Soluble polyvinylpyrrolidine and bovine serum albumin adsorb polyphenols from soybean suspension cultures.
Soybean (Glycine max [L.] Merrill, cv. Dare) suspension cultures grown in Gamborg B5 medium became discolored and the cells began aggregating after 1 week in culture, especially in the absence of 2,4-dichlorophenoxyacetic acid (2,4-D). The addition of either soluble polyvinylpyrrolidine (PVP) or bovine serum albumin (BSA) to cultures grown in Gamborg B5 medium with 2,4-D prevents discoloration and cell aggregation by adsorbing excess polyphenols from the cells. Transfer of the PVP-treated cultures to fresh medium without 2,4-D stimulated the recurrence of excess polyphenols. Cultures pretreated with BSA did not develop excess polyphenols when transferred to fresh 2,4-D-free medium. Addition of either PVP or BSA to cultures grown in the absence of 2,4-D was found to inhibit growth.


Exendin-4 reduces fasting and postprandial glucose and decreases energy intake in healthy volunteers.
Exendin-4 is a long-acting potent agonist of the glucagon-like peptide 1 (GLP-1) receptor and may be useful in the treatment of type 2 diabetes and obesity. We examined the effects of an intravenous infusion of exendin-4 (0.05 pmol. kg(-1). min(-1)) compared with a control saline infusion in healthy volunteers. Exendin-4 reduced fasting plasma glucose levels and reduced the peak change of postprandial glucose from baseline (exendin-4, 1.5 +/- 0.3 vs. saline, 2.2 +/- 0.3 mmol/l, P < 0.05). Gastric emptying was delayed, as measured by the paracetamol absorption method. Volunteers consumed 19% fewer calories at a free-choice buffet lunch with exendin-4 (exendin-4, 867 +/- 79 vs. saline 1,075 +/- 93 kcal, P = 0.012), without reported side effects. Thus our results are in accord with the possibility that exendin-4 may be a potential treatment for type 2 diabetes, particularly for obese patients, because it acts to reduce plasma glucose at least partly by a delay in gastric emptying, as well as by reducing calorie intake.


Speech technology in 2001: new research directions.
Research in speech recognition and synthesis over the past several decades has brought speech technology to a point where it is being used in "real-world" applications. However, despite the progress, the perception remains that the current technology is not flexible enough to allow easy voice communication with machines. The focus of speech research is now on producing systems that are accurate and robust but that do not impose unnecessary constraints on the user. This chapter takes a critical look at the shortcomings of the current speech recognition and synthesis algorithms, discusses the technical challenges facing research, and examines the new directions that research in speech recognition and synthesis must take in order to form the basis of new solutions suitable for supporting a wide range of applications.


Intercalation-Induced Ordered Nanostructure in the Interlayer Modified with Methylviologen by Molecular Dynamics Simulation.
Intercalation of phenol in montmorillonite, a representative layered material, has historically been investigated, and modification of the interlayer with methylviologen (Mont-MV) results in color change due to formation of a charge-transfer complex. Its detailed nanostructure, however, has yet been revealed owing to its small gallery height and poor crystallinity. In the present study, we performed molecular dynamics simulation to investigate structural changes in Mont-MV by the intercalation of phenol. The value of the basal spacing of Mont-MV was well consistent with that reported experimentally, and the MV cations were distributed horizontally. Successive intercalation of phenol revealed that the interlayer swelled nonlinearly and both the MV cations and phenol molecules were tilted, which were roughly parallel to each other. The obtained ordered nanostructure was similar to that reported in the charge-transfer complex crystal of the MV cation and the naphthol derivative. Thus, the parallel orientation in the interlayer was found to be the key for the color reaction. Combined with the fact that the phenol molecules interacted with the Mont layers, the role of the MV cation was found to be that of a pillar for providing sufficient gallery height, and the formation of the charge-transfer complex is the secondarily derived function.


[Testicular torsion in polyorchism].
A clinical case of a 21-year-old patient with polyorchism and torsion of the right testicle described. Polyorchism revealed in 2016. According to urgent indications, the operation performed on the right orchipexy. The postoperative period was uneventful. A control study after 2 years of pathology from the organs of the scrotum not revealed.


A risk score based on real-world data to predict early death in acute promyelocytic leukemia.
With increasingly effective treatments, early death (ED) has become the predominant reason for therapeutic failure in patients with acute promyelocytic leukemia (APL). To better prevent ED, patients with high-risk of ED must be identified. Our aim was to develop a score that predicts the risk of ED in a real-life setting. We used APL patients in the populationbased Swedish AML Registry (n=301) and a Portuguese hospital-based registry (n=129) as training and validation cohorts, respectively. The cohorts were comparable with respect to age (median, 54 and 53 years) and ED rate (19.6% and 18.6%). The score was developed by logistic regression analyses, risk-per-quantile assessment and scoring based on ridge regression coefficients from multivariable penalized logistic regression analysis. White blood cell count, platelet count and age were selected by this approach as the most significant variables for predicting ED. The score identified low-, high- and very high-risk patients with ED risks of 4.8%, 20.2% and 50.9% respectively in the training cohort and with 6.7%, 25.0% and 36.0% as corresponding values for the validation cohort. The score identified an increased risk of ED already at sub-normal and normal white blood cell counts and, consequently, it was better at predicting ED risk than the Sanz score (AUROC 0.77 vs. 0.64). In summary, we here present an externally validated and population-based risk score to predict ED risk in a real-world setting, identifying patients with the most urgent need of aggressive ED prevention. The results also suggest that increased vigilance for ED is already necessary at sub-normal/normal white blood cell counts.


An interactive web-based method of outreach to college students at risk for suicide.
From 2002 to 2005, the authors tested an interactive, Web-based method to encourage college students at risk for suicide to seek treatment. The authors invited students at 2 universities to complete an online questionnaire that screened for depression and other suicide risk factors. Respondents received a personalized assessment and were able to communicate anonymously with a clinical counselor online. At-risk students were urged to attend in-person evaluation and treatment. A total of 1,162 students (8% of those invited) completed the screening questionnaire; 981 (84.4%) were designated as at high or moderate risk. Among this group, 190 (19.4%) attended an in-person evaluation session with the counselor, and 132 (13.5%) entered treatment. Students who engaged in online dialogues with the counselor were 3 times more likely than were those who did not to come for evaluation and enter treatment. The method has considerable promise for encouraging previously untreated, at-risk college students to get help.


Molecular imprinting of glycoproteins: From preparation to cancer theranostics.
Glycoprotein imprinted polymers have rapidly grown as excellent receptors for cancer targeting, diagnostics, inhibition, and nanomedicines as they specifically target glycans and glycosites overexpressed in various tumors. Compared to natural antibodies, they are easy to synthesize, stable, and cost-efficient. Currently, no study specifically discusses glycoproteins imprinting strategies for cancer theranostics. In this review, firstly we explored various factors involved in designing and synthesis of glycoprotein imprinted materials, including, the characteristics and choice of monomers for imprinting, types of templates and their interactions involved, and the imprinting methods. Secondly, the integration of these MIPs with different probes that have been applied for in vitro and in vivo targeting for cancer diagnostics including biosensing and bioimaging, and image-guided therapeutic applications as nanomedicines. These Glycoprotein imprinted polymers have been found to specifically target the glycoprotein biomarkers and glycosylated cell receptors overexpressed in different cancers and have been reported as excellent diagnostic tools. As nanomedicines, they have been potentially employed in various modes of cancer therapy such as targeted drug delivery, photodynamic therapy, photothermal therapy, and nanoMIPs themselves as therapeutics for locally killing tumor cells. Although the research is still in its early stages and no real-world clinical trials on humans have been conducted, nanoMIPs have a promising future in this field. We believe these findings will pave the way for MIPs in advanced diagnostics, antibody treatment, and immunotherapy as future nanomedicine for real-world cancer theranostics.


Multi-Laboratory Validation of a Loop-Mediated Isothermal Amplification Method for Screening Salmonella in Animal Food.
Loop-mediated isothermal amplification (LAMP) has gained wide popularity in the detection of Salmonella in foods owing to its simplicity, rapidity, and robustness. This multi-laboratory validation (MLV) study aimed to validate a Salmonella LAMP-based method against the United States Food and Drug Administration (FDA) Bacteriological Analytical Manual (BAM) Chapter 5 Salmonella reference method in a representative animal food matrix (dry dog food). Fourteen independent collaborators from seven laboratories in the United States and Canada participated in the study. Each collaborator received two sets of 24 blind-coded dry dog food samples (eight uninoculated; eight inoculated at a low level, 0.65 MPN/25 g; and eight inoculated at a high level, 3.01 MPN/25 g) and initiated the testing on the same day. The MLV study used an unpaired design where different test portions were analyzed by the LAMP and BAM methods using different preenrichment protocols (buffered peptone water for LAMP and lactose broth for BAM). All LAMP samples were confirmed by culture using the BAM method. BAM samples were also tested by LAMP following lactose broth preenrichment (paired samples). Statistical analysis was carried out by the probability of detection (POD) per AOAC guidelines and by a random intercept logistic regression model. Overall, no significant differences in POD between the Salmonella LAMP and BAM methods were observed with either unpaired or paired samples, indicating the methods were comparable. LAMP testing following preenrichment in buffered peptone water or lactose broth also resulted in insignificant POD differences (P > 0.05). The MLV study strongly supports the utility and applicability of this rapid and reliable LAMP method in routine regulatory screening of Salmonella in animal food.


Does Zoledronate Prevent Femoral Head Collapse from Osteonecrosis? A Prospective, Randomized, Open-Label, Multicenter Study.
Osteonecrosis of the femoral head frequently leads to collapse of the necrotic portion and subsequent degenerative joint disease of the hip, which is the most common diagnosis leading to total hip arthroplasty in young adults. Bisphosphonate therapy has been reported to potentially retard the collapse. We conducted a two-year prospective, randomized, open-label, multicenter study to determine whether zoledronate prevents the collapse and reduces the need for total hip arthroplasty. We randomly assigned patients who had Steinberg stage-I or II nontraumatic osteonecrosis of the femoral head with a necrotic area of ≥30% to either the zoledronate group or the control group. Patients in the zoledronate group received 5 mg of zoledronate intravenously per year for two years, while patients in the control group did not receive this medication. The primary efficacy outcome was the survival rate in terms of the occurrence of collapse (≥2 mm). The patients were observed for a minimum of two years after enrollment. A total of 110 patients (110 hips) underwent randomization; fifty-five patients were assigned to the zoledronate group and fifty-five, to the control group. During the two-year follow-up, twenty-nine femoral heads in the zoledronate group and twenty-two in the control group collapsed (p > 0.05). Nineteen hips in the zoledronate group and twenty in the control group underwent total hip arthroplasty (p > 0.05). Zoledronate for Steinberg stage-I or II osteonecrosis of the femoral head, with a medium to large necrotic area, did not prevent the collapse of the femoral head or reduce the need for total hip arthroplasty. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.


Transcription factor ZNF25 is associated with osteoblast differentiation of human skeletal stem cells.
The differentiation of human bone marrow derived skeletal stem cells (known as human bone marrow stromal or mesenchymal stem cells, hMSCs) into osteoblasts involves the activation of a small number of well-described transcription factors. To identify additional osteoblastic transcription factors, we studied gene expression of hMSCs during ex vivo osteoblast differentiation. Clustering of gene expression, and literature investigation, revealed three transcription factors of interest - ZNF25, ZNF608 and ZBTB38. siRNA knockdown of ZNF25 resulted in significant suppression of alkaline phosphatase (ALP) activity. This effect was not present for ZNF608 and ZBTB38. To identify possible target genes of ZNF25, we analyzed gene expression following ZNF25 siRNA knockdown. This revealed a 23-fold upregulation of matrix metallopeptidase 1 and an 18-fold upregulation of leucine-rich repeat containing G protein-coupled receptor 5 and RAN-binding protein 3-like. We also observed enrichment in extracellular matrix organization, skeletal system development and regulation of ossification in the entire upregulated set of genes. Consistent with its function as a transcription factor during osteoblast differentiation of hMSC, we showed that the ZNF25 protein exhibits nuclear localization and is expressed in osteoblastic and osteocytic cells in vivo. ZNF25 is conserved in tetrapod vertebrates and contains a KRAB (Krueppel-associated box) transcriptional repressor domain. This study shows that the uncharacterized transcription factor, ZNF25, is associated with differentiation of hMSC to osteoblasts.


A disputed evidence on obesity: comparison of the effects of Rcan2(-/-) and Rps6kb1(-/-) mutations on growth and body weight in C57BL/6J mice.
It is widely accepted that body weight and adipose mass are tightly regulated by homeostatic mechanisms, in which leptin plays a critical role through hypothalamic pathways, and obesity is a result of homeostatic disorder. However, in C57BL/6J mice, we found that Rcan2 increases food intake and plays an important role in the development of age- and diet-induced obesity through a leptin-independent mechanism. RCAN2 was initially identified as a thyroid hormone (T3)-responsive gene in human fibroblasts. Expression of RCAN2 is regulated by T3 through the PI3K-Akt/PKB-mTOR-Rps6kb1 signaling pathway. Intriguingly, both Rcan2(-/-) and Rps6kb1(-/-) mutations were reported to result in lean phenotypes in mice. In this study we compared the effects of these two mutations on growth and body weight in C57BL/6J mice. We observed reduced body weight and lower fat mass in both Rcan2(-/-) and Rps6kb1(-/-) mice compared to the wild-type mice, and we reported other differences unique to either the Rcan2(-/-) or Rps6kb1(-/-) mice. Firstly, loss of Rcan2 does not directly alter body length; however, Rcan2(-/-) mice exhibit reduced food intake. In contrast, Rps6kb1(-/-) mice exhibit abnormal embryonic development, which leads to smaller body size and reduced food intake in adulthood. Secondly, when fed a normal chow diet, Rcan2(-/-) mice weigh significantly more than Rps6kb1(-/-) mice, but both Rcan2(-/-) and Rps6kb1(-/-) mice develop similar amounts of epididymal fat. On a high-fat diet, Rcan2(-/-) mice gain body weight and fat mass at slower rates than Rps6kb1(-/-) mice. Finally, using the double-knockout mice (Rcan2(-/-) Rps6kb1(-/-)), we demonstrate that concurrent loss of Rcan2 and Rps6kb1 has an additive effect on body weight reduction in C57BL/6J mice. Our data suggest that Rcan2 and Rps6kb1 mutations both affect growth and body weight of mice, though likely through different mechanisms.


Pathogenicity of rabies viruses isolated in China: two fixed strains and a street strain.
To investigate the virulence characteristics of two fixed strains (CTN and aG) and a street strain (HN10) of rabies viruses isolated in China. ICR mice of different age groups were inoculated with CTN, aG and HN10 rabies virus strains via the intracracerebral (i.c.) or intramuscular (i.m.) routes, and observed for 20 days. The CTN strain was pathogenic to 7-day-old suckling mice that received i.c. inoculations and 3-day-old suckling mice that received i.m. inoculations. The aG strain was pathogenic to 4-week-old mice that received i.c. inoculations and 7-day-old suckling mice that received i.m. inoculations. The HN10 strain was pathogenic to mice of all age groups via both inoculation routes. In moribund mice, the viruses had spread to most regions of the brain. The CTN and HN10 strains had similar dissemination patterns in the brain; both viral antigens could be found in the dentate gyrus (DG), whereas few viral antigens were present in the DG from specimens that had been infected with the aG strain. A comprehensive sequence analysis of the G protein suggested that differences in gene sequences may be responsible for producing strain-specific differences in pathogenicity and distribution in the brain.


Morphogenesis and Auxin Sensitivity of Transgenic Tobacco with Different Complements of Ri T-DNA.
Leaf explants of hairy root tobacco (Nicotiana tabacum) regenerants characteristically differentiate roots from the wound margins on hormonefree medium. The same response can be elicited on normal tobacco by culturing the explants in the presence of auxin. We show here that the spontaneous rooting of transformed plants is neither due to the activity of right T-DNA-borne auxin genes nor to a substantially altered balance of endogenous hormones. Rather, an increased sensitivity to auxin is conferred to transformed cells by the left T-DNA (TL-DNA). Analysis of the morphogenetic behavior of transgenic tobacco plants obtained by transferring segments of TL-DNA cloned in a binary vector system allowed us to pinpoint TL-DNA genes responsible for this increased auxin sensitivity of hairy root tissues. Three genes (open reading frames 10, 11, 12) are responsible for the spontaneous rooting of leaf explants and confer to transgenic plants an exaggerated response to auxin.


A review of embodiment in autism spectrum disorders.
In classical approaches to cognition, sensory, motor, and emotional experiences are stripped of domain-specific perceptual and sensorimotor information, and represented in a relatively abstract form. In contrast, the embodied cognition framework suggests that our representations retain the initial imprint of the manner in which information was acquired. In this paper, we argue that individuals with autism spectrum disorders (ASD) display impairments in the temporal coordination of motor and conceptual information (as shown in gesture research) and striking deficits in the interpersonal mimicry of motor behaviors (as shown in yawning research) - findings we believe are consistent with an embodied account of ASD that includes, but goes beyond, social experiences and is driven in part by significant but subtle motor deficits. In this paper, we review the research examining an embodied cognition account of ASD, and discuss its implications.


Statistical coronary motion models for 2D+t/3D registration of X-ray coronary angiography and CTA.
Accurate alignment of intra-operative X-ray coronary angiography (XA) and pre-operative cardiac CT angiography (CTA) may improve procedural success rates of minimally invasive coronary interventions for patients with chronic total occlusions. It was previously shown that incorporating patient specific coronary motion extracted from 4D CTA increases the robustness of the alignment. However, pre-operative CTA is often acquired with gating at end-diastole, in which case patient specific motion is not available. For such cases, we investigate the possibility of using population based coronary motion models to provide constraints for the 2D+t/3D registration. We propose a methodology for building statistical motion models of the coronary arteries from a training population of 4D CTA datasets. We compare the 2D+t/3D registration performance of the proposed statistical models with other motion estimates, including the patient specific motion extracted from 4D CTA, the mean motion of a population, the predicted motion based on the cardiac shape. The coronary motion models, constructed on a training set of 150 patients, had a generalization accuracy of 1mm root mean square point-to-point distance. Their 2D+t/3D registration accuracy on one cardiac cycle of 12 monoplane XA sequences was similar to, if not better than, the 4D CTA based motion, irrespective of which respiratory model and which feature based 2D/3D distance metric was used. The resulting model based coronary motion estimate showed good applicability for registration of a subsequent cardiac cycle.


[Legionellosis in a newborn infant].
We describe a case of successful therapy of a neonatal Legionellosis with Erythromycin. On his 6th day of life a full term newborn with normal body weight was affected by a severe pneumonia. This was at first resistant to therapy and required mechanical ventilation. Diagnosis of Legionella pneumophila serotype 1 was made by culture from bronchial lavage. Only few cases of neonatal Legionellosis have been reported until now. In three cases diagnosis was made post mortem.


Host location, survival and fecundity of the Oriental rat flea Xenopsylla cheopis (Siphonaptera: Pulicidae) in relation to black rat Rattus rattus (Rodentia: Muridae) host age and sex.
Host choice and fecundity are two factors that may contribute to the variation in flea counts observed when assessing the potential risk of flea-borne transmission of pathogens from rodents to humans. Using the black rat, Rattus rattus Linnaeus, as host the effects of age and sex on host choice and fecundity of the Oriental rat flea, Xenopsylla cheopis Rothschild, were examined experimentally at 25 degrees C and 80% rh. During the first two days of emergence from cocoons, female fleas dominated the sex ratio by 4:1 but from the third day onwards this switched to a male-dominated sex ratio of 4:1. The sex of the flea did not influence their host-seeking behaviour. Newly emerged fleas of both sexes were not influenced by the rat's presence and at seven days old both sexes demonstrated similar levels of attraction toward the rat host. The sex of the rat did not affect flea host-seeking behaviour. There was a 50-70% decline in the initial number of adult fleas during the first week after their release onto a rat host, and this decline was greatest on juvenile rats. Flea fecundity was also significantly lower on juvenile rat hosts but no differences due to the sex of the rat were observed. This experimental study supports the hypothesis that differences in flea count due to host sex, reported in field surveys, result from sexual differences in host behaviour and not from discriminatory host-seeking behaviour by X. cheopis. Differences in flea count due to host age may be affected by differences in X. cheopis fecundity, which may itself be mediated by host behaviour such as grooming.


Cocaine modulation of frontostriatal expression of Zif268, D2, and 5-HT2c receptors in high and low impulsive rats.
Impulsivity shares high comorbidity with substance abuse in humans, and high impulsivity (HI) in rats has been identified as a predictive factor for cocaine addiction-like behavior. Despite the evidence that high impulsivity is associated with altered function of corticostriatal networks, the specific neural substrates underlying the increased vulnerability of impulsive individuals to develop cocaine addiction remain unknown. We therefore investigated specific neural correlates of HI within the corticostriatal circuitry and determined how they interact with a protracted history of cocaine self-administration. We used in situ hybridization to map brain expression of two major genes implicated in impulsivity, encoding the dopamine D2 receptor (DA D2R) and the 5-HT2c receptor (5-HT2cR), and an immediate early gene associated with neuronal plasticity, zif268, in groups of rats selected for HI and low impulsivity (LI) on a 5-choice serial reaction time task (5-CSRTT) immediately after 5-CSRTT training, and following 10 or 50 days of cocaine self-administration. HI rats exhibited decreased DA D2R mRNA in the mesolimbic pathway, and increased 5-HT2cR mRNA in the orbitofrontal cortex compared with LI rats. HI rats also showed decreased zif268 mRNA in the ventral and dorsomedial striatum. Cocaine exposure decreased striatal D2R mRNA in both HI and LI rats, decreased 5-HT2cR mRNA differentially in striatal and prefrontal areas between HI and LI rats, and selectively decreased zif268 mRNA in the orbitofrontal and infralimbic cortices of HI animals. These findings implicate novel markers underlying the vulnerability of impulsive rats to cocaine addiction that localize to the OFC, infralimbic cortex, and striatum.


Multitiered 2D pi-stacked conjugated polymers based on pseudo-geminal disubstituted [2.2]paracyclophane.
Interchain interactions between pi-systems have a strong effect on the electronic structure of conjugated organic materials. This influence has previously been explored by the spectroscopic and electrochemical characterization of molecules in which pairs of conjugated oligomers are held in a stacked fashion by attachment to a rigid scaffold. We have prepared a new polymer which uses a pseudo-geminal disubstituted [2.2]paracyclophane scaffold to hold 1,4-bis(phenylethynyl)-2,5-dialkoxybenzene (PE(3)) chromophores in a pi-stacked fashion over their entire length and in an extended multitier arrangement. Solutions of this new polymer display a Stokes shift of 171 nm, compared to just ca. 30 nm for previous models in which only the terminal phenyl rings of the PE(3) chromophore are held in a stacked arrangement. This suggests that interchain interactions of pi-systems over their entire length in a multitier assembly provides for relaxation of the excited state to a stable "phane" electronic state which is responsible for emission. This stabilization is not available in the stacked dimer or other regioisomers of the polymer which possess lesser degrees of overlap. Thus, the architecture of the soluble polymer mimics that of segments of conjugated polymers in semiconducting thin films and will provide a platform for the exploration of the nature of charge carriers and excitons in these important materials.


Concentration and Metabolic Turnover of Indoles in Germinating Kernels of Zea mays L.
The amounts and rates of metabolic turnover of the indolylic compounds in germinating kernels of sweet corn were determined. Knowledge of pool size and rate of pool turnover has permitted: (a) identification of indole-3-acetyl-myo-inositol as the major chemical form for transport of indole-3-acetic acid (IAA) from endosperm to shoot; (b) demonstration that the free IAA of the endosperm is turning over rapidly with a half-life of 3.2 hours; (c) identification of esters of IAA as the immediate precursors of IAA in the endosperm and shoot; (d) demonstration that neither tryptophan nor tryptamine is a major precursor of IAA for the seed or shoot; (e) identification of IAA-myo-inositol glycosides as precursors of IAA-myo-inositol.It is concluded that seedlings of Zea mays utilize esters of IAA, and not tryptophan or its derivatives, for the IAA requirements of the germinating seedling.


Rescuing stalled or damaged replication forks.
In recent years, an increasing number of studies have shown that prokaryotes and eukaryotes are armed with sophisticated mechanisms to restart stalled or collapsed replication forks. Although these processes are better understood in bacteria, major breakthroughs have also been made to explain how fork restart mechanisms operate in eukaryotic cells. In particular, repriming on the leading strand and fork regression are now established as critical for the maintenance and recovery of stalled forks in both systems. Despite the lack of conservation between the factors involved, these mechanisms are strikingly similar in eukaryotes and prokaryotes. However, they differ in that fork restart occurs in the context of chromatin in eukaryotes and is controlled by multiple regulatory pathways.


Convolutional Neural Network-Based Technique for Gaze Estimation on Mobile Devices.
Eye tracking is becoming a very popular, useful, and important technology. Many eye tracking technologies are currently expensive and only available to large corporations. Some of them necessitate explicit personal calibration, which makes them unsuitable for use in real-world or uncontrolled environments. Explicit personal calibration can also be cumbersome and degrades the user experience. To address these issues, this study proposes a Convolutional Neural Network (CNN) based calibration-free technique for improved gaze estimation in unconstrained environments. The proposed technique consists of two components, namely a face component and a 39-point facial landmark component. The face component is used to extract the gaze estimation features from the eyes, while the 39-point facial landmark component is used to encode the shape and location of the eyes (within the face) into the network. Adding this information can make the network learn free-head and eye movements. Another CNN model was designed in this study primarily for the sake of comparison. The CNN model accepts only the face images as input. Different experiments were performed, and the experimental result reveals that the proposed technique outperforms the second model. Fine-tuning was also performed using the VGG16 pre-trained model. Experimental results show that the fine-tuned results of the proposed technique perform better than the fine-tuned results of the second model. Overall, the results show that 39-point facial landmarks can be used to improve the performance of CNN-based gaze estimation models.


Trends of Inequalities in Early Initiation of Breastfeeding in Ethiopia: Evidence from Ethiopian Demographic and Health Surveys, 2000-2016.
Early initiation of breastfeeding (EIBF) is a costless practice with numerous neonates' survival benefits. Thus, any disparity results in an unacceptably high neonatal death rate but socioeconomic disparities on EIBF have not been well explored in Ethiopia. Therefore, this study is aimed at assessing the socioeconomic inequalities of EIBF in Ethiopia from 2000 to 2016. The Ethiopian demographic and health survey data and the World Health Organization's Health Equity Assessment Toolkit were used to investigate the inequalities in EIBF across the wealth quintile, education, residence, and subnational region. Difference, ratio, slope index inequality (SII), relative index inequality (RII), and population attributable risk (PAR) were used as equity summary measures. In Ethiopia, EIBF practice was 47.4% in 2000, 66.2% in 2005, 51.5% in 2011, and 73.3% in 2016. Wealth-related inequality was observed in the 2000, 2005, and 2011 survey years with SII of -7.1%, -8.8%, and 8.7%, respectively, whereas educational-related inequality was observed in 2005 and 2011 with SII of -11.7% and 6.5%, respectively. However, significant change in wealth-, education-, and residence-related inequalities was detected in 2011. Regional inequality on EIBF was observed in all survey years with a difference of 35.7%, 38.0%, 29.1%, and 48.5% in the 2000, 2005, 2011, and 2016 survey years, respectively. But a significant change in regional inequality was noted in 2016 with a PAR of 17.2%. In Ethiopia, the wealth-, residence-, and educational-related inequalities of EIBF increased significantly between the years 2000 and 2011. However, regional inequality persistently increased from 2000 to 2016. Overall, one-sixth of the national level EIBF was decreased due to regional disparity in 2016. The northern regions of Ethiopia (Tigray, Afar, and Amhara) poorly performed compared to the peer regions. Therefore, interventions targeting them would significantly improve the national level of EIBF.


Effect of cellulose and ispaghula husk on fasting blood glucose of developing rats.
Fasting blood sugar was measured at the beginning and end of a 4-wk dietary period during which weanling rats were fed either a fibre-free diet, or a similar diet containing cellulose or ispaghula husk. The fibre-free group showed no significant change, but the groups fed cellulose or ispaghula showed a significant fall in fasting blood sugar.


Polymerase chain reaction-based mutageneses identify key transporters belonging to multigene families involved in Na+ and pH homeostasis of Synechocystis sp. PCC 6803.
Primary ion pumps and antiporters exist as multigene families in the Synechocystis sp. PCC 6803 genome and show very strong homologies to those found in higher plants. The gene knock-outs of five putative Na+/H+ antiporters (slr1727, sll0273, sll0689, slr1595 and slr0415) and seven cation ATPases (sll1614, sll1920, slr0671-72, slr0822, slr1507-08-09, slr1728- 29 and slr1950) in the model cyanobacterium (http://www.kazusa.or.jp/cyano/cyano.html) were performed in this study relying on homologous recombination with mutagenenic fragments constructed using a fusion polymerase chain reaction (PCR) approach. The impacts of these gene knock-outs were evaluated in terms of Na+ and pH, and light-induced acidification and alkalization that are asso-ciated with inorganic carbon uptake. Two of the five putative antiporter mutants exhibit a characteristic interplay between the pH and Na+ dependence of growth, but only one of the antiporters appears to be necessary for high NaCl tolerance. On the other hand, the mutation of one of the two copper-trafficking ATPases produces a cell line that shows acute NaCl sensitivity. Additionally, disruptions of a putative Ca2+-ATPase and a gene cluster encoding a putative Na+-ATPase subunit also cause high NaCl sensitivity. The findings and possible mechanisms are discussed in relation to the potential roles of these transporters in Synechocystis sp. PCC 6803.


Complete maternal uniparental isodisomy of chromosome 4 in a subject with major depressive disorder detected by high density SNP genotyping arrays.
Uniparental isodisomy (iUPD) is a rare genetic condition caused by non-disjunction during meiosis that ultimately leads to a duplication of either the maternal or paternal chromosome in the affected individual. Two types of disorders can result, those due to imprinted genes and those due to homozygosity of recessive disease-causing mutations. Here, we describe the third known case of complete chromosome 4 iUPD of maternal origin. This condition became apparent during whole genome linkage studies of psychiatric disorders in the Portuguese population. The proband is an adult female with normal fertility and no major medical complaints, but a history of major depressive disorder and multiple suicide attempts. The proband's siblings and parents had normal chromosome 4 genotypes and no history of mood disturbance. A brief review of other studies lends support for the possibility that genes on chromosome 4 might confer risk for mood disorders. We conclude that chromosome 4 maternal uniparental disomy (UPD) is a rare disorder that may present with a major depressive phenotype. The lack of a common disease phenotype between this and two other cases of chromosome 4 iUPD [Lindenbaum et al. [1991] Am J Med Genet 49(Suppl 285):1582; Spena et al. [2004] Eur J Hum Genet 12:891-898) would suggest that there is no vital maternal gene imprinting on chromosome 4. However, since there is no reported case of paternal chromosome 4 UPD, paternal gene imprinting on chromosome 4 cannot be excluded.


Mammographic analysis of calcifications.
Because mammographically detected calcifications are frequently the only sign of breast cancer, the breast radiography equipment, screen-film imaging package, and film processing should be optimized to detect such calcifications. For this purpose, dedicated units with molybdenum targets, microfocal spot magnification capability, reciprocating grids, and high output x-ray tubes are required. With the greater use of state-of-the-art mammography, intraductal carcinoma, or DCIS, manifested only by calcifications is being detected more frequently than ever. DCIS can be of the comedo, cribriform, or micropapillary types. Comedocarcinoma, characterized by linear and branching (casting) calcifications, is the most aggressive type, and it has the highest rate of recurrence after breast-conserving surgery. Cribriform and micropapillary calcifications are characteristically punctate and vary in size and shape. In addition to histologic type, the recurrence of DCIS is related to its extent at detection and whether adequate tissue was removed at the time of breast-conserving surgery. Biopsies for suspicious calcifications should be followed immediately by specimen radiography to verify their removal. If breast-conserving surgery is elected for DCIS, the resected segment of tissue should be examined with pathologic techniques designed to determine whether the margins are clear of tumor. For DCIS and invasive cancers with extensive intraductal component, microfocus magnification mammography over the surgical site is recommended prior to radiotherapy to identify any residual tumor calcifications. Although state-of-the-art mammography is very sensitive in the detection of calcifications, it is low in specificity, thus resulting in a large number of false-positive mammograms and a relatively low true-positive biopsy rate. While some benign calcifications cannot be distinguished from those of malignancy, the number of biopsies for benign conditions can be decreased by careful analysis of the mammograms in a search for features indicating benignity.


Multisample Online Learning for Probabilistic Spiking Neural Networks.
Spiking neural networks (SNNs) capture some of the efficiency of biological brains for inference and learning via the dynamic, online, and event-driven processing of binary time series. Most existing learning algorithms for SNNs are based on deterministic neuronal models, such as leaky integrate-and-fire, and rely on heuristic approximations of backpropagation through time that enforces constraints such as locality. In contrast, probabilistic SNN models can be trained directly via principled online, local, and update rules that have proven to be particularly effective for resource-constrained systems. This article investigates another advantage of probabilistic SNNs, namely, their capacity to generate independent outputs when queried over the same input. It is shown that the multiple generated output samples can be used during inference to robustify decisions and to quantify uncertainty-a feature that deterministic SNN models cannot provide. Furthermore, they can be leveraged for training in order to obtain more accurate statistical estimates of the log-loss training criterion and its gradient. Specifically, this article introduces an online learning rule based on generalized expectation-maximization (GEM) that follows a three-factor form with global learning signals and is referred to as GEM-SNN. Experimental results on structured output memorization and classification on a standard neuromorphic dataset demonstrate significant improvements in terms of log-likelihood, accuracy, and calibration when increasing the number of samples used for inference and training.


Efficacy of support groups for spouses of patients with spinal cord injury and its impact on their quality of life.
The need for a sound social support system, and its positive impact on physical, mental and behavioural health in the ever-increasing spinal cord injury (SCI) clientele, is undeniable. It is evident from recent research that spousal support should be weighed as an important contributing factor to the ongoing health and well-being of their SCI partners. Stress (severe depressive symptoms) to the care-giving spouses, and implications on their health and thereby the SCI partner, is often underestimated. Thus the present study is an attempt to treat this highly susceptible population through the provision of support groups. This study was a two-group experimental design. The study results bring to light the definite impact of SCI on the spouse's well-being. Thus it is essential to direct research towards life domains designed to improve the quality of life of these individuals. This research demonstrates the unquestionable positive effect of group therapy on the impact of well-being of spouses of SCI survivors. This finding may only be the tip of the iceberg and further research with a larger sample size must be conducted for the adequate generalization of this study.


Role of human immunodeficiency virus and cytomegalovirus in AIDS encephalitis.
Approximately half of patients with advanced acquired immune deficiency syndrome (AIDS) develop a subcortical dementia. The brains of all autopsies on AIDS patients performed at UCSD between 1982 and 1986 (N = 93) were studied. Neuropathologic changes consistent with a viral encephalitis were present in 54 brains (58%). Human immunodeficiency virus (HIV) antigens were detected in 37 of the brains (40%), most frequently in macrophages, multinucleated giant cells, and endothelial cells. Cytomegalovirus (CMV) was detected in 31 of the brains (33%), 22 of which also contained HIV. Cellular localization of CMV antigens suggests that CMV disseminates to the central nervous system hematogenously where the virus can infect endothelial cells, glia, and neurons. While the temporal course of the appearance of these two viruses within the CNS is not clear, the common simultaneous occurrence of both viruses within the brains of AIDS patients suggests that in vivo interaction between them may play a role in the pathogenesis of AIDS-associated encephalitis. Given the significant neurologic symptoms described in AIDS patients, the paucity of viral antigens suggests a pathogenic mechanism of indirect CNS damage rather than direct viral infection.


Differential associations between subjective age and depressive symptoms among urban and rural Chinese older adults.
Objectives: Little research has investigated the prospective association between subjective-aging-perception and depressive symptoms in Chinese older adults. The aim of this study is to evaluate the differential associations of feeling old with depressive symptoms among urban and rural community-dwelling Chinese older adults using panel data drawn from two waves of nationally representative surveys.Method: We conducted secondary data analysis and utilized the data of 5,685 urban and 5,612 rural community-dwelling older adults aged 60 years and above who participated in both the 2006 and the 2010 Sample Survey on the Aged Population in Urban/Rural China (SSAPUR). A single-item measure of subjective age was used to distinguish between feeling old and feeling not old.Results: Ordinary least regression analyses indicated that the longitudinal effect of subjective age on depressive symptoms existed only in the urban sample (p<.001) but not in the rural sample and that feeling not old was related to less depressive symptoms in the urban sample, after controlling for baseline measures of depressive symptoms and sociodemographic and health factors.Conclusion: This study provides new longitudinal evidence of the impact of subjective age on depression among Chinese older individuals. The findings provide useful information for depression interventions among urban older Chinese individuals.


Sexual reinforcement in the female rat.
Sexual reinforcement in the female rat was studied in a preparation that allowed continuous operant responding for access to a male rat leading to intromission. Experiment 1 used a high operant level nose-poke response to test the possible reinforcing effects of some components of access to a male. A simple tone stimulus used as a conditioned reinforcer and two odor stimuli, target male bedding and emulsified preputial gland, were tested. None of these contingent events altered responding above or below operant level. Access to the male, which was always accompanied by intromission, immediately increased response rate when it was made contingent upon the nose-poke response. Performance on fixed-ratio schedules was erratic, and response rate was low in comparison to typical food-reinforced responding. An interresponse-time analysis indicated, however, that some effect of the ratio contingency may have been present. In Experiment 2, several modifications of the procedure were tested with the objective of creating a more tractable preparation for behavior analysis. Response type and the hormone delivery method were changed, and 2 target males were used instead of 1. The latter tripled the average number of reinforcers earned in a single session. Differences between sexual and other reinforcers are discussed in terms of procedural, quantitative, and motivational aspects of the sexual reinforcement procedure.


[Value of early management of patients with chronic renal failure].
The objective of early referral in patients with chronic renal failure is to prevent complications as the disease progresses to the stage where dialysis or transplantation become necessary. Early diagnosis requires a systematic assessment of glomerular function in all patients with signs suggestive of renal disease. Screening programs are also recommended in populations at risk with vascular disease, diabetes, occupational exposure to nephrotoxic substances, or a potentially nephrotoxic treatment. Once stabilized, chronic renal failure usually progresses inevitably to end-stage disease. In France, the estimated annual incidence of chronic renal failure defined as creatininemia > 200 or 300 mumol/l is approximately 200 patients per million inhabitants and that of end-stage disease at 80 per million. Although access to replacement therapy is not limited in France, a certain number of patients are still seen at a late stage of the disease. When dialysis is initiated after the development of severe uremia, patients generally have a poor nutritional status, more severe acidosis and anemia and poorly controlled hypertension; the first dialysis session often occurs in an emergency setting. In this issue of La Presse Médicale, Jungers et al. demonstrate the higher morbidity and increased cost of the first hospitalization in patients without prior follow-up. An optimal treatment aimed at preserving renal function as long as possible can have a beneficial effect on preventing higher morbidity and mortality after beginning substitution therapy. Nephrology referral should be centered on controlling anemia with recombinant human erythropoietin, high blood pressure with appropriate drugs (particularly converting enzyme inhibitors), nutritional status with adapted protein-calorie intake, and renal osteodystrophy with calcium carbonate or recombinant growth hormone in children. Patients must also be prepared for definite dialysis both in terms of medical risk (hepatitis B vaccination) and psychosocial adaptation.


Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after intravenous and intramuscular administrations in sheep.
To evaluate the pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after administrations of enrofloxacin in sheep. Crossover study performed by i.v. and i.m. administrations of 2.5 mg of enrofloxacin/kg of body weight to 2 groups of 3 sheep. After a 15-day resting period, the drug administration was repeated, using the alternative route. 6 clinically normal Massese sheep of either sex. Blood samples were collected at suitable intervals over a 24-hour period, and plasma concentrations of enrofloxacin and its main metabolite ciprofloxacin were determined by a high-performance liquid chromatography method. Pharmacokinetic variables for both substances after i.v. and i.m. enrofloxacin administrations were calculated by use of statistical moments and were analyzed, using a crossover ANOVA. After i.v. administration of enrofloxacin, a rapid distribution phase was followed by a slower elimination phase. When the same dose was administered IM, enrofloxacin was rapidly and almost completely absorbed, with bioavailability of 85%. After 24 hours, the mean plasma concentration of ciprofloxacin was similar to that of the parent drug. The large volume of distribution indicates that enrofloxacin is widely distributed in the body of sheep. The fraction of enrofloxacin metabolized to ciprofloxacin (35 and 55% for i.v. and i.m. administrations, respectively) suggests that, in this species, the antimicrobial activity of enrofloxacin could be attributable, at least in part, to its main metabolite ciprofloxacin. i.v. or i.m. administration of 2.5 mg of enrofloxacin/kg provides plasma concentrations higher than mean inhibitory concentration for most pathogens in sheep.


Molecular analysis of DNA adducts and hprt mutations produced by 6-nitrosochrysene in Chinese hamster ovary cells.
We have characterized the mutational spectrum of 6-nitrosochrysene in the hprt gene of Chinese hamster ovary (CHO-K1) cells and also examined the adducts formed by this compound in CHO-K1 cells by quantitative 32P-postlabeling analysis. Seventy percent of the identified mutations were simple basepair substitutions, and they occurred more often at A:T (14/17) than at G:C. Furthermore, 13 of the basepair substitutions at A:T had the mutated dA, the probable adducted residue, on the non-transcribed DNA strand. The preference for mutation at A:T contrasted sharply with the distribution of adducts formed by 6-nitrosochrysene: 80% of the identified adducts were with dG, while only 20% were probably formed through binding with dA. Analyses conducted with excision-repair-defective CHO-UV5 cells revealed both a preference for basepair substitution at A:T and an adduct profile that were similar to those found for repair-proficient CHO-K1 cells. However, basepair substitutions from CHO-UV5 cell mutants had the mutated dAs distributed randomly between the non-transcribed and transcribed DNA strands. The mutational spectra found for solvent control CHO-K1 and CHO-UV5 cells differed from those of the 6-nitrosochrysene-treated cultures. These findings suggest that 6-nitrosochrysene-induced mutations are targeted to DNA damage, but that 6-nitrosochrysene-derived dA adducts are much more effective at producing mutations than 6-nitrosochrysene-derived dG adducts. The extreme strand bias for mutated dAs in the CHO-K1 mutational spectrum appears to result from preferential removal of 6-nitrosochrysene-induced DNA lesions from the transcribed DNA strand.


Targeting IL-15 as a therapeutic strategy in organ transplant rejection.
Much effort is currently directed towards generating and evaluating agents that target the individual components of the alloimmune response, with a view to promoting allograft survival accompanied by minimum side effects. Recently, there has been considerable interest in inhibiting individual cytokine/receptor interactions since they are key elements in pathways for differentiation of immune effector cells. This article examines the utility of targeting interactions of interleukin (IL)-15 with its receptor as a strategy for disabling the T-cell activation events following recognition of foreign major and minor histocompatibility antigens. Experimental evidence suggests that interrupting IL-15/IL-15R interaction may be of therapeutic value in preventing allograft rejection.


Somatosensory areas S2 and PV project to the superior colliculus of a prosimian primate, Galago garnetti.
As part of an effort to describe the connections of the somatosensory system in Galago garnetti, a small prosimian primate, injections of tracers into cortex revealed that two somatosensory areas, the second somatosensory area (S2) and the parietal ventral somatosensory area (PV), project densely to the ipsilateral superior colliculus, while the primary somatosensory area (S1 or area 3b) does not. The three cortical areas were defined in microelectrode mapping experiments and recordings were used to identify appropriate injection sites in the same cases. Injections of wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) were placed in S1 in different mediolateral locations representing body regions from toes to face in five galagos, and none of these injections labeled projections to the superior colliculus. In contrast, each of the two injections in the face representation of S2 in two galagos and three injections in face and forelimb representations of PV in three galagos produced dense patches of labeled terminations and axons in the intermediate gray (layer IV) over the full extent of the superior colliculus. The results suggest that the higher-order somatosensory areas, PV and S2, are directly involved in the visuomotor functions of the superior colliculus in prosimian primates, while S1 is not. The somatosensory inputs appear to be too widespread to contribute to a detailed somatotopic representation in the superior colliculus, but they may be a source of somatosensory modulation of retinotopically guided oculomotor instructions.


Sustainment stories: a qualitative analysis of barriers to sustainment of the National Rural Transitions of Care Nurse Program.
Understanding how to successfully sustain evidence-based care coordination interventions across diverse settings is critical to ensure that patients continue to receive high quality care even after grant funding ends. The Transitions Nurse Program (TNP) is a national intervention in the Veterans Administration (VA) that coordinates care for high risk veterans transitioning from acute care VA medical centers (VAMCs) to home. As part of TNP, a VA facility receives funding for a full-time nurse to implement TNP, however, this funding ends after implementation. In this qualitative study we describe which elements of TNP sites planned to sustain as funding concluded, as well as perceived barriers to sustainment. TNP was implemented between 2016 and 2020 at eleven VA medical centers. Three years of funding was provided to each site to support hiring of staff, implementation and evaluation of the program. At the conclusion of funding, each site determined if they would sustain components or the entirety of the program. Prior to the end of funding at each site, we conducted midline and exit interviews with Transitions nurses and site champions to assess plans for sustainment and perceived barriers to sustainment. Interviews were analyzed using iterative, team-based inductive deductive content analysis to identify themes related to planned sustainment and perceived barriers to sustainment. None of the 11 sites planned to sustain TNP in its original format, though many of the medical centers anticipated offering components of the program, such as follow up calls after discharge to rural areas, documented warm hand off to PACT team, and designating a team member as responsible for patient rural discharge follow up. We identified three themes related to perceived sustainability. These included: 1) Program outcomes that address leadership priorities are necessary for sustainment.; 2) Local perceptions of the need for TNP or redundancy of TNP impacted perceived sustainability; and 3) Lack of leadership buy-in, changing leadership priorities, and leadership turnover are perceived barriers to sustainment. Understanding perceived sustainability is critical to continuing high quality care coordination interventions after funding ends. Our findings suggest that sustainment of care coordination interventions requires an in-depth understanding of the facility needs and local leadership priorities, and that building adaptable programs that continually engage key stakeholders is essential.


Environmentally induced functional shifts in phytoplankton and their potential consequences for ecosystem functioning.
Phytoplanktonic organisms are particularly sensitive to environmental change, and, as they represent a direct link between abiotic and biotic compartments within the marine food web, changes in the functional structure of phytoplankton communities can result in profound impacts on ecosystem functioning. Using a trait-based approach, we examined changes in the functional structure of the southern North Sea phytoplankton over the past five decades in relation to environmental conditions. We identified a shift in functional structure between 1998 and 2004 which coincides with a pronounced increase in diatom and decrease in dinoflagellate abundances, and we provide a mechanistic explanation for this taxonomic change. Early in the 2000s, the phytoplankton functional structure shifted from slow growing, autumn blooming, mixotrophic organisms, towards earlier blooming and faster-growing microalgae. Warming and decreasing dissolved phosphorus concentrations were linked to this rapid reorganization of the functional structure. We identified a potential link between this shift and dissolved nutrient concentrations, and we hypothesise that organisms blooming early and displaying high growth rates efficiently take up nutrients which then are no longer available to late bloomers. Moreover, we identified that the above-mentioned functional change may have bottom-up consequences, through a food quality-driven negative influence on copepod abundances. Overall, our study highlights that, by altering the phytoplankton functional composition, global and regional changes may have profound long-term impacts on coastal ecosystems, impacting both food-web structure and biogeochemical cycles.


Downstream targets of let-60 Ras in Caenorhabditis elegans.
In Caenorhabditis elegans, let-60 Ras controls many cellular processes, such as differentiation of vulval epithelial cells, function of chemosensory neurons, and meiotic progression in the germ line. Although much is known about the let-60 Ras signaling pathway, relatively little is understood about the target genes induced by let-60 Ras signaling that carry out terminal effector functions leading to morphological change. We have used DNA microarrays to identify 708 genes that change expression in response to activated let-60 Ras.


Calorie restriction in nonhuman primates: effects on diabetes and cardiovascular disease risk.
The effects of calorie restriction (CR) on life span, disease, and aging in physiological systems have been documented extensively in rodent models. However, whether CR has similar effects in longer-lived species more closely related to humans remains unknown. Studies of CR and aging using nonhuman primates (rhesus monkeys) have been ongoing for several years at the National Institute on Aging and the University of Wisconsin-Madison. The majority of data published from these studies are consistent with the extensive findings reported in rodents. For example, monkeys on CR weigh less and have less body fat. Monkeys on CR also exhibit lower body temperature, fasting blood glucose and insulin, and serum lipids. In addition, insulin sensitivity is increased in monkeys on CR. Recent efforts in the NIA study have focused on the effect of this intervention on risk factors for various age-related diseases, in particular for diabetes and cardiovascular disease. We have shown that monkeys on CR have lower blood pressure, reduced body fat, and a reduced trunk:leg fat ratio. Also, monkeys on CR have reduced triglycerides and cholesterol and have increased levels of HDL2B. Low levels of this HDL subfraction have been associated with increased cardiovascular disease in humans. In short-term studies, older (> 18 years) monkeys on CR exhibit reductions in insulin and triglycerides before changes in body composition and fat distribution became evident. These and other findings have suggested that CR might have beneficial effects on certain disease risk factors independent of reductions in body weight or prevention of obesity.


Carotid intima-media thickness: knowledge and application to everyday practice.
Heart disease is the primary cause of death in the United States. Fortunately, intervention measures can reduce the risk of cardiovascular disease (CVD) after a patient has been accurately assessed. Atherosclerotic disease, one of the driving forces behind CVD, is not always detected by traditional risk assessment. Carotid intima-media thickness (CIMT), as measured by B-mode ultrasound, is a surrogate marker for atherosclerosis and can be used to detect an accelerated disease process and subclinical disease. Advantages of CIMT are that it is noninvasive, relatively inexpensive, and can be repeatedly performed with no adverse effects on the patient. Carotid intima-media thickness is associated with CVD and is an independent predictor of stroke and myocardial infarction. Therefore, CIMT is valuable for clarifying CVD risk, particularly for patients with intermediate risk by conventional risk assessment. Screening for subclinical disease even in low-risk patients may have benefit, especially for those with a family history of premature CVD or those with any of the National Cholesterol Education Program risk factors. The detection of subclinical atherosclerosis allows the physician to implement prevention efforts prior to a devastating CVD event and to investigate possible reasons for increased arterial thickening, such as an occult underlying insulin-resistant condition or residual lipid risk markers. Treatment with several types of drugs has been demonstrated to halt the progression or even reduce CIMT. Carotid intima-media thickness is currently limited by the lack of standardized protocols that may affect reproducibility from measure to measure. Efforts to draft a standardized protocol are underway by the Society of Atherosclerosis Imaging and Prevention that will address this issue. Carotid intima-media thickness provides a valuable tool for physicians to clarify the CVD risk of their patients. Practical implications of CIMT for everyday clinical practice are addressed.


Comparison of dilute acid and sulfite pretreatments on Acacia confusa for biofuel application and the influence of its extractives.
Chemical components of lignocellulosic biomass may impede biofuel processing efficiency. To understand whether the heartwood of Acacia confusa is suitable for biofuel application, extractive-free heartwood of A. confusa was subjected to dilute acid (DA) or sulfite pretreatments. Sugar recoveries were used to evaluate the performance of different pretreatments. Cell wall properties, such as 4-O-alkylated lignin structures, S/G ratios, and xylan contents, of the pretreated samples showed significant correlations with the enzymatic saccharification of glucan. The 4% bisulfite-pretreated samples produced higher total sugar recoveries than DA-treated samples. The highest total sugar recoveries from DA and sulfite pretreatment were 52.0% (170 °C for 20 min) and 65.3% (4% NaHSO3 and 1% H2SO4), respectively. The results also demonstrated that the existence of extractives in the heartwood of A. confusa hindered the sugar recoveries from both the pretreatments and enzymatic saccharification. Total sugar recoveries were reduced 11.7-17.7% in heartwood samples with extractives.


Poststroke aphasia recovery assessed with functional magnetic resonance imaging and a picture identification task.
Stroke patients often display deficits in language function, such as correctly naming objects. Our aim was to evaluate the reliability and the patterns of poststroke language recovery using a picture identification task during functional magnetic resonance imaging (fMRI) at 4 T. Four healthy subjects and 4 subjects with left middle cerebral artery stroke with chronic (>1 year) aphasia were enrolled in the study. In each subject, 10 fMRI scans were performed over a 10-week period using a picture-identification task. The active condition involved presenting subject with a panel of 4 figures (eg, drawings of 4 animals) every 6 seconds and asking the subject to indicate which figure matched the written name in the center. The control condition was a same/different judgment task with pairs of geometric figures (squares, octagons, or combination) presented every 6 seconds. Thirty-second active/control blocks were repeated 5 times each, and responses were recorded. The stoke subjects and controls had similar demographic characteristics, including age (46 vs 53 years), personal handedness (Edinburg Handedness Inventory, 89 vs 95), familial handedness (93 vs 95), and years of education (14.3 vs 14.8). For the active condition, the controls performed better than the stroke subjects (97.7% vs 89.1%; P < .001); the 2 groups performed similarly for the control condition (99.5% vs 98.8%; P = .23). On fMRI, the controls exhibited bilateral, L > R positive blood oxygenation level-dependent (BOLD) activations in frontal and temporal language areas and symmetric retrosplenial and posterior cingulate areas and symmetric negative BOLD activations in bilateral frontotemporal language networks. In contrast, the stroke subjects exhibited positive BOLD activations predominantly in peristroke areas and negative BOLD activations in the unaffected (right) hemisphere. Both groups displayed high activation reliability (as measured by the intraclass correlation coefficient [ICC]) in the left frontal and temporal language areas, although in the stroke subjects the ICC in the frontal regions was spread over a much larger peristroke area. This study documents the utility of the picture-identification task for poststroke language recovery evaluation. Our data suggest that adult stroke patients use functional peristroke areas to perform language functions.


Solar rhythm in the regulation of photoperiodic flowering of long-day and short-day plants.
In photoperiodic flowering, long-day (LD) plants are induced to flower seasonally when the daylight hours are long, whereas flowering in short-day (SD) plants is promoted under short photoperiods. According to the widely accepted external coincidence model, flowering occurs in LD Arabidopsis when the circadian rhythm of the gene CONSTANS (CO) peaks in the afternoon, when it is light during long days but dark when the days are short. Nevertheless, extending this explanation to SD flowering in rice, Oriza sativa, requires LD and SD plants to have 'opposite light requirements' as the CO orthologue in rice, HEADING-DATE1 (Hd1), promotes flowering only under short photoperiods. This report proposes a role of the plant's solar rhythm in promoting seasonal flowering. The interaction between rhythmic genes entrained to the solar clock and those entrained to the circadian clock form the basis of an internal coincidence model that explains both LD and SD flowering equally well. The model invokes no presumption of opposite light requirements between LD and SD plants, and further argues against any specific requirement of either light or darkness for SD flowering. Internal coincidence predicts the inhibition of SD flowering of the rice plant by a night break (a brief interruption of light), while it also provides a plausible explanation for how a judiciously timed night break promotes Arabidopsis flowering even on short days. It is the timing of the light transitions (sunrise and sunset) rather than the duration of light or darkness per se that regulates photoperiod-controlled flowering.


The immunoexpression of glomerular NF-κB in proteinuric patients with proliferative and non-proliferative glomerulopathies.
Recent studies suggest that NF-κB activation plays an essential role in the activation of mesangial cells and macrophages through the transcriptional induction of inflammatory mediators of glomerular inflammation and injury. The aim of the present study was to determine, using an image analysis system, glomerular immunoexpression of NF-κB (nuclear translocation of p65) in proteinuric patients with proliferative and non-proliferative glomerulopathies. Thirty-six proteinuric patients with idiopathic proliferative glomerulopathies (PG group) and 28 proteinuric participants with non-proliferative glomerulopathies (NPG group) were examined by percutaneous renal biopsy. As a control 12 biopsy specimens of the kidneys removed because of trauma were used. In the PG group the mean values of the glomerular immunoexpression of NF-κB were significantly increased as compared to both NPG patients and controls. In the PG but not in the MPG group glomerular immunoexpression of NF-κB was significantly positively correlated with the degree of proteinuria. Moreover, in the PG group glomerular immunoexpression of NF-κB was positively correlated with the mesangial cells, mesangial area and glomerular monocytes/macrophages. In conclusion, our results strongly suggest a role of NF-κB in glomerular injury in proteinuric patients with proliferative glomerulopathies.


[Effect of BMP-2 and -3 overexpression on osteogenic and chondrogenic differentiation of prenatal mouse intervertebral disc cells in vitro].
To investigate the effect of recombinant adenovirus-mediated bone morphogenetic protein (BMP)-2 and -3 over expressions on chondrogenesis and osteogenesis of prenatal mouse intervertebral disc cells and provide experimental evidences for the application of BMPs in the therapy of disc diseases. The prenatal mouse intervertebral disc cells were infected with a recombinant adenovirus expressing BMP-2 and BMP-3 for 5-7 days, and the expressions of collagen type I (Col I), collagen type II (Col II), aggrecan, osteocalcin, osteoprotegerin and osteopontin mRNAs were detected with RT-PCR. The expression of cartilage matrix was evaluated with toluidine blue staining, and alkaline phosphatase (ALP) activity was detected with ALP reading and ALP staining. BMP-2 and -3 overexpression did not enhance chondrogenesis and osteogenesis of annulus fibrosus (AF) cells or cause significant increases in the expressions of Col I, Col II or aggrecan mRNA in nucleus pulposus (NP) cells. Adenovirus-mediated overexpression of BMP-2 and BMP-3, however, promoted osteogenesis of NP cells and significantly increased the expression of osteocalcin mRNA; the overexpression of BMP-2, but not BMP-3, enhanced the mRNA expressions of osteoprotegerin and osteopontin. Toluidine blue staining demonstrated that BMP-2 and BMP-3 overexpression did not obviously affect the secretion of cartilage matrix. In NP cells, BMP-2 and -3 overexpression significantly enhanced ALP activity, which was not observed in AF cells. Adenovirus-mediated BMP-2 and -3 overexpression can promote the osteogenic differentiation of NP cells but can not affect osteogenesis of AF cells or chondrogenesis of NP cells.


Automated large-scale file preparation, docking, and scoring: evaluation of ITScore and STScore using the 2012 Community Structure-Activity Resource benchmark.
In this study, we use the recently released 2012 Community Structure-Activity Resource (CSAR) data set to evaluate two knowledge-based scoring functions, ITScore and STScore, and a simple force-field-based potential (VDWScore). The CSAR data set contains 757 compounds, most with known affinities, and 57 crystal structures. With the help of the script files for docking preparation, we use the full CSAR data set to evaluate the performances of the scoring functions on binding affinity prediction and active/inactive compound discrimination. The CSAR subset that includes crystal structures is used as well, to evaluate the performances of the scoring functions on binding mode and affinity predictions. Within this structure subset, we investigate the importance of accurate ligand and protein conformational sampling and find that the binding affinity predictions are less sensitive to non-native ligand and protein conformations than the binding mode predictions. We also find the full CSAR data set to be more challenging in making binding mode predictions than the subset with structures. The script files used for preparing the CSAR data set for docking, including scripts for canonicalization of the ligand atoms, are offered freely to the academic community.


Synthesis and accumulation of nitrite in soybean nodules supplied with nitrate.
Nodulated soybean plants (Glycine max [L.] Merr) were grown in sand culture without combined N or with a continuous supply of nitrate in nutrient solution. Moderate nitrate concentration (30 milligrams N per liter) had little effect on nodule weight/plant while high nitrate concentration (100 milligrams N per liter) depressed nodule weight/plant by 70 to 80% with harvests 30 to 60 days after planting and initiation of nitrate treatments.The effect of nitrate supply on ammonium, amino, and ureide nitrogen concentrations in nodules was small and inconsistent. In contrast, nitrate and nitrite concentrations in nodules were directly proportional to nitrate supply and inversely proportional to nodule weight/plant. Correlations between nitrate or nitrite concentration in nodules and nodule weight/plant were highly significant.Cytosol from soybean nodules was found to contain NADH-dependent nitrate reductase activity (typical activity was 0.1 micromole per milligram protein x hour). A Rhizobium japonicum mutant (derived from strain 61A76) lacking nitrate reductase was employed to show that the cytosol enzyme activity is of host origin. Growth of nodules formed by the mutant lacking nitrate reductase was inhibited by nitrate. These nodules did contain nitrite although concentrations of nitrite (about 0.3 microgram N per gram fresh weight) were low relative to nitrite concentrations (about 1.5 microgram N per gram fresh weight) in nodules formed by R. japonicum strain 61A76. The overall results support the idea that the depression of legume nodule growth by nitrate is directly related to the metabolism of nitrate in nodules.


Numerical assessment of heat and mass transportation in [Formula: see text] nanofluids influenced by Soret and Dufour effects.
The current flow model is dedicated to capture the role of Dufour and Soret on heat and mass transmission of rotating flow of [Formula: see text] and [Formula: see text]water nanoparticles due to exponential stretching under the action of thermal radiation, magnetic, and Eckert numbers. The problem is modelled in terms if partial differential equations (PDEs) with associated physical conditions. The ordinary differential equations (ODEs) are obtained via suitable transformations. The reduced nonlinear ODEs set is tackled via a new scheme. We suggested significant improvements in the traditional technique and further formulated an extended version of wavelets scheme-based Chebyshev polynomials thoughts. The detailed procedure of the wavelet scheme and flow chart are provided. To validate the numerical outcomes; a comparative study with numerical technique RK (order-4) is also provided. Furthermore; numerical consequences of velocity, concentration and temperature profiles are further examined using several plots. The graphical plots, compared and convergence analyses are endorsing that our proposed modifications are worthy. Velocities profiles in view of [Formula: see text] nanofluid are lower than the [Formula: see text] nanofluid. Temperature and concentration profiles are dominant when [Formula: see text] nanofluid is considered.


[Neonatal lupus erythematosus and neurologic involvement: an incidental association?].
Neonatal lupus erythematosus is a rare disorder characterized by cutaneous lesions of the face and/or congenital heart block. The transplacental transfer of maternal anti-Ro/SSA, anti-La/SSB, or anti-U1RNP antibodies is responsible for the development of the disease. Few cases of neonatal lupus erythematosus with neurological involvement were reported in the medical literature. A 36-week GA female infant presented with neonatal lupus erythematosus comprising cutaneous, hematologic and hepatic disorders with a favorable outcome. However, cutaneous atrophy and hyperpigmentation persisted. Spastic paraparesis was diagnosed at the age of six months. The neurological lesions in neonatal lupus erythematosus could either be related to the presence of anti-Ro/SSA antibodies of maternal origin, or of anticardiolipin antibodies.


Service needs and service gaps among refugees with disabilities resettled in the United States.
To examine the adequacy of existing service systems in addressing the needs of refugees with disabilities resettled in the U.S.A. A cross-disability group of eight Cambodian and seven Somali refugees were purposively selected to participate in a 2-year qualitative study in the Midwestern U.S.A. Ten disability/refugee service providers and key experts on refugee resettlement were also recruited to participate. Data sources included in-depth interviews, focus groups, participant observations and social network surveys with disabled refugees. Participant observations and semi-structured interviews were also conducted with service providers and key experts. Data were analyzed using coding procedures based on a grounded theory approach. Disabled refugee participants experienced several unmet disability-related needs and limited access to resettlement resources on account of their disability. These findings were associated with refugee service providers having limited awareness of disability rights and resources and a narrow biomedical perspective of disability. Additionally there was a disconnection between refugee and disability service systems resulting from resource limitations within agencies, mistrust between the different service entities, and a lack of cross-cultural nuance among disability service organizations. These findings contribute important insights to the literature on disability disparities. Disabled refugees resettled in the U.S.A. have many unmet needs associated with gaps in-service delivery stemming from disconnections between refugee and disability service systems.


Impact of persistent cortical activity (up States) on intracortical and thalamocortical synaptic inputs.
The neocortex generates short epochs of persistent activity called up states, which are associated with changes in cellular and network excitability. Using somatosensory thalamocortical slices, we studied the impact of persistent cortical activity during spontaneous up states on intrinsic cellular excitability (input resistance) and on excitatory synaptic inputs of cortical cells. At the intrinsic excitability level, we found that the expected decrease in input resistance (high conductance) resulting from synaptic barrages during up states is counteracted by an increase in input resistance due to depolarization per se. The result is a variable but on average relatively small reduction in input resistance during up states. At the synaptic level, up states enhanced a late synaptic component of short-latency thalamocortical field potential responses but suppressed intracortical field potential responses. The thalamocortical enhancement did not reflect an increase in synaptic strength, as determined by measuring the evoked postsynaptic current, but instead an increase in evoked action potential (spike) probability due to depolarization during up states. In contrast, the intracortical suppression was associated with a reduction in synaptic strength, apparently driven by increased presynaptic intracortical activity during up states. In addition, intracortical suppression also reflected a reduction in evoked spike latency caused by depolarization and the abolishment of longer-latency spikes caused by stronger inhibitory drive during up states. In conclusion, depolarization during up states increases the success of excitatory synaptic inputs to reach firing. However, activity-dependent synaptic depression caused by increased presynaptic firing during up states and the enhancement of evoked inhibitory drive caused by depolarization suppress excitatory intracortical synaptic inputs.


Synergistic properties of the terpenoids aromadendrene and 1,8-cineole from the essential oil of Eucalyptus globulus against antibiotic-susceptible and antibiotic-resistant pathogens.
The aim of the present study was to investigate the chemical composition of the essential oil of the fruits of Eucalyptus globulus and to examine the potential application of the fruit oil against multidrug-resistant bacteria. GLC/MS analysis in the fruit oil showed that aromadendrene was the main compound followed by 1,8-cineole and globulol. The three most abundant components of the fruit oil were also tested individually against microorganisms. In addition, the synergistic effects of combinations of the major constituents (aromadendrene and 1,8-cineole) of the fruit oil were also investigated. All Gram-positive bacteria were susceptible to the fruit oil with different degrees of susceptibility as determined by microdilution method. The oil exerted a marked inhibition against multidrug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) Enterococcus faecalis. The results indicated that aromadendrene might be responsible for the antimicrobial properties, whereas 1,8-cineole and globulol exhibited low activities. The checkerboard assay demonstrated that combinations of 1,8-cineole and aromadendrene reduce the MIC in most cases in an additive way, whereas the time-kill assay indicates a synergistic effect.


Identification of CCND3 and BYSL as candidate targets for the 6p21 amplification in diffuse large B-cell lymphoma.
Increases in gene dosage through DNA amplification represents a common feature of many tumors and can result in the up-regulation of tumor-promoting genes. Our recent genome-wide, array-based comparative genomic hybridization analysis of 66 cases of diffuse large B-cell lymphoma found that genomic gain of 6p21 was observed in as many as 17 cases, including 14 cases with low-level copy number gain and three cases with high-level copy number gains (amplifications). To identify the target gene(s) for 6p21 amplification, we constructed a detailed amplicon map at the region of genomic amplification with the aid of high-resolution contig array-based comparative genomic hybridization glass slides, consisting of contiguously ordered bacterial artificial chromosome/P1-derived artificial chromosome clones covering 3 Mb throughout the 6p21 amplification region. Alignment of the amplifications identified a minimally overlapping 800 kb segment containing 15 genes. Quantitative expression analysis of the genes from both patient samples and the SUDHL9 cell line revealed that CCND3 and BYSL (1.9 kb telomeric to the CCND3 gene locus) are the targets of 6p21 genomic gain/amplification. Although it is known that t(6;14)(p21;q32) induces aberrant overexpression of CCND3 in B-cell malignancies, we were able to show that CCND3, which encodes the cyclin D family member protein that controls the G1-S phase of cell cycle regulation, can also be a target of genomic gain/amplification. Overexpression of CCND3 through genomic amplification is likely to lead to aberrant cell cycle control, although the precise biological role of BYSL with respect to tumorigenesis remains to be determined.


Nitrate and Nitrite Reduction in Relation to Nitrogenase Activity in Soybean Nodules and Rhizobium japonicum Bacteroids.
Soybean (Glycine max L. cv Williams) seeds were sown in pots containing a 1:1 perlite-vermiculite mixture and grown under greenhouse conditions. Nodules were initiated with a nitrate reductase expressing strain of Rhizobium japonicum, USDA 110, or with nitrate reductase nonexpressing mutants (NR(-) 108, NR(-) 303) derived from USDA 110. Nodules initiated with either type of strain were normal in appearance and demonstrated nitrogenase activity (acetylene reduction). The in vivo nitrate reductase activity of N(2)-grown nodules initiated with nitrate reductase-negative mutant strains was less than 10% of the activity shown by nodules initiated with the wild-type strain. Regardless of the bacterial strain used for inoculation, the nodule cytosol and the cell-free extracts of the leaves contained both nitrate reductase and nitrite reductase activities. The wild-type bacteroids contained nitrate reductase but not nitrite reductase activity while the bacteroids of strains NR(-) 108 and NR(-) 303 contained neither nitrate reductase nor nitrite reductase activities.Addition of 20 millimolar KNO(3) to bacteroids of the wild-type strain caused a decrease in nitrogenase activity by more than 50%, but the nitrate reductase-negative strains were insensitive to nitrate. The nitrogenase activity of detached nodules initiated with the nitrate reductase-negative mutant strains was less affected by the KNO(3) treatment as compared to the wild-type strain; however, the results were less conclusive than those obtained with the isolated bacteroids.The addition of either KNO(3) or KNO(2) to detached nodules (wild type) suspended in a semisolid agar nutrient medium caused an inhibition of nitrogenase activity of 50% and 65% as compared to the minus N controls, and provided direct evidence for a localized effect of nitrate and nitrite at the nodule level. Addition of 0.1 millimolar sucrose stimulated nitrogenase activity in the presence or absence of nitrate or nitrite. The sucrose treatment also helped to decrease the level of nitrite accumulated within the nodules.


Single shot interferogram analysis for optical metrology.
We report a novel constrained optimization method for single shot interferogram analysis. The unknown test wavefront is estimated as a minimum L2-norm squared solution whose phase is constrained to the space spanned by a finite number of Zernike polynomials. Using a single frame from standard phase shifting datasets, we demonstrate that our approach provides a phase map that matches with that generated using phase shifting algorithms to within λ/100 rms error. Our simulations and experimental results suggest the possibility of a simplified low-cost high quality optical metrology system for performing routine metrology tests involving smooth surface profiles.


Prevalence of Anemia Among Children and Adolescents in Rural Area of Khulais in Saudi Arabia.
Introduction The decreased absolute circulating red blood cell count or the inability of red blood cells to meet physiological needs is called anemia. Anemia can affect mental health, learning capacity, and the ability to concentrate. The present study aimed to assess the prevalence of anemia among children and adolescents living in the rural areas of Khulais, Saudi Arabia. Methods This cross-sectional study including 417 individuals was conducted at Khulais Hospital in the rural areas in Saudi Arabia to estimate the prevalence of anemia among children and adolescents. The inclusion criterion for the study was that participants must be Saudi citizens. Data for this study were collected in March 2021. The age of the children ranged from 7 to 11 years, whereas that of adolescent males and females was between 12 and 18 years. Results In total, the study included 147 male adolescents, 123 female adolescents, and 147 children participants. The overall prevalence of anemia among adolescents was high (39.1%). The prevalence of anemia was 44.9% (66/147), 46.3% (57/123), and 27.2% (40/147) in male adolescents (age 12-18 years), female adolescents (age 12-18 years), and children (age 7-11 years), respectively. Statistical analysis revealed an association between the prevalence of anemia and the increasing age of participants from rural areas. Conclusion The present study results indicate that the prevalence of anemia in the rural areas of Saudi Arabia is high. The high prevalence can be explained by several factors, such as parents' low socioeconomic status and living in rural areas, which limits the availability as well as different types of nutritious food and thereby negatively affects the nutritional status of such children and adolescents.


A novel AIE-active camphor-based fluorescent probe for simultaneous detection of Al3+ and Zn2+ at dual channels in living cells and zebrafish.
A novel dual-functional probe N'-(2-hydroxy-5-((4,7,7-trimethyl-3-oxobicyclo[2.2.1] heptan-2-ylidene)methyl) benzylidene)picolinohydrazide (PSH) was constructed from natural camphor. This probe showed strong yellow-green fluorescence at 535 nm due to its aggregation-induced emission (AIE) feature. Interestingly, the probe PSH displayed a significant turn-on fluorescence response towards Al3+ (green fluorescence at 500 nm) and Zn2+ (orange fluorescence at 555 nm) at two different emissive channels. The detection limits of PSH towards Al3+ and Zn2+ were found to be 12.1 nM and 14.2 nM, respectively. PSH exhibited excellent selectivity and anti-interference performance and could distinguish between Al3+/Zn2+ and identify whether Zn2+ exists in the PSH-Al3+ complex by adding ATP. The binding mechanisms between PSH and Al3+/Zn2+ ions were supported by 1H NMR, HRMS analysis, and density functional theory (DFT) calculations. Based on its outstanding sensing properties, the probe PSH was used to establish molecular logic function gates. Moreover, the probe PSH could be applied to detect Al3+ and Zn2+ in real environmental water, and fluorescence detection was well demonstrated by test strips. Furthermore, the probe PSH was employed for imaging Al3+ and Zn2+ in HeLa cells and zebrafish.


Aspergillus tubingensis Endocarditis: A Case Report and Review of the Literature.
Aspergillus endocarditis is a rare infection that may affect immunocompetent patients following heart valve replacement or heart surgery. We report the case of a 39 year old woman with a history of intravenous drug use who developed endocarditis with direct examination of the resected valve and vegetation showing the presence of mycelia. Cultures were positive for an Aspergillus of section Nigri, which was subsequently identified as Aspergillus tubingensis by sequencing. The clinical course was favorable following surgery and prolonged antifungal therapy (8 months in total). Antifungal susceptibility testing showed good in vitro activity of amphotericin B, voriconazole and echinocandins against planktonic cells of this A. tubingensis isolate. However, only amphotericin B displayed significant activity against biofilms. In vitro combinations of voriconazole or amphotericin B with echinocandins did not meet the criteria of synergism. Our review of the literature identified 17 other cases of endocarditis attributed to Aspergillus of section Nigri with an overall mortality rate of 57% (100% in the absence of surgery). Endocarditis caused by Aspergillus niger and related cryptic species are rare events, for which surgical management appears to be crucial for outcome. While amphotericin B was the only antifungal drug displaying significant anti-biofilm activity, the type and duration of antifungal therapy remain to be determined.


Thromboembolism in gynecologic oncology.
The risk of thrombo-embolic complications increases in surgical gynaecological oncology as a consequence of difficult and long-lasting interventions. In gynaecologic operations without any drug prophylaxis thrombosis has been reported by 24-29%, whereas in operations of progressed oncological findings thrombo-embolic complications arise in almost every second case. Such complications have to be taken seriously due to difficulty treatable sequelae (post-thrombic syndrome) and due to potentially lethal pulmonary embolism. Furthermore, they are important causes of postoperative early mortality. Diagnosis of a deep thrombosis is insecure even for experienced clinicians. We have various diagnostical means at our disposal, such as phlebography, sounding and 125-iodine-fibrinogen-testing. Differentiated drug medication for the prevention and therapy of thrombo-embolism is definitely indicated. There are also different kinds of physical and drug-aided means, which can be applied according to the individual situation.


Associations of School Connectedness With Adolescent Suicidality: Gender Differences and the Role of Risk of Depression.
Previous studies have not examined associations of school connectedness with adolescent suicidal behaviours stratified by gender, while including a measure of depression. We analyzed survey data to determine whether there are independent protective associations of higher school connectedness with suicidal behaviours in Canadian adolescents, while controlling for potential confounders, including risk of depression; and whether such associations differ by gender. Using data from a stratified cluster sample of randomly selected classes of students in schools in 3 of Canada's Atlantic provinces, we used multiple logistic regression to examine whether associations of risk of depression, measured using the 12-item Center for Epidemiologic Studies-Depression scale, lessened protective associations of higher school connectedness with suicidal behaviours in grades 10 and 12 students, while stratifying by gender. After adjusting for risk of depression, higher school connectedness was independently associated with decreased suicidal ideation in both genders and with suicidal attempt in females. In males, higher connectedness was no longer protective for suicide attempt when risk of depression was included in the model. School connectedness, which is felt to have positive influences on many types of adolescent behaviour, appears to also be both directly and indirectly protective for suicidality. These effects may occur through different pathways in females and males. Given the protection it offers both genders, including those at risk and not at risk of depression, increasing school connectedness should be considered as a universal adolescent mental health strategy. Studies that examine school connectedness should include analyses that examine potential differences between males and females.


Modulation by palmitoylcarnitine of protein kinase C activation.
Palmitoylcarnitine, a reported protein kinase C inhibitor, enhanced the phorbol ester dependency of the enzyme, augmenting protein kinase C activity in the presence of phorbol esters such as phorbol 12,13-dibutyrate while inhibiting the basal activity measured in the presence of calcium plus phosphatidylserine. Weakly potent phorbol esters such as phorbol 12,13-diacetate and 4-O-methylphorbol 12-myristate 13-acetate were full agonists like phorbol 12,13-dibutyrate for activation of protein kinase C in the presence of palmitoylcarnitine. On the other hand, 1,2-diacylglycerols such as 1,2-diolein were only partially stimulatory. Palmitoylcarnitine did not interfere with the association of protein kinase C with phosphatidylserine, suggesting that its action was on protein kinase C activation per se rather than on priming. A long fatty acid ester, quaternary amine, and anionic charge were needed for the palmitoylcarnitine-like action. Phosphatidylcholine, which possesses these features, partially mimicked the action of palmitoylcarnitine. Palmitoylcarnitine thus appears to be a lipophilic modulator of protein kinase C rather than a simple inhibitor. The results raise the possibility that differences in response between phorbol esters and diacylglycerols may reflect differential ability to activate protein kinase C in the appropriate lipid environment rather than the existence of unique targets for one or the other compound.


The aquaporin-4 water channel as a potential drug target in neurological disorders.
Aquaporin-4 (AQP4) is a water transporting protein expressed at the plasma membrane of astrocytes throughout the central nervous system (CNS). Analysis of AQP4 knockout mice has suggested its broad involvement in brain water balance, neuroexcitation, glial scarring, neuroinflammation, and even neurodegenerative and neuropsychiatric disorders. Broad clinical utility of AQP4 modulators has been speculated. Area covered: This review covers the biology of AQP4, evidence for its roles in normal CNS function and neurological disorders, and progress in AQP4 drug discovery. Expert opinion: Critical examination of available data reduces the lengthy potential applications list to AQP4 inhibitors for early therapy of ischemic stroke and perhaps for reduction of glial scarring following CNS injury. Major challenges in identification and clinical development of AQP4 inhibitors include the apparent poor druggability of AQPs, the many homologous AQP isoforms with broad tissue distribution and functions, technical issues with water transport assays, predicted undesired CNS and non-CNS actions, and the need for high blood-brain barrier permeation. To date, despite considerable effort, validated small-molecule AQP4 inhibitors have not been advanced. However, a biologic ('aquaporumab') is in development for neuromyelitis optica, an autoimmune inflammatory demyelinating disease where CNS pathology is initiated by binding of anti-AQP4 autoantibodies to astrocyte AQP4.


Mapping of the bone morphogenetic protein 1 gene (BMP1) to 8p21: removal of BMP1 from candidacy for the bone disorder in Langer-Giedion syndrome.
Fifteen cosmids containing sequences from the human bone morphogenetic protein 1 gene (BMP1) were isolated from a cosmid library. The probe was a 483-bp DNA obtained by the reverse transcriptase-PCR method using primers designed according to the reported BMP1 sequence. When the positive cosmids were tested for chromosome fluorescence in situ hybridization, all showed signals at 8p21. The results indicated that BMP1 is not responsible for Langer-Giedion syndrome, whose putative gene has been assigned to 8q24.