-Pta transformations. It is also shown that the corresponding bacteriostatic effects of these antibacterial peptides are closely related to the differences in structure and composition. This method can improve the biological activity of the antibacterial peptide and drug resistance that is normally difficult to achieve. The present study provides a good theoretical basis for further research on antimicrobial peptide structures and functions.


Delayed Visual Feedback and Behavior.
By means of video-tape recording the visual presentation of a person's behavior as he carries out some task, can be delayed in such a way that the individual sees what he is doing a short time after he has done it. The effects of this delay of visual feedback on a variety of simple visual-motor tasks are found to be both marked and deleterious, and in some respects similar to the effects of delayed auditory feedback on speech and motor tasks.


High spatial resolution and speed in MRSI.
The in vivo applications of magnetic resonance spectroscopic imaging (MRSI) have expanded significantly over the past 10 years and have reached the point where clinical trials are underway for a number of different diseases. One of the limiting factors in the widespread use of this technology has been the lack of widely available tools for obtaining data which are localized to sufficiently small tissue volumes to make an impact upon diagnosis and treatment planning. This is especially difficult within the timeframe of a clinical MR examination, which requires that both anatomic and metabolic data are acquired and processed. Recent advances in the hardware and software associated with clinical scanners have provided the potential for improvements in the spatial and time resolution of imaging and spectral data. The two areas which hold the most promise in terms of MRSI data are the use of phased array coils and the implementation of echo planar k-space sampling techniques. These could have immediate impact for 1H MRSI and may prove valuable for future applications of 31P MRSI.


Effect of calmidazolium on Ca(+2) movement and proliferation in human osteosarcoma cells.
In human MG63 osteosarcoma cells, the effect of calmidazolium on [Ca(2+)](i) and proliferation was explored using fura-2 and ELISA, respectively. Calmidazolium, at concentrations greater than 0.1 micromol/L, caused a rapid increase in [Ca(2+)](i) in a concentration-dependent manner (EC(50) = 0.5 micromol/L). The calmidazolium-induced [Ca(2+)](i) increase was reduced by 66% by removal of extracellular Ca(2+). In Ca(2+)-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2+)-ATPase, caused a monophasic increase in [Ca(2+)](i), after which the effect of calmidazolium to increase [Ca(2+)](i) was completely inhibited. U73122, an inhibitor of phospholipase C (PLC), abolished histamine (but not calmidazolium)-induced increases in [Ca(2+)](i). Pretreatment with phorbol 12-myristate 13-acetate to activate protein kinase C inhibited the calmidazolium-induced increase in [Ca(2+)](i) in Ca(2+)-containing medium by 47%. Separately, it was found that overnight treatment with 2-10 micromol/L calmidazolium inhibited cell proliferation in a concentration-dependent manner. These results suggest that calmidazolium increases [Ca(2+)](i) by stimulating extracellular Ca(2+) influx and also by causing release of intracellular Ca(2+) from the endoplasmic reticulum in a PLC-independent manner. Calmidazolium may be cytotoxic to osteosarcoma cells.


The significance of substance P in physiological and malignant haematopoiesis.
The role of substance P (SP) in physiological haematopoiesis is well established. However, it also seems to be important in the neoplastic transformation of bone marrow, leading to the development of acute leukaemia in children, and also metastases to bone marrow of solid tumours (particularly neuroblastoma and breast cancer) in early stages of these diseases. This review summarises the available data on SP involvement in both processes. In the future, SP antagonists may be used as anti-neoplastic drugs, for example by direct or indirect blocking of tumour cell proliferation through inhibition of growth factor production and interleukin-1b synthesis.


[Late results of our treatment method in calcaneus fractures].
The authors treated their patients, who had fractures of the calcaneus body in association with dislocation, by means of a new method: repositioning was effected by means of a special apparatus, retention via percutaneous screw osteosynthesis. Previously, they had used a Kirschner wire drilled from the tuber calcanei. The types of fracture differ very widely; the authors subdivide them into three groups, taking into consideration the involvement of the posterior talocalcaneal joint surfaces. The patients were subsequently followed up, and the results of 182 fractures of the calcaneum were evaluated, taking numerous different aspects into consideration. The authors were thus able to establish that the results of the treatment are greatly improved by accurate repositioning followed by percutaneous screw osteosynthesis.


The Hospital for the Ruptured and Crippled renamed the Hospital for Special Surgery 1940; the war years 1941-1945.
In 1939, the 75th anniversary program marking the founding of the Hospital for the Ruptured and Crippled (R & C), the oldest orthopaedic hospital in the nation, was held at the hospital site in New York City. Dr. Philip D. Wilson, Surgeon-in-Chief since 1935, used this event to mark the return of the hospital to its leadership role in the country. When the Hospital for the Ruptured and Crippled first opened its doors on May 1, 1863, the name of the hospital was not unusual; it described the type of patients treated. In 1940, the Board of Managers with guidance from Dr. Wilson changed the name to the Hospital for Special Surgery (HSS). In 1941, with Britain engaged in a European war, Dr. Wilson felt there was a need for the Americans to support the British. He personally organized the American Hospital in Britain, a privately funded voluntary unit, to help care for the wounded. After the United States actually entered World War II in December 1941, HSS quickly organized support at all levels with a significant number of professional and auxiliary staff, eventually enlisting in the military. Even with such staff turnover, the hospital continued to function under Dr. Wilson's leadership. After the war ended in 1945, Wilson forged ahead to further restore HSS as a leader in musculoskeletal medicine and surgery.


Alternative RNA splicing complexes containing the scaffold attachment factor SAFB2.
The scaffold attachment factor SAFB1 and its recently discovered homologue SAFB2 might provide an important link between pre-mRNA splicing, intracellular signalling and transcription. Using novel mono-specific antisera, we found endogenous SAFB2 protein has a different spatial distribution from SAFB1 within the nucleus where it is found in much larger nuclear complexes (up to 670 kDa in size), and a distinct pattern of expression in adult human testis. By contrast, SAFB1 protein predominantly exists either as smaller complexes or as a monomeric protein. Our results suggest stable core complexes containing components comprised of SAFB1, SAFB2 and the RNA binding proteins Sam68 and hnRNPG exist in parallel with free SAFB1 protein. We found that SAFB2 protein, like SAFB1, acts as a negative regulator of a tra2beta variable exon. Despite showing an involvement in splicing, we detected no stable interaction between SAFB proteins and SR or SR-related splicing regulators, although these were also found in stable higher molecular mass complexes. Each of the detected alternative splicing regulator complexes exists independently of intact nucleic acids, suggesting they might be pre-assembled and recruited to nascent transcripts as modules to facilitate alternative splicing, and/or they represent nuclear storage compartments from which active proteins are recruited.


[The triple test].
Until the late 80s advanced maternal age was the main indication for prenatal chromosomal diagnosis. The triple test has introduced a noninvasive method for all women to determine the risk of chromosomal abnormality. Not only women aged over 35 years, but also those less than 35 years of age may benefit from the triple test. An exactly performed triple test will allow a diagnosis in 70% of all cases with trisomy 21. Additionally, a positive triple test will be found in 9% of all screened women. 1-2% of the women with a positive triple test will exhibit a fetus with trisomy 21. A false-negative result will be found in 0.1%. Beside trisomy 21, the triple test allows also the diagnosis of pregnancies with a high risk of trisomy 18 and Turner syndrome. The value of the triple test is mainly determined by the quality of the laboratory and the exactness of the determination of the gestational age, which is done mainly by means of ultrasound. Ultrasound investigation also provides information about structural abnormalities. In future the triple test will increase in accuracy and it will be performed in the first trimester.


Unlocking the Potential of Immunotherapy in Cardiovascular Disease: A Comprehensive Review of Applications and Future Directions.
Immunotherapy has emerged as a pioneering therapeutic approach that harnesses the immune system's abilities to combat diseases, particularly in the field of oncology where it has led to significant advancements. However, despite its significant impact in the field of oncology, the potential of immunotherapy in the context of cardiovascular disease (CVD) has not been thoroughly investigated. The purpose of this narrative review is to address the existing knowledge and potential uses of immunotherapy in the field of cardiovascular disease (CVD), with the intention of filling the existing gap in understanding. Furthermore, the review thoroughly examines the future prospects of this swiftly advancing field, providing insights into the aspects that necessitate further investigation and addressing the forthcoming challenges. The review is organized into four distinct sections to enhance comprehension. The first section introduces immunotherapy, presenting the fundamental concepts and principles. The second section explores the immunomodulatory mechanisms in cardiovascular disease (CVD), with a specific focus on the intricate interplay between the immune system and the development of cardiovascular pathogenesis. The utilization of immunotherapy in specific cardiovascular conditions will be examined, investigating the application of immunotherapy in the context of different cardiovascular diseases. The future prospects and challenges in immunotherapy for cardiovascular diseases will be discussed, highlighting the potential areas for future research and addressing the barriers that must be overcome to effectively implement immunotherapeutic interventions in the management of cardiovascular diseases.


ssc-miR-7134-3p regulates fat accumulation in castrated male pigs by targeting MARK4 gene.
Castration of male pigs is a common practice used to reduce boar taint in commercial pork production, but it also significantly results in fat accumulation in carcass. Our previous study revealed a miRNA gene, ssc-miR-7134-3p that was implicated in adipogenesis. However, the relationship between ssc-miR-7134-3p and fat deposition due to castration is unknown. In the present study, we observed that ssc-miR-7134-3p targets the coding sequence (CDS) region of MARK4 based on bioinformatics analysis and dual-luciferase assays. Experiments using silent mutations and sub-cloning showed that ssc-miR-7134-3p binds independently to two adjacent sites in the MARK4 CDS. Subsequently, ssc-miR-7134-3p inhibits MARK4 protein expression in pig fibroblast cells, being consistent with the targeting demonstrated in vitro. We found higher MARK4 protein levels in the back fat of castrated pigs than in intact pigs, providing further evidence that MARK4 is involved in regulation of fat deposition. In addition, one SNP (g.2581A>G) in MARK4 was significantly associated with the back fat trait in Chinese and European pig populations. Taken together, we would conclude that ssc-miR-7134-3p targets the MARK4 gene for fat accumulation in the castrated male pigs.


Enhancement of the longitudinal transport by a weakly transversal drive.
Transport of Brownian particles in a two-dimensional asymmetric tube is investigated by applying a polarized field. From the Brownian dynamics simulations, we find that the longitudinal current can be enhanced remarkably by applying a weakly transversal drive. Multiple current reversals can be realized by altering the driving frequency of the polarized field. By coupling the longitudinal and transversal forces together, one can control the particle transport flexibly.


Mental health problems of undocumented migrants (UMs) in The Netherlands: a qualitative exploration of help-seeking behaviour and experiences with primary care.
To explore health-seeking behaviour and experiences of undocumented migrants (UMs) in general practice in relation to mental health problems. Qualitative study using semistructured interviews and thematic analysis. 15 UMs in The Netherlands, varying in age, gender, country of origin and education; inclusion until theoretical saturation was reached. 4 cities in The Netherlands. UMs consider mental health problems to be directly related to their precarious living conditions. For support, they refer to friends and religion first, the general practitioner (GP) is their last resort. Barriers for seeking help include taboo on mental health problems, lack of knowledge of and trust in GPs competencies regarding mental health and general barriers in accessing healthcare as an UM (lack of knowledge of the right to access healthcare, fear of prosecution, financial constraints and practical difficulties). Once access has been gained, satisfaction with care is high. This is primarily due to the attitude of the GPs and the effectiveness of the treatment. Reasons for dissatisfaction with GP care are an experienced lack of time, lack of personal attention and absence of physical examination. Expectations of the GP vary, medication for mental health problems is not necessarily seen as a good practice. UMs often see their precarious living conditions as an important determinant of their mental health; they do not easily seek help for mental health problems and various barriers hamper access to healthcare for them. Rather than for medication, UMs are looking for encouragement and support from their GP. We recommend that barriers experienced in seeking professional care are tackled at an institutional level as well as at the level of GP.


Combination of Multifunctional Nanoparticles and Interventional Techniques Makes Each Other Going Further in the Field of Cancer Treatment.
Nano-oncology and interventional oncology are both rapidly emerging fields in cancer therapies. Synergistic combination of the both fields offers drastic improvements in performance and efficacy of cancer killing agents. This review is to overview the studies focusing on these two crossing fields and to give an overlook of their future development. Interventional techniques such as selective arterial catheterization, irreversible electroporation (IRE) and radiofrequency ablation (RFA) dramatically enhanced cancer targetability and anticancer efficacy of nanoparticles (NPs). Furthermore, synergistic effects were observed when using different interventional techniques together on NPs directed cancer treatments. On the other hand, NPs improved thermal ablation as well by fundamentally improving heating efficiency, facilitating heat triggered local drug delivery, and increasing cancer control in marginal peri-ablated zones and distant regions. Crossing applications of the both techniques such as percutaneous delivery of near infrared (NIR) into deep tumors by needle insertion and conformal thermal ablation are highly anticipated.


The effect of multifilaments and monofilaments on cementless femoral revision hip components: an experimental study.
Cerclage wires are widely used in revision hip surgery to reattach the lid of a femoral osteotomy. The present study compared the influence of multifilaments and monofilaments on primary stability of revision hip stems with different fixation principles. A standardized extended proximal femoral osteotomy was performed in the anterior cortex of 6 synthetic femora. We used a high-resolution measuring device to explore spatial micromovements of a diaphyseal and a metaphyseal fixating revision stem. Both of these were implanted in 3 femora. The specimens were measured again after consecutive restabilization of osteotomies with multifilaments and monofilaments. The movement graphs generated defined relative micromovements between stems and bones and the stabilizing effect of the two wire systems compared. Both multifilaments and monofilaments effected a major reduction of relative micromovements for both fixation principles. There were no differences in relative movements between the multifilament and monofilament treatments for the diaphyseal fixating stem. Yet for the metaphyseal fixating stem a significantly better restabilization was observed with multifilaments. Both multifilaments and monofilaments can support the revision hip stem in bridging the extended proximal femoral osteotomy. Yet, which wiring system should be chosen depends on the fixation principle of the revision stem. Multifilaments seem to be advantageous when used with metaphyseal fixating stems. However, the use of multifilaments with diaphyseal fixating components should be reconsidered as this might constrict the periosteal vascularity.


Whole Genome Transcriptomic Analysis of Ovary Granulosa Cells Revealed an Anti-Apoptosis Regulatory Gene DLGAP5 in Polycystic Ovary Syndrome.
The mechanisms underlining pathogenesis of polycystic ovary syndrome (PCOS) remain largely unknown. Dysfunction of ovarian granulosa cells plays an important role. The present study performed the lncRNA and mRNA profiling by whole genome transcriptomic sequencing of ovary granulosa cells from women with PCOS and investigated the potential role of differentially expressed gens (DEGs) in the pathomechanism of PCOS. In total, 1,936 DEGs (30 upregulated and 1,906 downregulated mRNAs and lncRNAs) were identified in the ovary granulosa cells between control and PCOS group. Functional enrichment analysis showed that DEGs were mainly associated with cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, and olfactory transduction. qRT-PCR validated the upregulation of DLGAP5 mRNA in ovary from PCOS group when compared to control group. Immunostaining and TUNEL assays showed that DLGAP5 protein level was increased while apoptosis was decreased in follicles of ovary in PCOS group. In vitro functional assays showed that DLGPA5 knockdown repressed viability and proliferation, but enhanced apoptosis and disrupted cell cycle in granulosa cells; while DLGAP5 overexpression had the opposite effects in granulosa cells. In conclusion, the study showed differentially expressed lncRNA and mRNA profile in the granulosa cells in ovaries of PCOS. Functional results demonstrated that DLGAP5 is a dysregulated candidate gene in the pathogenesis of PCOS, especially granulosa cell apoptosis and proliferation.


A flow cytometry-based screen identifies MBNL1 modulators that rescue splicing defects in myotonic dystrophy type I.
Myotonic dystrophy Type 1 (DM1) is a rare genetic disease caused by the expansion of CTG trinucleotide repeats ((CTG)exp) in the 3' untranslated region of the DMPK gene. The repeat transcripts sequester the RNA binding protein Muscleblind-like protein 1 (MBNL1) and hamper its normal function in pre-mRNA splicing. Overexpressing exogenous MBNL1 in the DM1 mouse model has been shown to rescue the splicing defects and reverse myotonia. Although a viable therapeutic strategy, pharmacological modulators of MBNL1 expression have not been identified. Here, we engineered a ZsGreen tag into the endogenous MBNL1 locus in HeLa cells and established a flow cytometry-based screening system to identify compounds that increase MBNL1 level. The initial screen of small molecule compound libraries identified more than thirty hits that increased MBNL1 expression greater than double the baseline levels. Further characterization of two hits revealed that the small molecule HDAC inhibitors, ISOX and vorinostat, increased MBNL1 expression in DM1 patient-derived fibroblasts and partially rescued the splicing defect caused by (CUG)exp repeats in these cells. These findings demonstrate the feasibility of this flow-based cytometry screen to identify both small molecule compounds and druggable targets for MBNL1 upregulation.


Synthesis of chromeno[2,3-b]indol-11(6H)-one via PhI(OAc)2-mediated intramolecular oxidative C(sp(2))–N(H2) bond formation.
Various chromeno[2,3-b]indol-11(6H)-ones were conveniently constructed via phenyliodine(III) diacetate (PIDA)-mediated intramolecular oxidative annulation. This method, while realizing a direct oxidative C–N bond formation between an aromatic ring and a pendent free-NH2 moiety, features a metal-free protocol, mild reaction conditions, simple workup, and the ready availability of the starting substrates.


Fluvirosaones A and B, Two Indolizidine Alkaloids with a Pentacyclic Skeleton from Flueggea virosa.
Fluvirosaones A (1) and B (2), together with virosecurinine (3), were isolated from Flueggea virosa. Their structures were determined by physical, spectroscopic, and X-ray analysis and confirmed through comparison of the calculated and experimental 13C NMR and electronic circular dichroism (ECD) data. Compounds 1 and 2 represent the first examples of a pentacyclic Securinega alkaloid containing a pentacyclic system and an α,β-unsaturated ketone. Plausible biogenetic pathways of compounds 1 and 2 are proposed.


Phylogenetic analysis of Bacillus cereus isolates from severe systemic infections using multilocus sequence typing scheme.
Bacillus cereus strains from cases of severe or lethal systemic infections, including respiratory symptoms cases, were analyzed using multilocus sequence typing scheme of B. cereus MLST database. The isolates were evenly distributed between the two main clades, and 60% of them had allele profiles new to the database. Half of the collection's strains clustered in a lineage neighboring Bacillus anthracis phylogenetic origin. Strains from lethal cases with respiratory symptoms were allocated in both main clades. This is the first report of strains causing respiratory symptoms to be identified as genetically distant from B. anthracis. The phylogenetic location of the presented here strains was compared with all previously submitted to the database isolates from systemic infections, and were found to appear in the same clusters where clinical isolates from other studies had been assigned. It seems that the pathogenic strains are forming clusters on the phylogenetic tree.


Cochlear implantation for patients with single-sided deafness or asymmetrical hearing loss: a systematic review of the evidence.
A systematic review of the literature to evaluate the clinical outcome of cochlear implantation for patients with single-sided deafness (SSD) or asymmetrical hearing loss (AHL). We searched the PubMed, Embase, Cochrane Library, and CINAHL databases from their inception up to December 10, 2013 for SSD or AHL and cochlear implantation or their synonyms. In total, 781 articles were retrieved, of which 15 satisfied the eligibility criteria. Our outcomes of interest were speech perception in noise, sound localization, quality of life (QoL), and tinnitus. Critical appraisal showed that six studies reported on less than five patients or that they carried a low directness of evidence or a high risk of bias. Therefore, we extracted the data of nine studies (n = 112). Patient numbers, age, duration of deafness, classification of deafness, pure tone audiometry, follow-up duration, and outcome measurements were extracted from all nine articles. Because of large heterogeneity between studies, we were not able to pool data in a meta-analysis. We therefore summarized the results of the studies specified per outcome. There are no high-level-of-evidence studies concerning cochlear implantation in patients with SSD or AHL. Current literature suggests important benefits of cochlear implantation regarding sound localization, QoL, and tinnitus. Varying results were reported for speech perception in noise, possibly caused by the large clinical heterogeneity between studies. Larger and high-quality studies are certainly warranted.


Superoxide dismutase and catalase activities of cultured erythrocytes infected with Plasmodium falciparum.
It has already shown that catalase activity is significantly decreased in red cells of patients with P. falciparum. The mechanism suggested was by this enzyme inactivation through increased H2O2 generated during malarial infection. The present study was performed to verify this hypothesis. Catalase activities of red cells with high or low parasitemia in patients with P. falciparum were found to be lower than those of normal red cells. However, P. falciparum-infected red cells cultured for one week showed similar SOD and catalase levels to normal red cells. There was also no significant difference in the catalase levels between the parasitized and non-parasitized red cells. The difference in catalase activity of infected red cells before and after culture could be explained in terms of the activation of mononuclear cells and macrophages in vivo. During the sojourn of the parasitized red cells in close proximity to the macrophages of the spleen, they might trigger oxidative bursts resulting in increased H2O2. In order to protect themselves from oxidant damage, the catalase in the infected red cells could be inactivated by H2O2 resulting in the reduction of this enzyme.


Staff personhood in dementia care settings: "Do they care about me?"
This article aims to examine RCAs' own experiences of personhood in dementia care settings. Conceptually, person-centred care entails fostering the personhood of residents and the residential care aides (RCAs) who provide much of their hands-on care. To date, however, staff personhood has been overlooked in the empirical literature. The study was part of a larger focused ethnographic project exploring how the organisational care environment impedes or facilitates the provision of quality dementia care. Semi-structured interviews with 23 RCAs and more than 230 hours of participant observation were conducted in two nursing homes with specialised dementia units in British Columbia, Canada. Two overarching themes, "personhood undermined-management-staff relations" and "personhood undermined-workplace policies and practices" emerged, illustrating how, despite exposure to features believed beneficial to their working environment (e.g., favourable staffing ratios, relatively good remuneration), RCAs encountered repeated affronts to their personhood. The first theme encompasses the importance of being known (i.e., as persons and of their job demands) and valued (i.e., appreciated for their work in non-monetary terms). The second highlights the salience of work-life balance, full-staffing coverage and supportive human resource practices. RCAs' experiences reveal how the ongoing search for cost-efficiencies, cost-containment and cost-accountability overshadows their individuality, indicating a key disconnect between conceptual ideals and workplace realities. Organisations are encouraged to consider creating person-centred management and workplace practices that provide tangible evidence that RCAs, and their work, matter.


Mid-wave infrared metasurface microlensed focal plane array for optical crosstalk suppression.
Spatial crosstalk is one of the fundamental drawbacks of diminishing pixel size in mid-wave infrared focal plane arrays (IR-FPAs). We proposed an IR-FPA using the concept of optical phase discontinuities for substantial optical crosstalk suppression. This IR-FPA consists of asymmetrically tailored V-shaped optical antennas. Full-wave simulations confirmed major improvements in narrowing the intensity distribution of incident light beam by over 30-folds and concentrating these distributions in the central pixel of IR-FPA by achieving optical crosstalks of <1%.


Tuning the contact conductance of anchoring groups in single molecule junctions by molecular design.
A tetraphenylmethane tripod functionalized with three thiol moieties in the para position can serve as a supporting platform for functional molecular electronic elements. A combined experimental scanning tunneling microscopy break junction technique with theoretical approaches based on density functional theory and non-equilibrium Green's function formalism was used for detailed charge transport analysis to find configurations, geometries and charge transport pathways in the molecular junctions of single molecule oligo-1,4-phenylene conductors containing this tripodal anchoring group. The effect of molecular length (n = 1 to 4 repeating phenylene units) on the charge transport properties and junction configurations is addressed. The number of covalent attachments between the electrode and the tripodal platform changes with n affecting the contact conductance of the junction. The longest homologue n = 4 adopts an upright configuration with all three para thiolate moieties of the tripod attached to the gold electrode. The contact conductance of the tetraphenylmethane tripod substituted by thiols in the para position is higher than that substituted in the meta position. Such molecular arrangement is highly conducting and allows well-defined directional positioning of a variety of functional groups.


Enzymatic epoxidation: synthesis of 7,8-epoxy-1-octene, 1,2-7,8-diepoxyoctane, and 1,2-Epoxyoctane by Pseudomonas oleovorans.
The kinetics of the enzymatic formation of 7,8-epoxy-1-octene, 1,2-7,8-diepoxyoctane, and 1,2-epoxyoctane by growing and resting cell suspensions of Pseudomonas oleovorans are described. Formation of 1,2-epoxyoctane occurs concurrently with exponential growth on 1-octene, providing that 1-octene is in excess. Conversion of 1,7-octadiene to 7,8-epoxy-1-octene by cells growing on octane lags behind exponential growth and continues into the stationary phase, terminating upon cell death. Formation of 1,2-7,8-diepoxyoctane does not begin until the cells are well into the stationary phase and also continues until cell death. Results with growing and resting cell suspensions suggest that the various substrates compete for the same enzyme system; that viable cells are essential for substrate transport and epoxidation by whole cells; and that whole cells may concentrate and sequester the epoxides, rendering them unrecoverable by our current methods.


Expression of the full-length HCV core subgenome from HCV gentoype-1a and genotype-3a and evaluation of the antigenicity of translational products.
Hepatitis C virus (HCV) infection is a major public health problem in India. Detection of HCV and its genotypes by simple and economic assays is a prime requirement in the planning of antiviral treatments for patients infected with this virus. Although commercial assays are available for the detection of both HCV RNA and genotypes, efforts aimed at the development of simple and economical systems for these measurements are still going on. The present study was designed to clone and express the HCV CORE gene from HCV genotype-1a and genotype-3a and use the peptides to develop immunoassays for the detection of genotype-specific antibodies in sera samples. One hundred and thirty-five serum samples from patients with liver and renal diseases were screened for HCV RNA by real-time PCR, followed by HCV genotyping in RNA-positive sera by restriction fragment length polymorphism, sequencing, and phylogenetic analysis. The HCV CORE gene was amplified from sera carrying HCV genotype-1a and genotype-3a and cloned and expressed in the pET19b vector. The translational products were used to develop a western blot assay for the detection of genotype-specific anti-HCV antibodies. The HCV CORE gene, from both genotypes, was cloned and expressed successfully, with production of a 26 kDa recombinant protein in either case. Using peptides in a western blot assay, 101 sera samples were tested for the anti-HCV CORE antibody. Each peptide showed a reaction with anti-HCV total antibody without showing any genotype-specific binding. This indicates that individual peptides obtained from different genotypes do not have a genotype-specific epitope to bind with antibodies. Cloning and expression of the HCV CORE gene from genotype-1a and genotype-3a was successful. However, the peptides formed did not show genotype-specific binding with anti-HCV.


Antibody landscapes after influenza virus infection or vaccination.
We introduce the antibody landscape, a method for the quantitative analysis of antibody-mediated immunity to antigenically variable pathogens, achieved by accounting for antigenic variation among pathogen strains. We generated antibody landscapes to study immune profiles covering 43 years of influenza A/H3N2 virus evolution for 69 individuals monitored for infection over 6 years and for 225 individuals pre- and postvaccination. Upon infection and vaccination, titers increased broadly, including previously encountered viruses far beyond the extent of cross-reactivity observed after a primary infection. We explored implications for vaccination and found that the use of an antigenically advanced virus had the dual benefit of inducing antibodies against both advanced and previous antigenic clusters. These results indicate that preemptive vaccine updates may improve influenza vaccine efficacy in previously exposed individuals.


Device architecture and precision nanofabrication of microring-resonator filter banks for integrated photonic systems.
To achieve the maximum benefit of electronic-photonic integrated circuits wavelength-division multiplexing must be used. This requires the design and fabrication of a highly integratable photonic device, capable of performing multiplexing/demultiplexing operations with low loss and minimal crosstalk. A filter bank consisting of high-index-contrast microring-resonator filters, with accurately spaced resonant frequencies can meet these requirements. This paper describes the basic architecture of microring-resonator filter banks, and how to maximize performance while keeping fabrication challenges reasonable. The greatest challenge in fabricating such devices is achieving the dimensional precision, on the scale of tens of picometers, needed to attain accurately spaced resonant frequencies. To do this, a fabrication method based on varying the electron-beam dose during scanning-electron beam lithography is used. This approach is used to create a dual twenty-channel filter bank, comprised of second-order silicon-rich silicon nitride microring resonators. The average resonant frequency spacing is off from the target spacing by only 3 GHz, corresponding to a dimensional precision of 75 pm. This approach is also shown to be compatible with the fabrication process for silicon microring resonators. Furthermore, it is shown that any remaining resonant frequency errors can be corrected with postfabrication thermal tuning. Also, a method of using the contra-propagating mode of a microring-resonator filter is demonstrated, enabling a single filter bank to multiplex/demultiplex two signals at the same time.


Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine Sulfonamides as an Important Scaffold for Anticancer Drug Discovery-In Vitro and In Silico Evaluation.
Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulfonamides (MM-compounds) are a relatively new class of heterocyclic compounds that exhibit a wide variety of biological actions, including anticancer properties. Here, we used caspase enzyme activity assays, flow cytometry analysis of propidium iodide (PI)-stained cells, and a DNA laddering assay to investigate the mechanisms of cell death triggered by the MM-compounds (MM134, -6, -7, and -9). Due to inconsistent results in caspase activity assays, we have performed a bromodeoxyuridine (BrdU) incorporation assay, colony formation assay, and gene expression profiling. The compounds' cytotoxic and pro-oxidative properties were also assessed. Additionally, computational studies were performed to demonstrate the potential of the scaffold for future drug discovery endeavors. MM-compounds exhibited strong micromolar (0.06-0.35 µM) anti-proliferative and pro-oxidative activity in two cancer cell lines (BxPC-3 and PC-3). Activation of caspase 3/7 was observed following a 24-h treatment of BxPC-3 cells with IC50 concentrations of MM134, -6, and -9 compounds. However, no DNA fragmentation characteristics for apoptosis were observed in the flow cytometry and DNA laddering analysis. Gene expression data indicated up-regulation of BCL10, GADD45A, RIPK2, TNF, TNFRSF10B, and TNFRSF1A (TNF-R1) following treatment of cells with the MM134 compound. Moreover, in silico studies indicated AKT2 kinase as the primary target of compounds. MM-compounds exhibit strong cytotoxic activity with pro-oxidative, pro-apoptotic, and possibly pro-necroptotic properties that could be employed for further drug discovery approaches.


Cardiovascular and pharmacological implications of haem-deficient NO-unresponsive soluble guanylate cyclase knock-in mice.
Oxidative stress, a central mediator of cardiovascular disease, results in loss of the prosthetic haem group of soluble guanylate cyclase (sGC), preventing its activation by nitric oxide (NO). Here we introduce Apo-sGC mice expressing haem-free sGC. Apo-sGC mice are viable and develop hypertension. The haemodynamic effects of NO are abolished, but those of the sGC activator cinaciguat are enhanced in apo-sGC mice, suggesting that the effects of NO on smooth muscle relaxation, blood pressure regulation and inhibition of platelet aggregation require sGC activation by NO. Tumour necrosis factor (TNF)-induced hypotension and mortality are preserved in apo-sGC mice, indicating that pathways other than sGC signalling mediate the cardiovascular collapse in shock. Apo-sGC mice allow for differentiation between sGC-dependent and -independent NO effects and between haem-dependent and -independent sGC effects. Apo-sGC mice represent a unique experimental platform to study the in vivo consequences of sGC oxidation and the therapeutic potential of sGC activators.


The psychosocial impact of nausea and vomiting during pregnancy as a predictor of postpartum depression.
This study examined the extent to which psychosocial impact of nausea and vomiting during pregnancy predicts postpartum depression using a retrospective design. Data from a cross-sectional survey investigating women's experiences of nausea and vomiting during pregnancy were used (N = 861). Hierarchical logistic regression models revealed that the psychosocial impact of nausea and vomiting in pregnancy appears to be predictive of postpartum depression, independent of depression status before and during pregnancy. Our findings indicate that assessing the psychosocial impact of nausea and vomiting in pregnancy during antenatal care may identify women at risk of postpartum depression.