[Emigration from the Soviet Union during its last years. Part 2].
The author "deals with the emigration of the citizens of the previous Soviet Union to the Federal Republic of Germany, the United States of America and to some other countries. It contains the data on numbers of ethnic Germans [who] emigrated to the Federal Republic of Germany during the years 1968-1981, on emigrants coming to the United States, by country of birth and on those receiving the status of permanent [residence] in the United States during 1961-1989." Future migration trends are estimated, and the impact of political changes and economic development is considered. (SUMMARY IN ENG AND RUS)


Topotecan can compensate for protracted radiation treatment time effects in high grade glioma xenografts.
Several studies reported that prolongation of overall treatment time of fractionated radiotherapy reduces the chance of tumor control. In the present study, we hypothesize that combining topotecan with irradiation could compensate for this detrimental time effect on the radioresponse. Therefore, we investigated the efficiency of different schedules of topotecan (TPT), radiotherapy (RT) or concomitant combination TPT + RT. Experiments were performed in two human high-grade glioma xenograft models (U87 and GBM Nan1). TPT and RT were delivered at a total dose of 3 mg/kg and 40 Gy, respectively. For the TPT + RT groups, TPT was injected 5 min before radiation. Total radiation doses were delivered in 5, 10, 20, or 30 fractions over 1, 2, 4, or 6 weeks, respectively. The efficiency of TPT, RT, and TPT + RT was evaluated by tumor growth delay (TGD). At this low total dose, and independent of the schedule, no efficacy was found in TPT-treated glioma xenografts. Conversely, radiotherapy-induced antitumor effect decreased with prolongation of treatment time. For TPT + RT combination, antitumor activity was not influenced by schedule, and tumor response was always comparable to those measured for the shortest and the most efficient irradiation schedule (i.e. 1 week). When treatment was delivered over 4 or 6 weeks in U87 glioma xenografts, therapeutic enhancement ratios reached 2.6 and 3.7, respectively. This indicated that the interaction between ionizing radiation and topotecan was synergistic. The present study demonstrated that concomitant topotecan can compensate for the detrimental effect of treatment time protraction on radiotherapy efficacy in two malignant glioma xenografts.


[Facial aesthetic lipostructure].
Coleman's lipostructrure, based on the use of specific material and on a strict methodology has reconciled the surgeons with adipocyte transfer. The quality of the lipostructure results depends significantly on: The topography of the graft locations (the best results being obtained in the malar, chin and cheek units), the candidates (better results in young women, less than 60 years). The quality of the lipostructure results has influenced our surgical strategy: Lipostructure can be used alone, or frequently associated with a face lift. We adopted a regional operatoring strategy: A more limited zone of face lift undermining enabling us to target lower cheeks and neck, adjunction of lipostructure in adjacent anterior locations. In our experience the association face lift-lipostructure gives good and natural results. Lipostructure is currently the best way to restore facial volumes.


Medical errors reported by French general practitioners in training: results of a survey and individual interviews.
French interns in general practice are, like all medical students, exposed to medical errors during their training. To measure the professional and personal impact of medical errors on French general practitioner (GP) trainees. Quantitative and qualitative study of medical errors and GP trainees enrolled at Paris Diderot University. An online anonymous questionnaire was sent to all GP trainees at Paris Diderot University and recorded semi-structured interviews were conducted with 10 volunteers. 70 of the 392 (18%) interns contacted replied to the questionnaire and 10 semi-structured interviews were then conducted. 97% of the participants had already made a medical error. Even with the extreme, conservative assumption that non-respondents would have reported no errors, the prevalence of self-reported medical errors in the whole sample would still have been 17%. 64% said they were at least strongly affected by their error and 74% made constructive changes to their work after the error. The interns revealed that the emotional impact of their errors were great with feelings such as guilt that could remain for more than 2 years after the event. 33% would have liked to talk more about the circumstances of their error with their superior. Most interns suggest more training on medical errors and more open-minded discussion when the error actually happens rather than formal training at the university. Medical errors remain a sensitive subject that is not broached enough in our university but interns need to talk about their experiences with their peers to improve risk management and prevent the recurrence of new errors.


UBIAD1 and CoQ10 protect melanoma cells from lipid peroxidation-mediated cell death.
Cutaneous melanoma is the deadliest type of skin cancer, although it accounts for a minority of all skin cancers. Oxidative stress is involved in all stages of melanomagenesis and cutaneous melanoma can sustain a much higher load of Reactive Oxygen Species (ROS) than normal tissues. Melanoma cells exploit specific antioxidant machinery to support redox homeostasis. The enzyme UBIA prenyltransferase domain-containing protein 1 (UBIAD1) is responsible for the biosynthesis of non-mitochondrial CoQ10 and plays an important role as antioxidant enzyme. Whether UBIAD1 is involved in melanoma progression has not been addressed, yet. Here, we provide evidence that UBIAD1 expression is associated with poor overall survival (OS) in human melanoma patients. Furthermore, UBIAD1 and CoQ10 levels are upregulated in melanoma cells with respect to melanocytes. We show that UBIAD1 and plasma membrane CoQ10 sustain melanoma cell survival and proliferation by preventing lipid peroxidation and cell death. Additionally, we show that the NAD(P)H Quinone Dehydrogenase 1 (NQO1), responsible for the 2-electron reduction of CoQ10 on plasma membranes, acts downstream of UBIAD1 to support melanoma survival. By showing that the CoQ10-producing enzyme UBIAD1 counteracts oxidative stress and lipid peroxidation events in cutaneous melanoma, this work may open to new therapeutic investigations based on UBIAD1/CoQ10 loss to cure melanoma.


Assessment of Post-Radiation Time Effect on Gene Expression Profiles of Saccharomyces cerevisiae Samples After Appling a UV Laser.
Introduction: Widespread application of lasers in different fields of medicine implies more investigations into the molecular mechanism of laser effects on the human body. Network analysis of the dysregulated genes of Saccharomyces cerevisiae samples are irradiated by a UV laser and harvested 30 minutes after radiation compared with a 15-minute group is the aim of this research. Methods: The significant dysregulated genes interacted via the STRING database, and the central nodes were determined by "Networkanalyzer" application of Cytoscape software. The critical genes and the related biological terms were identified via action map analysis and gene ontology assessment. Results: The gene expression profiles of the samples with 30-minute post-radiation time were different from the samples with 15 minutes of post-radiation time. 9 potent central genes, 50% of which were similar to the nodes of the 15-minute group, were identified. The terms "positive regulation of telomere maintenance" were targeted in the two sample groups. Conclusion: In spite of large alteration in the gene expression profiles of the samples, the results indicated that the main affected biological term for the 15-minute and 30-minute groups was similar.


MR contrast media in neuroimaging: a critical review of the literature.
MR contrast media are commonly used but do not have evidence-based guidelines for their application. This investigation seeks to define specific methodological problems in the MR contrast media literature and to suggest guidelines for an improved study design. To evaluate the reported clinical efficacy of MR contrast media in neuroimaging, we performed a critical review of the literature. From 728 clinical studies retrieved via MEDLINE, we identified 108 articles that evaluated contrast media efficacy for a minimum of 20 patients per study. The articles were randomly assigned to four readers (a fifth reader reviewed all of the articles) who were blinded to article titles, authors, institutions, and journals of publication. The readers applied objective, well-established methodological criteria to assign each article a rating of A, B, C, or D. One hundred one of 108 articles received a D rating, six received a C rating, and one received a B rating. In general, the Methods sections of the evaluated articles did not contain details that would allow the reader to calculate reliable measures of diagnostic accuracy, such as sensitivity and specificity. Specifically, a common problem was failure to establish and uniformly apply an acceptable standard of reference. In addition, images were not always interpreted independently from the reference standard. Radiologists and clinicians need to determine the applicability of any published study to their own practices. Unfortunately, the studies we reviewed commonly lacked clear descriptions of patient demographics, the spectrum of symptomatology, and the procedure for assembling the study cohort. Finally, small sample sizes with inadequate controls were presented in almost all of the articles. Although MR contrast media are widely used and play an essential role in lesion detection and confidence of interpretation, no rigorous studies exist to establish valid sensitivity and specificity estimates for their application. On the basis of this review, we herein describe basic methods to document improvements in technology. Such studies are essential to devise measures of diagnostic accuracy, which can form the basis for further studies that will assess diagnostic and therapeutic impact and, ultimately, patient outcomes.


Pneumonia in solid organ transplant recipients: a prospective multicenter study.
Pneumonia frequently affects solid organ transplant (SOT) recipients, with high morbidity and mortality. However, the few studies on pneumonia in this population are mainly retrospective, single-center, and long-term studies, or include patients with only one type of SOT or a specific etiology. We performed a point prevalence study to investigate epidemiology, diagnosis, therapy, and outcome of pneumonia in an unselected SOT population. Italian and Spanish transplant centers were invited to report on all SOT recipients with pneumonia treated during 2 separate weeks (1 each in February and June 2012). In total, 35 centers (18 in Italy, 17 in Spain) agreed to participate and collected 54 cases. The incidence of pneumonia was 10.1 episodes/1000 recipients/year. Pneumonia was classified as late (>6 months) in 70.4% of cases. Pneumonia was also classified as community-acquired (CAP), healthcare-associated (HCAP), and hospital-acquired (HAP) pneumonia in 40.7%, 38.9%, and 20.4% of cases, respectively. An attempt to microbiological diagnosis (≥1 sample) was made in 94.4% of patients, with a diagnostic yield of 60.7%. Causative agents included bacteria (87.1%), virus (29%), and fungi (6.4%). A multidrug-resistant bacterium was isolated in 18.2%, 40%, and 100% of patients with CAP, HCAP, and HAP (P = 0.007), respectively. Overall, 11.1% of patients were admitted to the intensive care unit, 3.7% developed graft rejection, and graft function deteriorated in 18.5%. In-hospital mortality was 1.9%. Pneumonia remains a frequent problem in SOT recipients, although it occurs later in patients who are in better physical health. Therefore, harmful pathogens and worse outcome are less common than previously thought.


Effects of major-histocompatibility-complex-encoded subunits on the peptidase and proteolytic activities of human 20S proteasomes. Cleavage of proteins and antigenic peptides.
The proteasome is responsible for the non-lysosomal degradation of misfolded, transient, or ubiquitin-tagged proteins. This fact and the identification of two major-histocompatibility-complex-(MHC)-encoded proteasomal subunits, LMP2/7, suggest an important role of the proteasome in antigen processing. Using purified 20S proteasomes from a wild-type and a LMP2/7-deletion T lymphoblastoid cell line, we analyzed the effect of LMP2/7 on the peptidase and proteolytic activities of the complex in the context of various purification and activation methods. The incorporation of LMP2/7 alters the peptidase activity against fluorogenic substrates, but these effects are not reflected in the time-dependent degradation pattern of oxidized insulin B chain or of peptide epitopes of an antigenic protein. No effect of LMP2/7 on the degradation pattern of these substrates was observed by either reverse-phase chromatography, pool sequencing, or mass spectrometry. The 20S proteasome can cleave insulin B chain at nearly every position, showing that the P1 position alone does not determine the cleavage sites. The maximum of the length distribution of the end products, makes these ideal candidates for MHC display; yet we find that a natural epitope derived from human histone H3 is further degraded by 20S proteasomes. Alanine scans and substitutions with related amino acids of this epitope indicate that, as in insulin B chain, the cleavage sites are not determined by the P1 position alone.


Assessing the relationship between functional impairment/recovery and depression severity: a pooled analysis.
The objective of this study was to explore the relationship between assessments of functional impairment, emotional well-being, and depression symptoms. Data were pooled from 3530 outpatients with major depressive disorder enrolled in 10 desvenlafaxine clinical trials. The primary outcome measures included (a) the 17-item Hamilton Rating Scale for Depression (HAM-D17) as a measure of depressive symptom severity and (b) the Sheehan Disability Scale (SDS) and five-item World Health Organization Well-Being Index (WHO-5) as measures of functional impairment and well-being. A linear regression model was used to identify the SDS and WHO-5 values that equate to the predetermined clinically relevant three-point difference between active treatment and placebo on the HAM-D17. A receiver operating characteristic analysis was conducted to determine the SDS score that equates to a remission of depression symptoms (i.e. HAM-D17≤7). An approximate three-point difference between active treatment and placebo on the SDS (2.8) and WHO-5 (2.5) was determined to be clinically relevant in relation to improvements in depressive symptoms. An SDS of less than or equal to 7 was equivalent to a remission of depression symptoms, providing a definition of functional remission. A better understanding of the relationship between depressive symptoms and functional impairment and well-being may provide clinicians with a more comprehensive means of assessing treatment effects in major depressive disorder.


Incidence of malocclusion between primary and mixed dentitions among Brazilian children. A 5-year longitudinal study.
To determine the incidence of malocclusion in a 5-year follow-up of school children and verify the hypothesis that individuals with previous malocclusion are more prone to maintain the same characteristics in the transition from primary to mixed dentition. School children, ages 8 to 11 years, participated. Inclusion criteria consisted of normal occlusion in primary dentition or subsequent malocclusions, anterior open bite and/or posterior crossbite and/or overjet measuring more than 3 mm, and that subjects had not submitted to orthodontic treatment and adenoidectomy. Data collection was based on evaluation of occlusion in school children in the actual stage of mixed dentition. Descriptive, Chi-square, and relative risk (RR) 95% confidence interval (CI) analyses were carried out. The greatest incidence of malocclusion was found in children with malocclusion (94.1%) when compared with those without malocclusion (67.7%) (RR = 1.4 [1.2-1.6]; P < .001). Anterior open bite (RR = 3.1 [1.7-5.8]), posterior crossbite (RR = 7.5 [4.9-11.5]), and overjet greater than 3 mm (RR = 5.2 [3.4-8.0]) in the primary dentition are risk factors for malocclusion in early mixed dentition. Spontaneous correction of the anterior open bite was confirmed in 70.1% of cases. Posterior crossbite and overjet greater than 3 mm were persistent in 87.8% and 72.9% of children. Malocclusion incidence was high. Individuals with previous anterior open bite, greater overjet, and posterior crossbite had greater risk of having the same characteristics in the mixed dentition.


Dynamics of erythropoiesis following renal transplantation.
We examined the temporal dynamics of the correction of anemia following renal transplantation in 65 recipients using a sensitive radioimmunoassay for erythropoietin to determine the effects of modern immunosuppressive agents, delayed graft function, and early acute rejection. Pretransplant mean erythropoietin (25.6 +/- 3.3 mU/ml) was only 25% of the expected value at the mean hematocrit of 27.2 +/- 0.7, and erythropoietin correlated positively with hematocrit (r = 0.37, P less than 0.05). Following onset of graft function, erythropoietin increased to 109 +/- 13 mU/ml and then decreased in a negative feedback fashion over the next several months. Delayed graft function was associated with delay in the assumption of this orderly process irrespective of the immunosuppressive regimen used. Cyclosporine A produced a biphasic response despite delayed graft function in recipients with underlying adult polycystic kidney disease. Correction of anemia required resumption of graft function. Onset of acute graft rejection within the first month posttransplantation (14 episodes in 11 patients) abrogated the hematopoietic response until the rejection was successfully reversed. We conclude that a major cause for the anemia of renal failure is subnormal production of erythropoietin. Following transplantation, anemia corrects in an orderly manner with restoration of the normal biofeedback process between erythropoietin and red cell mass. This process is delayed by failure of graft to function initially and interrupted by acute early rejection, re-commencing following successful reversal.


Simultaneous removal of nitrate/phosphate with bimetallic nanoparticles of Fe coupled with copper or nickel supported on chelating resin.
Given the prevalence of nitrate and phosphate in surface and groundwater, it is important to develop technology for the simultaneous removal of nitrate and phosphate. In this study, we prepared the bimetallic nanoparticles of Fe coupled with copper or nickel supported on chelating resin DOW 3N (D-Fe/Ni and D-Fe/Cu) for removing nitrate and phosphate simultaneously. XPS profiles revealed that Cu has better ability than Ni to increase the stability of Fe nanoparticles and prevent nZVI from oxidation. The results showed that nitrate removal efficiencies by D-Fe/Ni and D-Fe/Cu were 98.7% and 95.5%, respectively and the phosphate removal efficiencies of D-Fe/Cu and D-Fe/Ni were 99.0% and 93.0%, respectively. Besides adsorption and coprecipitation as reported in previous studies, the mechanism of phosphate removal also includes the adsorption of the newly formed polymeric ligand exchanger (PLE). Moreover, in previous studies, the presence of phosphate had significant negative effects on the reduction of nitrate. However, in this study, the removal efficiency of nitrate was less affected with the increasing concentration of phosphate for D-Fe/Cu. This was mainly because D-Fe/Cu had higher adsorption capacity of phosphate due to the newly formed PLE according to the XPS depth profile analysis.


CD83 on dendritic cells: more than just a marker for maturation.
CD83 has been known for a long time to be one of the best markers for mature dendritic cells (DCs). Studies with herpes simplex virus type 1 (HSV-1)-infected DCs, whereby the viral infection leads to the degradation of CD83, as well as investigations inhibiting CD83 mRNA transport, have provided evidence that CD83 might also be important for DC biology. Recently, we have shown that the soluble extracellular CD83 domain inhibits DC-mediated T-cell proliferation, representing the first report describing a functional role for CD83.


[Effects of habitat patch on Lophura nycthemera population].
To understand the relationships between the distribution of Lophura nycthemera population and the attributes of habitat patch,this paper investigated the population of L. nycthemera in the National Gutian Mountain Natural Reserve and its periphery area in Zhejiang Province from September 1998 to August 1999. The relative population density of L. nycthemera in each patch was determined by transect census with collecting molted feathers, and the effects of vegetation and landscape characteristics on the relative population density and patch occupancy were analyzed by statistic methods. The results showed that the occurrence of L. nycthemera was significantly affected by patch area,total cover,arbor cover,and shrub height. High frequency occurrence of L. nycthemera was observed in the patches with large area, dense total cover, dense arbor cover and high shrub height, and high relative population density was found in large size patches. There was a significant positive linear correlation between relative population density and patch area.


[Risk factors analysis of acute kidney injury in patients with exertional heatstroke].
Objective: To explore the risk factors of acute renal injury (AKI) in exertional heat radiation disease (EHS) . Methods: In november 2019, the clinical data of 69 EHS patients admitted from July 2015 to September 2019 were reviewed. The general data, laboratory indexes, Glasgow score (GCS) at admission, 24-hour acute physiology and chronic health score Ⅱ (APACHE Ⅱ) , exposure time rate and physical labor intensity were collected. According to the occurrence of AKI, the patients were divided into AKI group and non-AKI group, 31 and 38 in each group. The differences of general data and laboratory indexes between the two groups were compared, and the t and Mann-Whitney U test were used to compare the two groups. The enumeration data are expressed by examples and constituent ratio (%) . Independent sample χ(2) test is used for inter-group comparison, and multiple test is used for multi-sample comparison. The correlation was analyzed by linear regression. Risk factors were analyzed by Logistic regression analysis. Results: At discharge, 31 of 69 EHS patients developed AKI. Compared with the non-AKI group, the heart rate, white blood cell count, lactic acid, D-dimer and myoglobin were higher; MAP, platelet count and PH were lower in the AKI group. The difference was statistically significant (P<0.05) . APACHE Ⅱ score, core temperature, time to drop to 38.5 ℃, contact time rate, platelet count, pH, lactic acid, D-dimer and myoglobin were all correlated with creatinine (r=0.57, 0.42, 0.80, 0.78, 0.57, 0.43, 0.51, 0.55, 0.79) . APACHE Ⅱ score, time to drop to 38.5C, Lac and MYO are the risk factors of AKI in EHS patients. Multivariate Logistic regression analysis showed that the time required to drop to 38.5C was an independent risk factor for the occurrence of AKI. Conclusion: AKI is a serious complication of EHS. EHS complicated with AKI, should be identified early and effective intervention measures should be taken.


Protein intake does not depend on the dose of dialysis delivered--provided Kt/V is adequate.
A link between malnutrition and the dialysis dose has been recently postulated on the basis of the direct relationship between Kt/V and nPCR and an increase in dialysis therapy has been also proposed in malnourished patients or when nPCR is less than 1 g/kg b.w., but the clinical meaning of such a relationship is unclear. Both dietary protein intake and nPCR were simultaneously determined in a selected population of 35 well-dialysed patients (Kt/V > 0.8) and were related to the delivered dialysis dose. No relationship was found between measured Kt/V (1.10 +/- 0.20) and dietary protein intake (PI, 0.98 +/- 0.20 g/kg) and similarly no relationship was evident between the dialysis dose and nPCR (0.99 +/- 0.20 g/kg). Although the mean nPCR value was similar to that of protein intake, nPCR exceeded protein intake when PI was less than 1 g/kg b.w. Our results demonstrate that if the dialysis dose is adequate, protein intake is a dialysis--independent or patient--dependent variable. They also show that at least 0.9 to 1.0 g protein per kg b.w are required to maintain nitrogen balance even in well-dialysed patients.


[Abortion, an important problem of modern societies].
Each civilization is faced with an issue of choosing to be for or against life. Likewise, the society we are currently building cannot evade answering the question of on which side it stands, that of life or that of death? Consumptionist and hedonistic lifestyles of a majority of people make the answer to this question still more important. The mass-media do not inform societies about the true scale of havoc wrought both in somatic and psychic dimension in women who submit themselves to abortion. The actual trend is to try to suppress the humane sensitivity and consciousness which rise against lack of respect for the Godbegotten gift of a new life.


Translocation of glucokinase in pancreatic beta-cells during acute and chronic hyperglycemia.
Glucokinase (GK) plays a key role in the regulation of glucose-induced insulin secretion, and questions have been raised about its relationship to the glucose transporter GLUT2 and its function in diabetes. This study examined the location of immunostained GK and GLUT2 in beta-cells using confocal microscopy. On double stained sections from pancreases of normal fed rats, GLUT2 Texas Red staining was restricted to the plasma membrane, and GK fluorescein isothiocyanate staining was found in a limited area of cytoplasm that was perinuclear with slight extension toward the apical pole. The GK staining occupied 8.6 +/- 1.7% of total cytoplasmic area and was almost never adjacent to the GLUT2 staining of the plasma membrane. To determine whether the GK staining pattern is altered by metabolic perturbation, normal rats were made acutely hyperglycemic with iv glucose injections; after 20 min the GK staining changed from being localized to become diffusely distributed throughout the cytoplasm. To examine the influence of chronic hyperglycemia, rats were subjected to 90% partial pancreatectomy (Px), which produced glucose levels of 10.9-20.8 mM. When studied 6 or 14 days after Px, those rats with glucose levels greater than 17.7 mM had an altered GK staining pattern that was variable; in some beta-cells GK staining was diffuse and in others the localized staining pattern was preserved. GLUT2 staining was reduced overall, but variability between cells was observed, unlike the more uniform reductions seen with hyperglycemia of longer duration. Other rats received islet transplants to prevent hyperglycemia after Px; their GK and GLUT2 staining patterns were normal. These findings indicate that GK is translocated in association with acute and chronic hyperglycemia. The translocation of this key enzyme for glucose recognition by beta-cells may lead to altered rates of insulin secretion during acute perturbations of fuel provision and in the diabetic state.


[Clinicopathologic analysis of 19 cases of usual type vulvar intraepithelial neoplasia].
To reclassify the patients with former diagnosis of vulvar intraepithelial neoplasia (VIN)II, VINII-III, VINIII, Bowen disease and Bowenoid papulosis according to the 2004 modified terminology of International Society for the Study of Vulvar Disease (ISSVD) and evaluate the effects of surgical treatment. According to the 2004 modified terminology of ISSVD, a retrospective review of the histological slides of 19 cases, who diagnosed as VINII, VINII-III, VINIII, Bowen disease and Bowenoid papulosis treated in Peking Union Medical College Hospital from 1999 to 2006, were performed to reclassify by pathologist and the clinicopathologic data were also analyzed. According to the 2004 modified terminology of ISSVD, all 19 cases were reclassified as usual type VIN and were belonged to the subtype of warty type except one, the only Bowen disease patient whose one of focuses belonged to the subtype of basaloid type and the other focus belonged to the subtype of warty type. The primary cure rate of extended local excision was 89% (17/19). There were two cases recurred during follow-up period, and were cured by second surgical treatment and the focuses of recurrence site were still diagnosed as warty type VIN. The patients with former diagnosis of VINII, VINII-III, VINIII, Bowen disease and Bowenoid papulosis are basically reclassified as usual type VIN (warty type) according to the 2004 modified terminology of ISSVD. The results showed that the diagnosis of VIN could be simplified by new terminology. The surgical excision is the good choice and combined cytologic and human papillomavirus (HPV) test during follow up is also important for patients of VIN.


Assessing the Contributions of Motor Enzymes and Microtubule Dynamics to Mitotic Chromosome Motions.
During my graduate work with Keith Porter, I became fascinated by the mitotic spindle, an interest that has motivated much of my scientific work ever since. I began spindle studies by using electron microscopes, instruments that have made significant contributions to our understanding of spindle organization. Such instruments have helped to elucidate the distributions of spindle microtubules, the interactions among them, their molecular polarity, and their associations with both kinetochores and spindle poles. Our lab has also investigated some processes of spindle physiology: microtubule dynamics, the actions of microtubule-associated proteins (including motor enzymes), the character of forces generated by specific spindle components, and factors that control mitotic progression. Here, I give a personal perspective on some of this intellectual history and on what recent discoveries imply about the mechanisms of chromosome motion.


The role of infrequent and extraordinary deep dives in leatherback turtles (Dermochelys coriacea).
Infrequent and exceptional behaviours can provide insight into the ecology and physiology of a particular species. Here we examined extraordinarily deep (300-1250 m) and protracted (>1h) dives made by critically endangered leatherback turtles (Dermochelys coriacea) in the context of three previously suggested hypotheses: predator evasion, thermoregulation and exploration for gelatinous prey. Data were obtained via satellite relay data loggers attached to adult turtles at nesting beaches (N=11) and temperate foraging grounds (N=2), constituting a combined tracking period of 9.6 years (N=26,146 dives) and spanning the entire North Atlantic Ocean. Of the dives, 99.6% (N=26,051) were to depths <300 m with only 0.4% (N=95) extending to greater depths (subsequently termed ;deep dives'). Analysis suggested that deep dives: (1) were normally distributed around midday; (2) may exceed the inferred aerobic dive limit for the species; (3) displayed slow vertical descent rates and protracted durations; (4) were much deeper than the thermocline; and (5) occurred predominantly during transit, yet ceased once seasonal residence on foraging grounds began. These findings support the hypothesis that deep dives are periodically employed to survey the water column for diurnally descending gelatinous prey. If a suitable patch is encountered then the turtle may cease transit and remain within that area, waiting for prey to approach the surface at night. If unsuccessful, then migration may continue until a more suitable site is encountered. Additional studies using a meta-analytical approach are nonetheless recommended to further resolve this matter.


Understanding the Perception of Islamic Medicine Among the Malaysian Muslim Community.
This study was conducted to identify and describe the patients' perceptions of Islamic medicine based on gender, age, marital, educational level and working status among the Malaysian Muslim population. A nationwide interviewer-administered questionnaire survey was conducted in 2013. An open-ended questionnaire pertaining to Islamic medicine was used to increase the probability of capturing maximum data. This survey implemented a multistage design, stratified by state, proportionate to the size of the state population and was representative of the Malaysian population. Post-survey classification of results was performed accordingly. Complex data analysis was carried out using SPSS 16.0. The discussion was identified and categorised into various sections. The paper concludes that Islamic medicine has a major influence in the Malaysian Muslim community compared to other alternatives. Further, its potential for growth and importance especially for treating spiritual ailments cannot be denied. The respondents indicated that two factors motivate Islamic medicine in Malaysia: (1) the Muslim community opts for alternative healing because of their dissatisfaction with conventional methods; (2) Islamic medicine focuses only on healing spiritual-related problems. The average perception of respondents is that the function of Islamic medicine in healing physical diseases is undervalued and that it is not suitable to replace the functions of modern health institutions.


Transesophageal echocardiography-guided aortic thrombectomy in a patient with a mobile thoracic aortic thrombus.
Thoracic aortic thrombi are a well-known cause of distal embolic phenomena. There is a paucity of case reports because of the rarity of this condition, and thus clear management guidelines are lacking. The authors present a case of a mobile thoracic aortic thrombus managed by a surgical approach. This report demonstrates how intraoperative transesophageal echocardiography (TEE) proved to be critical in guiding surgical management. The utility of TEE in the diagnosis and management of aortic thrombi is also discussed. In addition, currently reported management strategies for this complex condition are reviewed.


A call to action: supporting health care reform through sustaining the home care & hospice network.
On February 24, 2009, President Barack Obama addressed a joint session of the 111th Congress and promised the American people that despite the Nation's current economic crisis, "We will rebuild, we will recover, and the United States of America will emerge stronger than before". As a central tenet of the 44th President's blueprint for restoring the country, he has committed to investing some $675 billion to move the nation toward health care coverage for all. In an effort to help make this a reality, the president has begun a series of public meetings to advance the discourse. I was privileged to be part of the initial Health Care Summit held at the White House on March 5, and look forward to participating in future discussions with policymakers and stakeholders.


Nimesulide reduces interleukin-1beta-induced cyclooxygenase-2 gene expression in human synovial fibroblasts.
To characterize the effects of nimesulide (NIM) on basal and induced cyclo-oxygenase-2 (COX-2) gene expression in human synovial fibroblasts (HSF) and to define the intracellular mechanisms that mediate the changes in COX-2 expression and synthesis in response to the drug. HSF were incubated with NIM and NS-398 (0, 0.03, 0.3, 3 microg/ml) in the absence or presence of the COX-2 inducers interleukin-1beta (IL-1beta) or endotoxin (LPS). Treated cells were analysed for COX-2 mRNA and protein by Northern and Western blotting analysis, respectively. Putative transcriptional, post-transcriptional, and signaling effects of NIM on basal and induced-COX-2 expression were investigated by human COX-2 promoter studies, calcium studies, reactive oxygen species (ROS) evaluations, electrophoretic mobility shift analysis (EMSA) and half-life studies of COX-2 mRNA. NIM inhibited IL-1beta-induced COX-2 expression and protein at sub and therapeutic concentrations (0.03-0.3 microg/ml) while the non-specific NSAID, naproxen, did not. Both drugs suppressed PGE2 release by about 95%. NIM had no effect on (1) IL-1beta-induced increases in NF-kappaB or c/EBP signaling, or (2) human COX-2 promoter activity. Stability of induced COX-2 mRNA was unaffected by NIM treatments. Pre-treatment of cells with O(2)radical scavengers (e.g. PDTC) or with Ca(++)channel blockers (e.g. verapamil) had a modest effect on IL-1beta-induced COX-2 expression. NIM blocked ionomycin+thapsigargin and H(2)O(2)-induced increases in COX-2 protein synthesis. NIM inhibits cytokine-induced COX-2 expression and protein at sub and therapeutic concentrations. At least part of this activity may be the result of NIM inhibition of calcium and/or free radical generation induced by cytokines.


An investigation on intestinal absorption of a new anticancer drug, 2-methoxyestradiol.
In this paper, the intestinal absorptive property of a new anticancer drug, 2-methoxyestradiol (2ME2) was investigated by in situ rat intestinal recirculation perfusion experimental techniques. The results indicated that the concentrations of 2ME2 had no influence on absorption rate constant (ka) of 2ME2 and the small intestinal absorption of 2ME2 was a first-order process with passive diffusion mechanism within the concentration tested. 2ME2 was well absorbed at each intestinal segment except duodenum and the best site of intestinal absorption of 2ME2 was the ileum. In addition, the PH of drug perfusate and the concentration of SDS had significant effects on absorption kinetics. Faintly basic environment profitted small intestinal absorption of 2ME2. Tween 80 and SDS could not enhance the intestinal absorption of 2ME2. The above study provided a theoretical foundation for developing effective oral preparations with higher bioavailability to treat cancers. In addition, the improved ligation way for studying the best site of intestinal absorption of 2ME2, should be used extensively in related studies because of decreasing number of experimental rats and saving time.


Use of quantitative pharmacology in the development of HAE1, a high-affinity anti-IgE monoclonal antibody.
HAE1, a high-affinity anti-IgE monoclonal antibody, is discussed here as a case study in the use of quantitative pharmacology in the development of a second-generation molecule. In vitro, preclinical, and clinical data from the first-generation molecule, omalizumab, were heavily leveraged in the HAE1 program. A preliminary mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) model for HAE1 was developed using an existing model for omalizumab, together with in vitro binding data for HAE1 and omalizumab. When phase I data were available, the model was refined by simultaneously modeling PK/PD data from omalizumab studies with the available HAE1 phase I data. The HAE1 clinical program was based on knowledge of the quantitative relationship between a pharmacodynamic biomarker, suppression of free IgE, and clinical response (e.g., lower exacerbation rates) obtained in pivotal studies with omalizumab. A clinical trial simulation platform was developed to predict free IgE levels and clinical responses following attainment of a target free IgE level (</=10 IU/ml). The simulation platform enabled selection of four doses for the phase II dose-ranging trial by two independent methods: dose-response non-linear fitting and linear mixed modeling. Agreement between the two methods provided confidence in the doses selected. Modeling and simulation played a large role in supporting acceleration of the HAE1 program by enabling data-driven decision-making, often based on confirmation of projections and/or learning from incoming new data.


Effects of catecholamines infused into the brain of young chickens.
1. (-)-Noradrenaline, (-)-alpha-methylnoradrenaline and (-)-isoprenaline were infused into various brain regions of 12-21 day chicks. When infused into the hypothalamic area, but not the cerebral hemisphere or posterior mesencephalon, these amines produced behavioural sleep, lowered temperature and blood pressure and reduced oxygen consumption; electrocortical sleep activity usually ensued but this was not marked and frequently dissociation between electrocortical activity and behaviour occurred. After monoamine oxidase inhibition, which prolonged the action of noradrenaline, dopamine had similar effects.2. The effects of the catecholamines were prevented or substantially reduced by pretreatment with phenoxybenzamine given intravenously or into the hypothalamus but not by intravenous injection of propranolol. However, intrahypothalamic infusion of propranolol prevented the temperature, but not the behavioural effects of noradrenaline. The implications of this are discussed.3. That the effects were similar but more intense, apart from electrocortical changes, and of longer duration than those seen after intravenous injection of catecholamines suggests that in young chicks these amines penetrate from the blood into the brain and elicit their effects through a localized region, presumably the hypothalamus.


A yeast selection system for the detection of proteasomal activation.
The ubiquitin proteasome system (UPS) is a complex cellular machinery that catalyzes degradation of misfolded or damaged proteins and regulates turnover of native proteins in eukaryotic cells, thus playing a crucial role in maintaining protein homeostasis. The UPS has emerged as a drug target for a diverse range of diseases characterized by accumulation of misfolded or aggregated proteins. While enhancement of UPS activity is widely recognized as a promising strategy to prevent accumulation of aberrant, off-pathway protein conformations and ameliorate the phenotypes of a wide range of protein misfolding diseases, the molecular mechanisms underlying activation of proteasomal degradation are poorly characterized. We report the development of a yeast selection platform for genome-wide selection of UPS activators. We engineered the Saccharomyces cerevisiae selection marker orotidine-5'-phosphate decarboxylase (URA3) to function as a substrate of proteasomal degradation through fusion to UPS-sensitive tags. The resulting UPS-sensitive URA3 variant links UPS activity to cell growth. The yeast selection platform reported in this study will open the way to high-throughput, genome-wide studies aimed at identifying modulators of UPS function that might provide novel target for therapeutic applications.


Fluorescence quenching in model membranes. 3. Relationship between calcium adenosinetriphosphatase enzyme activity and the affinity of the protein for phosphatidylcholines with different acyl chain characteristics.
The dependence of function and lipid binding affinity of an integral transport protein on the fatty acyl chain characteristics of a membrane-forming phospholipid have been determined. When a newly developed fluorescence quenching technique [London, E., & Feigenson, G. W. (1981) Biochemistry (first paper of three in this issue); London, E., & Feigenson, G. W. (1981) Biochemistry (preceding paper in this issue)] is used for examining lipid-protein interactions in membranes, the Ca2+ ATPase from rabbit sarcoplasmic reticulum is found to bind with equal affinity a large variety of phosphatidylcholines used to reconstitute the protein into enzymatically active vesicles, regardless of fatty acyl chain length or details of unsaturation. In parallel with the lipid binding studies, we have measured the sensitivity of the catalytic activity of the Ca2+ ATPase to the fatty acyl chain characteristics of the phosphatidylcholine membranes in which the enzyme was reconstituted. The enzyme appears to be sensitive only to the effective fatty acyl chain length, which determines the thickness of the bilayer in which the protein is inserted and displays little sensitivity to such details of unsaturation as degree, position, and isomeric type. Both ATP hydrolyzing and Ca2+ transporting activities of the enzyme were similarly affected by bilayer thickness, and maximum activity was observed in membranes of intermediate thickness. These observations are reconciled in a number of possible models for the manner in which this integral protein interacts with membranes of varying thickness. A freeze-thaw method was used to reconstitute the Ca2+ ATPase, and the vesicles so obtained have been characterized by gel permeation chromatography, density gradient centrifugation, and electron microscopy, (thin section). Convenient methods are described for (a) rapidly separating reconstituted Ca2+ ATPase from unincorporated protein simultaneously in a large number of small samples, giving good recovery of fractionated vesicles without significant dilution, and (b) measuring leakiness to Ca2+ of reconstituted vesicles. Additionally, the gel and liquid-crystal phase transition temperature and bilayer thickness have been determined respectively by differential thermal analysis and low-angle X-ray diffraction for some of the synthetic phosphatidylcholines, which range in chain length from 12 to 24 carbon atoms.


The prevalence of giardia intestinalis in dyspeptic and diabetic patients.
Background and Aims. We aimed to investigate the prevalence of Giardiasis in patients with dyspepsia and patients with diabetes mellitus. Methods. 400 patients and 100 healthy persons were included in this clinical prospective study. The number of patients in each group was equal, 200 dyspeptic and 200 diabetic, respectively. The antigen of G. lntestinalis was determined in the stool specimens by ELISA method. Results. The frequency of Giardiasis was 7% in dyspeptic and 15% in diabetic patients. There was no positive results in any of the healthy persons. There was a significant difference in prevalence rate of Giardiasis between patients with dyspepsia and diabetes mellitus (P < 0.05). Conclusions. These results revealed that the prevalence of Giardiasis in dyspepsia and with diabetes mellitus was high in our country. This is the first study investigating the prevalence of Giardiasis in diabetic patients. To investigate Giardiasis in diabetic patients, who have dyspepsia or not, may be a good approach for public health.


The Role of Physical Activity and Mortality in Hemodialysis Patients: A Review.
Available data indicated that physical activity was related to improved outcomes in hemodialysis patients. Multiple observational studies involving different cohorts have reported that increased physical activity level was associated with decreased mortality among hemodialysis patients. Therefore, promoting physical activity has become an increasingly critical and promising approach to improving cardiovascular health and clinical outcomes in hemodialysis patients. This review summarizes the published articles regarding physical activity and hemodialysis patients, focusing on mortality and strategy to promote physical activity.


Reduction of common cold symptoms by encapsulated juice powder concentrate of fruits and vegetables: a randomised, double-blind, placebo-controlled trial.
Dietary supplements have been suggested in the prevention of the common cold, but previous investigations have been inconsistent. The present study was designed to determine the preventive effect of a dietary supplement from fruits and vegetables on common cold symptoms. In a randomised, double-blind, placebo-controlled trial, healthcare professionals (mainly nursing staff aged 18-65 years) from a university hospital in Berlin, Germany, were randomised to four capsules of dietary supplement (Juice Plus+®) or matching placebo daily for 8 months, including a 2-month run-in period. The number of days with moderate or severe common cold symptoms within 6 months (primary outcome) was assessed by diary self-reports. We determined means and 95 % CI, and differences between the two groups were analysed by ANOVA. A total of 529 subjects were included into the primary analysis (Juice Plus+®: 263, placebo: 266). The mean age of the participants was 39·9 (sd 10·3) years, and 80 % of the participants were female. The mean number of days with moderate or severe common cold symptoms was 7·6 (95 % CI 6·5, 8·8) in the Juice Plus+® group and 9·5 (8·4, 10·6) in the placebo group (P = 0·023). The mean number of total days with any common cold symptoms was similar in the Juice Plus+® and in the placebo groups (29·4 (25·8, 33·0) v. 30·7 (27·1, 34·3), P = 0·616). Intake of a dietary supplement from fruits and vegetables was associated with a 20 % reduction of moderate or severe common cold symptom days in healthcare professionals particularly exposed to patient contact.


[Biological function of some elements and their compounds. IV. Silicon, silicon acids, silicones].
The review is devoted for the occurance, meaning of silicon and their compounds, especially silicon acids and silicones. Silicon participates in biosynthesis of collagen, the basic component of connective tissue. It strengthens and makes the walls of blood vessels more flexible, diminishes capillaries permeability, accelerates healing processes, has a sebostatic activity, strengthens hair and nails. This element has a beneficial effect on phosphorylation of proteins saccharides, and nucleotides. It is also essential for the formation of cytoskeleton and other cellular structures of mechanical or supportive function. Silicon is an initial substrate for obtaining silicones. These are synthetic polymers, in which silicon atoms are bound by oxygen bridges. They are used in almost all kinds of products due to their most convenient physical and chemical properties: moistening and film-forming, giving liquid form increasing solubility. Silicon acids form colloid gel, silica gel, with absorptive abilities, like active carbon.


Remarkable rare-earth metal silicide oxides with planar Si6 rings.
New rare-earth silicide oxides, La10Si8O3 (1) and Ce10Si8O3 (2), were synthesized through high-temperature reactions of the pure elements under controlled oxygen atmosphere conditions. The remarkable silicides crystallize in a unique crystal structure (space group P6/mmm; a = 10.975(3) A (La) and 10.844(1) A (Ce); c = 4.680(1) A (La) and 4.561(1) A (Ce)) that features a 3-D framework of corner-shared O-centered (La/Ce)6 octahedra, reminiscent of hexagonal tungsten bronzes, with planar Si6 rings enclosed within its hexagonal channels. Band structure calculations indicate the compounds are metallic, with optimized La-Si bonds, and a benzene-like [Si6]6- anion. Compound 1 exhibits temperature independent paramagnetism. Compound 2 exhibits Curie-Weiss paramagnetism, and an antiferromagnetic ordering below 7 K.


Importance of Erythrocyte Deformability for the Alignment of Malaria Parasite upon Invasion.
Invasion of erythrocytes by merozoites is an essential step for the survival and progression of malaria parasites. To invade red blood cells (RBCs), apicomplexan parasites have to adhere with their apex to the RBC membrane. This necessary apex-membrane contact (or alignment) is not immediately established because the orientation of a free merozoite with respect to the RBC membrane is random when an adhesion contact first occurs. Therefore, it has been suggested that after the initial adhesion, merozoites facilitate their proper alignment by inducing considerable membrane deformations, frequently observed before the invasion process. This proposition is based on a positive correlation between RBC membrane deformation and successful invasion; however, the role of RBC mechanics and its deformation in the alignment process remains elusive. Using a mechanically realistic model of a deformable RBC, we investigate numerically the importance of RBC deformability for merozoite alignment. Adhesion between the parasite and RBC membrane is modeled by an attractive potential that might be inhomogeneous, mimicking possible adhesion gradients at the surface of a parasite. Our results show that RBC membrane deformations are crucial for successful merozoite alignment and require interaction strengths comparable to adhesion forces measured experimentally. Adhesion gradients along the parasite body further improve its alignment. Finally, an increased membrane rigidity is found to result in poor merozoite alignment, which can be a possible reason for a reduction in the invasion susceptibility of RBCs in several blood diseases associated with membrane stiffening.


Paravertebral schwannoma with high uptake of fluorodeoxyglucose on positron emission tomography.
A paravertebral mass was discovered in a 27-year-old woman, while investigating a painful shoulder and arm. CT, MRI and fine needle aspiration cytology (FNAC) pointed in the direction of a benign mass, but positron emission tomography (PET) showed a high uptake of [(18)F]fluorodeoxyglucose (FDG), which was indicative of a malignant lesion. Pathological analysis of the thoracoscopically resected tumour gave us the final diagnosis of a benign schwannoma. This report demonstrates that a high uptake of FDG in a non-malignant mediastinal tumour is possible.


A quantitative protocol for DNA metabarcoding of springtails (Collembola).
We developed a novel protocol with superior quantitative analysis results for DNA metabarcoding of Collembola, a major soil microarthropod order. Degenerate PCR primers were designed for conserved regions in the mitochondrial cytochrome c oxidase subunit I (mtCOI) and 16S ribosomal RNA (mt16S) genes based on published collembolan mitogenomes. The best primer pair was selected based on its ability to amplify each gene, irrespective of the species. DNA was extracted from 10 natural communities sampled in a temperate forest (with typically 25-30 collembolan species per 10 soil samples) and 10 mock communities (with seven cultured collembolan species). The two gene regions were then amplified using the selected primers, ligated with adapters for 454 technology, and sequenced. Examination of the natural community samples showed that 32 and 36 operational taxonomic units (defined at a 90% sequence similarity threshold) were recovered from the mtCOI and mt16S data, respectively, which were comparable to the results of the microscopic identification of 25 morphospecies. Further, sequence abundances for each collembolan species from the mtCOI and mt16S data of the mock communities, after normalization by using a species as the internal control, showed good correlation with the number of individuals in the samples (R = 0.91-0.99), although relative species abundances within a mock community sample estimated from sequences were skewed from community composition in terms of the number of individuals or biomass of the species. Thus, this protocol enables the comparison of collembolan communities in a quantitative manner by metabarcoding.


Mixed infections may promote diversification of mutualistic symbionts: why are there ineffective rhizobia?
While strategy variation is a key feature of symbiotic mutualisms, little work focuses on the origin of this diversity. Rhizobia strategies range from mutualistic nitrogen fixers to parasitic nonfixers that hoard plant resources to increase their own survival in soil. Host plants reward beneficial rhizobia with higher nodule growth rates, generating a trade-off between reproduction in nodules and subsequent survival in soil. However, hosts might not discriminate between strains in mixed infections, allowing nonfixing strains to escape sanctions. We construct an adaptive dynamics model of symbiotic nitrogen-fixation and find general situations where symbionts undergo adaptive diversification, but in most situations complete nonfixers do not evolve. Social conflict in mixed infections when symbionts face a survival-reproduction trade-off can drive the origin of some coexisting symbiont strategies, where less mutualistic strains exploit benefits generated by better mutualists.


Reducing measles mortality in India.
A large-scale campaign to promote measles vaccinations has substantially reduced the number of children dying from the disease in India.


Chemical functionality of poly(methylenephosphine): phosphine-borane adducts and methylphosphonium ionomers.
The chemical functionality of poly(methylenephosphine) n-Bu[MesP-CPh2]nH (2) is examined in reactions with two isoelectronic species, namely BH3 and CH3+. The potential reactivity of polymer 2 is modelled by examining the reactivity of molecular phosphines bearing similar substituents as the polymer. In particular, the phosphine-borane adducts Mes(Me)P(BH3)-CPh2H (4a) and Mes(Me)P(BH3)-CPh2SiMe2H (4b) are prepared from the reaction of BH3.SMe2 with Mes(Me)P-CPh2H (3a) or Mes(Me)P-CPh2SiMe2H (3b), respectively. Treating 3a with MeOTf affords the methylated model compound, [Mes(Me)2P-CPh2H]OTf (5). X-Ray crystal structures are reported for each model compound. The reaction of n-Bu[MesP-CPh2]nH (Mn = 3.89 x 10(4), PDI = 1.34) with BH3.SMe2 affords the phosphine-borane polymer n-Bu[MesP(BH3)-CPh2]nH (6) (Mn = 4.13 x 10(4), PDI = 1.26). In contrast, methylation of phosphine polymer 2 gives n-Bu[MesP-CPh2]x-/-[MesP(Me)-CPh2]yH.(OTf)y (7) where approximately 50% of the phosphine moieties are methylated (from 31P NMR).


Discordance between cytologic results in multiple thyroid nodules within the same patient.
To examine the frequency of discordant cytologic results between multiple thyroid nodules biopsied in the same patient. In a retrospective chart review of 441 consecutive patients, 326 (73.9%) had 2 or more nodules with colloid and/or thyroid cells recovered. Cytology was classified as (A) colloid only, (B) benign colloid nodule with or without degeneration, (C) Hashimoto's, or (D) follicular or Hürthle cell neoplasm, hyperplasia or suspicious for malignancy. Discordance was defined as having at least 2 different categories in the same patient. Twenty-four predetermined factors were analyzed, including demographics, laboratory values and ultrasound characteristics. The results, by category, were A, 164 (18.4%); B, 575 (64.6%); C, 131 (14.7%); and D, 20 (2.2%). Overall, 126 of 326 (38.7%) patients had at least 1 discordant grouping between their nodules. Of 326 patients, 165 had 2, 94 had 3, 48 had 4, 14 had 5, and 5 had 6 nodules biopsied, of which 48 (29.1%), 39 (41.5%), 29 (60.4%), 8 (57.1%) and 2 (40.0%), respectively, showed diagnostic discordances (p = 0.0007). The high rate (38.7%) of discordance between biopsies of multiple nodules in the same patient support a recommendation to biopsy all nodules that otherwise meet criteria for biopsy, as opposed to only the largest one.


Normal vector method for convergence improvement using the RCWA for crossed gratings.
The rigorous coupled wave analysis (RCWA) is a widely used method for simulating diffraction from periodic structures. Since its recognized formulation by Moharam [J. Opt. Soc. Am. A12, 1068 and 1077 (1995)], there still has been a discussion about convergence problems. Those problems are more or less solved for the diffraction from line gratings, but there remain different concurrent proposals about the convergence improvement for crossed gratings. We propose to combine Popov and Nevière's formulation of the differential method [Light Propagation in Periodic Media (Dekker, 2003) and J. Opt. Soc. Am. A18, 2886 (2001)] with the classical RCWA. With a suitable choice of a normal vector field we obtain a better convergence than for the formulations that are known from the literature.


MMR-proficient and MMR-deficient colorectal cancer cells: 5-Fluorouracil treatment response and correlation to CD133 and MGMT expression.
Cancer stem cells (CSCs) from colorectal cancer (CRC), characterized by CD133 expression, have been associated with 5-fluorouracile (5-FU) chemoresistance. DNA repair mechanisms, such as O6-alkylguanine DNA alkyltransferase (MGMT) and mismatch repair (MMR) systems, have also been correlated to 5-FU resistance in CRC. The aim of this study was to evaluate the modulation of CD133 and MGMT in MMRproficient and MMR-deficient CRC cells under 5-FU treatment and the effect of this drug in CSCs. CD133 and MGMT methylation status were determined in MMR-proficient (SW480 and HT29) and MMR-deficient (RKO and HCT116) cell lines by methylation-specific PCRs. SW480 and RKO were selected to determine modulation of CD133, MGMT and MMR expression after 5-FU treatment by qPCR. In addition, CD133, MGMT and MMR were analyze in SW480 and RKO CSCs. No association between promoter methylation and MGMT and CD133 expression was found. 5-FU treatment increased CD133 expression independently to MMR status in SW480 and RKO and was able to increase hMLH1 expression in RKO, a MMR-deficient cell line. RKO/ CSCs overexpressed CD133 and MMR (hMSH2 and hMSH6) while SW480/CSCs showed a significant increase in CD133, MMR (hMLH1, hMSH2 and hMSH6) and MGMT, moreover 5-FU resistance than parental cell lines. Thus, although CSCs 5-FU chemoresistance appears to be independently to MMR status, hMLH1 might play a key role in CSC response to 5-FU. New drugs exploding these differences could benefit the prognostic of patients with CRC.


Gender identity disorder.
Gender Identity Disorder (GID) is a relatively rare condition of atypical gender development in which there is a psychological perception of self as masculine or feminine which is incongruent with ones phenotype. GID replaced the term Transsexualism in DSM-IV in 1994. The demographics of GID in Ireland have not been established. Since 2000 we have received 52 referrals of individuals with confirmed GID to our endocrine service for consideration for hormonal treatment (HT). Of the 52 patients 45 have male to female (MTF) GID (mean age 38.9 years) and 7 have female to male (FTM) GID (mean age 30.7 years). The age at presentation in this group is approximately 9 years older than in international series for both MTF (39 years v 30yrs) and FTM (31 yrs v 22yrs). The karyotype where analysed has been normal for their phenotypic sex. Twenty-three of the patients had received HT prior to attending our clinic that in only one case had been prescribed by a specialist. A number of patients had obtained HT via the internet or from overseas sources without medical review. Eighteen of the patients have been or are married and 14 of the group have children. The scale of referrals confirms that GID exists in the Irish population to a significant degree. Thus an appropriate care pathway for people with the condition needs to be established. This will facilitate optimum medical management of the patient group and a coherent approach to the many difficult social issues faced individuals with this disorder.


Anti-hepcidin therapy for iron-restricted anemias.
In this issue of Blood, Cooke et al demonstrate the potential of a fully human anti-hepcidin antibody as a novel therapeutic for iron-restricted anemias such as anemia of inflammation, cancer, or chronic kidney disease (formerly known as "anemia of chronic diseases").


Characterization of CD4 glycoprotein determinant-HIV envelope protein interactions: perspectives for analog and vaccine development.
The CD4 surface determinant, previously associated as a phenotypic marker for helper/inducer subsets of T lymphocytes, has now been critically identified as the binding/entry protein for human immunodeficiency viruses (HIV). The human CD4 molecule is readily detectable on monocytes, T lymphocytes, and brain tissues. Soluble HIV (HTLV IIIB) envelope protein (gp120) binds native or recombinant CD4 with equal affinity estimated to be 4 to 8 nM kDa. All human tissue sources of CD4 bind radiolabeled gp120 to the same relative degree; however, the murine homologous protein, L3T4, does not bind the HIV envelope protein. Lack of sufficient recognition by the recombinant L3T4 molecule suggests divergence in the gp120-binding epitope. The binding of gp120 to CD4 is dependent upon intact sulfhydryl bonds within cysteine residues and glycosylation. Deglycosylated native gp120 is unable to bind CD4 under physiological conditions. Recombinant deglycosylated fragments cannot bind to the CD4 receptor, although they serve as immunogen for neutralizing antibody development. A number of synthetic peptides to putative critical domains of gp120 have been studied for their antagonism of native gp120 binding. Peptide T analogs or synthetic cogeners of Neuroleukin proposed to bind the CD4 determinant involved in gp120 binding had no competitive displacement of native gp120 binding as assessed by two independent methods that measure gp120 interaction with CD4. Recombinant C-terminal fragments, also containing other putative domains, did not displace native gp120 from CD4. Glycosylation appears to be critical in the maintenance of the structure of the binding domain of gp120. Native gp120 binding to CD4 is sufficient for the activation of cellular metabolism that alters target cell gene expression and differentiation, suggesting that the virus binding contributes to the activation of the host cell.


Reducing the treatment gap for mental disorders: a WPA survey.
The treatment gap for people with mental disorders exceeds 50% in all countries of the world, approaching astonishingly high rates of 90% in the least resourced countries. We report the findings of the first systematic survey of leaders of psychiatry in nearly 60 countries on the strategies for reducing the treatment gap. We sought to elicit the views of these representatives on the roles of different human resources and health care settings in delivering care and on the importance of a range of strategies to increase the coverage of evidence-based treatments for priority mental disorders for each demographic stage (childhood, adolescence, adulthood and old age). Our findings clearly indicate three strategies for reducing the treatment gap: increasing the numbers of psychiatrists and other mental health professionals; increasing the involvement of a range of appropriately trained non-specialist providers; and the active involvement of people affected by mental disorders. This is true for both high income and low/middle income countries, though relatively of more importance in the latter. We view this survey as a critically important first step in ascertaining the position of psychiatrists, one of the most influential stakeholder communities in global mental health, in addressing the global challenge of scaling up mental health services to reduce the treatment gap.


An impossible journey? The development of Plasmodium falciparum NF54 in Culex quinquefasciatus.
Although Anopheles mosquitoes are the vectors for human Plasmodium spp., there are also other mosquito species-among them culicines (Culex spp., Aedes spp.)-present in malaria-endemic areas. Culicine mosquitoes transmit arboviruses and filarial worms to humans and are vectors for avian Plasmodium spp., but have never been observed to transmit human Plasmodium spp. When ingested by a culicine mosquito, parasites could either face an environment that does not allow development due to biologic incompatibility or be actively killed by the mosquito's immune system. In the latter case, the molecular mechanism of killing must be sufficiently powerful that Plasmodium is not able to overcome it. To investigate how human malaria parasites develop in culicine mosquitoes, we infected Culex quinquefasciatus with Plasmodium falciparum NF54 and monitored development of parasites in the blood bolus and midgut epithelium at different time points. Our results reveal that ookinetes develop in the midgut lumen of C. quinquefasciatus in slightly lower numbers than in Anopheles gambiae G3. After 30 hours, parasites have invaded the midgut and can be observed on the basal side of the midgut epithelium by confocal and transmission electron microscopy. Very few of the parasites in C. quinquefasciatus are alive, most of them are lysed. Eight days after the mosquito's blood meal, no oocysts can be found in C. quinquefasciatus. Our results suggest that the mosquito immune system could be involved in parasite killing early in development after ookinetes have crossed the midgut epithelium and come in contact with the mosquito hemolymph.


The interaction between current smoking and hemoglobin on the risk of advanced fibrosis in patients with biopsy-proven nonalcoholic fatty liver disease.
Higher hemoglobin levels have been associated with an increased risk for nonalcoholic fatty liver disease. Although the mechanism underlying this association is elusive, smoking has been previously related to both higher hemoglobin concentrations and an increased risk of fibrosis in nonalcoholic fatty liver disease. The present study was conducted to investigate formally the interaction among current smoking, hemoglobin levels, and risk for advanced fibrosis in patients with biopsy-proven nonalcoholic fatty liver disease. We examined 433 Turkish patients with biopsy-proven nonalcoholic fatty liver disease. Advanced fibrosis (F ≥ 3) was identified on liver biopsy in 80 cases, whereas 84 patients were current smokers. Logistic regression models were used to evaluate the effect of current smoking on risk for advanced fibrosis, after adjusting for the effects of age, sex, BMI, diabetes, and metabolic syndrome. Preliminary analyses revealed the presence of substantial statistical interaction between current smoking and hemoglobin levels (P < 0.001). In separate multivariable analyses conducted in the entire cohort and in the subgroups of patients with high and low hemoglobin levels (according to median value in the study cohort: 14.4 g/l), current smoking was associated with increased risk for advanced fibrosis in patients with high hemoglobin (odds ratio: 3.32, 95% confidence interval: 1.23-7.21, P < 0.01) but neither in those with low hemoglobin (odds ratio: 0.71, 95% confidence interval: 0.28-1.81, P = 0.52) nor in the entire study cohort (odds ratio: 1.18, 95% confidence interval: 0.73-2.14, P = 0.79). Hemoglobin acts as a modifier in the association between current smoking and advanced fibrosis in nonalcoholic fatty liver disease.


Nucleotide and negatively charged lipid-dependent vesicle aggregation caused by SecA. Evidence that SecA contains two lipid-binding sites.
SecA which is an overall acidic protein was found to induce an increase in the turbidity of a solution of vesicles consisting of negatively charged phospholipids. This increase was found to be due to an aggregation of the vesicles mediated by SecA. The SecA-mediated vesicle aggregation was not found for zwitterionic 1,2-dioleoyl-sn-glycero-3-phosphocholine and showed a large dependence on both temperature and ionic strength. Furthermore it was shown that ATP and to a lesser extent ADP+Pi were able to reduce the SecA-mediated vesicle aggregation, while no effect could be seen for a non-hydrolysable ATP analog AMP-PNP. Using the steady state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene present in 1,2-dioleoyl-sn-glycero-3-phosphoglycerol vesicles we could show that SecA inserts in the bilayer. Monolayer studies confirmed that SecA is able to cause close contact between two membranes and gave a direct insight into the different types of lipid-protein interactions involved. From our results we propose that the SecA monomer possesses two lipid-binding sites which in the functional dimer conformation are responsible for the SecA-mediated vesicle aggregation.


Variation in use of informatics tools among providers in a diabetes clinic.
A goal of health information technology (HIT) is to help eliminate variation when it may compromise safety, efficiency, or quality of care. This study utilized direct observation and semi-structured interviews to examine variability in HIT use among four nurse practitioners and four physicians in an ambulatory diabetes clinic and to assess the impact of this variability on patient care. While use of informatics tools for information access and communication was similar among all users, variability existed in patterns of data entry into the EMR. The study provides direction for developing new functionality that may be needed in HIT and suggests changes to existing functionality. By designing tools that meet user needs and workflows, adoption of informatics applications may be enhanced and patient safety and user satisfaction improved.


Cigarette sharing and gifting in rural China: a focus group study.
To understand the reasons behind gifting and sharing cigarettes in China's rural areas and how these practices contribute to smoking initiation and hamper smoking cessation efforts. A convenience sample of 31 current smokers and nonsmokers was selected from a rural farming town in Hunan, China. Participants were divided into 6 focus groups according to gender and smoking status. Focus groups discussed the reasons behind gifting and sharing cigarettes as well as the effect these practices have on tobacco initiation and cessation. In rural China, individual cigarettes are primarily shared as a mechanism to convey respect and intimacy. Packs of cigarettes are given primarily due to their convenience as well as being well liked by both smokers and nonsmokers. Sharing individual cigarettes by both peers and older relations contributed to individuals beginning to smoke. Sharing cigarettes among friends was also a major hindrance to smoking cessation. Gifting and sharing cigarettes significantly contribute to smoking in rural China. Future tobacco control efforts should discourage both these activities to reduce tobacco usage. Tobacco control measures should also aim to inform adults about the health consequences of giving cigarettes to adolescents. Similarly, more information on the benefits of smoking cessation should be provided to China's rural elderly population. This information could lead to increased community support of cessation efforts and ultimately result in reductions in smoking in rural China.


Dense ionic fluids confined in planar capacitors: in- and out-of-plane structure from classical density functional theory.
The ongoing scientific interest in the properties and structure of electric double layers (EDLs) stems from their pivotal role in (super)capacitive energy storage, energy harvesting, and water treatment technologies. Classical density functional theory (DFT) is a promising framework for the study of the in- and out-of-plane structural properties of double layers. Supported by molecular dynamics simulations, we demonstrate the adequate performance of DFT for analyzing charge layering in the EDL perpendicular to the electrodes. We discuss charge storage and capacitance of the EDL and the impact of screening due to dielectric solvents. We further calculate, for the first time, the in-plane structure of the EDL within the framework of DFT. While our out-of-plane results already hint at structural in-plane transitions inside the EDL, which have been observed recently in simulations and experiments, our DFT approach performs poorly in predicting in-plane structure in comparison to simulations. However, our findings isolate fundamental issues in the theoretical description of the EDL within the primitive model and point towards limitations in the performance of DFT in describing the out-of-plane structure of the EDL at high concentrations and potentials.


Identifying as a Good Parent: Considering the Communication Theory of Identity for Parents of Children Receiving Palliative Care.
Background: Parents of seriously ill children are at risk of psychosocial morbidity, which may be mitigated by competent family-centered communication and role-affirming conversations. Parent caregivers describe a guiding desire to do a good job in their parenting role but also depict struggling under the intense weight of parental duty. Objectives and Design: Through this case study, the Communication Theory of Identity (CTI) provides a framework for conceptualizing how palliative care teams can help parents cope with this reality. CTI views communication with care teams as formative in the development and enablement of parental perceptions of their "good parenting" role. Results: Palliative care teams may consider the four frames of identity (personal, enacted, relational, and communal) as meaningful dimensions of the parental pursuit to care well for an ill child. Conclusion: Palliative care teams may consider compassionate communication about parental roles to support the directional virtues of multilayered dynamic parental identity.


Function and cell surface phenotype of dendritic cells from rat cornea.
To isolate dendritic cells (DC) from rat corneas and to examine their functions and surface markers in vitro. Cells were isolated enzymatically from dissected rat corneas and cultured for various intervals of time. Dendritic cells were enriched immunomagnetically from corneal cell preparations using monoclonal antibodies against DC surface antigens and tested for functional activity in lymphocyte stimulation assays. In vivo migration of DC was induced by traumatizing the corneal epithelium. Wholemounts of epithelial sheets were stained immunofluorescently with anti-DC antibodies and examined by confocal microscopy. Dendritic cells isolated from traumatized corneas were tested for functional activity. Corneal DC exhibited the properties of other members of the DC family, i.e., low buoyant density, lymphoid DC-specific markers, and lymphostimulatory function. In fresh unfractionated cell preparations of normal cornea, no functional activity was detected. However, DC immunomagnetically purified from fresh preparations were functionally active. Injury to the corneal epithelium induced the migration of DC from the periphery to the central cornea; DC measured in this situation showed significantly increased functional activity. Finally, IL-1 beta and GM-CSF enhanced the functional activity of corneal DC. Corneal DC have lymphostimulatory capacity in situ, but they may be maintained in a state of latency by the suppressive influence exerted by neighboring cells. Injury to the corneal epithelium results in functional activation of the corneal DC, which may be caused by cytokines such as IL-1 beta or GM-CSF. Thus, corneal DC may be important in the immune regulation of the anterior segment.


Perturbed cooperative-state feedback strategy for model predictive networked control of interconnected systems.
A perturbed cooperative-state feedback (PSF) strategy is presented for the control of interconnected systems in this paper. The subsystems of an interconnected system can exchange data via the communication network that has multiple connection topologies. The PSF strategy can resolve both issues, the sensor data losses and the communication network breaks, thanks to the two components of the control including a cooperative-state feedback and a perturbation variable, e.g., ui=Kijxj+wi. The PSF is implemented in a decentralized model predictive control scheme with a stability constraint and a non-monotonic storage function (ΔV(x(k))≥0), derived from the dissipative systems theory. Numerical simulation for the automatic generation control problem in power systems is studied to illustrate the effectiveness of the presented PSF strategy.


A novel steroid receptor co-activator protein (SRAP) as an alternative form of steroid receptor RNA-activator gene: expression in prostate cancer cells and enhancement of androgen receptor activity.
We have cloned a cDNA coding for a novel steroid receptor co-activator protein termed SRAP from a rat prostate library. Although the nucleotide sequence of the SRAP has 78.2% identity to that of the human steroid receptor RNA activator (SRA), a novel RNA molecule which was reported to act as an RNA transcript without being translated into protein [Lanz, McKenna, Onate, Albrecht, Wong, Tsai, Tsai and O'Malley (1999) Cell 97, 17-27], the cDNA of SRAP is capable of generating a functional protein. Glutathione S-transferase pull-down assays showed that SRAP associates with the partial androgen receptor (AR) protein composed of a DNA-binding domain and an activation function 2. Luciferase assays demonstrated that SRAP enhances the transactivation activity of the AR, the glucocorticoid receptor and the peroxisome proliferator-activated receptor gamma(1) in a ligand-dependent manner. Using a green fluorescent protein (GFP) fusion-protein construct, we demonstrated in vivo translation of the GFP-SRAP fusion protein in HeLa cells co-transfected with pSG5AR and reporter gene in the presence of 5 alpha-dihydrotestosterone (DHT). Co-transfection of the GFP-SRAP fusion protein expression plasmid enhanced the transactivation activity of AR whereas incorporation of mutations in SRAP of the fusion protein resulted in loss of enhancement of the transactivation activity. Northern blot analysis and reverse transcriptase PCR assays showed that SRAP and SRA are expressed in rat and human prostate cancer cell lines respectively. In HeLa cells and the human prostate cancer cells line DU-145, co-transfected with SRAP, the DHT-dependent transactivation activities of AR were not completely inhibited by the anti-androgen flutamide, but the transactivation activities still remained high even in the presence of 5 microM flutamide, suggesting that SRAP may play an important role in enhancing AR activity in prostate cancer.


Insuring against earthquakes: simulating the cost-effectiveness of disaster preparedness.
Ex-ante measures to improve risk preparedness for natural disasters are generally considered to be more effective than ex-post measures. Nevertheless, most resources are allocated after an event in geographical areas that are vulnerable to natural disasters. This paper analyses the cost-effectiveness of ex-ante adaptation measures in the wake of earthquakes and provides an assessment of the future role of private and public agencies in disaster risk management. The study uses a simulation model approach to evaluate consumption losses after earthquakes under different scenarios of intervention. Particular attention is given to the role of activity diversification measures in enhancing disaster preparedness and the contributions of (targeted) microcredit and education programmes for reconstruction following a disaster. Whereas the former measures are far more cost-effective, missing markets and perverse incentives tend to make ex-post measures a preferred option, thus occasioning underinvestment in ex-ante adaptation initiatives.


Artificial Allomelanin Nanoparticles.
Allomelanin is a type of nitrogen-free melanin most commonly found in fungi. Its existence enhances resistance of the organisms to environmental damage and helps fungi survive harsh radiation conditions such as those found on spacecraft and inside contaminated nuclear power plants. We report the preparation and characterization of artificial allomelanin nanoparticles (AMNPs) via oxidative oligomerization of 1,8-dihydroxynaphthalene (1,8-DHN). We describe the resulting morphological and size control of AMNPs and demonstrate that they are radical scavengers. Finally, we show that AMNPs are taken up by neonatal human epidermal keratinocytes and packaged into perinuclear caps where they quench reactive oxygen species generated following UV exposure.


A comparison of time dependent Cox regression, pooled logistic regression and cross sectional pooling with simulations and an application to the Framingham Heart Study.
Typical survival studies follow individuals to an event and measure explanatory variables for that event, sometimes repeatedly over the course of follow up. The Cox regression model has been used widely in the analyses of time to diagnosis or death from disease. The associations between the survival outcome and time dependent measures may be biased unless they are modeled appropriately. In this paper we explore the Time Dependent Cox Regression Model (TDCM), which quantifies the effect of repeated measures of covariates in the analysis of time to event data. This model is commonly used in biomedical research but sometimes does not explicitly adjust for the times at which time dependent explanatory variables are measured. This approach can yield different estimates of association compared to a model that adjusts for these times. In order to address the question of how different these estimates are from a statistical perspective, we compare the TDCM to Pooled Logistic Regression (PLR) and Cross Sectional Pooling (CSP), considering models that adjust and do not adjust for time in PLR and CSP. In a series of simulations we found that time adjusted CSP provided identical results to the TDCM while the PLR showed larger parameter estimates compared to the time adjusted CSP and the TDCM in scenarios with high event rates. We also observed upwardly biased estimates in the unadjusted CSP and unadjusted PLR methods. The time adjusted PLR had a positive bias in the time dependent Age effect with reduced bias when the event rate is low. The PLR methods showed a negative bias in the Sex effect, a subject level covariate, when compared to the other methods. The Cox models yielded reliable estimates for the Sex effect in all scenarios considered. We conclude that survival analyses that explicitly account in the statistical model for the times at which time dependent covariates are measured provide more reliable estimates compared to unadjusted analyses. We present results from the Framingham Heart Study in which lipid measurements and myocardial infarction data events were collected over a period of 26 years.


The role of metronidazole in the treatment of periodontal diseases.
This article discusses the ability of metronidazole to improve periodontal health. Review of the drug's pharmacology and potential side effects indicate that it poses little threat to humans of inducing acute toxicity, mutagenesis, or cancer if used according to recommended dosing regimens. Studies addressing metronidazole utilization in a variety of clinical conditions demonstrate that its routine use does not enhance root planing. However, adjunctive antibiotic therapy may be advantageous in the treatment of sites where effective root planing is precluded due to deep pockets or when anaerobic periodontal infections do not respond to conventional therapy.


Reversing the negative cycle: interpreting the mutual influence of adaptive, self-protective measures in the couple.
The author discusses factors that shape the subjective meanings each member of the couple gives to marital interactions and the intersubjective disjunctions between the partners that can result. These include adaptive, self-protective mechanisms, the wish for mastery, guilt, and defense against grieving. Through illuminating these factors, psychoanalytic couple therapy can enhance empathic awareness of how each partner's attitudes, actions, and once adaptive defenses can actualize the other's transference expectations and evoke his or her painful and traumatic childhood relationships and experiences.


Whole blood polymerase chain reaction in a neonate with disseminated herpes simplex virus infection and liver failure.
A late preterm neonate born by cesarean section with intact membranes presented at 9 days of life with shock and liver failure. Surface cultures were negative but whole blood polymerase chain reaction was positive for herpes simplex virus type 2, underscoring the value of this test in early diagnosis of perinatally acquired disseminated herpes simplex virus infection without skin lesions.


Interactions between glial progenitors and blood vessels during early postnatal corticogenesis: blood vessel contact represents an early stage of astrocyte differentiation.
The post-neurogenic period in the mammalian neocortex is characterized by the growth of astrocyte and oligodendrocyte populations and their incorporation into the network of the developing central nervous system (CNS). Many of these glial cells originate as progenitors in the subventricular zone (SVZ) and then migrate into white and gray matter before differentiating. What determines the specific cellular fate of progenitors in vivo is not known, however. In examining the early stages of gliogenesis from progenitors in the SVZ, we noted that interactions with cortical blood vessels took place at what appeared to be an early stage of glial differentiation. We have examined in more detail the interactions of progenitors with blood vessels in the early postnatal rat neocortex after labeling progenitors in vivo with a LacZ-encoding retrovirus. These early interactions are accompanied by an increase in intermediate filament expression, consistent with astrocytic differentiation. Because astrocytes interact with blood vessels and pia, we suggest that such contact represents an early stage in astrocytic differentiation. Furthermore, since angiogenesis and astrogenesis occur over a similar period, the growth of blood vessels may even play a role in the selection of astrocytic fate by a progenitor. As vessel growth slows, fewer progenitors may be directed toward an astrocyte fate, allowing more to differentiate into oligodendrocytes, perhaps explaining the shift from astrocyte genesis to oligodendrocyte genesis during early postnatal cortical development.


The use of the arcs software system to store and examine sleep research results.
Ready access to research results is essential if nurses are to keep current with the scientific knowledge available to guide practice. Sigma Theta Tau International has supported the development of a software system that facilitates ongoing storage of information from research reports and can be used to gain online access to continually updated databases of research results called "knowledgebases." One such experimental knowledgebase, the Sleep Promotion Knowledgebase, includes studies of correlates of poor sleep in adults as well as sleep interventions and outcomes. The authors describe the creation of the Sleep Promotion Knowledgebase using arcs BUILDER to store information about research reports and the scientific findings they contain. The use of arcs MAPPER to examine sleep promotion interventions also is described. The strengths and limitations of the software system are identified, and the potential uses of arcs to disseminate sleep research results are discussed.


Human serum transferrin: is there a link among autism, high oxalate levels, and iron deficiency anemia?
It has been previously suggested that large amounts of oxalate in plasma could play a role in autism by binding to the bilobal iron transport protein transferrin (hTF), thereby interfering with iron metabolism by inhibiting the delivery of iron to cells. By examining the effect of the substitution of oxalate for the physiologically utilized synergistic carbonate anion in each lobe of hTF, we sought to provide a molecular basis for or against such a role. Our work clearly shows both qualitatively (6 M urea gels) and quantitatively (kinetic analysis by stopped-flow spectrofluorimetry) that the presence of oxalate in place of carbonate in each binding site of hTF does indeed greatly interfere with the removal of iron from each lobe (in the absence and presence of the specific hTF receptor). However, we also clearly demonstrate that once the iron is bound within each lobe of hTF, neither anion can displace the other. Additionally, as verified by urea gels and electrospray mass spectrometry, formation of completely homogeneous hTF-anion complexes requires that all iron must first be removed and hTF then reloaded with iron in the presence of either carbonate or oxalate. Significantly, experiments described here show that carbonate is the preferred binding partner; i.e., even if an equal amount of each anion is available during the iron loading process, the hTF-carbonate complex is formed.


Amylolytic activity in fruits: comparison of different substrates and methods using banana as model.
Several methodologies have been developed for cereal amylolytic activity estimation, but there is lack of information about the application of these methods for fruits. Mature green banana fruit can achieve 20% of starch content which is degraded during the ripening period in a complex process involving alpha- and beta-amylases and alpha-1,4 and alpha-1,6-glucosidases, besides phosphorylases that can compete for the same substrates. Methods used to determine total hydrolytic activity and individual activity of enzymes involved in starch breakdown were compared for banana extracts in several ripening stages. Total hydrolytic activity was measured by DNS and iodometric methods. Endoamylolytic activity on amylose-azure substrate was also evaluated. BPNPG7 and PNPG5 chromogenic substrates were used for alpha- and beta-amylase activities, respectively. The results showed that methods that depend on the use of thermal treatment or on inhibitors to inactivate one of the enzymes were not adequate. The use of p-nitrophenol derivatives seemed to be the most specific, reproducible, and easiest method employed for single alpha- and beta-amylases activities determination in complex tissues. The DNS and iodometric methods can be used only for initial screenings of total hydrolytic activity, because the nonspecific substrate used in these procedures allows the action of more than one enzyme simultaneously.


Chemical Characterization, Nutritional and Bioactive Properties of Physalis peruviana Fruit from High Areas of the Atacama Desert.
Physalis peruviana L. belongs to the Solanaceae family and produces a spherical fruit used to treat various diseases. However, the chemical composition, nutritional characterization, and bioactive properties of the P. peruviana growing in the Andean region of the Atacama Desert have not been conducted so far. The results showed clear differences in the nutritional and bioactive characteristics of the fruits grown in arid environmental conditions, which were comparable to those from countries with a production tradition. The fruits studied showed a higher Ca, Cu, Mn, P, and Zn content and bioactive compounds such as flavonoids and tannins than those reported in the literature. UHPLC was performed to determine the main phenols. Gallic acid was identified as the predominant phenolic compound in this species (303.63 mg/100 g FW), of which to our knowledge no previous study has reported similar concentrations in this species. Moreover, Cape gooseberry extract has antioxidant and antimicrobial activity against Gram-positive and Gram-negative bacteria. Pseudomonas syringae (MIC 0.313 mg/mL and MBC 1.25 mg/mL) was the most susceptible bacterium. Meanwhile, Erwinia rhapontici was the most resistant bacterium (MIC and MIB 5.00 mg/mL). Furthermore, it was found to inhibit α-amylase activity with an IC50 value (39.28 µg/mL) similar to that of acarbose (35.74 µg/mL). These results expand the knowledge of the species cultivated in arid environmental conditions and suggest an alternative for the potential use of this fruit to manage chronic diseases such as diabetes.


Surface functionalization by decal-like transfer of thermally cross-linked urushiol thin films.
We have demonstrated surface functionalization through the decal-like transfer of thermally cross-linked urushiol thin films onto various substrates. Tensile adhesive strength measurements showed that the film adheres strongly to the surface of various substrates including chemically inert materials, such as polyolefins and thermosetting resins, because of the properties of urushiol. Furthermore, the highly cross-linked structure of urushiol made the films mechanically robust. These two properties allowed the fabrication of practicable thin films for indirect surface modification. Actually, the robust thin film served as a scaffold for an Au thin film, which was then bound to various substrates. Surface-texturing of nanodecal was also demonstrated as an application aspects.


Coronavirus Disease 2019: A Wake-Up Call for Neurosurgeons to Learn Percutaneous Tracheostomy.
Tracheostomy is a commonly performed operation in neurosurgical patients. It is an aerosol generating procedure and is considered a high-risk operation in times of the coronavirus disease 2019 pandemic. Though percutaneous tracheostomy has been around for some time, many neurosurgeons still perform open surgical tracheostomy as they have been trained in doing so and are well versed with the procedure. However, this pandemic is a wake-up call for them to learn a new skill that is simple, quick, and has several advantages over the traditional method.


Histologic classification of tumor-infiltrating lymphocytes in primary cutaneous malignant melanoma. A study of interobserver agreement.
The density and distribution of lymphocytes infiltrating the vertical growth phase of primary cutaneous melanomas has been suggested by several studies to be of prognostic significance. However, few pathologists comment on tumor-infiltrating lymphocytes (TILs), and there is the perception that the assessment of TILs is subject to great interobserver variability. We studied interobserver agreement on the categorization of TILs; 20 cases of primary cutaneous malignant melanoma with a vertical growth phase component were circulated among 3 pathologists and 3 dermatologists. For each case, TILs were classified as brisk, nonbrisk, or absent according to Clark. Only 1 pathologist (a dermatopathologist) was familiar with the classification of TILs. Observers were given written guidelines and a brief tutorial before their examination of the slides. Our results show that with little instruction, overall agreement among observers was good (kappa values, 0.6 or more), especially among pathologists (kappa values, > 0.7). Three observers had excellent agreement among each other (kappa values, > 0.75). These findings suggest that the categorization of TILs can be easily taught and can be applied with an acceptable level of reproducibility in routine diagnostic practice.