Second primary malignancies in colorectal cancer patients.
The prevalence of second primary malignancies (SPMs) in the western world is continually increasing with the risk of a new primary cancer in patients with previously diagnosed carcinoma at about 20%. The aim of this retrospective analysis is to identify SPMs in colorectal cancer patients in a single-institution cohort, describe the most frequent SPMs in colorectal cancer patients, and discover the time period to occurrence of second primary tumors. We identified 1174 patients diagnosed with colorectal cancer in the period 2003-2013, with follow-up till 31.12.2018, and median follow-up of 10.1 years, (median age 63 years, 724 men). A second primary neoplasm was diagnosed in 234 patients (19.9%). Older age patients, those with early-stage disease and those with no relapse have a higher risk of secondary cancer development. The median time from cancer diagnosis to development of CRC was 8.9 years for breast cancer and 3.4 years for prostate cancer. For the most common cancer diagnosis after primary CRC, the median time to development was 0-5.2 years, depending on the type of malignancy. Patients with a diagnosis of breast, prostate, or kidney cancer, or melanoma should be regularly screened for CRC. CRC patients should also be screened for additional CRC as well as cancers of the breast, prostate, kidney, and bladder. The screening of cancer patients for the most frequent malignancies along with systematic patient education in this field should be the standard of surveillance for colorectal cancer patients.


Percentage and severity of periodontal diseases in Turkish adults aged 35+ years, 2009-10.
This article presents data on the burden of periodontal diseases in Turkish adults aged 35 years or older. Within each region of Turkey, a rural and an urban area or city were selected in 2009-10 using a probability proportional to size method. In the selected towns, local officials who were familiar with their communities assisted in recruiting subjects. Loss of Attachment (LOA) was measured at six sites around each tooth present in the mouth, excluding third molars. Additionally, the Community Periodontal Index was used to assess the severity of periodontal diseases around 12 index teeth. Self-reported data on key risk factors were also collected. Weights were computed using a raking ratio adjustment procedure and used in all analyses. Almost all examined adults had some loss of periodontal attachment. The proportion of those with more than 3 mm LOA ranged from 43 percent in 35-44 year olds to 91 percent in those aged 65+ years. Among females, older age, low education status, smoking 11-40+ cigarettes a day, being employed, and presence of high number of missing tooth surfaces were associated with LOA > 3 mm. Among males LOA >3 mm was associated with older age, use of alcohol, and unemployment. The CPI data did not yield the same associations with periodontal diseases and risk factors. Periodontal diseases in Turkish adults are highly prevalent. A tailored common risk factor health promotion program is recommended to reduce the burden of periodontal infection in Turkey.


BMI in the Associations of Plant-Based Diets with Type 2 Diabetes and Hypertension Risks in Women: The E3N Prospective Cohort Study.
Few studies have evaluated the quality of plant-based diets in relation to chronic diseases, and the potential role of BMI is not clearly explored. To study the associations between plant-based diet indices and type 2 diabetes (T2D) and hypertension risks, as well as the extent to which the associations were modified and/or mediated by BMI. The study included 74,522 women from the Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale prospective cohort [mean (SD): age, 52.94 (6.7) years; BMI, 22.970 (3.328) kg/m2]. Dietary data were collected at baseline (1993) via an FFQ. Overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI) were developed. Multivariable Cox regression models were used to derive HRs and 95% CIs. Effect modification and mediation by BMI were explored. There were 3292 (4.64%) incident cases of T2D and 12,504 (27.14%) incident cases of hypertension over ∼20 years of follow-up. In the multivariable model further adjusted for BMI, higher adherence to PDI and hPDI was associated with lower T2D and hypertension risks, with an HR per 1-SD increase (95% CI) of 0.88 (0.85, 0.91) and 0.96 (0.94, 0.98) for PDI and 0.88 (0.85, 0.92) and 0.94 (0.92, 0.95) for hPDI, respectively. uPDI was not associated with T2D [0.98 (0.94, 1.01)], whereas a positive association was observed with hypertension: 1.04 (1.02, 1.06). There was interaction between PDI and uPDI, as well as BMI, on T2D (P-interaction < 0.001) but not on hypertension (P-interaction > 0.05). In addition, BMI mediated 26-59% and 0.2-59% of diet-T2D and diet-hypertension associations, respectively. Differential associations between plant-based diets and T2D and hypertension risks were observed among women in this large prospective study. Only healthier plant foods were associated with lower risks, partly through decreasing BMI. The protocol was registered at clinicaltrials.gov as NCT03285230.


Neonatal iron overload and tissue siderosis due to gestational alloimmune liver disease.
Gestational alloimmune liver disease is the main cause of the neonatal hemochromatosis phenotype, wherein severe neonatal liver disease is associated with iron overload and extrahepatic tissue siderosis. How fetal liver disease produces extrahepatic siderosis is not known. We hypothesized that fetal liver injury causes deficient hepcidin production and poor regulation of placental iron flux. Under the resulting conditions of iron overload, the tissue pattern of extrahepatic siderosis is determined by the normal expression of proteins involved in the import of non-transferrin-bound iron and the export of cellular iron. Liver and extrahepatic tissues from infants with gestational alloimmune liver disease were examined and compared to normal age-appropriate tissues. Serum iron indices indicate iron overload and excess non-transferrin bound iron in gestational alloimmune liver disease. The diseased liver showed significantly reduced hepcidin, hemojuvulin, and transferrin gene expression compared to the normal fetal and neonatal liver. Those extrahepatic tissues that are typically involved in pathological siderosis in neonatal hemochromatosis, whether from normal or diseased newborns, consistently expressed solute carrier family 39 (zinc transporter), member 14 (ZIP14) for non-transferrin-bound iron uptake and expressed little ferroportin for iron export. Excess non-transferrin-bound iron in gestational alloimmune liver disease may result from fetal liver injury that causes reduced synthesis of key iron regulatory and transport proteins. Whereas, the pattern of extrahepatic siderosis appears to be determined by the normal capacity of various tissues to import non-transferrin-bound iron and not export cellular iron.


Prostate-specific antigen as surrogate for characterizing prostate cancer subgroups.
To evaluate how serum prostate-specific antigen (PSA) levels in a population-based cohort of men with prostate cancer vary with age and intensity in the diagnostic activity and to describe the treatment selection processes associated with PSA level. All men in the Swedish National Prostate Cancer Register diagnosed during 1996-1997 were included. In 1996 the register included 19 counties, covering 61% of the Swedish male population, and in 1997 21 counties with 79% of the Swedish male population. A total of 8328 men were registered. PSA levels were missing in 341 cases. With increasing PSA there was a shift towards more advanced and poorly differentiated tumours. PSA at diagnosis increased with age, with the exception of patients younger than 50 years who had higher PSA values. The mean logarithm of PSA correlated negatively with the percentage of localized tumours (p < 0.005) and the age-adjusted incidence (p < 0.05) in each respective county in 1997. PSA was higher in men receiving radiotherapy compared with those treated with radical prostatectomy as well as in the group treated with bilateral orchiectomy compared with those receiving GnRH-analogues. If PSA is used as a surrogate measure of extent of tumour volume in a population of prostate cancer patients, our findings indicate that age distribution and differences in incidence (possibly due to variation in diagnostic activity) should be taken into account. In our cohort there was a selection process, probably in part guided by PSA level, when choosing type of curative or palliative treatment.


Cardiovascular actions of berberine.
Berberine, is an alkaloid from Hydrastis canadensis L., Chinese herb Huanglian, and many other plants. It is widely used in traditional Chinese medicine as an antimicrobial in the treatment of dysentery and infectious diarrhea. This manuscript describes cardiovascular effects of berberine and its derivatives, tetrahydroberberine and 8-oxoberberine. Berberine has positive inotropic, negative chronotropic, antiarrhythmic, and vasodilator properties. Both derivatives of berberine have antiarrhythmic activity. Some cardiovascular effects of berberine and its derivatives are attributed to the blockade of K+ channels (delayed rectifier and K(ATP)) and stimulation of Na+ -Ca(2+) exchanger. Berberine has been shown to prolong the duration of ventricular action potential. Its vasodilator activity has been attributed to multiple cellular mechanisms. The cardiovascular effects of berberine suggest its possible clinical usefulness in the treatment of arrhythmias and/or heart failure.


Cyclic changes in the organization of cell adhesions and the associated cytoskeleton, induced by stimulation of tyrosine phosphorylation in bovine aortic endothelial cells.
In this study we have investigated the relationships between the stimulation of tyrosine-specific protein phosphorylation and the state of assembly of cell-cell and cell-matrix adherens-type junctions. Bovine aortic endothelial (BAE) cells were treated with either the phosphotyrosine phosphatase inhibitor pervanadate or with epidermal growth factor (EGF), and the effect of the treatment on the organization of cell contacts and the actin cytoskeleton was evaluated by digital immunomicroscopy. We show here that pervanadate induced a dramatic (about 40-fold) increase in the level of phosphotyrosine labeling of cell-cell junctions, which reached maximal values following 20 minutes of incubation. Concomitantly, the junctional levels of vinculin, actin and plakoglobin increased, followed by a slower recruitment of cadherins to these sites. Upon longer incubation cell-cell junctions deteriorated and stress fibers and focal adhesions were formed. EGF stimulation of serum-starved BAE cells induced a rapid 'wave' of junctional tyrosine phosphorylation, followed by cyclic changes in the local levels of phosphotyrosine labeling. Periodic changes were also found in the intensity of labeling of junctional actin, vinculin and cadherins. These results suggest that tyrosine phosphorylation and the assembly of cell-cell adherens junctions are interdependent processes, and raise the possibility that the cross-talk between the two is responsible both for the regulation of junction formation and for adhesion-mediated signaling.


Efficient silencing of EGFP reporter gene with siRNA delivered by asymmetrical N4,N9-diacyl spermines.
It is important to obtain structure-activity relationship (SAR) data across cationic lipids for the self-assembly and nonviral intracellular delivery of siRNA. The aims of this work are to carry out a SAR study on the efficiency of asymmetrical N(4),N(9)-diacyl spermines in siRNA delivery and EGFP reporter gene silencing, with comparisons to selected mixtures composed of symmetrical N(4),N(9)-diacyl spermines. Another important aim of these studies is to quantify the changes in cell viability, assayed with alamarBlue, as a function of lipid structure. Therefore, we have designed, synthesized, purified, and assayed novel cationic lipids that are asymmetrical lipopolyamines based on spermine. Flow cytometry and fluorescence microscopy in an EGFP stably transfected HeLa cell line, measuring both delivery of fluorescently tagged siRNAs and silencing the EGFP signal, allowed quantitation of the differences between asymmetrical cationic lipids, mixtures of their symmetrical counterparts, and comparison with commercial nonviral delivery agents. Intracellular delivery of siRNA and gene silencing by siRNA differ with different hydrophobic domains. In these asymmetrical N(4),N(9)-diacyl spermines, lipids that enhance siRNA uptake do not necessarily enhance siRNA-induced inhibition of gene expression: C18 and longer saturated chains promote uptake, while more unsaturated C18 chains promote gene silencing. These properties are efficiently demonstrated in a new nontoxic cationic lipid siRNA vector, N(4)-linoleoyl-N(9)-oleoyl-1,12-diamino-4,9-diazadodecane (LinOS), which is also shown to be comparable with or superior to TransIT-TKO and Lipofectamine 2000.


Randomized control trial comparing calcium hydroxide and mineral trioxide aggregate for partial pulpotomies in cariously exposed pulps of permanent molars.
To compare the treatment outcomes when calcium hydroxide and mineral trioxide aggregate are used for partial pulpotomy in cariously exposed young permanent molars in a randomized control trial. Eighty-four teeth in 80 volunteers (aged 7-10 years) with reversible pulpitis and carious pulp exposures were randomly divided into two groups. Exposed pulps were severed using high-speed round burs until fresh pulp was seen. Cavities were irrigated with 2.5% sodium hypochlorite, and the pulp exposures were photographed and measured. Dycal or ProRoot MTA was placed on the pulp. Vitremer was placed over the material until the remaining cavity was 2 mm deep; amalgam was then placed. Teeth were evaluated for clinical symptoms and radiographic periapical changes after 24 h, 3 months, 6 months, 1 year and 2 years. Mean survival times and incidence of extraction were calculated using exact binomial confidence intervals. The median survival time for both ProRoot MTA and Dycal groups was 24 months. Three teeth had unfavourable outcomes with the incidence rate of 0.20/100 tooth-months with ProRoot MTA (95% CI: 0.02-0.71) and 0.11/100 tooth-months with Dycal (95% CI: 0.001-0.60). The incidence of unfavourable outcomes was 0.05/100 (95% CI: 0.001-0.30) and 2.38/100 (95% CI: 0.29-8.34) tooth-months in teeth with small (<5 mm(2) ) and large (>5 mm(2) ) pulp exposure areas, respectively. Partial pulpotomy in teeth of young patients with reversible pulpitis, either using ProRoot MTA or Dycal, resulted in favourable treatment outcomes for up to 2 years. The incidence of unfavourable outcomes tended to be higher in teeth with pulp exposure areas larger than 5 mm(2) .


Evidence for oxidative activation of mitoxantrone in human, pig, and rat.
A new metabolite of mitoxantrone in human, rat, and pig urine has been discovered by means of HPLC. The metabolite has been isolated by preparative HPLC from patient urine and is characterized by tandem mass spectrometry and UV-visible spectroscopy as 8,11-dihydroxy-4-(2-hydroxyethyl)-6-[[2-[(2-hydroxyethyl)amino]ethyl] amino]-1,2,3,4,7,12-hexahydronaphtho-[2,3-f]-chinoxaline-7,1 2-dione. Final structural proof has been obtained by independent synthesis. The new metabolite is a product of the enzymatic oxidation of the phenylenediamine substructure of mitoxantrone. An important biological consequence of the oxidative biotransformation is the possibility of covalent binding to intracellular targets via a highly electrophilic intermediate. Thus, alkylation may be an important mode of action of mitoxantrone. Incubation of mitoxantrone with horseradish peroxidase/hydrogen peroxide in the presence of glutathione led to the formation of two glutathione conjugates of mitoxantrone. Their structures have been elucidated by combination of IonSpray (Sciex, Canada) ionization and tandem mass spectrometry. Radioactive mitoxantrone, synthesized from sodium [14C]cyanide, was used to determine interspecies variations between human and rat. The collected rat urine was analyzed by HPLC using a radioactivity monitoring detector and revealed significant differences in the biotransformation of mitoxantrone in rat compared to human. The main metabolites thus far described in human urine are not observed in rat urine.


Reducing inappropriate emergency department attendances--a review of ambulance service attendances at a regional teaching hospital in Scotland.
Emergency Departments (ED) in the UK have seen increasing attendance rates in recent years. Departments are now seeking strategies to reduce their attendances. A review of all ambulance attendances to the ED at Ninewells Hospital was conducted to identify if patients presenting by ambulance could be seen and treated more appropriately in other parts of the health service. A retrospective review of ambulance attendances to the ED at Ninewells Hospital over 7 non-consecutive days. The ambulance patient report form and the ED notes were reviewed by the duty consultant to deem whether it was appropriate for the patient to be presented to the ED. If inappropriate, an alternative destination was suggested. Additional data was collected on the source of the ambulance call. There were 910 attendances in the 7 days. 295 (32%) presented by ambulance. 32 had incomplete data and were excluded. 185 (70%) and 179 (68%) of the 263 were deemed appropriate from review of the patient report form and notes respectively. Of the inappropriate, 74.4% and 79.7% had primary care suggested as an alternative. Patients who call for their own ambulance and NHS24 had higher rates of inappropriate attendances. The ambulance services present one-third of the patients to the ED at Ninewells Hospital. 30%-32% were found to be attending inappropriately and 74%-80% of these could have been managed in primary care. Reducing inappropriate ambulance attendances could reduce the departmental patient load by 11%.


Lack of Effect of Medium Supplementation With Pyruvate and Hormones on Cytochrome P450-mediated Activity of Rat Hepatocytes in Primary Culture.
The loss of cytochrome P450 (CYP) -dependent activity continues to be a problem in the use of cultured hepatocytes in xenobiotic toxicity studies. It has been reported that the inclusion of pyruvate and various hormones in the culture medium improves the maintenance of various hepatic functions, including that of CYP2C11 mRNA expression. We have studied this further, by investigating the effects of the addition of pyruvate and hormones on various CYP-dependent enzyme activities and on the CYP-dependent toxicity of precocene II in rat hepatocyte cultures. No beneficial effects of this medium supplementation could be demonstrated.


Baffle fenestration with subsequent transcatheter closure. Modification of the Fontan operation for patients at increased risk.
Ventricular dysfunction, elevated pulmonary vascular resistance, and residual distal pulmonary artery distortion contribute to early mortality after a Fontan operation; they may be transient or reversible. A baffle fenestration, allowing right-to-left shunting, maintains cardiac output and limits right atrial pressure. A baffle fenestration was surgically created at the time of a modified Fontan repair in 20 consecutive patients. Risk factors included pulmonary artery pressure of 18 mm Hg or more, end-diastolic pressure of 12 mm Hg or more, valvar regurgitation, pulmonary artery distortion, pulmonary vascular resistance of 2 Woods' units or more, ventricular outflow obstruction, and complex anatomy. Nineteen of 20 patients survived. After the operation, mean arterial oxygen saturation was 86%, mean right atrial pressure was 15 mm Hg, and mean duration of pleural effusions was 6 days. Twelve of 19 survivors tolerated early test occlusion and had permanent transcatheter umbrella closure. Four patients failed early test occlusion, with a significant decrease in venous O2 saturation and a rise in central venous pressure, due to ventricular dysfunction, pulmonary artery distortion, or aortopulmonary collaterals. Three of four had successful late closure of the fenestration after correction of these abnormalities.


Difficult-to-diagnose diabetes in a patient treated with cyclophosphamide - the contradictory roles of immunosuppressant agents: a case report.
Cyclophosphamide may induce autoimmune diabetes through a decrease in suppressor T cells and increase of proinflammatory T helper type 1 response in animal models. In humans, this association is not as clear due to the presence of other risk factors for hyperglycemia, but it could be a precipitant for acute complications. A 31-year-old Mestizo-Mexican woman with a history of systemic lupus erythematosus presented with severe diabetic ketoacidosis, shortly after initiating a multi-drug immunosuppressive therapy. She did not meet the diagnostic criteria for type 1 or type 2 diabetes and had no family history of hyperglycemic states. She persisted with hyperglycemia and high insulin requirements until the discontinuation of cyclophosphamide. After this episode, she recovered her endogenous insulin production and the antidiabetic agents were successfully withdrawn. After 1 year of follow up she is still normoglycemic. Cyclophosphamide may be an additional risk factor for acute hyperglycemic crisis. Glucose monitoring could be recommended during and after this treatment.


Primary pulmonary choriocarcinoma after human chorionic gonadotropin normalization following hydatidiform mole: a report of two cases.
Primary pulmonary choriocarcinoma (PPC) is rare and frequently leads to death. Two young patients presented with previous molar pregnancy and spontaneous serum human chorionic gonadotropin (hCG) normalization. Patient 1 was referred to our center after partial response to chemotherapy. Pulmonary lobectomy was performed, and hCG rapidly declined. During further chemotherapy, liver metastasis was detected by positron emission tomography. Right hepatectomy was performed, and hCG declined for 28 days, but increased again despite chemotherapy. This patient died from hepatic failure 3 years after diagnosis. Patient 2 presented with persistently high hCG, though the affected organ was not identified. Chemotherapy was unsuccessful. Patient reevaluation showed an isolated pulmonary mass. Pulmonary lobectomy was performed; 2 weeks later, hCG was normal and consolidation with 2 cycles of chemotherapy was administered. The patient has been in remission for 24 months. PPC was confirmed by histopathology and immunohistochemistry in both cases. Gestational origin of the tumor was confirmed by molecular genetic analysis (polymorphic microsatellite markers). The possibility of choriocarcinoma cannot be overlooked in young women with an isolated pulmonary mass. Early diagnosis, prompt chemotherapy, and surgical resection in a specialized center improves the prognosis.


Platelet Indices as Predictive Markers of Prognosis in Critically Ill Patients: A Prospective Study.
Platelets (PLTs) are dynamic blood molecules which perform multiple physiological functions. Platelet derangements are commonly encountered in intensive care units (ICUs). The relationship of PLT indices with all-cause mortality, acute physiology and chronic health evaluation IV (APACHE IV), diabetes mellitus (DM), and length of stay in ICU is debatable and hence this study was undertaken to bridge this gap of knowledge. Prospective data were collected for 20 months in the ICU of our hospital. Platelet indices were analyzed among survivors and non-survivors. Acute physiology and chronic health evaluation IV scores were used to study the relationship between PLT indices and illness severity. Receiver operating characteristic curves were constructed to compare the performances of PLT indices in predicting mortality, while the effect of DM on PLT indices was evaluated using regression analysis. A total of 170 out of 345 patients (119 survivors, 51 non-survivors) met the study criteria. Patients with decreased PLT count and plateletcrit (PCT) (p < 0.001 and 0.001, respectively), increased mean platelet volume (MPV) and platelet distribution width (PDW) (p = 0.014 and 0.004, respectively) had a significant correlation with increased risk of mortality than those with normal PLT indices. These patients also had a higher APACHE IV and acute physiology score (p < 0.001). No significant relationship was found between the PLT indices and the length of ICU stay. The influence of each PLT index adjusted to DM was significant in univariate regression analysis, whereas in multivariate only PDW had a significant influence. Patients with low PLT, PCT and high MPV, PDW were associated with more severe illness, poor prognosis, and a higher risk of mortality. Platelet distribution width is the preferred PLT index in a diabetic patient to predict clinical status. Platelet indices which are routinely available can be effectively used as a morbidity and mortality indicator in critically ill patients. Samuel D, Bhat AN, Prabhu VM. Platelet Indices as Predictive Markers of Prognosis in Critically Ill Patients: A Prospective Study. Indian J Crit Care Med 2020;24(9):817-822.


The National Institutes of Health's Biomedical Translational Research Information System (BTRIS): design, contents, functionality and experience to date.
The US National Institutes of Health (NIH) has developed the Biomedical Translational Research Information System (BTRIS) to support researchers' access to translational and clinical data. BTRIS includes a data repository, a set of programs for loading data from NIH electronic health records and research data management systems, an ontology for coding the disparate data with a single terminology, and a set of user interface tools that provide access to identified data from individual research studies and data across all studies from which individually identifiable data have been removed. This paper reports on unique design elements of the system, progress to date and user experience after five years of development and operation.


The effect of the dilated cardiomyopathy-causing Glu40Lys TPM1 mutation on actin-myosin interactions during the ATPase cycle.
Dilated cardiomyopathy (DCM), characterized by cardiac dilatation and contractile dysfunction, is a major cause of heart failure. DCM can result from mutations in the gene encoding cardiac α-tropomyosin (TM). In order to understand how the dilated cardiomyopathy-causing Glu40Lys mutation in TM affects actomyosin interactions, thin filaments have been reconstituted in muscle ghost fibers by incorporation of labeled Cys707 of myosin subfragment-1 and Cys374 of actin with fluorescent probe 1.5-IAEDANS and α-tropomyosin (wild-type or Glu40Lys mutant). For the first time, the effect of these α-tropomyosins on the mobility and rotation of subdomain-1 of actin and the SH1 helix of myosin subfragment-1 during the ATP hydrolysis cycle have been demonstrated directly by polarized fluorimetry. The Glu40Lys mutant TM inhibited these movements at the transition from AM(∗∗)·ADP·Pi to AM state, indicating a decrease of the proportion of the strong-binding sub-states in the actomyosin population. These structural changes are likely to underlie the contractile deficit observed in human dilated cardiomyopathy.


Photoinduced ultrafast dynamics of coumarin 343 sensitized p-type-nanostructured NiO films.
Photoinduced electron transfer from the valence band of nanocrystalline NiO, a p-type semiconductor, to an excited bound dye, coumarin 343, and the subsequent recombination have been measured by femtosecond transient absorbance spectroscopy probing with white light. It was found that both processes are nonexponential. The photoinduced electron transfer from the semiconductor to the excited bound dye has an ultrafast component (approximately 200 fs), which is comparable to the time constants measured for photoinduced electron injection in C343-TiO2 colloid solutions. The process is very efficient and constitutes the main path of deactivation of the excited dye. Back electron transfer is also remarkably fast, with the main part of the recombination process happening with a time constant of approximately 20 ps. Dye-sensitized nanostructured p-type semiconductors are attractive materials due to their potential use as photocathodes in dye-sensitized solar cells and solid electrolytes in solid-state dye-sensitized solar cells. To our knowledge, this is the first time that the photoinduced electron-transfer kinetics of a sensitized p-type semiconductor has been studied.


Dreaming and the brain: toward a cognitive neuroscience of conscious states.
Sleep researchers in different disciplines disagree about how fully dreaming can be explained in terms of brain physiology. Debate has focused on whether REM sleep dreaming is qualitatively different from nonREM (NREM) sleep and waking. A review of psychophysiological studies shows clear quantitative differences between REM and NREM mentation and between REM and waking mentation. Recent neuroimaging and neurophysiological studies also differentiate REM, NREM, and waking in features with phenomenological implications. Both evidence and theory suggest that there are isomorphisms between the phenomenology and the physiology of dreams. We present a three-dimensional model with specific examples from normally and abnormally changing conscious states.


Comparative effectiveness of recommended versus less intensive drug combinations in secondary prevention of acute coronary syndrome.
The secondary prevention treatment for acute coronary syndrome (ACS) is based on the combined use of drugs from four therapeutic classes (beta-blockers, antiplatelet agents, statins, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers). The objective of this study was to compare the long-term effectiveness of the recommended therapeutic combination with those of incomplete combinations in secondary prevention of ACS. This cohort study used data from a representative sample of the French national healthcare insurance system database. Patients hospitalised for an incident ACS between 2006 and 2011 and aged ≥20 years at the time of ACS were included in the study. Effectiveness in preventing the composite outcome ACS, transient ischemic attack, ischemic stroke or all-cause-death was estimated using time-fixed and time-dependent Cox proportional hazards models with different definitions of exposure (at inclusion or determined daily during follow-up) and adjustment for patient characteristics, co-morbidities and co-medications. Of the 2874 patients included in the study, 33.9% were women; median age was 67 years (interquartile range: 56-77). The median duration of follow-up was 3.6 years (interquartile range: 2.2-5.3). Compared with the use of recommended combination, use of combination with three classes increased the risk of the composite outcome from 1.25 (95% confidence interval (95%CI), [1.07-1.47]) in the time-fixed model and from 1.40 (95%CI, [1.15-1.70]) or 1.42 (95%CI, [1.13-1.79]) in the time-dependent models. After ACS, the use of incomplete drugs combinations compared with the recommended four drugs combination was associated with a higher risk of cardiovascular morbidity and all-cause mortality. Copyright © 2017 John Wiley & Sons, Ltd.


Release of Matrix Metalloproteinases-2 and 9 by S-Nitrosylated Caveolin-1 Contributes to Degradation of Extracellular Matrix in tPA-Treated Hypoxic Endothelial Cells.
Intracranial hemorrhage remains the most feared complication in tissue plasminogen activator (tPA) thrombolysis for ischemic stroke. However, the underlying molecular mechanisms are still poorly elucidated. In this study, we reported an important role of caveolin-1 (Cav-1) s-nitrosylation in matrix metalloproteinase (MMP)-2 and 9 secretion from tPA-treated ischemic endothelial cells. Brain vascular endothelial cells (bEND3) were exposed to oxygen-glucose deprivation (OGD) for 2 h before adding recombinant human tPA for 6 h. This treatment induced a significant increase of MMP2 and 9 in the media of bEND3 cells and a simultaneous degradation of fibronectin and laminin β-1, the two main components of extracellular matrix (ECM). Inhibition of MMP2 and 9 with SB-3CT completely blocked the degradation of fibronectin and laminin β-1. ODG+tPA treatment led to Cav-1 shedding from bEND3 cells into the media. Notably, OGD triggered nitric oxide (NO) production and S-nitrosylationof Cav-1 (SNCav-1). Meanwhile tPA induced activation of ERK signal pathway and stimulates the secretion of SNCav-1. Pretreatment of bEND3 cells with C-PTIO (a NO scavenger) or U0126 (a specific ERK inhibitor) significantly reduced OGD-induced S-nitrosylation of Cav-1 in cells and blocked the secretion of Cav-1 and MMP2 and 9 into the media as well as the degradation of fibronectin and laminin β-1 in OGD and tPA-treated cells. These data indicate that OGD-triggered Cav-1 S-nitrosylation interacts with tPA-induced ERK activation to augment MMP2 and 9 secretion and subsequent ECM degradation, which may account for the exacerbation of ischemic blood brain barrier damage following tPA thrombolysis for ischemic stroke.


Predicting walking METs and energy expenditure from speed or accelerometry.
a) Compare the predictive potential of speed and CSA(hip) (Computer Science Applications accelerometer positioned on the hip) for level terrain walking METs (1 MET = VO2 of 3.5 mL.kg(-1).min(-1)) and energy expenditure (kcal.min(-1)); b) cross-validate previously published CSA(hip)- and speed-based MET and energy expenditure prediction equations; c) measure self-paced walking speed, exercise intensity (METs) and energy expenditure in the middle aged population. Seventy-two 35- to 45-yr-old volunteers walked around a level, paved quadrangle at what they perceived to be a moderate pace. Oxygen consumption was measured using the criterion Douglas bag technique. Speed, CSA(hip), heart rate, and Borg rating of perceived exertion were also monitored. Speed explained 10% more variance of walking METs than CSA(hip). Speed and mass explained 8% more variance of walking energy expenditure (kcal.min) than CSA(hip) and mass. The best previously published regression equations predict our walking METs and energy expenditures within 95% prediction limits of +/- 0.7 METs and +/- 1.0 kcal.min(-1), respectively. Women paced themselves at a significantly higher mean speed (5.5 km.h(-1)) and intensity (4.1 METs) than their male counterparts (5.2 km.h(-1) and 3.8 METs). Both genders expended approximately 0.75 kcal.kg(-1) for every kilometer of level terrain walked. Speed-based MET and energy expenditure predictions during level terrain walking were more accurate than those utilizing CSA(hip).


Giant cell reparative granuloma of the petrous temporal bone: a case report and literature review.
Giant cell reparative granuloma (GCRG) is an unusual, benign bone lesion that most commonly affects the maxilla and mandible; skull involvement is rare. The etiology is uncertain but may be related to trauma. GCRG is difficult to distinguish from giant cell tumor of the bone and has a lower recurrence rate. Thirteen reports of temporal bone GCRG in 11 patients have been reported. One report of a petrous GCRG in a 3-year-old girl has been identified. A 38-year-old male presented with a 2-year history of fullness in his left ear, ipsilateral hearing loss, and intermittent cacosmia. Computed tomography and magnetic resonance imaging revealed a large left-sided anterior temporal extradural mass. The patient underwent a left frontotemporal craniotomy and resection of a left temporal fossa tumor that involved the petrous and squamous parts of the temporal bone. The patient's post-operative course was uneventful, except for increased hearing loss secondary to opening of the epitympanum. Follow-up at one month revealed no other problems. Histopathology of the specimen was consistent with a giant cell reparative granuloma.


The promotion of intrauterine contraception in low- and middle-income countries: a narrative review.
The contribution of copper-bearing intrauterine devices (IUDs) to overall contraceptive protection has declined in many countries, despite their well-known advantages. In response, initiatives to promote this method have been undertaken. To review and interpret the experience of interventions to promote use of IUDs in low- and middle-income countries in order to provide strategic guidance for policies and programs. We conducted a systematic search of Medline, Popline, Embase and Global Health electronic databases for relevant journal papers, reports and gray literature since 2010. Telephone interviews were held with two donors and six international family planning organizations. We identified a total of 31 publications. Four reported the results of randomized control trials and three were derived from quasi-experiments. The majority were based on service statistics. Eight publications concerned interventions for HIV-positive women or couples, nine for postpartum or postabortion cases and 14 for general populations. Intervention approaches included vouchers, franchising of private practitioners, mobile outreach services, placement of dedicated staff in high-volume facilities and demand creation. Most publications adduced evidence of a positive impact and some reported impressively large numbers of IUD insertions. Results to date on the uptake of IUDs in postpartum interventions are modest. There is also almost no evidence of effects on IUD use at national levels. Implant uptake generally exceeded IUD uptake when both were offered. The evidence base is weak and offers few lessons on what strategies are most effective. The overall impression is that IUD use can be increased in a variety of ways but that progress is hampered by persistent adverse perceptions by both providers and potential clients. Provider enthusiasm is a key to success. The lack of a population impact stems in part from the fact that nearly all interventions are initiated by international organizations, with limited national reach except in small countries, rather than by government agencies.


An ideal preparation for dermal regeneration: skin renewal growth factors, the growth factor composites from porcine platelets.
The use of growth factor composites from platelets has been introduced to many areas of clinical applications and studies. With the richest source of growth factors (GFs), beneficial effects have been shown on tissue regeneration and wound healing. However, animal and clinical studies have revealed inconsistent outcomes with the use of platelet-derived growth factors (PDGFs), which were likely due to variations in the presence and concentrations of GFs between various sources. Autologous PDGFs are considered to be safer, but they are limited by the feasibility of large-scale production to be used extensively in the acute phase, greater surface area, or general cosmetic applications. This study employed a simple process to obtain growth factor composites from activated platelets of porcine origin, namely skin renewal growth factors (SRGF). The functions of SRGF were subsequently evaluated on cultured human fibroblasts, keratinocytes, and melanocytes. Our data revealed that SRGF significantly promoted the proliferation of fibroblasts, accompanied by increased expression of collagens (types I, III, IV, and VIII) and proteoglycans. Diminished proliferation and arrested differentiation of keratinocytes were evidenced by the attenuated expression of laminin V and keratin 10. In addition, SRGF also suppressed the growth of melanocytes and reduced the expression of microphthalmia-associated transcription factor (MITF), tyrosinase, and paired box 3 (PAX3), which mediates melanogensis. Our results suggest that SRGF possesses beneficial properties and is a promising and cost-effective composition for the development of a safe cosmetic agent or topical products for skin regeneration. The development of SRGF may also provide an alternative strategy for tissue engineering.


The impact of a short depression and anxiety screening tool in epilepsy care in primary health care settings in Zambia.
Up to 60% of the 50 million persons with epilepsy (PWE) worldwide have depression and anxiety and 80% of PWE live in low-income regions. Common psychiatric comorbidities are often unrecognized and undertreated. We developed and validated a 10-item screening tool for the detection of depression and anxiety at primary healthcare clinics in Zambia in which the baseline detection rate among PWE was 1%. We trained primary care clinic workers in selected clinics to use this screening tool. A retrospective chart review was conducted for 120 consecutive PWE who received care one month after training. Detection improved from 1% to 49%, and treatment was frequently initiated. Of the 120 screened, 59 (49.2%) scored above cutoff point of 18. Of these persons, 43 (73.0%) were positive for depression, 16 (23.0%) were positive for anxiety, 38 (64.4%) received counseling, 18 (30.5%) received antidepressants, and 3 (5.1%) were referred to a psychiatrist. Use of this screening tool resulted in improved mental health care for PWE.


Phacoemulsification alone versus phacoemulsification combined with trabeculectomy for primary angle-closure glaucoma.
Surgical outcomes of phacoemulsification only and phacoemulsification combined with trabeculectomy were compared in patients with primary angle-closure glaucoma (PACG). Clinical records of 41 consecutive patients were retrospectively reviewed, and there was no difference in best-corrected visual acuity and intraocular pressure preoperatively and at the final follow-up in both study groups. Regarding the number of anti-glaucoma medications, it was higher in the phacoemulsification combined with trabeculectomy group preoperatively than the phacoemulsification only group (p = 0.045), but both groups were taking similar quantities of medication at the final follow-up (p = 0.6). In addition, postoperative hypotony (two cases) occurred only after phacoemulsification combined with trabeculectomy, but not after phacoemulsification only. In one case after phacoemulsification only, a second operation was needed. There were no additional postoperative complications. In conclusion, both phacoemulsification only and phacoemulsification combined with trabeculectomy showed good surgical outcomes in PACG patients. Both procedures might be equally effective in treating patients with PACG.


Finished Genome of Zymomonas mobilis subsp. mobilis Strain CP4, an Applied Ethanol Producer.
Zymomonas mobilis subsp. mobilis is one of the most rigorous ethanol-producing organisms known to date, considered by many to be the prokaryotic alternative to yeast. The two most applied Z. mobilis subsp. mobilis strains, ZM4 and CP4, derive from Recife, Brazil, and have been isolated from sugarcane fermentations. Of these, ZM4 was the first Z. mobilis representative strain to be sequenced and analyzed. Here, we report the finishing of the genome sequence of strain CP4, which is highly similar but not identical to that of ZM4.


Lifecourse socioeconomic position and weight change among blacks: The Pitt County study.
The elevated prevalence of obesity among U.S. blacks has been attributed to low socioeconomic position (SEP), despite inconsistent empirical findings. It is unclear whether low SEP at various lifecourse stages differentially influences adulthood BMI and BMI change. Among 1167 black adults in the Pitt County Study, we examined independent cross-sectional and longitudinal associations between SEP, measured in childhood and adulthood, and BMI and 13-year BMI change. Low vs. high childhood SEP was measured by parental occupation and childhood household deprivation; low vs. high adulthood SEP was assessed by employment status, education, and occupation. Using childhood and adulthood SEP, four lifecourse SEP categories were created: low-low, low-high, high-low, high-high. We found no consistent associations between SEP and BMI or BMI change among men. Among women, we observed the expected inverse association between SEP and BMI at baseline. In multivariable-adjusted analyses, socioeconomically advantaged women demonstrated larger 13-year increases in BMI: skilled vs. unskilled parental occupation (6.1 vs. 4.8 kg/m2, p = 0.04); college-educated vs. < high school (6.2 vs. 4.5 kg/m2, p = 0.04); white-collar vs. blue-collar job (5.8 vs. 4.8 kg/m2, p = 0.05); and high-high vs. low-low lifecourse SEP (6.5 vs. 4.6 kg/m2, p = 0.02). For women in this black cohort, lower SEP predicted earlier onset of obesity; however, low SEP was less predictive of BMI increases over time. Our findings demonstrate complex patterns of association between SEP and BMI change among black women.


Characterization of the honeybee venom proteins C1q-like protein and PVF1 and their allergenic potential.
Honeybee (Apis mellifera) venom (HBV) represents an ideal model to study the role of particular venom components in allergic reactions in sensitized individuals as well as in the eusociality of Hymenoptera species. The aim of this study was to further characterize the HBV components C1q-like protein (C1q) and PDGF/VEGF-like factor 1 (PVF1). C1q and PVF1 were produced as recombinant proteins in insect cells. Their allergenic properties were examined by determining the level of specific IgE antibodies in the sera of HBV-allergic patients (n = 26) as well as by their capacity to activate patients' basophils (n = 11). Moreover, the transcript heterogeneity of PVF1 was analyzed. It could be demonstrated that at least three PVF1 variants are present in the venom gland, which all result from alternative splicing of one transcript. Additionally, recombinant C1q and PVF1 from Spodoptera frugiperda insect cells exhibited specific IgE reactivity with approximately 38.5% of sera of HBV-allergic patients. Interestingly, both proteins were unable to activate basophils of the patients, questioning their role in the context of clinically relevant sensitization. Recombinant C1q and PVF1 can build the basis for a deeper understanding of the molecular mechanisms of Hymenoptera venoms. Moreover, the conflicting results between IgE sensitization and lack of basophil activation, might in the future contribute to the identification of factors that determine the allergenic potential of proteins.


Urinary uranium concentrations in an enlarged Gulf War veteran cohort.
Depleted uranium was first used on a large scale as a major component of munitions and armaments employed by the U.S. armed forces during the Gulf War in 1991. In response to concern that exposure to depleted uranium may have been a cause of health problems suffered by returning veterans of that war, an already existing surveillance program following depleted uranium "friendly fire" victims was enlarged to assess the wider veteran community's exposure to depleted uranium. Between August 1998 and December 1999, 169 Gulf War veterans submitted 24-h urine samples for determination of urinary uranium concentration and questionnaires describing their potential exposures to depleted uranium while in the Gulf War theatre. Depleted uranium exposure assessment was determined from 30 separate questionnaire items condensed into 19 distinct exposure scenarios. Results of urine uranium analysis were stratified into high and low uranium groups with 0.05 microg uranium/g creatinine being the cut point and approximate upper limit of the normal population distribution. Twelve individuals (7.1%) exhibited urine uranium values in the high range, while the remaining 157 had urine uranium values in the low range. A repeat test of urine for 6 of these 12 produced uranium results in the low range for 3 of these individuals. Exposure scenarios of the high and low uranium groups were similar with the presence of retained shrapnel being the only scenario predictive of a high urine uranium value. Results emphasize the unlikely occurrence of an elevated urine uranium result and consequently any uranium-related health effects in the absence of retained depleted uranium metal fragments in the veterans.


Efficacy of Sofosbuvir, Velpatasvir, and GS-9857 in Patients With Hepatitis C Virus Genotype 2, 3, 4, or 6 Infections in an Open-Label, Phase 2 Trial.
Studies are needed to determine the optimal regimen for patients with chronic hepatitis C virus (HCV) genotype 2, 3, 4, or 6 infections whose prior course of antiviral therapy has failed, and the feasibility of shortening treatment duration. We performed a phase 2 study to determine the efficacy and safety of the combination of the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the NS3/4A protease inhibitor GS-9857 in these patients. We performed a multicenter, open-label trial at 32 sites in the United States and 2 sites in New Zealand from March 3, 2015 to April 27, 2015. Our study included 128 treatment-naïve and treatment-experienced patients (1 with HCV genotype 1b; 33 with HCV genotype 2; 74 with HCV genotype 3; 17 with genotype HCV 4; and 3 with HCV genotype 6), with or without compensated cirrhosis. All patients received sofosbuvir-velpatasvir (400 mg/100 mg fixed-dose combination tablet) and GS-9857 (100 mg) once daily for 6-12 weeks. The primary end point was sustained virologic response 12 weeks after treatment (SVR12). After 6 weeks of treatment, SVR12s were achieved by 88% of treatment-naïve patients without cirrhosis (29 of 33; 95% confidence interval, 72%-97%). After 8 weeks of treatment, SVR12s were achieved by 93% of treatment-naïve patients with cirrhosis (28 of 30; 95% CI, 78%-99%). After 12 weeks of treatment, SVR12s were achieved by all treatment-experienced patients without cirrhosis (36 of 36; 95% CI, 90%-100%) and 97% of treatment-experienced patients with cirrhosis (28 of 29; 95% CI, 82%-100%). The most common adverse events were headache, diarrhea, fatigue, and nausea. Three patients (1%) discontinued treatment due to adverse events. In a phase 2 open-label trial, we found sofosbuvir-velpatasvir plus GS-9857 (8 weeks in treatment-naïve patients or 12 weeks in treatment-experienced patients) to be safe and effective for patients with HCV genotype 2, 3, 4, or 6 infections, with or without compensated cirrhosis. ClinicalTrials.gov ID: NCT02378961.


Optical Sensors and Methods for Underwater 3D Reconstruction.
This paper presents a survey on optical sensors and methods for 3D reconstruction in underwater environments. The techniques to obtain range data have been listed and explained, together with the different sensor hardware that makes them possible. The literature has been reviewed, and a classification has been proposed for the existing solutions. New developments, commercial solutions and previous reviews in this topic have also been gathered and considered.


Titanium dioxide nanoparticles increase sensitivity in the next generation of the water flea Daphnia magna.
The nanoparticle industry is expected to become a trillion dollar business in the near future. Therefore, the unintentional introduction of nanoparticles into the environment is increasingly likely. However, currently applied risk-assessment practices require further adaptation to accommodate the intrinsic nature of engineered nanoparticles. Combining a chronic flow-through exposure system with subsequent acute toxicity tests for the standard test organism Daphnia magna, we found that juvenile offspring of adults that were previously exposed to titanium dioxide nanoparticles exhibit a significantly increased sensitivity to titanium dioxide nanoparticles compared with the offspring of unexposed adults, as displayed by lower 96 h-EC(50) values. This observation is particularly remarkable because adults exhibited no differences among treatments in terms of typically assessed endpoints, such as sensitivity, number of offspring, or energy reserves. Hence, the present study suggests that ecotoxicological research requires further development to include the assessment of the environmental risks of nanoparticles for the next and hence not directly exposed generation, which is currently not included in standard test protocols.


Thalidomide use: past history and current implications for practice.
To review the history of thalidomide, examine fears emanating from its renewed usage, and discuss the nurse's critical role in patient education. Published articles, abstracts, books, and clinical experience. In the early 1960s, the teratogenic effects of thalidomide became widely known. The words thalidomide and birth defects became permanently linked as a result of pregnant women who used thalidomide as a sedative, thus giving birth to children with horrific birth defects. As researchers look at novel properties of drugs and new indications in the oncologic setting, thalidomide has made a comeback, particularly in the treatment of multiple myeloma. Patient education is important to combat fear in using and prescribing thalidomide and is essential in preventing birth defects and other side effects associated with thalidomide use. Nurses are vital in the patient-education process, yet on extensive nursing literature search revealed limited publications regarding thalidomide. Nurses can prevent thalidomide-associated birth defects through comprehensive patient education and can assist patients in decreasing any anxiety related to potential and actual side effects. With careful patient monitoring and comprehensive education of physicians, nurses, and patients, it is possible to reap the benefits of thalidomide and avoid the tragedy of misues. Nurses are in the forefront of education, and their expertise will empower patients to use thalidomide responsibly.


Association of gene variants of the renin-angiotensin system with accelerated hippocampal volume loss and cognitive decline in old age.
Genetic factors confer risk for neuropsychiatric phenotypes, but the polygenic etiology of these phenotypes makes identification of genetic culprits challenging. An approach to this challenge is to examine the effects of genetic variation on relevant endophenotypes, such as hippocampal volume loss. A smaller hippocampus is associated with gene variants of the renin-angiotensin system (RAS), a system implicated in vascular disease. However, no studies to date have investigated longitudinally the effects of genetic variation of RAS on the hippocampus. The authors examined the effects of polymorphisms of AGTR1, the gene encoding angiotensin-II type 1 receptor of RAS, on longitudinal hippocampal volumes of older adults. In all, 138 older adults (age ≥60 years) were followed for an average of about 4 years. The participants underwent repeated structural MRI and comprehensive neurocognitive testing, and they were genotyped for four AGTR1 single-nucleotide polymorphisms (SNPs) with low pairwise linkage disequilibrium values and apolipoprotein E (APOE) genotype. Genetic variants at three AGTR1 SNPs (rs2638363, rs1492103, and rs2675511) were independently associated with accelerated hippocampal volume loss over the 4-year follow-up period in the right but not left hemisphere. Intriguingly, these AGTR1 risk alleles also predicted worse episodic memory performance but were not related to other cognitive measures. Two risk variants (rs2638363 and rs12721331) interacted with the APOE4 allele to accelerate right hippocampal volume loss. Risk genetic variants of the RAS may accelerate memory decline in older adults, an effect that may be conferred by accelerated hippocampal volume loss. Molecules involved in this system may hold promise as early therapeutic targets for late-life neuropsychiatric disorders.


Leadership Ostracism Behaviors From the Target's Perspective: A Content and Behavioral Typology Model Derived From Interviews With Chinese Employees.
Leadership ostracism denotes a severe work stressor, potentially entailing more serious negative effects than other types of workplace ostracism. However, scholars have paid relatively little attention to ostracism carried out by leaders, leaving the phenomenon insufficiently accounted for in the literature. Hence, the present study aims to explore the content and typology of leadership ostracism behavior by in-depth interviews and inductive analyses based on grounded theory, in order to give a thorough presentation and description of the leadership ostracism concept as perceived and construed by Chinese subordinates. Respondents were invited using a snowball sampling technique, and the final sample consisted of 26 individuals employed in different Chinese firms. Based on the reported experience of the interviewees, 11 concrete leadership ostracism behaviors emerged from the data. Further analyses revealed a leadership ostracism behavioral typology model reflecting five core categories, i.e., general ignoring, neglect, exclusion, differential treatment, and undermining. These findings appear to partly replicate and partly expand on previous conceptualizations of workplace ostracism, indicating that leadership ostracism may reflect a distinct variant of the phenomenon, eligible to be studied in its own right. The present study also discusses certain culture-specific aspects of leadership ostracism that can be taken into consideration in future studies.


The Nanomaterial Registry: facilitating the sharing and analysis of data in the diverse nanomaterial community.
The amount of data being generated in the nanotechnology research space is significant, and the coordination, sharing, and downstream analysis of the data is complex and consistently deliberated. The complexities of the data are due in large part to the inherently complicated characteristics of nanomaterials. Also, testing protocols and assays used for nanomaterials are diverse and lacking standardization. The Nanomaterial Registry has been developed to address such challenges as the need for standard methods, data formatting, and controlled vocabularies for data sharing. The Registry is an authoritative, web-based tool whose purpose is to simplify the community's level of effort in assessing nanomaterial data from environmental and biological interaction studies. Because the Registry is meant to be an authoritative resource, all data-driven content is systematically archived and reviewed by subject-matter experts. To support and advance nanomaterial research, a set of minimal information about nanomaterials (MIAN) has been developed and is foundational to the Registry data model. The MIAN has been used to create evaluation and similarity criteria for nanomaterials that are curated into the Registry. The Registry is a publicly available resource that is being built through collaborations with many stakeholder groups in the nanotechnology community, including industry, regulatory, government, and academia. Features of the Registry website (http://www.nanomaterialregistry.org) currently include search, browse, side-by-side comparison of nanomaterials, compliance ratings based on the quality and quantity of data, and the ability to search for similar nanomaterials within the Registry. This paper is a modification and extension of a proceedings paper for the Institute of Electrical and Electronics Engineers.


The protein antigens secreted in vivo by adult male Schistosoma mansoni.
Adult schistosomes can be transferred surgically from donor C57BL/6 mice to the portal veins of naive recipients with complete success. This procedure bypasses larval development and the antibody response of the host is directed against, and can be used to identify, those antigens released only by viable, mature parasites. Serum collected from the recipient mice (WTS) was used in Western blotting studies to probe fractionated parasite protein. Twelve immunodominant proteins were identified, ranging in molecular weight from 14 to 208 kDa. The magnitude of the IgG response against each antigen could be divided into 2 categories, on the basis of optical densitometry of the blots. In addition, defined parasite fractions were probed with WTS by Western blotting, in order to determine the relative abundance and distribution of each antigen in schistosome tissue. To confirm and expand on these initial observations, oligospecific polyclonal antibody for each immunogen was affinity purified from Western blots; it was then used in immunocytochemistry to identify the sources of secretion for 8 of the 12 antigens, at the cellular level. From the results, it appeared that after the transfer of adult worms, the first antibodies detected were mostly directed against the gastrodermis. At later times additional reactivity was expressed against the tegumental membrane. These differences probably reflect the relative abundances of the gut and tegumental secretory products.


Immunological and pharmacological strategies to reactivate HIV-1 from latently infected cells: a possibility for HIV-1 paediatric patients?
The limitations to establishing a viral reservoir facilitated by early cART in children could play a critical role in achieving natural control of viral replication upon discontinuation of cART, which could be defined as 'functional cure'. Viral reservoirs could provide a persistent source of recrudescent viraemia after withdrawal of cART, despite temporary remission of HIV-1 infection, as observed in the 'Mississippi baby'. Intensification of cART has been proposed as a strategy to control residual replication and to diminish the reservoirs. The effects of cART intensification with maraviroc persisted after discontinuation of the drug in HIV-1-infected adults. However, in HIV-1-infected children, the emergence of CXCR4-using variants occurs very early, and the use of CCR5 antagonists in these children as intensification therapy may not be the best alternative. New treatments to eradicate HIV-1 are focused on the activation of viral production from latently infected cells to purge and clear HIV-1 reservoirs. This strategy involves the use of a wide range of small molecules called latency-reversing agents (LRAs). Histone deacetylase inhibitors (HDACi) such as givinostat, belinostat and panobinostat, and class I-selective HDACis that include oxamflatin, NCH-51 and romidepsin, are the most advanced in clinical testing for HIV-1 LRAs. Panobinostat and romidepsin show an efficient reactivation profile in J89GFP cells, a lymphocyte HIV-1 latently infected cell line considered a relevant model to study post-integration HIV-1 latency and reactivation. Clinical trials with panobinostat and romidepsin have been performed in children with other pathologies and it could be reasonable to design a clinical trial using these drugs in combination with cART in HIV-1-infected children.


Cranio-morphometric and aDNA corroboration of the Austronesian dispersal model in ancient Island Southeast Asia: Support from Gua Harimau, Indonesia.
The Austronesian language is spread from Madagascar in the west, Island Southeast Asia (ISEA) in the east (e.g. the Philippines and Indonesian archipelagoes) and throughout the Pacific, as far east as Easter Island. While it seems clear that the remote ancestors of Austronesian speakers originated in Southern China, and migrated to Taiwan with the development of rice farming by c. 5500 BP and onto the northern Philippines by c. 4000 BP (the Austronesian Dispersal Hypothesis or ADH), we know very little about the origins and emergence of Austronesian speakers in the Indonesian Archipelago. Using a combination of cranial morphometric and ancient mtDNA analyses on a new dataset from Gua Hairmau, that spans the pre-Neolithic through to Metal Period (5712-5591cal BP to 1864-1719 cal BP), we rigorously test the validity of the ADH in ISEA. A morphometric analysis of 23 adult male crania, using 16 of Martin's standard measurements, was carried out with results compared to an East and Southeast Asian dataset of 30 sample populations spanning the Late Pleistocene through to Metal Period, in addition to 39 modern samples from East and Southeast Asia, near Oceania and Australia. Further, 20 samples were analyzed for ancient mtDNA and assigned to identified haplogroups. We demonstrate that the archaeological human remains from Gua Harimau cave, Sumatra, Indonesia provide clear evidence for at least two (cranio-morphometrically defined) and perhaps even three (in the context of the ancient mtDNA results) distinct populations from two separate time periods. The results of these analyses provide substantive support for the ADH model in explaining the origins and population history of ISEA peoples.


Is the current public health message on UV exposure correct?
Current sun safety messages stress the importance of sun protection in avoiding the consequences of excessive exposure to ultraviolet radiation (UVR), such as skin cancers, cataracts and other eye diseases, and viral infections caused by UV-induced immunosuppression. However, adequate exposure to UVR has an important role in human health, primarily through UV-induced production of vitamin D, a hormone essential to bone health. Vitamin D insufficiency may be associated with increased risks of some cancers, autoimmune diseases and mental health disorders such as schizophrenia. Here, we review the evolution of current sun exposure practices and sun-safe messages and consider not only the benefits, but also the detrimental effects that such messages may have. UVR-induced vitamin D production can be inhibited by factors such as deep skin pigmentation, indoor lifestyles, older age, sun avoidance behaviours and clothing habits that limit skin exposure, with deleterious consequences for health. There is some early evidence that sun-safe messages are beginning to cause a decrease in skin cancer rates in young people. After the widespread promotion of sun safety, it may now be appropriate to refine public health messages to take better account of variations between groups and their susceptibility to the dangers and benefits of sun exposure.


Intercellular communication by exchange of cytoplasmic material via tunneling nano-tube like structures in primary human renal epithelial cells.
Transfer of cellular material via tunneling nanotubes (TNT) was recently discovered as a novel mechanism for intercellular communication. The role of intercellular exchange in communication of renal epithelium is not known. Here we report extensive spontaneous intercellular exchange of cargo vesicles and organelles between primary human proximal tubular epithelial cells (RPTEC). Cells were labeled with two different quantum dot nanocrystals (Qtracker 605 or 525) and intercellular exchange was quantified by high-throughput fluorescence imaging and FACS analysis. In co-culture, a substantial fraction of cells (67.5%) contained both dyes indicating high levels of spontaneous intercellular exchange in RPTEC. The double positive cells could be divided into three categories based on the preponderance of 605 Qtracker (46.30%), 525 Qtracker (48.3%) and approximately equal content of both Qtrackers (4.57%). The transfer of mitochondria between RPTECs was also detected using an organelle specific dye. Inhibition of TNT genesis by actin polymerization inhibitor (Latrunculin B) markedly reduced intercellular exchange (>60%) suggesting that intercellular exchange in RPTEC was in part mediated via TNT-like structures. In contrast, induction of cellular stress by Zeocin treatment increased tube-genesis in RPTEC. Our data indicates an unexpected dynamic of intercellular communication between RPTEC by exchange of cytosolic material, which may play an important role in renal physiology.


A novel MIP gene mutation associated with autosomal dominant congenital cataracts in a Chinese family.
The major intrinsic protein gene (MIP), also known as MIP26 or AQP0, is a member of the water-transporting aquaporin family, which plays a critical role in the maintenance of lifelong lens transparency. To date, several mutations in MIP (OMIM 154050) have been linked to hereditary cataracts in humans. However, more pathogenic mutations remain to be identified. In this study, we describe a four-generation Chinese family with a nonsense mutation in MIP associated with an autosomal dominant congenital cataract (ADCC), thus expanding the mutational spectrum of this gene. A large four-generation Chinese family affected with typical Y-suture cataracts combined with punctuate cortical opacities and 100 ethnically matched controls were recruited. Genomic DNA was extracted from peripheral blood leukocytes to analyze congenital cataract-related candidate genes. Effects of the sequence change on the structure and function of proteins were predicted by bioinformatics analysis. Direct sequencing of MIP in all affected members revealed a heterozygous nucleotide exchange c.337C>T predicting an arginine to a stop codon exchange (p.R113X). The substitution co-segregated well in all the affected individuals in the family and was not found in unaffected members or in the 100 unrelated healthy controls. Bioinformatics analysis predicted that the mutation affects the secondary structure and function of the MIP protein. We identified a novel mutation of MIP (p.R113X) in a Chinese cataract family. This is the first nonsense mutation of MIP identified thus far. This novel mutation is also the first disease-causing mutation located in the loop C domain of MIP. The results add to the list of mutations of the MIP linked to cataracts.


Nicotine-induced tolerance and receptor changes in four mouse strains.
The effects of chronic infusion of 3.0 mg/kg/hr of nicotine on the behavioral responses of four mouse strains (C3H, C57BL, BALB and DBA) to challenge doses of nicotine and on the levels of cholinergic receptors and enzymes were determined. Mice of the C57BL, BALB and DBA strains developed tolerance to the effects of nicotine on Y-maze activity, Y-maze rearing and body temperature. The C3H mice did not exhibit any evidence of tolerance to the effects of nicotine on these measures, but this strain did show tolerance to the effects of nicotine on acoustic startle response. None of the strains developed tolerance to the effects of nicotine on respiration rate, and only the BALB mice demonstrated tolerance to nicotine-induced bradycardia. Chronic nicotine treatment also elicited changes in putative brain nicotinic receptors. Increased binding of L-[3H]nicotine was seen in six brain regions in all four mouse strains. The changes in binding were similar for all the strains. The binding of alpha-[125I]bungarotoxin was also elevated in the four mouse strains, and modest differences among the strains were evident in this measure, with the C3H strain showing the smallest increases in four of the six brain regions. Chronic nicotine treatment did not alter brain muscarinic receptors, as measured with L-[3H]quinuclidinyl benzilate binding, nor were the activities of acetylcholinesterase or choline acetyltransferase altered, except that a small change in hippocampal choline acetyltransferase activity may have occurred. These results indicate that tolerance to nicotine is regulated by genetic factors and that changes in brain nicotinic receptor numbers are not sufficient to explain the development of tolerance.


Use of phosphodiesterase-5 inhibitors by college students.
The objective of this study was to identify the use of phosphodiesterase type 5 inhibitors among university students from the city of Sao Paulo (SP) in Brazil. Male students (n=350) replied to a questionnaire about diagnosis of erectile dysfunction, the frequency and reason for the use of phosphodiesterase type 5 inhibitors, the specific medication used, whether their use was accompanied by a medical prescription and any reported side-effects. The results shows that a total of 53 (14.7%) students had already used this kind of medication without a prescription or medical diagnosis for erectile dysfunction, of which 53% reported using sildenafil, 37% tadalafil and 10% vardenafil. The main adverse side-effects reported were headache (23%) and flushing (10%) and the main reasons for using the inhibitor were curiosity (70%) and erectile improvement (12%).


Three-dimensional motion analysis of arm-reaching movements in healthy and hemispinalized common marmosets.
Spinal cord injury (SCI) is a devastating neurological injury. At present, pharmacological, regenerative, and rehabilitative approaches are widely studied as therapeutic interventions for motor recovery after SCI. Preclinical research has been performed on model animals with experimental SCI, and those studies often evaluate hand and arm motor function using various indices, such as the success rate of the single pellet reaching test and the grip force. However, compensatory movement strategies, involuntary muscle contraction, and the subject's motivation could affect the scores, resulting in failure to assess direct recovery from impairment. Identifying appropriate assessments of motor impairment is thus important for understanding the mechanisms of motor recovery. In this study, we developed a motion capture system capable of reconstructing three-dimensional hand positions with millimeter and millisecond accuracy and evaluated hand kinematics during food retrieval movement in both healthy and hemispinalized common marmosets. As a result, the endpoint jerk, representing the accuracy of hand motor control, was asserted to be an appropriate index of upper limb motor impairment by eliminating the influence of the subject's motivation, involuntary muscle contraction, and compensatory strategies. The result also suggested that the kinematics of the limb more consistently reflects motor restoration from deficit due to spinal cord injury than the performance in the single pellet reaching test. Because of recent attention devoted to the common marmoset as a nonhuman primate model for human diseases, the present study, which clarified arm-reaching movements in spinalized marmosets, provides fundamental knowledge for future therapeutic studies.


The Effects of Mangiferin (Mangifera indica L) in Doxorubicin-induced Cardiotoxicity in Rats.
The cardiotoxicity effect of doxorubicin (DOX), a widely used antitumor agent has restricted its clinical application. The aim of the current study was to explore the potential protective effect of mangiferin, a naturally occurring glucosylxanthone, that have antioxidant activity by its iron-complexing ability in mitochondria, against DOX-induced cardiac toxicity in rats in comparison with other antioxidants namely Sylimarin (SYL) and Vitamin E (VitE). Mangiferin was given orally to rats at a dose of 50, and 100 mg/kg for 5 weeks, and DOX was injected at a total dose of 15 mg/kg. Cardiac toxicity was evaluated by lactate dehydrogenase and creatine kinase in the serum, malondialdehyde (MDA) level in plasma and cardiac tissue, and antioxidant enzyme superoxide dismutase (SOD) in cardiac tissue. Mangiferin protected against DOX-induced increased mortality and electrocardiogram abnormality and decreased biochemical markers of cardiac toxicity i. e., lactate dehydrogenase and creatine phosphokinase isoenzyme. In addition, elevation of plasma and cardiac tissue levels of MDA in response to DOX treatment were significantly attenuated. The reduction of cardiac activity of SOD was significantly reduced in contrast with the other antioxidant SYL and Vit E. Histopathologically, mangiferin treatment showed significant reduction in inflammatory cell number, fibrotic area, and necrotic foci as compared with DOX only-treated rats. These results suggested that mangiferin had better protective effect against DOX-induced cardiac toxicity in comparison with SYL and VitE, thus besides the antioxidant activity, different mechanism may be involved in the action of mangiferin and need to be clarified in the future studies.


The Non-Coding RNA Ontology (NCRO): a comprehensive resource for the unification of non-coding RNA biology.
In recent years, sequencing technologies have enabled the identification of a wide range of non-coding RNAs (ncRNAs). Unfortunately, annotation and integration of ncRNA data has lagged behind their identification. Given the large quantity of information being obtained in this area, there emerges an urgent need to integrate what is being discovered by a broad range of relevant communities. To this end, the Non-Coding RNA Ontology (NCRO) is being developed to provide a systematically structured and precisely defined controlled vocabulary for the domain of ncRNAs, thereby facilitating the discovery, curation, analysis, exchange, and reasoning of data about structures of ncRNAs, their molecular and cellular functions, and their impacts upon phenotypes. The goal of NCRO is to serve as a common resource for annotations of diverse research in a way that will significantly enhance integrative and comparative analysis of the myriad resources currently housed in disparate sources. It is our belief that the NCRO ontology can perform an important role in the comprehensive unification of ncRNA biology and, indeed, fill a critical gap in both the Open Biological and Biomedical Ontologies (OBO) Library and the National Center for Biomedical Ontology (NCBO) BioPortal. Our initial focus is on the ontological representation of small regulatory ncRNAs, which we see as the first step in providing a resource for the annotation of data about all forms of ncRNAs. The NCRO ontology is free and open to all users, accessible at: http://purl.obolibrary.org/obo/ncro.owl.


Women are considerably more exposed to intimate partner violence than men in Rwanda: results from a population-based, cross-sectional study.
Intimate partner violence (IPV) against women is an important, yet often neglected public health issue. The existence of gender norms imbalance expressed by men's and women's attitudes in relation to power and decision-making in intimate relationships may influence the magnitude of IPV. The aim of this study was to investigate the prevalence and potential risk factors of physical, sexual and psychological IPV in young men and women in Rwanda. This population-based, cross-sectional study included a representative sample of men and women from the Southern Province of Rwanda. Face-to-face interviews were performed using the World Health Organization (WHO) questionnaire for violence exposure to estimate past year and earlier in life IPV occurrence. Risk factor patterns were analyzed by use of bi- and multivariate logistic regression. Women were, to a considerably higher extent, exposed to physical, sexual and psychological IPV than men. Of the women, 18.8% (n = 78) reported physical abuse in the past year, compared to 4.3% (n = 18) of men. The corresponding figures for women and men for sexual abuse were 17.4% (n = 71) and 1.5% (n = 6), respectively, and for psychological abuse, the corresponding figures were 21.4% (n = 92) and 7.3% (n = 32). Findings illustrate that violence against women was recurrent, as the highest frequency (>3 times) dominated in women for the various acts of all forms of violence. Identified risk factors for women's exposure to physical violence were being low educated, having poor social support, being poor and having many children. For men exposed to physical violence, no statistically significant risk factor was identified. In this setting, IPV exposure was more common in women than men in the Southern Province of Rwanda. Promotion of gender equality at the individual level is needed to make a positive difference in a relatively short term perspective. Men's lower reporting of IPV confirms women's subordinate position, but men's denial of incidents could also explain the gender role pattern.


Trauma surgeon personality and job satisfaction: results from a national survey.
Personality is correlated with job satisfaction, whereas job satisfaction is linked to performance. This study examines personality of practicing trauma surgeons in relation to their job satisfaction. The dominant theory in personality research is the five-factor model, which includes: extraversion, agreeableness, conscientiousness, emotional stability, and openness. The sample was identified from American Association for Surgery of Trauma, Eastern Association for Surgery of Trauma, and Western Trauma Association membership. A web-based survey of demographics and empirically supported measures was created. Four hundred and twelve trauma surgeons (49 +/- 14-years-old, 85% male) completed the survey. When comparing satisfied to unsatisfied trauma surgeons on personality variables, extraversion (5.0 +/- 1.6 vs 4.4 +/- 1.6, P = 0.014) and emotional stability (5.8 +/- 1.1 vs 5.4 +/- 1.2, P = 0.007) were significantly higher in satisfied surgeons. Moderate correlations were found for job satisfaction with emotional stability (r = 0.20, P < 0.01) and extraversion (r = 0.20, P < 0.01). Logistic regression of personality variables highlighted the significance of emotional stability and extraversion in prediction of job satisfaction. Extraversion and emotional stability are the most significant personality factors to job satisfaction of trauma surgeons. These findings may have important implications for surgical resident recruitment, job performance, and retention.


Target Identification and Mode of Action of Four Chemically Divergent Drugs against Ebolavirus Infection.
Here, we show that four chemically divergent approved drugs reported to inhibit Ebolavirus infection, benztropine, bepridil, paroxetine and sertraline, directly interact with the Ebolavirus glycoprotein. Binding of these drugs destabilizes the protein, suggesting that this may be the mechanism of inhibition, as reported for the anticancer drug toremifene and the painkiller ibuprofen, which bind in the same large cavity on the glycoprotein. Crystal structures show that the position of binding and the mode of interaction within the pocket vary significantly between these compounds. The binding constants (Kd) determined by thermal shift assay correlate with the protein-inhibitor interactions as well as with the antiviral activities determined by virus cell entry assays, supporting the hypothesis that these drugs inhibit viral entry by binding the glycoprotein and destabilizing the prefusion conformation. Details of the protein-inhibitor interactions of these complexes and their relation with binding affinity may facilitate the design of more potent inhibitors.


Trajectories of aggression from toddlerhood to age 9 predict academic and social functioning through age 12.
Using longitudinal data from the NICHD Study of Early Child Care and Youth Development, we examined behavior problems and social and academic outcomes from ages 9 through 12 in children classified into five trajectories of physical aggression, on the basis of maternal ratings obtained from 24 months through 9 years (N = 1195). Outcome data were obtained from teacher reports, observations of children's behavior, and children's self-reports. Children on the high-stable aggression trajectory (3% of sample) showed the most severe adjustment problems, including poorer social skills, higher levels of externalizing problems, and more self-reported peer problems; those on the moderate-stable aggression trajectory (15%) showed poor regulation and inattention. Although children with moderate levels of early aggression that decreased sharply by school entry (12%) appeared well adjusted at follow-up, those who showed a low level of stable aggression (25%) evidenced some unanticipated social and behavior problems. Children in the contrast group (45%) were consistently very low in aggression from toddlerhood onward. Results highlight links between different patterns (stable or decreasing) and levels (high, moderate, low, very low) of aggression across childhood and children's later adjustment. For example, even quite low aggression that is stable appears to be a risk factor for some social problems; in contrast, moderate aggression that decreases sharply to no aggression by school entry is associated with good adjustment at age 12.


Mutation of structural determinants lining the N-methyl-D-aspartate receptor channel differentially affects phencyclidine block and spermine potentiation and block.
Spermine and other endogenous polyamines potentiate, block and permeate the N-methyl-D-aspartate receptor channel. To identify structural determinants of the N-methyl-D-aspartate channel that mediate spermine's actions, we generated mutant receptors with asparagine (N) to glutamine (Q) or arginine (R) substitutions in the selectivity filter of the channel. We demonstrate that mutation of the three critical asparagines in this domain differentially affects block by phencyclidine and both potentiation and block by spermine. N-to-Q and N-to-R mutations in the N site of the NR1 subunit (N598 in NR1(011), N619 in NR1(100)) and N-to-Q mutations in the N and N + 1 sites (N595 and N596 in NR2A, respectively) of the NR2 subunit (Q/NN, R/NN, N/QN, N/NQ, Q/QN and Q/NQ receptors) reduced affinity for phencyclidine. The Q/NN receptor showed markedly reduced potentiation by spermine, with little or no change in spermine block. The R/NN receptor showed markedly reduced spermine potentiation and affinity for spermine at its block site. The N/QN, N/NQ and Q/QN mutant receptors showed somewhat enhanced spermine block, while the Q/ NQ double mutant exhibited significantly more enhanced spermine block. Thus, the asparagine residues critical to Ca2+ permeability and Mg2+ block of N-methyl-D-aspartate channels are also critical to block by spermine and phencyclidine. To examine the interaction of spermine and phencyclidine within the channel, we performed competition studies. Spermine appeared to compete with phencyclidine for binding to the receptor; however, blocks by phencyclidine and by spermine were not additive. The findings suggest that spermine can bind to a site in the external vestibule of the channel to impede phencyclidine binding, but allow Na+ influx.


Fluticasone propionate reduces bacterial airway epithelial invasion.
Fluticasone propionate reduces the frequency and severity of the episodes of exacerbation of chronic obstructive pulmonary disease (COPD). Streptococcus pneumoniae and Haemophilus influenzae are frequently isolated in these episodes. Both express phosphorylcholine, an epitope that mediates their interaction with airway epithelial cells via the platelet-activating factor receptor (PAFR). The present work studies the effects of fluticasone propionate on the expression of PAFR on human airway epithelial cells, the invasion of these cells by S. pneumoniae and H. influenzae, and the course of pneumococcal infection in vivo. The following were used in the experiments: S. pneumoniae and H. influenzae isolated from patients with COPD, cell cultures of type II pneumocytes and bronchoepithelial cells, and a mouse model of lung infection. Fluticasone propionate was found to reduce PAFR expression on the surface of the two cells types studied. All S. pneumoniae and H. influenzae isolates expressed phosphorylcholine. Treatment of both cells lines with fluticasone propionate reduced invasion of both microorganisms and reduced the bacterial load of mice infected with S. pneumoniae. Fluticasone propionate reduces the invasion of airway epithelial cells by Streptococcus pneumoniae and Haemophilus influenzae through its effect on platelet-activating factor receptor. These results may help explain the beneficial effects of fluticasone propionate on chronic obstructive pulmonary disease exacerbations.


[Serum concentration of type IV collagen in urological cancer--comparison with serum concentration of laminin].
In recent years, it has become clear that various extracellular substrates play an important role in the process of invasion and metastasis of malignant tumors. In a previous study, we reported that the serum concentration of laminin in renal cell carcinoma and prostate cancer is elevated, and furthermore, is remarkably high in patients with metastasis. However, in bladder cancer, this level is elevated only in those with metastasis, indicating that the serum concentration of laminin is useful as a marker for metastasis or clinical progression of the malignant tumor. In the present study, we measured the serum concentration of type IV collagen 7S-domain, which, as laminin constructs the basement membrane, and compared the result with the serum concentration of laminin, to evaluate the clinical significance of the findings. The serum concentration of type IV collagen 7S-domain was not elevated significantly in any tumor type, although the serum concentration of laminin was elevated in patients with renal cell carcinoma, prostate cancer and bladder cancer with metastasis. There were no significant differences in the serum concentration of type IV collagen 7S-domain in any group with metastasis.


Molecular and Morphological Characterization of Xiphinema chambersi Population from Live Oak in Jekyll Island, Georgia, with Comments on Morphometric Variations.
A population of Xiphinema chambersi from the root zone around live oak (Quercus virginiana Mill.) trees on Jekyll Island, GA, is described using both morphological and molecular tools and compared with descriptions of type specimens. Initially, because of a few morphological differences, this nematode was thought to represent an undescribed species. However, on further examination, the morphometrics of the nematodes from live oak tend to agree with most of the morphometrics in the original description and redescription of X. chambersi except for few minor differences in V% relative to body length, slightly shorter stylet length, different c value, and the number of caudal pores. We consider these differences to be part of the normal variation within this species and accordingly image this new population of X. chambersi and redescribe the species. The new population is characterized by having females with a body length of 2.1 to 2.5 mm; lip region slightly rounded and set off from head; total stylet length 170 to 193 µm; vulva at 20.4% to 21.8% of body length; a monodelphic, posterior reproductive system; elongate, conoid tail with a blunt terminus and four pairs of caudal pores, of which two pairs are subdorsal and two subventral. Sequence data from the D2-D3 region of the 28S rRNA molecule subjected to GenBank sequence comparison using BLAST showed that the sequence had 96% and 99% similarity with X. chambersi from Alabama and Florida, respectively. Phylogenetic relationships of X. chambersi with other xiphinematids based on analysis of this DNA fragment are presented. This finding represents a new location of X. chambersi in Georgia on live oak for this species.


Changing fortunes: analysis of fluctuating policy space for family planning in Kenya.
Policies relating to contraceptive services (population, family planning and reproductive health policies) often receive weak or fluctuating levels of commitment from national policy elites in Southern countries, leading to slow policy evolution and undermining implementation. This is true of Kenya, despite the government's early progress in committing to population and reproductive health policies, and its success in implementing them during the 1980s. This key informant study on family planning policy in Kenya found that policy space contracted, and then began to expand, because of shifts in contextual factors, and because of the actions of different actors. Policy space contracted during the mid-1990s in the context of weakening prioritization of reproductive health in national and international policy agendas, undermining access to contraceptive services and contributing to the stalling of the country's fertility rates. However, during the mid-2000s, champions of family planning within the Kenyan Government bureaucracy played an important role in expanding the policy space through both public and hidden advocacy activities. The case study demonstrates that policy space analysis can provide useful insights into the dynamics of routine policy and programme evolution and the challenge of sustaining support for issues even after they have reached the policy agenda.


Coupled GTPase and remodelling ATPase activities form a checkpoint for ribosome export.
Eukaryotic ribosomes are assembled by a complex pathway that extends from the nucleolus to the cytoplasm and is powered by many energy-consuming enzymes. Nuclear export is a key, irreversible step in pre-ribosome maturation, but mechanisms underlying the timely acquisition of export competence remain poorly understood. Here we show that a conserved Saccharomyces cerevisiae GTPase Nug2 (also known as Nog2, and as NGP-1, GNL2 or nucleostemin 2 in human) has a key role in the timing of export competence. Nug2 binds the inter-subunit face of maturing, nucleoplasmic pre-60S particles, and the location clashes with the position of Nmd3, a key pre-60S export adaptor. Nug2 and Nmd3 are not present on the same pre-60S particles, with Nug2 binding before Nmd3. Depletion of Nug2 causes premature Nmd3 binding to the pre-60S particles, whereas mutations in the G-domain of Nug2 block Nmd3 recruitment, resulting in severe 60S export defects. Two pre-60S remodelling factors, the Rea1 ATPase and its co-substrate Rsa4, are present on Nug2-associated particles, and both show synthetic lethal interactions with nug2 mutants. Release of Nug2 from pre-60S particles requires both its K(+)-dependent GTPase activity and the remodelling ATPase activity of Rea1. We conclude that Nug2 is a regulatory GTPase that monitors pre-60S maturation, with release from its placeholder site linked to recruitment of the nuclear export machinery.


PFO closure complications from the AGA registry.
To evaluate all complications that occurred during or after cardiac catheterizations for Amplatzer PFO device closure of patent foramen ovale (PFO), determine the cause of the complications and recommend techniques to minimize complications in the future. Rare complications were reported to the manufacturer of the Amplatzer PFO occluder since the introduction of the device. A panel of independent physicians reviewed all complications reported to the manufacturer to determine whether the complication was related to the device or related to the cardiac catheterization procedure. Demographic data, echocardiograms, operative reports, and time to occurrence of complications were reviewed. A total of 11 events were reported. Only two patients had device related complications (erosion), an incidence of 0.018%. Two patients were found to have additional atrial septal defect after PFO closure. Two patients were thought to have an inflammatory reaction without any serious sequelae. Five complications were related to the cardiac catheterization procedure (atrial appendage perforation). Device related complications after Amplatzer PFO occluder placement are extremely rare. Cardiac catheterization related complications appear to be the most common cause of the hemodynamic compromise. Careful manipulation of catheters and wires, recognition of the location of the catheter by fluoroscopy and echocardiography will decrease the risk of such complications.


Ligandless, anionic, arylpalladium halide intermediates in the Heck reaction.
We report the isolation and reactivity of a series of "ligandless," anionic arylpalladium complexes of the general structure [Pd(Ar)Br(2)](2)(2-) by the reaction of ((t)Bu(3)P)Pd(Ar)(Br) and bromide. These anionic complexes insert olefins at room temperature, and these fast insertions indicate that the anionic complexes are kinetically competent to be intermediates in Heck-Mizoroki reactions conducted under "ligandless" conditions (lacking added dative ligand). Kinetic studies showed that the anionic complexes insert olefins much faster than the corresponding neutral, P(t-Bu)(3)-ligated complexes. Addition of halide to the reaction of the neutral complex ((t)Bu(3)P)Pd(Ar)(Br) and styrene led to a significant rate acceleration, suggesting that the anionic complex forms rapidly and reversibly in situ from the neutral species prior to migratory insertion. These data, along with studies on the regioselectivity for reaction of aryl halides with butyl vinyl ether in the presence of the different starting catalysts, are consistent with the intermediacy of the same anionic, arylpalladium intermediates in Heck reactions catalyzed by palladium complexes containing bulky trialkylphosphine ligands as in reactions conducted under ligandless conditions.


Profiling of Vitamin D Metabolic Intermediates toward VDR Using Novel Stable Gene Reporter Cell Lines IZ-VDRE and IZ-CYP24.
Variety of xenobiotics, including therapeutically used vitamin D analogues or environmental and alimentary endocrine disruptors, may interfere with vitamin D receptor (VDR) signaling, with serious physiological or pathophysiological consequences. Therefore, it is of topical interest to have reliable and efficient in vitro screening tools for the identification of agonists and activators of human VDR. We present here two novel stably transfected human reporter cell lines allowing rapid, high-throughput, and selective identification of VDR agonists and activators. Human colon adenocarcinoma cells LS180 were stably transfected with reporter plasmids CYP24_minP-pNL2.1[Nluc/Hygro] (IZ-CYP24 cells contain the -326/-46 sequence from the human CYP24A1 promoter) or VDREI3_SV40-pNL2.1[Nluc/Hygro] (IZ-VDRE cells contain three copies of vitamin D response elements VDRE-I from the human CYP24A1 promoter). Both cell lines remained fully functional for over two months in the culture and also after cryopreservation. Luciferase inductions ranged from 10-fold to 25-fold (RLU 10(6)-10(7)) and from 30-fold to 80-fold (RLU 10(3)-10(4)) in IZ-VDRE and IZ-CYP24 cells, respectively. Time-course analyses revealed that detection of VDR activators is possible as soon as after 8 h of incubation. Cell lines were highly selective toward VDR agonists, displaying no cross-activation by retinoids, thyroids, and steroids. As a proof of concept, we used IZ-VDRE and IZ-CYP24 cells for profiling analogues of vitamin D, and intermediates in vitamin D2 and vitamin D3 metabolic pathways against VDR transcriptional activity. The data obtained revealed significant activation of VDR not only by obligatory ligands calcitriol and ergocalcitriol but also by their precursors and degradation products.