Nitric oxide mediates glutamate-induced mitochondrial depolarization in rat cortical neurons.
Mitochondria have been considered to be a target for glutamate neurotoxicity. The aim of the present work was to investigate the mechanisms leading to glutamate-mediated mitochondrial deenergization, as measured by mitochondrial membrane potential and cell respiration in cultured neurons. Glutamate exposure to cells induced pronounced mitochondrial depolarization associated with an impairment in neuronal respiration, leading to neuronal ATP depletion. These effects were prevented by both the nitric oxide (. NO) synthase inhibitor Nomega-nitro-l-arginine methyl ester and by the N-methyl-d-aspartate glutamate-subtype receptor inhibitor d-(-)-2-amino-5-phosphopentanoate. Our results suggest that glutamate causes ATP depletion by collapsing mitochondrial membrane potential through a.NO-mediated mechanism.


Choosing the correct laryngeal mask airway sizes and cuff inflation volumes in pediatric patients.
The laryngeal mask airway (LMA) is now standard airway management equipment in prehospital and Emergency Department (ED) care. Most providers may not be able to match the pediatric LMA sizes to the appropriate weights of pediatric patients. The exact inflation volumes are also difficult to memorize. To overcome this problem, we propose the following equations: Weight (kg) of patient = 2(2 x LMA), where LMA is the size; cuff inflation volume (mL) = 5 x LMA.


Multiple stressor effects on alpha, beta and zeta diversity of riverine fish.
We examined the effects of regional scale land use and local scale environmental and biotic stressors on alpha, beta and zeta diversities of native fish communities in wadeable streams and non-wadeable rivers in the Danube basin, Hungary. Relationships among land use and local scale environmental and biotic stressors were weak both in streams and rivers, suggesting that these stressors act relatively independently. Alpha diversity decreased strongly with increasing local scale environmental stressor intensity in rivers. On the contrary, its response to stressors was more obscure in streams, where the best-fit statistical model indicated the importance of the interaction between land use, local scale environmental and biotic stressors, while the secondly ranked model highlighted the negative impact of local scale environmental stressors. Analysis of variance using distance matrices provided evidence that stressors alone and in interactions explained compositional differences of pairs of study sites (beta diversity). Considering the degree of overall degradation, both local (alpha) and among-site (beta and zeta) diversity indices responded to increasing stressor intensity, generally negatively. Riverine fish communities showed higher degrees of similarity (lower beta and higher zeta) than stream fish communities. They also showed increasing similarity (i.e. homogenization) with increasing overall stressor intensity, unlike stream fish communities, which showed no relationship with overall stressor intensity. Our results suggest that the relationships between land use and local scale environmental and biotic stressors can be complex and so do their effects on biodiversity. While stressor specific indices can provide information on the role of specific stressors in some cases, the examination of overall stressor effects is needed to assess realistically the effects of anthropogenic disturbances on native fish diversity. Diversity indices that quantify among-site changes in species composition, such as measures of beta and zeta diversity, can be fruitful for better understanding the role of multiple stressors in structuring ecological communities.


An improved formulation of Nocht's azure-eosin stain for plastic embedded material.
The popular azure-eosin stain of Nocht has been reformulated to provide consistent, intense staining of semithin sections of water-miscible methacrylate embedded tissues.


Co-crystal formation based on structural matching.
A co-crystal is defined as a single crystalline structure composed of two or more components with no proton transfer which are solid at room temperature. Our group has come up with the following rationale selection of co-formers for initial co-crystal screening: 1) selection of co-formers with the highest potential for hydrogen bonding with the API and 2) selection of co-formers with diversity of secondary structural characteristics. We demonstrate the feasibility of this technique with a Novartis drug candidate A. In the first tier, 20 co-formers were screened and two hits were identified. By examining the two co-formers, which worked from the first round, a second round of screening was undertaken with more focused chemical matter. Nineteen co-crystal formers closely related to the two hits in the first screen were screened in the second tier. From this screen five hits were identified. All the hits were compared for their physical and chemical stability and dissolution profile. Based on the comparison 4-aminobenzoic co-crystal was chosen for in-vivo comparison with the free form. The co-crystal had 12 times higher exposure than the free form thus overcoming the solubility limited exposure.


Bis-(ethanol-κO)bis(1-ferrocenyl-4,4,4-tri-fluoro-butane-1,3-dionato-κ2 O,O')nickel(II).
In the title compound, [NiFe2(C5H5)(C9H5F3O2)2(C2H6O)2], the central NiII ion is observed in an octa-hedral coordination environment. The chelating β-diketonate ligands are substituted by ferrocene, a lipophilic organometallic moiety. The ferrocene groups have the normal geometry, with eclipsed cyclo-penta-diene rings. Coordinated ethanol mol-ecules are engaged in inter-molecular hydrogen bonds, and the crystal is further stabilized by weak C-H⋯F and C-H⋯π contacts.


Evaluation of flavonoids binding to DNA duplexes by electrospray ionization mass spectrometry.
In this study, electrospray ionization mass spectrometry (ESI-MS) was used to investigate the binding interactions of ten flavonoid aglycones and ten flavonoid glycosides with DNA duplexes. Relative binding affinities of the flavonoids toward DNA duplexes were estimated based on the fraction of bound DNA. The results revealed that the 4'-OH group of flavonoid aglycones was essential for their DNA-binding properties. Flavonoid glycosides with sugar chain linked on ring A or ring B showed enhanced binding toward the duplexes over their aglycone counterparts, whereas glycosylation of the flavonol quercetin on ring C exhibited a less pronounced effect. The aglycone skeletons and other hydroxyl substitutions on the aglycone also have an effect on the fractions of bound DNA. Upon collision-induced dissociation, the complexes containing flavonoid aglycones underwent the predominant ejection of a neutral ligand molecule, suggesting an intercalative DNA-binding mode. However, for complexes containing flavonoid glycosides, the loss of nucleobase increased to different extents, indicating a stronger binding or different binding mode. The results may provide not only a deeper insight into the DNA-binding properties of flavonoids but also a useful guideline for the design of efficient DNA-binding agents for chemotherapy.


Xanthones from the twigs of Garcinia oblongifolia and their antidiabetic activity.
Three new xanthones, oblongixanthone F-H (1-3), along with eight known xanthones (4-11), were isolated from an EtOAc extract of the twigs of Garcinia oblongifolia. Their structures were elucidated by spectroscopic analysis including 1D- and 2D-NMR spectroscopy and mass spectrometry. The antidiabetic effects of all isolated compounds were evaluated by in vitro α-glucosidase and PTP1B inhibition assays. Compound 11 was the most active compound, and inhibited α-glucosidase and PTP1B with IC50 values of 1.7±0.5 and 14.1±3.5μM, respectively.


Roles of endoplasmic reticulum stress and autophagy on H2O2‑induced oxidative stress injury in HepG2 cells.
Endoplasmic reticulum stress (ERS) can be induced by a variety of physiological and pathological factors including oxidative stress, which triggers the unfolded protein response to deal with ERS. Autophagy has been hypothesized to be a means for tumor cells to increase cell survival under conditions of hypoxia, metabolic stress and even chemotherapy. Although they may function independently from each other, there are also interactions between responses to oxidative stress injury induced by pathologic and pharmacological factors. The aim of the present study was to investigate the effects of ERS and autophagy on H2O2‑induced oxidative stress injury in human HepG2 hepatoblastoma cells. It was demonstrated that exposure of HepG2 cells to H2O2 decreased cell viability and increased reactive oxygen species (ROS) levels in a dosage‑dependent manner. In addition, apoptosis and autophagy rates were elevated and reduced following cell exposure to H2O2 + the ERS inducer Tunicamycin (TM), and to H2O2 + the ERS inhibitor Salubrinal (SAL), compared with the cells treated with H2O2 alone, respectively. Further studies revealed that TM enhanced the expression of ERS‑related genes including glucose‑regulated protein‑78/binding immunoglobulin protein, inositol‑requiring kinase‑I and activating transcription factor 6 and C/EBP‑homologous protein 10, which were attenuated by SAL compared with cells exposed to H2O2 alone. The data from the present study also demonstrated that LC3II/LC3‑I and p62, members of autophagy‑related genes, were increased and decreased in cells treated with H2O2 + TM compared with cells treated with H2O2, respectively, indicating that autophagy was stimulated by ERS. Furthermore, a reduction in the levels of pro caspase‑3 and pro caspase‑9, and elevation level of caspase‑12 were observed in cells exposed to H2O2 + TM compared with cells treated with H2O2, respectively, suggesting apoptosis induced by H2O2 was enhanced by ERS or autophagy triggered by H2O2. The above results suggest that the ERS inducer may be a potential target for pharmacological intervention targeted to ERS or autophagy to enhance oxidative stress injury of tumor cells induced by antitumor drugs.


[The sacral neuromodulation in double incontinence treatment: a review].
Urinary and fecal incontinence are common conditions which are frequently associated and defining double incontinence. When conservative treatments fail, sacral nerve modulation (SNM) is considered to be a first-line treatment for patients with urge urinary incontinence and for patients with fecal incontinence. The present article aims to determine the effect of SNM on the treatment of double incontinence. A medline search for clinical studies with SNM and double incontinence was carried out, extracted data were reviewed and analysed. The results of SNM in patients with double incontinence has been reported in seven studies (120 patients). The percentage of patients suffering from double incontinence improved on the urinary and fecal incontinence varied between 32% to 75%. This review reports the effectiveness of the SNM on the urinary and fecal incontinence in this population of double incontinence patients. Its main advantage would be to treat two incontinence by a single treatment. The search of predictive factors of success must be given.


Photocatalytic degradation of organic pollutants by carbon quantum dots functionalized g-C3N4: A review.
Graphitic carbon nitride (g-C3N4) has received much attention due to its unique characteristics of stable physicochemical features, facile preparation, and inexpensive cost. However, the bulk g-C3N4 has a weak capacity for pollutant degradation and needs to be modified for real application. Therefore, extensive research has been done on g-C3N4, and the discovery of the novel zero-dimensional nanomaterials known as carbon quantum dots (CQDs) provided it with a unique modification option. In this review, the development for the removal of organic pollutants by g-C3N4/CQDs was discussed. Firstly, the preparation of g-C3N4/CQDs were introduced. Then, the application and the degradation mechanism of g-C3N4/CQDs were briefly described. And the discussion of the influencing factors on g-C3N4/CQDs' ability to degrade organic pollutants came in third. Finally, the conclusions of photocatalytic degradation of organic pollutants by g-C3N4/CQDs and future perspectives followed. This review will strengthen the understanding of the photocatalytic degradation of real organic wastewater by g-C3N4/CQDs, including their preparation, application, mechanism, and influencing factors.


A recalcitrant acrodermatitis continua of Hallopeau successfully treated with etanercept.
Acrodermatitis continua of Hallopeau (ACH) is considered as a localized form of pustularpsoriasis that is usually refractory to the treatment. The condition is characterized by sterile pustules, onychodystrophy, anonychia, and osteolysis of distal phalanges. The authors report a case of recalcitrant ACH who previously failed to topical corticosteroid, methotrexate, acitretin, and phototherapy and rapidly responded to etanercept in combination with acitretin. The primary varicella infection occurred during the therapy. The patient was able to discontinue etanercept within four months after starting the treatment. The lesion was then under-controlled by acitretin and topical clobetasol ointment with an 8-month clinical remission.


An In Situ Investigation of the Protein Corona Formation Kinetics of Single Nanomedicine Carriers by Self-Regulated Electrochemiluminescence Microscopy.
Protein coronas are present extensively at the bio-nano interface due to the natural adsorption of proteins onto nanomaterials in biological fluids. Aside from the robust property of nanoparticles, the dynamics of the protein corona shell largely define their chemical identity by altering interface properties. However, the soft coronas are normally complex and rapidly changing. To real-time monitor the entire formation, we report here a self-regulated electrochemiluminescence (ECL) microscopy based on the interaction of the Ru(bpy)3 3+ with the nanoparticle surface. Thus, the heterogeneity of the protein corona is in situ observed in single nanoparticle "cores" before and after loading drugs in nanomedicine carriers. The label-free, optical stable and dynamic ECL microscopy minimize misinterpretations caused by the variation of nanoparticle size and polydispersity. Accordingly, the synergetic actions of proteins and nanoparticles properties are uncovered by chemically engineered protein corona. After comparing the protein corona formation kinetics in different complex systems and different nanomedicine carriers, the universality and accuracy of this technique were well demonstrated via the protein corona formation kinetics curves regulated by competitive adsorption of Ru(bpy)3 3+ and multiple proteins on surface of various carriers. The work is of great significance for studying bio-nano interface in drug delivery and targeted cancer treatment.


Temporal relationships between stress protein induction, progesterone withdrawal, and apoptosis in corpora lutea of ewes treated with prostaglandin F2 alpha.
Immunofluorescent staining was used to detect in situ alterations in inducible heat shock (stress) protein (HSP)-70 production and DNA fragmentation (indicative of apoptotic cell death) in luteal tissues obtained from sheep after in vivo administration of a luteolytic dose of PGF2 alpha. Accumulation of HSP-70 was localized to PG-sensitive (i.e., large) luteal cells. Cytoplasmic HSP-70 increased within 2 h after treatment. Luteal concentrations of progesterone decreased precipitously thereafter. Expression of HSP-70 diminished by 16 h. An increase in immunostained digoxigenin-labeled DNA was not detected until the onset of structural involution at 16 h; both large and small steroidogenic cells were affected. It is suggested that HSP-70 induction by PGF2 alpha is a prelude to steroid depletion and active apoptotic death of luteal cells.


A role for the androgen-receptor in clinically localized and advanced prostate cancer.
Earlier studies of androgen-receptor (AR) expression using frozen prostate tissue, and later studies using archived specimens, produced the consensus that ligand-stabilized AR is nuclear, AR expression is similar in benign epithelia and stroma, AR expression is greater in secretory epithelia than basal cells, and AR expression is more variable in prostate cancer (CaP) than in benign prostatic hyperplasia (BPH). Accurate measurement of AR expression remains technically challenging but necessary to evaluate the relevance of AR to clinical CaP. Recent studies demonstrated that AR expression in epithelia and stroma may be prognostic in clinically localized CaP, and AR expression may play a role in racial differences in CaP mortality and predict response to androgen deprivation therapy. High levels of AR and AR-regulated gene expression indicate a central role for AR in growth regulation of castration-recurrent CaP. New treatments for the lethal phenotype of CaP require better understanding of AR transactivation during androgen deprivation therapy.


Changes in gallbladder volume in healthy dogs after food was withheld for 12 hours followed by ingestion of a meal or a meal containing erythromycin.
To assess the influence of meal ingestion and orally administered erythromycin on gallbladder volume in dogs. 22 healthy dogs. Ultrasonographically determined gallbladder dimensions in unsedated dogs were used to calculate volume. Measurements were recorded after food was withheld for 12 hours (time 0) and 15, 30, 45, 60, 90, and 120 minutes after a 100-g meal without (n = 22) or with erythromycin (1.0 mg/kg [7], 2.5 mg/kg [7], and both dosages [8]). Gallbladder ejection fraction represented the percentage of volume change from time 0. Intraday and interday coefficients of variation determined operator repeatability and physiologic variation. We did not detect significant differences in gallbladder volume per unit of body weight between treatments at time 0 or in ejection fraction percentage within or between treatments. Median time 0 gallbladder volume was 0.6 mL/kg (range, 0.4 to 1.9) but was > 1.0 mL/kg in 3 of 22 (14%) dogs and <or= 1.0 mL/kg in 19 of 22 (86%) dogs. Twenty dogs achieved an ejection fraction >or= 25% with at least 1 treatment, but 2 dogs with a gallbladder volume <or= 1.0 mL/kg at time 0 did not. Intraday and interday coefficients of variation were 18% and 25%, respectively. Gallbladder volume <or= 1.0 mL/kg at time 0 and ejection fraction >or= 25% were typical. No treatment consistently induced greater gallbladder contraction. Dogs with a gallbladder volume > 1.0 mL/kg and ejection fraction < 25% may require a combined meal and erythromycin protocol.


Diffusion of water vapor in binary and ternary gas mixtures at increased pressures.
Diffusion of water vapor was measured at 25 degrees C in the binary systems water vapor-He and water vapor-N2 at approximately 1, 4 10, 20 and 50 atm. Diffusion was also measured in the ternary system water vapor-He-O2 in both 2%O2-98%He, and at 1 and 20 atm. At 1 atm, comparison of binary diffusion coefficients (delta) shows that water vapor diffuses 3.3 times more readily in He than in N2. Values of delta at elevated pressures were reduced in proportion to 1/p, the absolute pressure, in qualitative agreement with Chapman-Enskog theory. However, the reduction in Delta was less than predicted at pressure above 4 atm in water vapor-N2 and above 20 atm in water vapor-He. The deviations from theory are more pronounced in N2 than in He, and become larger at higher pressures. When 26% O2 is present in the ternary system water vapor-He-O2, diffusion of water vapor is reduced to about 60% of its rate in pure He. In contrast, 2% O2 in He has little effect on diffusion of water vapor.


Surprisingly rich repertoire of Wnt genes in the demosponge Halisarca dujardini.
Wnt proteins are secreted signalling molecules found in all animal phyla. In bilaterian animals, including humans, Wnt proteins play key roles in development, maintenance of homeostasis and regeneration. While Wnt gene repertoires and roles are strongly conserved between cnidarians and bilaterians, Wnt genes from basal metazoans (sponges, ctenophores, placozoans) are difficult or impossible to assign to the bilaterian + cnidarian orthologous groups. Moreover, dramatic differences in Wnt numbers among basal metazoan exist, with only three present in the genome of Amphimedon queenslandica, a demosponge, and 21 in the genome of Sycon ciliatum, a calcisponge. To gain insight into the ancestral Wnt repertoire and function, we have chosen to investigate Wnt genes in Halisarca dujardini, a demosponge with relatively well described development and regeneration, and a very distant phylogenetic relationship to Amphimedon. Here we describe generation of a eukaryotic contamination-free transcriptome of Halisarca dujardini, and analysis of Wnt genes repertoire and expression in this species. We have identified ten Wnt genes, with only one orthologous to Amphimedon Wnt, and six appearing to be a result of a lineage specific expansion. Expression analysis carried out by in situ hybridization of adults and larvae revealed that two Halisarca Wnts are expressed in nested domains in the posterior half of the larvae, and six along the adult body axis, with two specific to the osculum. Strikingly, expression of one of the Wnt genes was elevated in the region undergoing regeneration. Our results demonstrated that the three Poriferan lineages (Demospongiae, Calcarea and Homoloscleromorpha) are characterized by highly diverse Wnt gene repertoires which do not display higher similarity to each other than they do to the non-sponge (i.e. ctenophore, cnidarian and bilaterian) repertoires. This is in striking contrast to the uniform Wnt repertoires in Cnidarians and Bilaterians, suggesting that the Wnt family composition became "fixed" only in the last common ancestor of Cnidarians and Bilaterians. In contrast, expression of Wnt genes in the apical region of sponge adults and the posterior region of sponge larvae suggests conservation of the Wnt role in axial patterning across the animal kingdom.


Comparison of quantitative flow ratio, Pd/Pa and diastolic hyperemia-free ratio versus fractional flow reserve in non-culprit lesion of patients with non ST-segment elevation myocardial infarction.
To investigate the correlation between quantitative flow ratio (QFR), Pd/Pa, diastolic hyperemia-free ratio (DFR) and fractional flow reserve (FFR, gold standard) in non-culprit lesion (NCL) of patients with non ST-segment elevation myocardial infarction (NSTEMI). The non-hyperemic pressure ratio (NHPR) and the angiography-based indexes have been developed to overcome the limitation of the use of the FFR. Between January and December 2019, 184 NCL from 116 NSTEMI patients underwent physiologic assessment and were included in the study. NCLs were investigated with QFR, Pd/Pa, DFR, and FFR. Mean values of QFR, Pd/Pa, DFR and FFR were 0.85 ± 0.10, 0.92 ± 0.07, 0.93 ± 0.05 and 0.84 ± 0.07, respectively. DFR and FFR showed a good correlation (r = 0.76). Bland and Altman plot showed a mean difference of 0.080. DFR Diagnostic accuracy was 88%. The area under the ROC curve (AUC) for DFR was 0.946 (95%CI 0.90-0.97, p = .0001). Similar findings were reported for Pd/Pa (r = 0.73; mean difference 0.095, diagnostic accuracy 84%, AUC 0.909 [95%CI 0.85-0.94, p = .0001]) and QFR (r = 0.68; mean difference 0.01; diagnostic accuracy 88%, AUC 0.964 [95% CI 0.91-0.98, p = .0001]). FFR, QFR, Pd/Pa and DFR identified 31%, 32%, 30% and 32% potentially flow-limiting lesions, respectively. In NSTEMI patients, QFR, Pd/Pa and DFR showed equivalence as compared to gold standard FFR in the discrimination of non-culprit lesions requiring revascularization.


Covalent organic framework: A state-of-the-art review of electrochemical sensing applications.
Covalent organic framework (COF), a kind of porous polymer with crystalline properties, is a periodic porous framework material with precise regulation at atomic level, which can be formed by the orderly connection of pre-designed organic construction units through covalent bonds. Compared with metal-organic frameworks, COFs exhibit unique performance, including tailor-made functions, stronger load ability, structural diversity, ordered porosity, intrinsic stability and excellent adsorption features, are more conducive to the expansion of electrochemical sensing applications and the universality of applications. In addition, COFs can accurately integrate organic structural units with atomic precision into ordered structures, so that the structural diversity and application of COFs can be greatly enriched by designing new construction units and adopting reasonable functional strategies. In this review, we mainly summarized state-of-the-art recent advances of the classification and synthesis strategy of COFs, the design of functionalized COF for electrochemical sensors and COFs-based electrochemical sensing. Then, an overview of the considerable recent advances made in applying outstanding COFs to establish electrochemical sensing platform, including electrochemical sensor based on voltammetry, amperometry, electrochemical impedance spectroscopy, electrochemiluminescence, photoelectrochemical sensor and others. Finally, we discussed the positive outlooks, critical challenges and bright directions of COFs-based electrochemical sensing in the field of disease diagnosis, environmental monitoring, food safety, drug analysis, etc.


Left ventricular systolic circular index: an echocardiographic measure of transseptal pressure ratio.
An echocardiographic index of left ventricular (LV) short axis circularity can be defined by the equation: left ventricular systolic circularity index (LVSCI) = 4 pi(LV area) X 100/(LV perimeter). This index was measured from two-dimensional echocardiograms in 98 children (ages 1 day to 19 years) with congenital heart disease, and results were compared to right ventricular/left ventricular peak systolic pressure ratios (RVP/LVP) determined at cardiac catheterization. LVSCI was also computed in 50 children without cardiovascular or pulmonary disease to define the normal range. A short axis image of the left ventricle at the level of the papillary muscles was obtained from the left parasternal position. Area and perimeter were determined by computer planimetry of the LV endocardium at end systole. LVSCI was measured from three consecutive beats and averaged. In the normal group all values of LVSCI exceeded 93% (mean 96%). In the group with congenital heart disease RVP/LVP correlated exponentially with LVSCI: RVP/LVP = e2.6-0.04 LVSCI; with r = 0.88, SEE = 0.39, and p less than 0.001. If patients with suprasystemic right ventricular pressures (RVP/LVP greater than 1.2) are excluded, there is a linear correlation between RVP/LVP and LVSCI: RVP/LVP = 2.3-0.021 LVSCI; with r = 0.80, SEE = 0.14, and p less than 0.001. LVSCI could distinguish between patients with normal, mildly elevated, moderately elevated, and severely elevated RVP/LVP. We conclude that LVSCI is a readily determined parameter that is independent of age or body size and predicts RVP/LVP in children with congenital heart disease.


Relationship between expression of genes involved in cell cycle control and apoptosis in diffuse large B cell lymphoma: a preferential survivin-cyclin B link.
Accumulating evidence suggests that lack of balance between proliferation and apoptosis may lead to clonal expansion and cancer emergence. In diffuse large B cell lymphoma (DLBCL), survivin expression by tumor cells has been recently described as a poor prognostic marker. We assessed the relationship between survivin gene up-regulation and several other factors involved in either cell cycle or apoptosis control. The expression of 34 genes from 27 cases of DLBCL with typical IPI factor-related poor prognostic outcome was analyzed by RNase protection assay. Using non-neoplastic tissues and low grade lymphomas as control, survivin expression was high in 80% of the cases without significant relation to patient overall survival (P = 0.64). However, the expression of several genes encoding for cell cycle inhibitors, cyclins, Bcl-2 or IAP family factors was significantly associated with the survivin up-regulation. Gene expression profiling showed that both survivin and cyclin B expression can define two subgroups of DLBCL: the previously described germinal center-like and activated B-like lymphomas, determined by protein expression analysis. We also identified a preferential survivin-cyclin B relationship (P = 0.017), suggesting that cyclin B over-expression, when linked to survivin over-expression in aggressive forms of lymphoma, might demonstrate a specific G2/M transition promotion.


Mitral valve replacement combined with coronary artery bypass graft surgery in patients with moderate-to-severe ischemic mitral regurgitation.
Ischemic mitral regurgitation (IMR) is associated with increased mortality. Even after coronary artery bypass grafting (CABG), IMR reduces survival. Several studies have shown increased perioperative mortality for mitral valve replacement (MVR) in this situation, but the subject remains controversial. To investigate the impact of MVR on immediate outcomes in patients with moderate-to-severe IMR undergoing concomitant CABG compared with those undergoing CABG only. We performed a retrospective study of 42 patients undergoing CABG+MVR (n=16) or CABG only (n=26) at the Division of Cardiovascular Surgery of PROCAPE, between May 2007 and April 2010. Preoperative clinical characteristics, procedural characteristics, major and minor complications after surgery, preoperative and postoperative left ventricular ejection fraction (LVEF) by echocardiography, and outcome (survivor or death) were assessed. Mean patient age was 63.4 ± 8.5 years, and 64.8% (n=23) were male. The CABG+MVR group showed lower rates of postoperative low cardiac output (6.3% vs. 42.3%, p=0.014) and atrial fibrillation (6.3% vs. 38.5%, p=0.021). Both groups had higher mean LVEF in the postoperative compared with the preoperative period, but the average gain in LVEF in the CABG+MVR group was higher than in the CABG-only group (8.88 ± 2.39 vs. 4.31 ± 1.23, p<0.001). There was no significant difference in operative mortality (6.3% vs. 7.7%, p=0.679). CABG+MVR can be performed safely in patients with moderate-to-severe IMR. CABG+MVR resulted in lower rates of complications than CABG only. Both surgical approaches resulted in significant improvement of postoperative LVEF. However, there was greater improvement in the CABG+MVR group.


Prediction models for transfer of arsenic from soil to corn grain (Zea mays L.).
In this study, the transfer of arsenic (As) from soil to corn grain was investigated in 18 soils collected from throughout China. The soils were treated with three concentrations of As and the transfer characteristics were investigated in the corn grain cultivar Zhengdan 958 in a greenhouse experiment. Through stepwise multiple-linear regression analysis, prediction models were developed combining the As bioconcentration factor (BCF) of Zhengdan 958 and soil pH, organic matter (OM) content, and cation exchange capacity (CEC). The possibility of applying the Zhengdan 958 model to other cultivars was tested through a cross-cultivar extrapolation approach. The results showed that the As concentration in corn grain was positively correlated with soil pH. When the prediction model was applied to non-model cultivars, the ratio ranges between the predicted and measured BCF values were within a twofold interval between predicted and measured values. The ratios were close to a 1:1 relationship between predicted and measured values. It was also found that the prediction model (Log [BCF]=0.064 pH-2.297) could effectively reduce the measured BCF variability for all non-model corn cultivars. The novel model is firstly developed for As concentration in crop grain from soil, which will be very useful for understanding the As risk in soil environment.


Comparison of preference-based utilities of the 15D, EQ-5D and SF-6D in patients with HIV/AIDS.
This article compares preference-based utilities from the multiattribute utility instrument 15D with those derived from the EQ-5D and the Short Form 36 (SF-6D) in patients with HIV/AIDS. In particular, we wanted to examine if the finer descriptive system of the 15D would result in better discriminative capacity or responsiveness. In a prospective observational study of 60 Norwegian patients with HIV/AIDS from two hospitals, the authors compared scores, assessed associations with disease staging systems, and assessed test-retest reliability and responsiveness of the instruments. On average, the 15D gave higher utility scores than the other two measures, the mean utility scores were: 15D--0.86, SF-6D--0.73, and EQ-5D Index--0.77. Test-retest reliability was acceptable for all measures, with intraclass correlation coefficients between 0.78 and 0.94. The correlation between scores of the 3 scales was substantial (p = 0.74-0.80). There was no major difference in responsiveness between the measures. The different measures gave different utility values in this sample of patients with HIV/AIDS, although many of the measurement properties were similar. There was no evidence for better discriminative capacity or responsiveness for the 15D, than for the two other multiattribute measures.


An MRI-based multi-objective radiomics model predicts lymph node status in patients with rectal cancer.
To apply a multi-objective radiomics model based on pre-operative magnetic resonance imaging (MRI) for improving diagnostic accuracy of LN metastasis in rectal cancer patients. This study consisted of 91 patients diagnosed with rectal cancer from April 2018 to March 2019. All patients underwent rectal MRI before surgery without any other treatment. Clinical data, subjective radiologist assessments, and radiomic features of LNs were obtained. A total of 1409 radiomic features were extracted from T2WI LN images. Multi-objective optimization with the iterative multi-objective immune algorithm (IMIA) was used to select radiomic features to build prediction models. Predictive performances of radiomic, radiologist, and combined radiomic and radiologist models were assessed for accuracy by receiver operating characteristics (ROC) curves. For the radiologist analysis, heterogeneity was the only significant independent predictor of LN status. The sensitivity, specificity, and accuracy of the subjective radiologist analysis were 72.09%, 73.81%, and 78.12%, respectively. The sensitivity, specificity, and accuracy of the solitary radiomic model consisting of 10 features were 89.81%, 82.57%, and 87.77%, respectively. The sensitivity, specificity, and accuracy of the combined model, which consisted of 12 radiomic and radiologist features, were 92.23%, 84.69%, and 89.88%, respectively. The combined model had the best prediction performance with an AUC of 0.94. The multi-objective radiomics model based on T2WI images was very useful in predicting pre-operative LN status in rectal cancer patients.


Intra- and inter-rater reliability of the anterior atlantodental interval measurement from conventional lateral view flexion/extension radiographs.
An investigation of intra- and inter-rater reliability anterior atlantodental interval (AADI) measurements was conducted using flexion/extension plain radiographs. Flexion and extension lateral radiographs of individuals investigated for atlantoaxial instability were measured for AADI on three occasions. Intra-rater intraclass correlation coefficients (ICC) were calculated for both flexion (0.99) and extension (0.96). Inter-rater ICCs were 0.93 and 0.84 for flexion and extension, respectively. The AADI measurement proved to be reproducible with a minimal standard of error, between and within raters.


Characterization of native plant growth promoting rhizobacteria and their anti-oomycete potential against Phytophthora capsici affecting chilli pepper (Capsicum annum L.).
Phytophthora capsici is a notorious fungus which infects many crop plants at their early and late growth stages. In the present study, twelve P. capsici isolates were morphologically characterized, and based on pathogenicity assays; two highly virulent isolates causing post-emergence damping-off on locally cultivated chilli pepper were screened. Two P. capsici isolates, HydPak1 (MF322868) and HydPk2 (MF322869) were identified based on internal transcribed spacer (ITS) sequence homology. Plant growth promoting rhizobacteria (PGPR) play a significant role in disease suppression and plant growth promotion in various crops. Out of fifteen bacterial strains recovered from chilli rhizosphere, eight were found potential antagonists to P. capsici in vitro. Bacterial strains with strong antifungal potential were subjected to biochemical and molecular analysis. All tested bacterial strains, were positive for hydrogen cyanide (HCN), catalase production and indole-3-acetic acid (IAA) production (ranging from 6.10 to 56.23 µg ml-1), while siderophore production varied between 12.5 and 33.5%. The 16S rRNA sequence analysis of tested bacterial strains showed 98-100% identity with Pseudomonas putida, P. libanensis, P. aeruginosa, Bacillus subtilis, B. megaterium, and B. cereus sequences available in the National Center for Biotechnology Information (NCBI) GenBank nucleotide database. All sequences of identified bacteria were submitted to GenBank for accessions numbers (MH796347-50, MH796355-56, MH801129 and MH801071). Greenhouse studies concluded that all tested bacterial strains significantly suppressed the P. capsici infections (52.3-63%) and enhanced the plant growth characters in chilli pepper. Efficacy of many of these tested rhizobacteria is being first time reported against P. capsici from Pakistan. Plant growth promoting rhizobacteria (PGPR) exhibiting multiple traits may be used in the development of new, eco-friendly, and effective bioformulations as an alternative to synthetic fungicides.


Competition for soil water between annual plants and blue oak (Quercus douglasii) seedlings.
We examined the competitive effects of two annual species on soil water potential and blue oak (Quercus douglasii Hook & Arn.) seedling growth and water relations. Two densities of the annual grass Bromus diandrus (Roth.) (100/dm2, 3.6/dm2) and one density of the annual forb Erodium botrys (Cav.) (3.6/dm2) comprised plant neighborhoods around the oak seedlings grown in 1 m deep boxes. Rates of soil water depletion differed among neighborhoods. Soil in the Erodium neighborhoods dried significantly more slowly than did soil in the Bromus neighborhoods at either density. Differences in the rates of soil water depletion were correlated both with the 30% lower root biomass developed by Erodium, and the lower water extraction rates of Erodium relative to Bromus roots at constant root biomass. These results suggest that the annual species are not equivalent competitors for water: fibrous grass roots had greater competitive effect than did forb tap-roots. In a control container without an annual neighborhood, soil water potentials remained high for the duration of the experiment. Oak seedling emergence and growth responses were significantly affected by annual plant density. High density of annual plants suppressed oak root growth and shoot emergence. Only 20% of the acorns planted in high density Bromus neighborhoods showed aboveground shoot growth; 56% of those planted in low density Bromus or Erodium emerged. Ninety percent emerged in the control box. Relative growth rates of oak seedling roots and shoots were directly dependent on soil water potentials. Soil water was also closely correlated with oak seedling predawn water potentials and gas conductance measurements. Higher soil water potentials greater dry weights, and longer growing seasons were found for oak seedlings in the Erodium neighborhood and the container with no annuals than in Bromus neighborhoods of either density. These results suggest that competition for soil water with introduced annual species contributes to the increased rate of blue oak seedling mortality currently observed in California woodland systems.


Cost-minimization analysis favors outpatient quick diagnosis unit over hospitalization for the diagnosis of potentially serious diseases.
Quick diagnosis units (QDUs) are a promising alternative to conventional hospitalization for the diagnosis of suspected serious diseases, most commonly cancer and severe anemia. Although QDUs are as effective as hospitalization in reaching a timely diagnosis, a full economic evaluation comparing both approaches has not been reported. To evaluate the costs of QDU vs. conventional hospitalization for the diagnosis of cancer and anemia using a cost-minimization analysis on the proven assumption that health outcomes of both approaches were equivalent. Patients referred to the QDU of Bellvitge University Hospital of Barcelona over 51 months with a final diagnosis of severe anemia (unrelated to malignancy), lymphoma, and lung cancer were compared with patients hospitalized for workup with the same diagnoses. The total cost per patient until diagnosis was analyzed. Direct and non-direct costs of QDU and hospitalization were compared. Time to diagnosis in QDU patients (n=195) and length-of-stay in hospitalized patients (n=237) were equivalent. There were considerable costs savings from hospitalization. Highest savings for the three groups were related to fixed direct costs of hospital stays (66% of total savings). Savings related to fixed non-direct costs of structural and general functioning were 33% of total savings. Savings related to variable direct costs of investigations were 1% of total savings. Overall savings from hospitalization of all patients were €867,719.31. QDUs appear to be a cost-effective resource for avoiding unnecessary hospitalization in patients with anemia and cancer. Internists, hospital executives, and healthcare authorities should consider establishing this model elsewhere.


Lentviral-mediated RNAi to inhibit target gene expression of the porcine integrin αv subunit, the FMDV receptor, and against FMDV infection in PK-15 cells.
shRNA targeting the integrin αv subunit, which is the foot-and-mouth disease virus (FMDV) receptor, plays a key role in virus attachment to susceptible cells. We constructed a RNAi lentiviral vector, iαv pLenti6/BLOCK -iT™, which expressed siRNA targeting the FMDV receptor, the porcine integrin αv subunit, on PK-15 cells. We also produced a lentiviral stock, established an iαv-PK-15 cell line, evaluated the gene silencing efficiency of mRNA using real-time qRT-PCR, integrand αv expression by indirect immunofluorescence assay (IIF) and cell enzyme linked immunosorbent assays (cell ELISA), and investigated the in vivo inhibitory effect of shRNA on FMDV replication in PK-15 cells. Our results indicated successful establishment of the iαv U6 RNAi entry vector and the iαv pLenti6/BLOCK -iT expression vector. The functional titer of obtained virus was 1.0 × 10(6) TU/mL. To compare with the control and mock group, the iαv-PK-15 group αv mRNA expression rate in group was reduced by 89.5%, whilst IIF and cell ELISA clearly indicated suppression in the experimental group. Thus, iαv-PK-15 cells could reduce virus growth by more than three-fold and there was a > 99% reduction in virus titer when cells were challenged with 10(2) TCID(50) of FMDV. Iαv-PK-15 cells were demonstrated as a cell model for anti-FMDV potency testing, and this study suggests that shRNA could be a viable therapeutic approach for controlling the severity of FMD infection and spread.


Recovery of bacteria from goats' milk following freezing and the prevalence of bacterial infection in milk from goats with an elevated somatic cell count.
To establish the prevalence of bacterial infection of goats with high somatic cell counts and to determine the effect of freezing milk samples on the probability of culturing the same pathogen again. Milk samples were collected from both halves of 99 goats with a somatic cell count >650,000 cells/ml. The milk samples were split into four aliquots with one of the aliquots being cultured immediately. The other three aliquots were frozen at -20 degrees C, and successive aliquots of 39 samples from which pathogens were isolated at Day 0 were thawed and cultured 28, 56 and 84 days later. Coagulase-negative staphylococci were the most common isolates. Freezing and thawing did not significantly reduce either the number of isolates cultured or the number of colony forming units from these successive aliquots. However, three of 39 selected pathogens were not cultured at one or more of the successive thawings. Goats from herds that were housed had a higher probability of having a pathogen isolated from milk than goats from herds kept on pasture. Freezing of milk samples may be used for subsequent culture of bacteria from goats' milk.


Enlarged pi-electronic network of a meso-meso, beta-beta, beta-beta triply linked dibenzoporphyrin dimer that exhibits a large two-photon absorption cross section.
Enlargement of the pi-electronic network of meso-meso, beta-beta, beta-beta triply linked diporphyrin has been exploited by preparing a corresponding dibenzo-fused porphyrin dimer that exhibits a perturbed absorption spectrum and a large two-photon absorption cross section.


Identifying complex patients in family medicine for potential benefit from a case manager: a short questionnaire derived from the INTERMED Self-Assessment (IMSA) questionnaire.
To investigate how useful the Intermed-Self Assessment (IMSA) questionnaire and its components were for identifying which patient candidates would benefit most from case management (CM) in general practice. The study was carried out in a group family medicine practice in Lausanne comprising seven GPs and four medical assistants, from February to April 2019. All the patients attending the practice between February and April 2019 were invited to complete the IMSA questionnaire. Additionally, their GPs were asked for their opinions on the potential benefits of each patient being assigned a case manager. Each IMSA item's value has been assessed as a predictor of GPs' opinions by using multivariate logistic models. A score including items retained as predictor was built. Three hundred and thirty one patients participated in the study (participation rate: 62%). Three items from the 20 item IMSA were sufficient to predict GPs' opinions about whether their patients could be expected to benefit if assigned a case manager. Those items addressed the patient's existing chronic diseases (item1), quality of life in relation to existing diseases (item 3), and their social situation (item 9). Using these three items as a score, a cut-off at 4 gave a sensitivity of 70% (ability to correctly identify patients who could benefit from a CM) and specificity of 73% (ability to correctly identify patients who should not benefit from a CM) and concerned about one patient in two. Identifying complex patients suitable for case management remains a challenge for primary care professionals. This paper describes a novel approach using a structured process of combining the results of standardized tools such as the one defined in this study, and the experience of the primary care team.


Maize productivity and soil properties in the Loess Plateau in response to ridge-furrow cultivation with polyethylene and straw mulch.
Ridge-furrow with full film mulching (RFFM) is widely used in the Loess Plateau (LP) to increase maize yield. However, continuous RFFM application may cause excessive depletion of soil organic carbon (SOC) and soil water storage (SWS). The present study tested four production systems, namely, (1) RFFM; (2) ridge-furrow with polyethylene film and straw mulching (RFFSM); (3) non-contoured seedbed with film mulching (FFM); and (4) non-contoured seedbed without mulching (CK) in 2013 and 2014 to identify an optimal technique to increase maize yield yet minimizing the negative effects. SWS under RFFSM was significantly higher by 5.4% and 13.4% compared to RFFM and CK, respectively. The changes in SOC were -0.2, -0.2, and -0.4 g·kg-1 for RFFM, FFM, and CK, respectively, and 0.3 g·kg-1 for RFFSM. Increased root residue and extra external carbon input to soil under RFFSM directly contributed to SOC recovery. RFFSM had a comparable grain yield but higher water use efficiency compared to RFFM. The combination of RFFSM is promising for improving SOC stocks, water storage, and maize productivity.


Pattern of human chorionic gonadotropin binding in the polycystic ovary.
The histologic evolution of polycystic ovaries in the estradiol valerate-treated rat coincides with the development of a unique plasma pattern of luteinizing hormone. To assess the role of luteinizing hormone in polycystic ovaries, it is necessary to evaluate the luteinizing hormone sensitivity of the specific tissues in the polycystic ovary. Therefore, we examined the pattern of luteinizing hormone binding sites in polycystic ovaries. Rats at 4 or 8 weeks after estradiol valerate treatment each received an intrajugular injection of iodine 125-labeled human chorionic gonadotropin. Some rats also received a 1000-fold excess of unlabeled human chorionic gonadotropin in the same injection. Ovaries were prepared for autoradiography. Dense accumulations of grains occurred over the theca of normal and atretic secondary follicles in all ovaries and over clusters of secondary interstitial cells. The iodine label was variable over the typically hypertrophied theca of precystic follicles. The theca of definitive cysts showed little or no label. These results indicate that cyst formation coincides with the loss of luteinizing hormone/human chorionic gonadotropin binding to the affected follicles.


Mechanism-based quantitative structure-activity relationships for the inhibition of substituted phenols on germination rate of Cucumis sativus.
Comparative inhibition activity (GC50) of 42 structurally diverse substituted phenols on seed germination rate of Cucumis sativus was investigated. Quantitative structure-activity relationships (QSARs) were developed by using hydrophobicity (1-octanol/water partition coefficient, logKow) and electrophilicity (the energy of the lowest unoccupied molecule orbital, Eluma) for the toxicity of phenols according to their modes of toxic action. Most phenols elicited their response via a polar narcotic mechanism and a highly significant log Kow-based model was obtained (GC50 = 0.92 log Kow + 1.99, r2 0.84, n = 29). The inclusion of E(lumo) greatly improved the predictive power of the polar narcotic QSAR (GC50 = 0.88 log Kow - 0.30E(lumo) + 1.99, r2 = 0.93, n = 29). pKa proved to be an insignificant influencing factor in this study. Poor correlation with hydrophobicity and strong correlation with electrophilicity were observed for the nine bio-reactive chemicals. Their elevated toxicity was considerably underestimated by the polar narcotic logKow-dependent QSAR. The nine chemicals consist of selected nitro-substituted phenols, hydroquinone, catechol and 2-aminophenol. Their excess toxic potency could be explained by their molecular structure involving in vivo reaction with bio-macromolecules. Strong dissociation of carboxyl group of the four benzoic acid derivatives greatly decreased their observed toxicity. In an effort to model all chemicals including polar narcotics and bio-reactive chemicals, a response-surface analysis with the toxicity, logKow and E(lumo) was performed. This resulted in a highly predictive two-parameter QSAR for most of the chemicals (GC50 = 0. 70 logKow - 0.66E(lumo) + 2.17, r2 = 0.89, n = 36). Catechol and 2,4-dinitrophenol proved to be outliers of this model and their much high toxicity was explained.


Distinctive E-cadherin and epidermal growth factor receptor expression in metastatic and nonmetastatic head and neck squamous cell carcinoma: predictive and prognostic correlation.
The authors investigated whether coexpression and localization of E-cadherin (E-cad) and epidermal growth factor receptor (EGFR) had predictive and/or prognostic correlations with lymph node metastasis and/or survival in patients with squamous cell carcinoma of the head and neck (SCCHN). Immunohistochemistry (IHC) of archival tissue was performed to measure expression of EGFR and E-cad in surgical specimens of SCCHN (n = 143) that included primary tumors (PTs) with positive lymph nodes (Tu+Met) and their paired lymph node metastases (LnMet), PTs with negative lymph nodes (Tu(-Met)), and benign tissue biopsies as normal controls. IHC staining was quantified as a weighted index and as the ratio of membrane to cytoplasmic staining. Correlative expression between EGFR and E-cad also was examined in SCCHN cell lines by immunoblotting and immunofluorescence analyses. Three distinct expression patterns of EGFR and E-cad were observed. Membrane localization of E-cad was significantly lower in the Tu+Met group than in the Tu(-Met) group (P = .01) and was associated inversely with lymph node status (P = .009). Wilcoxon analysis of the combined markers demonstrated that expression and/or membrane localization of EGFR and E-cad were correlated with disease-free survival and overall survival in patients with SCCHN. The study of SCCHN cell lines demonstrated that cells with positive but low EGFR expression and with negative E-cad expression were relatively resistant to the EGFR tyrosine kinase inhibitor erlotinib. The current study suggested that examining not only the expression but also the localization of EGFR and E-cad simultaneously may have clinical relevance in predicting lymph node metastasis, patient survival, and response to EGFR-targeted therapy in patients with SCCHN.


Effects of peritoneal dialysis solutions on the peritoneal membrane: clinical consequences.
This review provides an overview of recent studies that show the clinical significance of biocompatibility of peritoneal dialysis fluids.


Highly Luminescent Ternary Nanocomposite of Polyaniline, Silver Nanoparticles and Graphene Oxide Quantum Dots.
Quantum dots (QDs) with photostability show a potential application in optical sensing and biological imaging. In this work, ternary nanocomposite (NC) of high fluorescent polyaniline (PANI)/2-acrylamido-2-methylpropanesulfonic acid (AMPSA) capped silver nanoparticles (NPs)/graphene oxide quantum dots (PANI/Ag (AMPSA)/GO QDs) have been synthesized by in situ chemical oxidative polymerization of aniline in the presence of Ag (AMPSA) NPs and GO QDs. Ag (AMPSA) NPs and GO QDs were prepared by AgNO3 chemical reduction and glucose carbonization methods, respectively. The prepared materials were characterized using UV-visible, Fourier transform infrared (FTIR), photoluminescence and Raman spectroscopies, X-Ray diffractometer (XRD) and high- resolution transmission electron microscopy (HRTEM). HRTEM micrographs confirmed the preparation of GO QDs with an average size of 15 nm and Ag (AMPSA) NPs with an average size of 20 nm. PANI/Ag (AMPSA)/GO QDs NC showed high and stable emission peak at 348 nm. This PANI/Ag (AMPSA)/GO QDs NC can emerge as a new class of fluorescence materials that could be suitable for practical sensing applications.


Production of antibody against C3c epitopes which are inaccessible on native C3.
Anti-C3c antiserum was induced by immunizing rabbits with autologous erythrocytes coated with human C3b/C3bi. By absorption with human plasma this antiserum was rendered specific for C3c epitopes which are not expressed on native C3. This specificity may be analogous to that of immunoconglutinin.


The unequal burden of the Covid-19 pandemic: Capturing racial/ethnic disparities in US cause-specific mortality.
Despite a growing body of literature focused on racial/ethnic disparities in Covid-19 mortality, few previous studies have examined the pandemic's impact on 2020 cause-specific mortality by race and ethnicity. This paper documents changes in mortality by underlying cause of death and race/ethnicity between 2019 and 2020. Using age-standardized death rates, we attribute changes for Black, Hispanic, and White populations to various underlying causes of death and show how these racial and ethnic patterns vary by age and sex. We find that although Covid-19 death rates in 2020 were highest in the Hispanic community, Black individuals faced the largest increase in all-cause mortality between 2019 and 2020. Exceptionally large increases in mortality from heart disease, diabetes, and external causes of death accounted for the adverse trend in all-cause mortality within the Black population. Within Black and White populations, percentage increases in all-cause mortality were similar for men and women, as well as for ages 25-64 and 65+. Among the Hispanic population, however, percentage increases in mortality were greatest for working-aged men. These findings reveal that the overall impact of the pandemic on racial/ethnic disparities in mortality was much larger than that captured by official Covid-19 death counts alone.


Cancer expression quantitative trait loci (eQTLs) can be determined from heterogeneous tumor gene expression data by modeling variation in tumor purity.
Expression quantitative trait loci (eQTLs) identified using tumor gene expression data could affect gene expression in cancer cells, tumor-associated normal cells, or both. Here, we have demonstrated a method to identify eQTLs affecting expression in cancer cells by modeling the statistical interaction between genotype and tumor purity. Only one third of breast cancer risk variants, identified as eQTLs from a conventional analysis, could be confidently attributed to cancer cells. The remaining variants could affect cells of the tumor microenvironment, such as immune cells and fibroblasts. Deconvolution of tumor eQTLs will help determine how inherited polymorphisms influence cancer risk, development, and treatment response.


Influence of Chronic Obstructive Pulmonary Disease on Volatile Organic Compounds in Patients with Non-Small Cell Lung Cancer.
The etiology of lung cancer is multifactorial. Exposure to tobacco smoke and the role played by the carcinogenic compounds that it contains would explain the common association between lung cancer and chronic obstructive pulmonary disease (COPD), which is closely linked to tobacco use. In both diseases, sustained inflammation is caused by increased oxidative stress (for example, lipid peroxidation). This generates low molecular weight substances called volatile organic compounds (VOC) that are excreted during breathing. VOC metabolomics provides an indirect measure of oxidative stress. The aim of this study was to establish the relative influence of COPD on the VOC profile in patients with non-small cell lung cancer (NSCLC), by first studying the possible variation of VOC associated with lung cancer histology. Exhaled air was tested in 107 NSCLC patients, who were divided into 2 groups: NSCLC with COPD and non-COPD with NSCLC. The exhaled air sample was obtained with the BIOVOC® sampler, and transferred to desorption tubes for later analysis by thermal desorption-gas chromatography-mass spectrometry. The VOC analysis showed lineal aldehydes and carboxylic acids. No statistically significant differences were found in VOC associated with histology. NSCLC and COPD patients present a 1.7-fold (1.1-2.7) greater probability of detection of propionic acid (95% CI: 1.22-6.2) than patients without COPD or NSCLC (p = 0.013).


Impaired induction of vasoactive intestinal polypeptide after sciatic nerve injury in the streptozotocin-diabetic rat.
This study was designed to assess the effects of experimental diabetes and nerve crush injury upon vasoactive intestinal polypeptide (VIP) content and axonal transport in the dorsal root ganglia (DRG) and sciatic nerve. Sciatic nerve crush injury in control and 3-week streptozotocin-diabetic rats was followed 6.5 days later by placement of 2 constricting ligatures above the site of injury. After 12 h, the L4 and L5 DRG and sciatic nerve were removed for VIP radioimmunoassay. Similar samples were also taken from control and diabetic rats whose nerve had been ligated without a preceding crush. VIP was increased over 2-fold in ganglia and 4-fold in nerves of crush-injured controls compared to uninjured controls (both P < 0.01). Crush injury also increased ganglion and nerve VIP in diabetic rats (P < 0.05 and 0.01, respectively) but the increase was less than what occurred in crush-injured controls (both P < 0.05). The accumulation of VIP proximal to a sciatic ligature was similar in control and diabetic rats and was not altered in either group by crush injury, while retrograde transport of VIP was initiated by crush injury in both control and diabetic rats. These data show that short-term diabetes does not alter the amount and peripheral axonal transport of VIP in the sciatic nerve but impairs the ability of peripheral nerve to respond to injury.


Social and financial incentives for overcoming a collective action problem.
Addressing public health externalities often requires community-level collective action. Due to social norms, each person's sanitation investment decisions may depend on the decisions of neighbors. We report on a cluster randomized controlled trial conducted with 19,000 households in rural Bangladesh where we grouped neighboring households and introduced (either financial or social recognition) rewards with a joint liability component for the group, or asked each group member to make a private or public pledge to maintain a hygienic latrine. The group financial reward has the strongest impact in the short term (3 months), inducing a 7.5-12.5 percentage point increase in hygienic latrine ownership, but this effect dissipates in the medium term (15 months). In contrast, the public commitment induced a 4.2-6.3 percentage point increase in hygienic latrine ownership in the short term, but this effect persists in the medium term. Non-financial social recognition or a private pledge has no detectable effect on sanitation investments.


Technique for order of preference by similarity to ideal solution (TOPSIS) method for the generation of external preference mapping using rapid sensometric techniques.
External preference mapping is a powerful tool to explain consumer preference or rejection. Combining the technique for order of preference by similarity to ideal solution (TOPSIS) multicriteria analysis with rapid descriptive techniques can improve preference map (PREFMAP) results. This study was conducted to compare the PREFMAPs generated with rapid descriptive flash profile (FP), check-all-that-apply (CATA), and Napping® versus PREFMAPs constructed with FP-TOPSIS, CATA-TOPSIS, and Napping-TOPSIS. Only 38.46%, 63.66%, and 42% of sensory attributes initially generated by FP, CATA, and Napping techniques respectively were considered for the determination of their weight W and allocation as positive or negative in the TOPSIS technique. The PREFMAPs constructed with FP-TOPSIS, CATA-TOPSIS, and Napping-TOPSIS presented a better explanation of the preference and rejection than the PREFMAPs directly generated with rapid sensory techniques. The results of the multiple factor analysis and coefficient Rv indicated similarities in the sensory vocabularies used after the TOPSIS technique. The combination of the TOPSIS technique with rapid sensory techniques is a reliable alternative for the construction of PREFMAPs in order to identify the sensory attributes responsible for preference and rejection of food products. © 2020 Society of Chemical Industry.


Heterotopic Mucosal Grafting Enables the Delivery of Therapeutic Neuropeptides Across the Blood Brain Barrier.
The blood-brain barrier represents a fundamental limitation in treating neurological disease because it prevents all neuropeptides from reaching the central nervous system (CNS). Currently, there is no efficient method to permanently bypass the blood-brain barrier. To test the feasibility of using nasal mucosal graft reconstruction of arachnoid defects to deliver glial-derived neurotrophic factor (GDNF) for the treatment of Parkinson disease in a mouse model. The Institutional Animal Care and Use Committee approved this study in an established murine 6-hydroxydopamine Parkinson disease model. A parietal craniotomy and arachnoid defect was repaired with a heterotopic donor mucosal graft. The therapeutic efficacy of GDNF (2 μg/mL) delivered through the mucosal graft was compared with direct intrastriatal GDNF injection (2 μg/mL) and saline control through the use of 2 behavioral assays (rotarod and apomorphine rotation). An immunohistological analysis was further used to compare the relative preservation of substantia nigra cell bodies between treatment groups. Transmucosal GDNF was equivalent to direct intrastriatal injection at preserving motor function at week 7 in both the rotarod and apomorphine rotation behavioral assays. Similarly, both transmucosal and intrastriatal GDNF demonstrated an equivalent ratio of preserved substantia nigra cell bodies (0.79 ± 0.14 and 0.78 ± 0.09, respectively, P = NS) compared with the contralateral control side, and both were significantly greater than saline control (0.53 ± 0.21; P = .01 and P = .03, respectively). Transmucosal delivery of GDNF is equivalent to direct intrastriatal injection at ameliorating the behavioral and immunohistological features of Parkinson disease in a murine model. Mucosal grafting of arachnoid defects is a technique commonly used for endoscopic skull base reconstruction and may represent a novel method to permanently bypass the blood-brain barrier.


Degradation and selective ligninolysis of wheat straw and banana stem for an efficient bioethanol production using fungal and chemical pretreatment.
Lignocelluloses from agricultural, industrial, and forest residues constitute a majority of the total biomass present in the world. Environmental concerns of disposal, costly pretreatment options prior to disposal, and increased need to save valuable resources have led to the development of value-added alternate technologies such as bioethanol production from lignocellulosic wastes. In the present study, biologically pretreated (with the fungus, Pleurotus ostreatus HP-1) and chemically pretreated (with mild acid or dilute alkali) wheat straw (WS) and banana stem (BS) were subsequently subjected to enzymatic saccharification (with mixture of 6.0 U/g of filter paper cellulase and 17 U/g of β-glucosidase) and were evaluated for bioethanol production using Saccharomyces cerevisiae NCIM 3570. Biological and chemical pretreatments removed up to 4.0-49.2 % lignin from the WS and BS which was comparatively higher than that for cellulose (0.3-12.4 %) and for hemicellulose (0.7-21.8 %) removal with an average 5.6-49.5 % dry matter loss. Enzymatic hydrolysis yielded 64-306.6 mg/g (1.5-15 g/L) reducing sugars from which 0.15-0.54 g/g ethanol was produced from Saccharomyces cerevisiae NCIM 3570.


Hepatocellular carcinoma detection in liver cirrhosis: diagnostic performance of contrast-enhanced CT vs. MRI with extracellular contrast vs. gadoxetic acid.
To evaluate the diagnostic performance of contrast-enhanced CT vs. MRI with extracellular contrast agents (EC-MRI) vs. MRI with gadoxetic acid (EOB-MRI) for HCC detection in patients with liver cirrhosis using liver explant as the reference. The additional value of hepatobiliary phase (HBP) post Gadoxetic acid was also assessed. Two-hundred seventy-seven consecutive patients who underwent liver transplantation over a 9 year period and imaging within 90 days of were retrospectively included. Imaging consisted in CT (n = 100), EC-MRI (n = 77) and EOB-MRI (n = 100), the latter subdivided into dynamic EOB-MRI and full EOB-MRI (dynamic+HBP). Three radiologists retrospectively categorized lesions ≥ 1 cm using the LI-RADSv2017 algorithm. Dynamic EOB-MRI was re-evaluated with the addition of HBP. Results were correlated with explant pathology. Pathology demonstrated 265 HCCs (mean size 2.1 ± 1.4 cm) in 177 patients. Per-patient sensitivities were 86.3% for CT, 89.5% for EC-MRI, 92.8% for dynamic EOB-MRI and 95.2% for full EOB-MRI (pooled reader data), with a significant difference between CT and dynamic/full EOB-MRI (p = 0.032/0.002), and between EC-MRI and full EOB-MRI (p = 0.047). Per-lesion sensitivities for CT, EC-MRI, dynamic EOB-MRI and full EOB-MRI were 59.5%,78.5%,69.7% and 76.8%, respectively, with a significant difference between MRI groups and CT (p-range:0.001-0.04), and no difference between EC-MRI and dynamic EOB-MRI (p = 0.949). For HCCs 1-1.9 cm, sensitivities were 34.4%, 64.6%, 57.3% and 67.3%, respectively, with all MRI groups significantly superior to CT (p ≤ 0.01) and full EOB-MRI superior to dynamic EOB-MRI (p = 0.002). EOB-MRI outperforms CT and EC-MRI for per-patient HCC detection sensitivity, and is equivalent to EC-MRI for per-lesion sensitivity. MRI methods outperform CT for detection of HCCs 1-1.9 cm. • MRI is superior to CT for HCC detection in patients with liver cirrhosis. • EOB-MRI outperforms CT and MRI using extracellular contrast agents (EC-MRI) for per-patient HCC detection sensitivity, and is equivalent to EC-MRI for per-lesion sensitivity. • The addition of hepatobiliary phase images improves HCC detection when using gadoxetic acid.


Optimization of two charge transfer reactions for colorimetric determination of two beta 2 agonist drugs, salmeterol xinafoate and salbutamol, in pharmaceutical and biological samples.
Beta 2 agonists are well known for their use in the treatment of asthma and COPD however in the last few years new indications of beta 2 agonist appeared like reduction of local fats and treatment of preterm labour which required the formulation of new dosage forms and administration strategies. The new developments require accurate, economic and feasible methods the determination of these drugs to facilitate testing the newly introduced dosage forms and to study the pharmacokinetics and pharmacodynamics regarding the modern uses. In this study two rapid, sensitive and economic colorimetric methods for the determination of salmeterol xinafoate and salbutamol in pharmaceutical dosage forms and spiked plasma were developed and validated. The developed methods depends on the optimized reaction of the studied drugs with two charge transfer reagents, 2,3-dochloro-5,6-dicyano-1,4-benzoquonone (DDQ) and chloranilic acid (CA) to produce coloured complexes measured at 460 and 529 nm for DDQ and CA respectively. The developed methods showed high accuracy of 99.52 ± 1.108, 101.03 ± 0.389, 100.04 ± 1.520 and 100.3 ± 0.951 for salmetrol xinafoate and salbutamol with DDQ and CA respectively. The proposed methods were successfully used for the determination of the studied drugs in their dosage forms and spiked plasma with high accuracy and precision and the results were compared to reported methods.


Obesity at Age 6 Months Is Associated with Shorter Preschool Leukocyte Telomere Length Independent of Parental Telomere Length.
To assess whether early modifiable dietary factors and obesity measures are associated with leukocyte telomere length at 3-5 years of age after controlling for the heritability of leukocyte telomere length in a prospective cohort of low-income Latina mothers and their children in San Francisco. We analyzed data from the Latinx, Eating and Diabetes cohort, a prospective study of 97 woman-infant dyads. We used linear regression models to evaluate associations between early dietary factors and obesity measures and child leukocyte telomere length at 3-5 years of age. Multivariable models included child age at the time of telomere collection, breastfeeding at 6 months (yes/no), obesity at 6 months, maternal education, child sex, and maternal and paternal leukocyte telomere length. Data for 73 of the 97 children at 3-5 years of age were analyzed. Any breastfeeding at 6 months was positively associated (β = 0.14; P = .02) and obesity at 6 months was negatively associated (β = -0.21; P < .001) with leukocyte telomere length in bivariate analyses. In multivariable models including parental leukocyte telomere length, obesity at 6 months was associated with a shorter leukocyte telomere length at 3-5 years of age (β = -0.15; P = .02). Analyses of dietary factors showed high flavored milk consumption at 3 years of age was associated with shorter leukocyte telomere length after adjustment for possible confounders. In a low-income Latinx population, obesity at 6 months of age is negatively associated with cellular health at 3-5 years of age after controlling for genetic factors (parental leukocyte telomere length) associated with leukocyte telomere length. Early life obesity may be more deleterious for cellular health than obesity later in childhood.


Intraoperative radiation therapy in surgical oncology.
This is the first publication about intraoperative radiation therapy (IORT) to be written for surgeons through a collaborative effort of surgeons and radiation therapists. This article introduces the basic concepts of radiation therapy and the rationale of its use in the operating room, and presents the advantages for the surgeon and radiation therapist to work together for the benefit of our patients.


Components of self-esteem in affective patients and non-psychiatric controls.
Decrease in self-esteem (SE) is found in all mood disorders during inter-episode phases. This trait was associated with relapse and suicidality but its genetic basis is still undefined, probably because SE has multiple components. The aim of the current study was to ascertain which of those components were altered in a sample of affective patients. Three hundred and thirty-one outpatients with bipolar (N=199) and major depressive MD (N=132) disorders in remission for at least three months and one hundred controls completed the Rosenberg Self-esteem Scale (RSE; [Rosenberg, M., 1965. The measurement of self-esteem, Society and the Adolescent Self-Image. Princeton University Press, pp.16-36]). Principal component analysis was performed to identify RSE factor structure. Extracted factors were compared across case and control groups in the whole sample (N=431) and in a sub-sample (N=301) with low self-esteem (RSE <20). PCA yielded a two-factor solution with self-confidence (SC) and self-deprecation (SD) that was largely consistent with the existing literature. Such factors were both associated with lower scores in affective patients than controls (SC: F=52, p<0.01; SD: F=43, p<0.01). However in the low RSE group only self-confidence was found to be decreased in subjects with mood disorders (SC: F=13.8, p<0.01; SD: F=0.05, p=0.9). These findings suggest that self-esteem deficit in affective disorders might involve specific components. Implications for research and clinical practice are discussed.


Differential host utilization by two parasites in a population of ponderosa pine.
We compared phloem characteristics of individual Pinus ponderosa attacked by the dwarf-mistletoe Arceuthobium vaginatum (Viscaceae) or by the beetle Dendroctonus ponderosae (Scolytidae) or by neither species. We quantified total nonstructural carbohydrates and a broad range of chemical elements for these three categories of trees. There were significant differences between trees parasitized by Arceuthobium, trees parasitized by Dendroctonus, and non-infected trees. Discriminant function analysis of trees attacked by either Arceuthobium or Dendroctonus correctly predicted group membership for 59 of 60 trees tested. Some of the differences detected may be induced, but many probably are not. Given that the accumulation of certain elements and compounds is under genetic control, and that both parasites often cause severe reductions in fitness, including death of their host, our results suggest that the two parasites may generate diversifying selection in ponderosa pine populations.


Biliary Stent Migration: A Rare Cause of a Bladder Stone.
Our patient presented with dysuria and pneumaturia without any prior urologic instrumentation. History included choledocolithiasis requiring endoscopic retrograde cholangiopancreatography and biliary stenting. Imaging showed a large bladder stone. The patient was taken to surgery and found to have diverticulitis. The sigmoid was resected and the bladder was found to have a small fistula tract. The bladder was opened and a large calculus was identified and extracted. The stone was opened and found to contain a biliary stent. Although biliary stenting is generally considered safe, migration can occur. This is the only report of biliary stent migration into the bladder and subsequent stone formation.


Probabilistic health risk assessment for residents exposed to potentially toxic elements near typical mining areas in China.
Public health problems caused by toxic elements in mining areas have always been an important topic worldwide. However, existing studies have focused on single exposure routes and common toxic elements, which might underestimate the risks faced by residents. In this study, three typical mining areas in central China were selected to assess the health risks of 14 potentially toxic elements through five exposure routes using Monte Carlo simulations. The results indicated that the 95th percentile non-carcinogenic risk values to humans via rice and vegetable ingestion ranged from 9.8 to 26.0 and 6.2 to 19.0. The corresponding carcinogenic risks ranged from 1.4E-2 to 6.3E-2 and from 2.9E-3 to 2.3E-2, respectively. Therefore, residents face serious health risks. Multi-element analysis showed that cadmium (Cd), boron (B), and arsenic (As) were the main contributors to rice non-carcinogenicity, whereas Cd and nickel (Ni) were the main elements of rice carcinogenicity. B and lead (Pb) played an essential role in the non-carcinogenesis of vegetables, and B, Ni, and Cd played an essential role in carcinogenesis. Accidental ingestion is the main route of soil exposure. In these three areas, the probability of non-carcinogenic risk faced by adults was 40%, 0%, and 1%, respectively, while the probabilities for children were 100%, 62%, and 83%, respectively. Regarding carcinogenicity, the risk for both adults and children was up to 100%. This study emphasizes the overall health risks in polluted areas via multi-route and multi-element analysis. This conclusion is helpful to comprehensively assess the potential health risks faced by residents in mining areas and provide baseline data support and a scientific basis for formulating reasonable risk control measures.


Use of rigid internal fixation in the repair of complex and comminuted mandible fractures.
An overview of the use of rigid internal fixation using the AO method for the repair of complex mandibular injuries is presented. The end result of such an approach is the return of the patient as rapidly as possible to his or her normal status with return to normal alimentation, normal mobility of the mandible, normal airway, and normal access to the oral cavity.


Neoadjuvant concurrent radiochemotherapy in locally advanced (IIIA-IIIB) non-small-cell lung cancer: long-term results according to downstaging.
To report the efficacy of induction treatment (IT) protocol with concurrent radiochemotherapy in locally advanced non-small-cell lung cancer (NSCLC), and to analyze downstaging as a surrogate end point. Patients with histo- or cytologically confirmed stage IIIA or IIIB NSCLC were treated according to an IT protocol followed by surgery. Downstaging was assessed for all resected patients. In the period between February 1992 and July 2000, 92 patients were enrolled in the study (57 IIIA, 35 IIIB). Response was observed in 63 patients; 56 patients underwent radical resection. Patients downstaged to stage 0-I (DS 0-I) showed a statistically significant improved disease-free survival (26.2 months pStage 0-I versus 11.2 months pStage II-III; P=0.0116) and overall survival (median 32.5 months pStage 0-I versus 18.3 months pStage II-III; P=0.025). Patients with DS 0-I had a significantly lower probability (P=0.0353) of developing distant metastases estimated in 0.2963 odds ratio. Neoadjuvant radiochemotherapy is feasible with good pathological DS results. Pathological downstaging was confirmed to have high predictive value. Its use is suggested in the short-term evaluation of induction protocols efficacy in locally advanced NSCLC.


Warped rhythms: Epileptic activity during critical periods disrupts the development of neural networks for human communication.
It is well established that temporal lobe epilepsy-the most common and well-studied form of epilepsy-can impair communication by disrupting social-emotional and language functions. In pediatric epilepsy, where seizures co-occur with the development of critical brain networks, age of onset matters: The earlier in life seizures begin, the worse the disruption in network establishment, resulting in academic hardship and social isolation. Yet, little is known about the processes by which epileptic activity disrupts developing human brain networks. Here we take a synthetic perspective-reviewing a range of research spanning studies on molecular and oscillatory processes to those on the development of large-scale functional networks-in support of a novel model of how such networks can be disrupted by epilepsy. We seek to bridge the gap between research on molecular processes, on the development of human brain circuitry, and on clinical outcomes to propose a model of how epileptic activity disrupts brain development.


Effect of dexmedetomidine constant rate infusion on the bispectral index during alfaxalone anaesthesia in dogs.
To assess the effect of two rates of infusion of dexmedetomidine on the bispectral index (BIS) in dogs anaesthetized with alfaxalone constant rate infusion (CRI). Prospective, randomized, 'blinded' experimental study. Six healthy Beagles (three females and three males). Dogs received as premedication saline (group D0), 1 μg kg(-1) (group D1) or 2 μg kg(-1) (group D2) dexmedetomidine, intravenously (IV). Anaesthesia was induced with alfaxalone (6 mg kg(-1) to effect IV) and maintained with alfaxalone at 0.07 mg kg(-1) minute(-1) and a CRI of saline (D0) or dexmedetomidine 0.5 μg kg(-1) hour(-1) (D1) or 1 μg kg(-1) hour(-1) (D2) for 90 minutes. BIS, electromyography (EMG), signal quality index (SQI) and suppression ratio (SR) were measured at 10 minute intervals and the median values were calculated. Nociceptive stimuli were applied every 30 minutes and BIS and cardiorespiratory values were compared before and after stimuli. Cardiorespiratory parameters were recorded throughout the study. BIS and EMG values differed significantly among groups, being lower in D2 (71 ± 8) than in D0 (85 ± 10) and D1 (84 ± 9). SQI was always over 90% and SR was zero throughout all the treatments. There were no significant differences between pre- and post-stimulus values of BIS, EMG and SQI for any treatment, although in D0 and D1, heart rate, respiratory rate and arterial pressures increased significantly after the nociceptive stimulus. Administration of dexmedetomidine (2 μg kg(-1) + CRI 1 μg kg(-1) hour(-1) ) decreases the BIS values and avoids the autonomic responses of a nociceptive stimulus during alfaxalone anaesthesia at 0.07 mg kg(-1) minute(-1) in dogs. However, further studies are needed to verify whether this combination produces an adequate degree of hypnosis under surgical situations.


The impact of falls in an inner-city elderly African-American population.
To describe the impact of falls in an elderly African-American urban community and to identify predictors of poor recovery from falls. Prospective cohort study. Emergency departments of 11 hospitals in western Philadelphia. Interviews were conducted with 197 African-American persons 65 years and older residing in West Philadelphia who were treated at an emergency department because of a fall. Second interviews were conducted a median of 7 months after the fall with a sample of 70 patients who had not recovered at the time of the first interview. Information abstracted from emergency department medical records and information on recovery obtained from two subsequent interviews. A median of 8 weeks after the fall occurred, 43% of persons reported continued pain or restriction in their usual activities as a result of the fall. Predictors of poor recovery included the presence of grandchildren in the household, hearing impairment, severity of the injury, and injury to the lower extremities. Having someone present at the time of the fall was associated with a lower risk of poor recovery. Forty-one percent of the 70 persons interviewed a second time reported continued pain or restriction in usual activities a median of 7 months after the fall occurred. However, only 7% and 39% had received the services of a home health aide or physical therapist, respectively, and only 14% reported that a physician or other health professional had been particularly helpful since the fall had occurred. A large proportion of elderly African-American persons treated at emergency departments for falls experience continued pain and restriction of activities after the fall. Many individuals have not recovered 7 months or longer after the fall and few persons report that a physician or other health professional has been particularly helpful since the fall occurred. We suggest that follow-up programs be developed for elderly persons in minority communities who come to emergency departments after a fall.


Locus coeruleus-to-dorsal raphe input examined by electrophysiological and morphological methods.
In order to examine the hypothesis that the locus coeruleus (LC) projects directly to the nucleus raphe dorsalis (DR), electrical stimulation was applied to the LC of rats while recording from single neurons in the region of the DR. Slow firing units of the DR were not influenced by the stimulation, although faster firing units in the nearby substantia grisea centralis (SGC) were. These latter cells become oscillatory in their firing rates during LC stimulation. In parallel studies a retrograde transport technique was imployed to obtain morphological evidence regarding projections to DR. Placements of horseradish peroxidase precisely in the DR resulted in very sparse labeling in the LC, although positive transport occurred to other areas. The results indicate that the LC does not project directly to slow firing DR neurons, but does influence faster firing celles in the region of the SGC, probably by complex routes. Suggestions are made for the integration of these findings with earlier fluorescence studies.


Adrenal androgens and human breast cancer: a new appraisal.
A clearer picture of the role of adrenal androgens in the etiology of breast cancer is beginning to emerge. Women who develop breast cancer in premenopausal years tend to have subnormal serum levels of adrenal androgens, while subjects who develop the disease in postmenopausal years have supranormal levels of these hormones. Androgens, by acting via the androgen receptor, oppose estrogen-stimulated cell growth in premenopausal years. In postmenopausal women, elevated adrenal androgen levels stimulate cell growth by the action of the unique adrenal androgen 5-androstene-3beta,17beta-diol, also termed hermaphrodiol, via its combination with the estrogen receptor in a hormone milieu lacking, or having low concentrations of, the classical estrogen 17beta-estradiol.


Comment on the use of the method of images for calculating electromagnetic responses of interacting spheres.
In this Comment, I argue that the method of images used by Huang, Yu, and Gu [Phys Rev. E 65, 021401 (2002)] and Huang, Karttunen, Yu, Dong, and Gu [Phys Rev. E., 69, 051402 (2004)] to calculate electromagnetic properties of interacting spheres at finite frequencies is inapplicable and does not provide a physically meaningful approximation.


The bioenergetics of mitochondria after cryopreservation.
The functional characteristics of rat liver mitochondria after cryopreservation with and without the addition of the cryoprotectant dimethyl sulfoxide (Me2SO) were evaluated. As criteria of functional integrity, polarographic measurements of substrate-linked oxygen consumption and luminescent assay of adenosine triphosphate (ATP) synthesis were considered before and after cryopreservation. The results demonstrated that mitochondrial damage after freezing was indicated by the polarographic studies but was not evident when ATP synthesis was considered. Me2SO present during cryopreservation was partially protective for mitochondrial substrate-linked oxygen consumption; however, simple exposure to and dilution from Me2SO effected some changes in mitochondrial function.


Performance evaluation of microbial fuel cell for landfill leachate treatment: Research updates and synergistic effects of hybrid systems.
Over half of century, sanitary landfill was and is still the most economical treatment strategy for solid waste disposal, but the environmental risks associated with the leachate have brought attention of scientists for its proper treatment to avoid surface and ground water deterioration. Most of the treatment technologies are energy-negative and cost intensive processes, which are unable to meet current environmental regulations. There are continuous demands of alternatives concomitant with positive energy and high effluent quality. Microbial fuel cells (MFCs) were launched in the last two decades as a potential treatment technology with bioelectricity generation accompanied with simultaneous carbon and nutrient removal. This study reviews capability and mechanisms of carbon, nitrogen and phosphorous removal from landfill leachate through MFC technology, as well as summarizes and discusses the recent advances of standalone and hybrid MFCs performances in landfill leachate (LFL) treatment. Recent improvements and synergetic effect of hybrid MFC technology upon the increasing of power densities, organic and nutrient removal, and future challenges were discussed in details.


Coronary risk factor screening and long-term follow up: year 1 of the Sydney Coronary Heart Disease Prevention Programme.
Ten thousand self-referred Sydney inhabitants were screened for major coronary risk factors over one year. Individual "problems" were referred to general practitioners for further assessment and treatment. Seventy-four per cent of subjects have attended a general practitioner where relevant. For subjects under 65 years, 29% had unsuspected hyperlipidaemia, 11% had unsuspected hypertension, and 0.6% had unsuspected diabetes. Nineteen per cent of subjects reported a past history of hypertension, of whom 46% appeared to be well-controlled (diastolic blood pressure less than 95 mmHg). The numbers of cigarette smokers fell with increasing age. Considering hyperlipidaemia, hypertension and cigarette smoking in subjects under 40 years of age, 10.4% of males and 4.9% of females had two or more coronary risk factors. Three hundred and fifty-four subjects selected at random, who claimed to be receiving treatment as a result of initial screening were invited for retesting eight and 15 months later. Significant falls were noted in body weight, blood pressure, and plasma cholesterol readings.


Mesostriatal projections from ventral tegmentum and dorsal raphe: cells project ipsilaterally or contralaterally but not bilaterally.
The cells of origin of the brainstem projection to the caudate-putamen (CP) were examined in the albino rat by the use of two fluorescent retrograde tracers. Nuclear yellow was injected into the CP of one hemisphere and granular blue was injected into the contralateral CP. Retrogradely labeled cells were studied in the substantia nigra (SN), ventral tegmental area (VTA) and dorsal raphe (DR). The results confirm previous findings indicating the existence of contralateral projections from SN and VTA to the CP. Cells on both sides of the midline of the DR also project to either CP. Contralaterally projecting SN/VTA cells were located in areas of these nuclei which corresponded to the center of the ipsilaterally projecting cell region; the exact locations depended on the placement of the injection in the CP. In DR, contralaterally projecting cells were most often observed near the midline, although labeled cells were occasionally observed in the lateral wings of the DR. Cells labeled by contralateral injections were interdigitated with, but not identical to, cells labelled by ipsilateral injections. That is, contralaterally projecting cells and ipsilaterally projecting cells constituted separate populations within the SN, VTA and DR.


A smartphone-integrated ratiometric fluorescence sensing platform for visual and quantitative point-of-care testing of tetracycline.
A smartphone-integrated ratiometric fluorescent sensing system (DPA-Ce-GMP-Eu) for visual and point-of-care testing (POCT) of tetracycline with high sensitivity and accuracy was developed. The blue fluorescence of DPA-Ce-GMP was changed into red by doping with Eu3+ duo to the energy transfer from Ce3+ to Eu3+. Upon exposure to tetracycline, coordination between Eu3+ and tetracycline blocks energy transfer from Ce3+ to Eu3+, converting the fluorescent color from red to blue. The tetracycline detection can be realized within a wide concentration range from 0.01 μM to 45 μM. The limit of detection (LOD) reaches as low as 6.6 nM. To realize quantitative point-of-care detection in real samples, a portable device with smartphone as signal reader and analyzer is further designed to integrate with the DPA-Ce-GMP-Eu sensing platform. The Color Picker APP installed in the smartphone can convert the Red, Green and Blue (RGB) channels of the fluorescence images into digital values. With milk as real sample, tetracycline can be on-site detected with LOD of 10.8 nM. This developed platform presents a great promise for POCT in practical application with merits of low cost, easy carry, simple operation, and excellent selectivity and repeatability.


What characterizes individuals developing chronic whiplash?: The Nord-Trøndelag Health Study (HUNT).
Most individuals experiencing whiplash accidents recover rapidly. A considerable proportion, however, develop chronic symptoms. Psychological factors may slow recovery, possibly by increasing the likelihood of other symptoms being misattributed to, and amplified by the whiplash injury. We aimed to investigate how pre-injury mental and somatic symptoms, self-rated health, use of health-services and medications, health-behavior and socio-demographics predict the development of chronic whiplash. Data from two waves of a large, population based study (HUNT2 (baseline) and HUNT3) were used. Individuals reporting no whiplash at baseline were identified in HUNT3. Characteristics reported at baseline were compared between those who had developed chronic whiplash in HUNT3 (n=199) and those who had not (n=20,600), using Pearson's chi-squared tests, independent sample t-tests and logistic regression analyses. Individuals developing chronic whiplash reported worse baseline health than those reporting no chronic whiplash. Poor self-rated health was a strong risk factor for subsequent chronic whiplash (OR=2.26, 95%CI: 1.68-3.04). Musculoskeletal pain also increased the risk (OR=1.21, 95%CI: 1.15-1.26), as did diffuse somatic symptoms (OR=2.09, 95%CI: 1.47-2.96), use of different health services (OR=1.31, 95%CI: 1.19-1.45), high use of medications (OR=1.28, 95%CI: 1.14-1.43) and symptoms of anxiety (OR=1.93, 95%CI: 1.39-2.68). Physical activity was protective (OR=0.67, 95%CI: 0.49-0.91). Most socio-demographic variables were not significantly associated with chronic whiplash. Poor somatic and mental pre-injury health increased the risk of subsequent chronic whiplash. This suggests that chronic whiplash is not merely an organic disorder, and highlights the importance of individual expectations, symptom reattribution and amplification in development of chronic whiplash.


2-Amino-6-vinyl purine as a tool for post synthetic conjugation of DNA with radio-, spin-, fluorescence labels and peptides.
We have previously demonstrated that 2-amino-6-vinylpurine is an efficient cross-linking agent with high selectivity towards cytidine. In this study, we applied this nucleobase analog to versatile conjugation of oligodeoxynucleotides with radio-, spin-, fluorescence- and peptide labels. The oligodeoxynucleotides incorporating 2-amino-6-vinylpurine nucleoside were reacted with amino- bearing nucleophies in an excess amount to give the corresponding conjugates in good yield.


Competitive reversals inside ecological reserves: the role of external habitat degradation.
Habitat degradation is the slow--and often subtle--deterioration in habitat quality that accompanies human activities through increases in road density, pesticide use, hunting pressure, etc. Such degradation is of particular concern in fragmented habitats where economic or jurisdictional boundaries rather than ecological ones determine the level of exploitation adjoining habitat patches endure. To examine the consequences habitat degradation might have on species interactions, we posited a patch of pristine habitat surrounded by "matrix" habitat whose degradation level was variable. Using a coupled pair of diffusive Lotka-Volterra competition equations with Robin (mixed) boundary conditions, we modeled the dynamics of two competing species inhabiting the pristine patch and incorporated matrix degradation through a tunable "hostility" parameter representing species' mortality rates in the matrix. We found that the numerical range of competition coefficients over which one species is the competitive dominant and the other inferior may grow or shrink as matrix quality deteriorates. In some cases, degradation of the exterior habitat would bring about a complete competitive reversal inside the preserve. This result, wherein a formerly inferior species supplants a formerly dominant one--even inside the "protected" remnant patch itself--has policy implications for both nature reserve design and management of human activities outside park boundaries.


Cutaneous leishmaniasis with atypical clinical manifestations: Case report.
This case report alerts to the existence of atypical forms of cutaneous leishmaniasis (CL). A woman with nodular cutaneous lesions over a neck with papules and pustules located deep in the hypodermis that formed plaques with subcutaneous induration and satellite papules was confirmed to have CL. After confirmation, the patient was treated with remission of the lesions, scarring and thickening of the skin.