Longitudinal effects of adjuvant chemotherapy and lymph node staging on patient-reported outcomes in endometrial cancer survivors: a prospective cohort study.
Most patients with endometrial cancer with localized disease are effectively treated and survive for a long time. The primary treatment is hysterectomy, to which surgical staging procedures may be added to assess the need for adjuvant therapy. Longitudinal data on patient-reported outcomes comparing different levels of primary treatment are lacking, especially when adjuvant radiotherapy is omitted. We assessed the impact of lymphadenectomy and adjuvant chemotherapy on patient-reported symptoms, function, and quality of life. We hypothesized that these treatment modalities would substantially affect patient-reported outcomes at follow-up. We prospectively included patients with endometrial cancer enrolled in the ongoing MoMaTEC2 study (ClinicalTrials.gov Identifier: NCT02543710). Patients were asked to complete the patient-reported outcome questionnaires European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire EN24 preoperatively and at 1 and 2 years of follow-up. Functional domains and symptoms were analyzed for the whole cohort and by treatment received. To assess the effect of the individual treatment modifications, we used mixed regression models. Baseline data were available for 448 patients. Of these patients, 339 and 219 had reached 1-year follow-up and 2-year follow-up, respectively. Treatment included hysterectomy (plus bilateral salpingo-oophorectomy) alone (n=177), hysterectomy and lymph node staging without adjuvant therapy (n=133), or adjuvant chemotherapy irrespective of staging procedure (n=138). Overall, patients reported improved global health status and quality of life (+9 units; P<.001), increased emotional and social functioning, and increased sexual interest and activity (P<.001 for all) from baseline to year 1, and these outcomes remained stable at year 2. Means of functional scales and quality of life were similar to age- and sex-weighted reference cohorts. Mean tingling and numbness and lymphedema increased after treatment. The group who received adjuvant chemotherapy had a larger mean reduction in physical functioning (-6 vs +2; P=.002) at year 1, more neuropathy (+30 vs +5; P<.001; year 1) at years 1 and 2, and more lymphedema at year 1 (+11 vs +2; P=.007) than the group treated with hysterectomy and salpingo-oophorectomy only. In patients not receiving adjuvant chemotherapy, patient-reported outcomes were similar regardless of lymph node staging procedures. Adjuvant chemotherapy independently increased fatigue, lymphedema, and neuropathy in mixed regression models. Patients with endometrial cancer receiving adjuvant chemotherapy reported significantly reduced functioning and more symptoms up to 2 years after treatment. For patients treated by surgery alone, surgical staging did not seem to affect the quality of life or symptoms to a measurable degree at follow-up. Therefore, subjecting patients to lymph node removal to tailor adjuvant therapy seems justified from the patient's viewpoint; however, efforts should increase to find alternatives to traditional chemotherapy.


Fourier transform infrared spectroscopy and chemometric analysis of white wine polysaccharide extracts.
Monovarietal white wines from Maria Gomes and Bical Portuguese Bairrada varieties were prepared according to different maceration and pectic enzyme clarification procedures. The polysaccharide-rich extracts, obtained by wine concentration, dialysis, and lyophilization, were fractionated by graded ethanol precipitation. A wide range of fractions rich in polysaccharides were obtained. Using the spectral region between 1200 and 800 cm(-)(1) of the FTIR spectra of the wine polysaccharide dry extracts, using PCA and CCA chemometric methods, it was possible to discriminate the extracts on the basis of their polysaccharide composition. Moreover, it was possible to identify the wine-making processes involved and their influence on the wine polysaccharides. Furthermore, a calibration model using a PLS1 was proposed for the quantification of mannose in the samples obtained by precipitation with 60% ethanol aqueous solutions. This information will allow an expeditious assessment and monitoring of the polysaccharide composition and modifications that occur during the wine-making processing and evolution.


The effects of tissue fixation alternatives on DNA content: a study on normal colon tissue.
The aim of this study is to investigate the effects of different fixatives on DNA, and to evaluate the fixation options for molecular studies including polymerase chain reaction (PCR) and fluorescence in-situ hybridization (FISH). Three normal-looking colonic segments from surgical resections were used for tissue sampling. The full thickness of the colonic tissues (3 mm diameter) was sampled. Tissues were fixed in 70% ethanol, 10% neutral-buffered formalin, Hollande, B5, Bouin, and Zenker solutions for 1, 2, 5, 12, 24, and 48 hours, and processed and embedded in paraffin in a standard protocol. Quantitative measurements of the extracted DNA were carried out. DNA quality was tested by PCR for the human beta globin gene. Tissue sections were also tested for the availability of FISH, by using a Her-2/neu protocol. All fixation alternatives were found to be reasonable sources of DNA for molecular studies, and they enabled the successful PCR amplification of a housekeeping gene. DNA yields were predominantly over 1000 bp in 70% ethanol and 24-hour 10% neutral-buffered formalin fixations. As for B5 and Hollande, the DNA molecules obtained were almost all smaller than 100 bp. All tissues fixed in formalin, ethanol, and Hollande were found suitable for Her-2/neu visualization after standard FISH applications, but tissues fixed in Zenker, B5, and Bouin were not found suitable.


Quaternion Locality-Constrained Coding for Color Face Hallucination.
Recently, the locality linear coding (LLC) has attracted more and more attentions in the areas of image processing and computer vision. However, the conventional LLC with real setting is just designed for the grayscale image. For the color image, it usually treats each color channel individually or encodes the monochrome image by concatenating all the color channels, which ignores the correlations among different channels. In this paper, we propose a quaternion-based locality-constrained coding (QLC) model for color face hallucination in the quaternion space. In QLC, the face images are represented as quaternion matrices. By transforming the channel images into an orthogonal feature space and encoding the coefficients in the quaternion domain, the proposed QLC is expected to learn the advantages of both quaternion algebra and locality coding scheme. Hence, the QLC cannot only expose the true topology of image patch manifold but also preserve the inherent correlations among different color channels. Experimental results demonstrated that our proposed QLC method achieved superior performance in color face hallucination compared with other state-of-the-art methods.


First International Conference on Public Health in Africa (CPHIA 2021).
The first international Conference on Public Health in Africa (CPHIA 2021) was hosted virtually by the African Union (AU) and Africa Centres for Disease Control and Prevention (Africa CDC) from 14-16 December 2021. This historic three-day conference focused on the need to address long-standing health challenges on the continent, including vaccine inequity and manufacturing capacity, the ongoing COVID-19 pandemic, and the need to build resilient health systems.


Genome Editing Provides New Insights into Receptor-Controlled Signalling Pathways.
Rapid developments in genome editing, based largely on CRISPR/Cas9 technologies, are offering unprecedented opportunities to eliminate the expression of single or multiple gene products in intact organisms and in model cell systems. Elimination of individual G protein-coupled receptors (GPCRs), both single and multiple G protein subunits, and arrestin adaptor proteins is providing new and sometimes unanticipated insights into molecular details of the regulation of cell signalling pathways and the behaviour of receptor ligands. Genome editing is certain to become a central component of therapeutic target validation, and will provide pharmacologists with new understanding of the complexities of action of novel and previously studied ligands, as well as of the transmission of signals from individual cell-surface receptors to intracellular signalling cascades.


Vesico-vaginal fistula in a patient with Meyer-Rokitansky-Kuster-Hauser syndrome.
This was a case of Gishiri cut in a patient with Meyer-Rokitansky-Kuster-Hauser syndrome resulting in a vesico-vaginal fistula and urethral loss. This followed an attempt to enlarge and lengthen the vagina to enhance penile penetration. Few cases of MRKH syndrome presenting with complications after an attempt at treatment by traditional birth attendants have been reported. This report is particularly of essence as most urinary fistulae in Nigeria are obstetric fistulae following prolonged obstructed labour.


Observation of long-range three-body coulomb effects in the decay of (16)Ne.
The interaction of an E/A=57.6-MeV ^{17}Ne beam with a Be target is used to populate levels in ^{16}Ne following neutron knockout reactions. The decay of ^{16}Ne states into the three-body ^{14}O+p+p continuum is observed in the High Resolution Array (HiRA). For the first time for a 2p emitter, correlations between the momenta of the three decay products are measured with sufficient resolution and statistics to allow for an unambiguous demonstration of their dependence on the long-range nature of the Coulomb interaction. Contrary to previous measurements, our measured limit Γ<80 keV for the intrinsic decay width of the ground state is not in contradiction to the small values (of the order of keV) predicted theoretically.


Photoresponsive Electrochemical DNA Biosensors Achieving Various Dynamic Ranges by Using Only-One Capture Probe.
The rational design of DNA capture probes for modulating the binding affinity to tune the dynamic range of electrochemical DNA (E-DNA) biosensors is valuable and effective. Most of current strategies, however, require designing several DNA capture probes to achieve the tunable dynamic range, which is cumbersome and costly. Herein, we develop the photoresponsive E-DNA biosensors with tunable dynamic ranges by using only one photocleavable capture probe (PC-CP). The photoresponsive PC-CP is a stem-loop DNA structure containing a photocleavable linker (PC-linker) in the loop. The PC-linker can be cleaved by UV irradiation to switch the structure of PC-CP, through which the binding affinity to the target could be tuned. In this way, the dynamic range, the sensitivity, and the specificity of photoresponsive E-DNA biosensors can be tuned. Furthermore, the developed photoresponsive E-DNA biosensors enable sensitive and selective detection of target DNA in complex samples with a tunable dynamic range, which offers the possibility of clinical applications.


Type IV pili-dependent gliding motility in the Gram-positive pathogen Clostridium perfringens and other Clostridia.
Bacteria can swim in liquid media by flagellar rotation and can move on surfaces via gliding or twitching motility. One type of gliding motility involves the extension, attachment and retraction of type IV pili (TFP), which pull the bacterium towards the site of attachment. TFP-dependent gliding motility has been seen in many Gram-negative bacteria but not in Gram-positive bacteria. Recently, the genome sequences of three strains of Clostridium perfringens have been completed and we identified gene products involved in producing TFP in each strain. Here we show that C. perfringens produces TFP and moves with an unusual form of gliding motility involving groups of densely packed cells moving away from the edge of a colony in curvilinear flares. Mutations introduced into the pilT and pilC genes of C. perfringens abolished motility and surface localization of TFP. Genes encoding TFP are also found in the genomes of all nine Clostridium species sequenced thus far and we demonstrated that Clostridium beijerinckii can move via gliding motility. It has recently been proposed that the Clostridia are the oldest Eubacterial class and the ubiquity of TFP in this class suggests that a Clostridia-like ancestor possessed TFP, which evolved into the forms seen in many Gram-negative species.


Asymmetric epoxidation of 2-arylidene-1,3-diketones: facile access to synthetically useful epoxides.
In this article the first enantioselective epoxidation reaction of acyclic and cyclic 2-arylidene-1,3-diketones is reported. Easily accessible or commercially available alpha,alpha-diaryl prolinols as the organocatalysts in the presence of tert-butyl hydroperoxide (TBHP) provide the corresponding epoxides in high to excellent yield (up to 99%) and up to 85% ee (ee >90% after crystallisation). These epoxides are pharmaceutically important building blocks and intermediates for the synthesis of densely functionalised epoxide derivatives.


[Open vs. closed abdomen in acute peritonitis. A comparative study].
Open abdomen is a management alternative that, however, is not exempt from complications. We evaluated, in a comparative manner, the handling with open abdomen (OA) against closed abdomen (CA) in treatment of patients with severe peritonitis for traumatic lesion. We carried out an observational, retrospective, longitudinal, and comparative study. It included patients managed with diagnosis severe peritonitis due to abdominal trauma between 1998 and 2000. They were divided into two groups, according to management with OA or CA. We compared age, sex, trauma type, severity of lesion, morbility and mortality. 12 patients were managed with OA, which presented longer hospitalization and 24 with CA who in turn presented a greater lesion severity. There were statistical differences in other parameters, including complications and mortality. However, patients managed with OA frequently presented more complications. OA does not improve morbility and mortality of patients, although they presented less severe lesions that those managed with CA.


Role of palmitoylation of cysteine 415 in functional coupling CB1 receptor to Gαi2 protein.
In this study, we investigated the role of CB1 palmitoylation in modulating the functional interaction with G proteins both in the absence and presence of agonist binding. Our data show that the nonpalmitoylated CB1 receptor significantly reduced its association with Gαi2 . The agonist stimulation induced a partial dissociation of Gαi2 proteins from the wild-type receptor, while on the C415A mutant the agonist binding was not able to induce a significant dissociation of Gαi2 from the receptor. The lack of palmitoyl chain seems to hamper the ability of the receptor to functionally interact with the Gαi2 and indicate that the palmitoyl chain is responsible for the functional transmission of the agonist-induced conformational change in the receptor of the G protein. These data were further corroborated by molecular dynamics simulations. Overall these results suggest that palmitoylation of the CB1 receptor finely tunes its interaction with G proteins and serves as a targeting signal for its functional regulation. Of note, the possibility to reversibly modulate the palmitoylation of CB1 receptor may offer a coordinated process of regulation and could open new therapeutic approaches.


Carbon Monoxide Being Hydrogen Sulfide and Nitric Oxide Molecular Sibling, as Endogenous and Exogenous Modulator of Oxidative Stress and Antioxidative Mechanisms in the Digestive System.
Oxidative stress reflects an imbalance between oxidants and antioxidants in favor of the oxidants capable of evoking tissue damage. Like hydrogen sulfide (H2S) and nitric oxide (NO), carbon monoxide (CO) is an endogenous gaseous mediator recently implicated in the physiology of the gastrointestinal (GI) tract. CO is produced in mammalian tissues as a byproduct of heme degradation catalyzed by the heme oxygenase (HO) enzymes. Among the three enzymatic isoforms, heme oxygenase-1 (HO-1) is induced under conditions of oxidative stress or tissue injury and plays a beneficial role in the mechanism of protection against inflammation, ischemia/reperfusion (I/R), and many other injuries. According to recently published data, increased endogenous CO production by inducible HO-1, its delivery by novel pharmacological CO-releasing agents, or even the direct inhalation of CO has been considered a promising alternative in future experimental and clinical therapies against various GI disorders. However, the exact mechanisms underlying behind these CO-mediated beneficial actions are not fully explained and experimental as well as clinical studies on the mechanism of CO-induced protection are awaited. For instance, in a variety of experimental models related to gastric mucosal damage, HO-1/CO pathway and CO-releasing agents seem to prevent gastric damage mainly by reduction of lipid peroxidation and/or increased level of enzymatic antioxidants, such as superoxide dismutase (SOD) or glutathione peroxidase (GPx). Many studies have also revealed that HO-1/CO can serve as a potential defensive pathway against oxidative stress observed in the liver and pancreas. Moreover, increased CO levels after treatment with CO donors have been reported to protect the gut against formation of acute GI lesions mainly by the regulation of reactive oxygen species (ROS) production and the antioxidative activity. In this review, we focused on the role of H2S and NO molecular sibling, CO/HO pathway, and therapeutic potential of CO-releasing pharmacological tools in the regulation of oxidative stress-induced damage within the GI tract with a special emphasis on the esophagus, stomach, and intestines and also two solid and important metabolic abdominal organs, the liver and pancreas.


Genetic analysis of the relationships between ischaemic heart disease and the blood lipid level.
The results of clinical-experimental research on the prevalence of ischaemic heart disease (IHD), the cholesterol (CS) and triglyceride (TG) level in a random sample of the male population of the city of Andizhan in the Uzbek SSR, aged 40-59 years (n = 593) have shown the following correlations between the mentioned variables: IHD - CS: rp = 0.61, IHD - TG: 0.64, CS - TG: 0.28. These findings suggest the existence of certain factors - genetic and/or environmental ones - common to the mentioned pairs of traits. Genetic analysis of the structure of common elements for IHD, CS and TG has shown that the genetic component of IHD liability is determined by genetic factors of the CS (50.2% and the TG level (47.3%). As regards the influence of environmental factors on IHD risk, statistical analysis has not so far permitted to draw any reliable conclusions.


Highly conserved upstream regions of the alpha 1-antitrypsin gene in two mouse species govern liver-specific expression by different mechanisms.
alpha 1-Antitrypsin (AT), the major elastase inhibitor in mammalian serum, is produced primarily in the liver. We have characterized AT gene structure and expression in the mouse species Mus caroli, which expresses high levels of AT in the kidneys as well as in the liver. Analysis of cDNA and genomic clones showed that the AT gene in M. caroli exhibits high sequence homology (greater than 90%) to the gene in laboratory mice (M. domesticus) throughout the coding and 5'-flanking regions. Despite this extensive sequence conservation, the functional organization of cis-acting regulatory elements governing liver-specific expression is strikingly different between these species. Transient-transfection assays showed that the proximal region of the M. caroli promoter (i.e., between -120 and -2 relative to the transcriptional start site) is 10-fold more active than the analogous region of M. domesticus in driving the expression of an indicator gene in cultured liver cells. The increased activity of the proximal region of the M. caroli AT promoter appears to be the result of one or both of the two base substitutions at positions -46 and -48. The weak proximal promoter in M. domesticus is compensated for by the presence of upstream, liver-specific enhancers between -199 and -520; the analogous region in M. caroli is inactive. Thus, during the course of evolution, the modest 7% sequence divergence that has occurred between the 5'-flanking regions of the AT genes in these two species has generated distinct, yet equally effective, modes of hepatocyte-specific expression.


[The early history of the Danish twin registry].
The Danish Twin Registry was initiated at the Copenhagen University Institute for Human Genetics in 1954 by professor Tage Kemp and his assistants, Bent Harvald and Mogens Hauge. The project was until 1960 primarily financed by US National Cancer Institutes. Twin pairs both of same and different sex, born 1870-1910 were drawn from the birth registers and followed-up through the national registers until death or present place of living. Later on same sex pairs born 1911-30 were added. Besided cancer a multitude of other disorders were registered. Intensive studies on identical twins grown up apart were undertaken by Niels Juel-Nielsen, on criminal behaviour by Karl O. Christiansen, on smoking habits by Elisabeth Raaschou-Nielsen, on peptic ulcer by Kaj Gotlieb Jensen, on schizophrenia by Margit Fischer. Among early remarkable results should be mentioned the modest influence of genetic versus environmental factors in most cases of cancer, the strong genetic impact in mental and moral qualities, the approximate genetic/environmental ratio of 50/50 for the orgin of criminal behaviour and a corresponding ratio of 25/75 for life expectancy. In 1971 the Danish Twin Registry was moved to Odense Universty.


Heterotopic ossification after closed femoral nailing.
Heterotopic ossification is defined as pathological bone formation in soft tissue, it usually occurs postoperatively and varies in amount from faint to massive ossification, which are frequently asymptomatic. The cause of heterotopic ossification is unknown, but it occurs more commonly after the procedure, in which considerable bone and soft tissue are dissected extensively. The heterotopic ossification in the abductor region of the hip following closed femoral nailing has rarely been documented. To assess the prevalence and type of heterotopic ossification after closed antegrade femoral nailing. A retrospective study was performed in patients who underwent closed antegrade femoral nailing. The occurrence of heterotopic bone was assessed by reviewing of the series of the follow-up films in this group of patients with sufficient duration of at least after 6 months post-operation. The size and extent of the heterotopic ossification were measured and graded according to Brumback classification. From 100 patients who were completely followed-up. There were 54 cases (54%) presented with heterotopic ossification. The heterotopic ossification are classified as grade I in 16 cases (16%), grade II in 13 cases (13%), grade III in 24 cases (24%) and grade IV in 1 case (1%). There was a significant different between the prevelence of heterotopic ossification in patients with trochnateric fractures when compared to patients with femoral shaft fractures (p-value < 0.05).


Infants possess an abstract expectation of ingroup support.
One pervasive facet of human interactions is the tendency to favor ingroups over outgroups. Remarkably, this tendency has been observed even when individuals are assigned to minimal groups based on arbitrary markers. Why is mere categorization into a minimal group sufficient to elicit some degree of ingroup favoritism? We consider several accounts that have been proposed in answer to this question and then test one particular account, which holds that ingroup favoritism reflects in part an abstract and early-emerging sociomoral expectation of ingroup support. In violation-of-expectation experiments with 17-mo-old infants, unfamiliar women were first identified (using novel labels) as belonging to the same group, to different groups, or to unspecified groups. Next, one woman needed instrumental assistance to achieve her goal, and another woman either provided the necessary assistance (help event) or chose not to do so (ignore event). When the two women belonged to the same group, infants looked significantly longer if shown the ignore as opposed to the help event; when the two women belonged to different groups or to unspecified groups, however, infants looked equally at the two events. Together, these results indicate that infants view helping as expected among individuals from the same group, but as optional otherwise. As such, the results demonstrate that from an early age, an abstract expectation of ingroup support contributes to ingroup favoritism in human interactions.


High Salinity Inhibits Soil Bacterial Community Mediating Nitrogen Cycling.
Salinization is considered a major threat to soil fertility and agricultural productivity throughout the world. Soil microbes play a crucial role in maintaining ecosystem stability and function (e.g., nitrogen cycling). However, the response of bacterial community composition and community-level function to soil salinity remains uncertain. Here, we used multiple statistical analyses to assess the effect of high salinity on bacterial community composition and potential metabolism function in the agricultural ecosystem. Results showed that high salinity significantly altered both bacterial alpha (Shannon-Wiener index and phylogenetic diversity) and beta diversity. Salinity, total nitrogen (TN), and soil organic matter (SOM) were the vital environmental factors shaping bacterial community composition. The relative abundance of Actinobacteria, Chloroflexi, Acidobacteria, and Planctomycetes decreased with salinity, whereas Proteobacteria and Bacteroidetes increased with salinity. The modularity and the ratio of negative to positive links remarkedly decreased, indicating that high salinity destabilized bacterial networks. Variable selection, which belongs to deterministic processes, mediated bacterial community assembly within the saline soils. Function prediction results showed that the key nitrogen metabolism (e.g., ammonification, nitrogen fixation, nitrification, and denitrification processes) was inhibited in high salinity habitats. MiSeq sequencing of 16S rRNA genes revealed that the abundance and composition of the nitrifying community were influenced by high salinity. The consistency of function prediction and experimental verification demonstrated that high salinity inhibited soil bacterial community mediating nitrogen cycling. Our study provides strong evidence for a salinity effect on the bacterial community composition and key metabolism function, which could help us understand how soil microbes respond to ongoing environment perturbation. IMPORTANCE Revealing the response of the soil bacterial community to external environmental disturbances is an important but poorly understood topic in microbial ecology. In this study, we evaluated the effect of high salinity on the bacterial community composition and key biogeochemical processes in salinized agricultural soils (0.22 to 19.98 dS m-1). Our results showed that high salinity significantly decreased bacterial diversity, altered bacterial community composition, and destabilized the bacterial network. Moreover, variable selection (61% to 66%) mediated bacterial community assembly within the saline soils. Functional prediction combined with microbiological verification proved that high salinity inhibited soil bacterial community mediating nitrogen turnover. Understanding the impact of salinity on soil bacterial community is of great significance for managing saline soils and maintaining a healthy ecosystem.


[Atypical course of uterine rupture during delivery].
Uterine rupture is a rare complication of pregnancy, occurring in 0.03% of deliveries in Denmark. This paper describes a case of asymptomatic uterine rupture in a 38-year-old woman. She was admitted with a history of excessive vaginal bleeding 14 days after a spontaneous delivery with the use of vacuum extraction. At the time of laparotomy, a complete uterine rupture was discovered and total hysterectomy was performed.


Sex differences in cocaine-associated memory: The interplay between CB1, mGluR5, and estradiol.
We know surprisingly little about the sex differences in the neurobiology of cocaine addiction, except females are more susceptible to the rewarding effects of cocaine than their male counterparts. Only a handful of recent studies have examined the neurobiology of cocaine-induced conditioned place preference (CPP) memory among female rodents. We contribute to this emerging line of research by documenting sex differences in cocaine-associated memory and illustrating the underlying signaling pathways in five experiments. Rimonabant (Rim), a cannabinoid CB1 antagonist and inverse agonist, exerted a facilitating effect for low-dose cocaine and an impairing effect for high-dose cocaine CPP memory in male mice, as in our previous study, but not in female mice. Nor did we observe the effect exist among CB1 knockout male mice, which indicated that the CB1 receptors played a mediating role. We also found that the metabotropic glutamate receptor 5 (mGluR5) was located in the same signaling pathway as CB1 in male mice. To clarify the mechanisms behind the sex differences, we used ovariectomized (OVX) female mice with estradiol benzoate (EB) replacement. In the OVX female mice, we showed that Rim-alone and EB-alone, but not Rim-and-EB-combined, facilitated the low-dose cocaine CPP memory. Moreover, 4-hydroxytamoxifen (4-OHT), an estrogen receptor (ER) antagonist, blocked Rim's and EB's facilitating effect. Finally, 2-methyl-6-(phenylethynyl)pyridine (MPEP), an mGluR5 antagonist, partially blocked EB's facilitating effect. In sum, we identified sex-specific effects of Rim on cocaine-induced CPP memory and the respective signaling pathways: mGluR5-CB1 for male mice and ER-mGluR5-CB1 for female mice. These findings may have merits for the development of sex-specific treatment for cocaine addiction.


Construction of novel Brassica napus genotypes through chromosomal substitution and elimination using interploid species hybridization.
A synthetic Brassica napus rapeseed with genome composition of A(r)A(r)C(c)C(c), made by combining A(r) from B. rapa (A(r)A(r)) and C(c) from B. carinata (B(c)B(c)C(c)C(c)), is valuable for making new genes available to breeders and gaining heterosis in crosses. An intergenomic hybrid A(n)A(r)C(n)C(c) was made from a hybrid between natural Brassica napus (A(n)A(n)C(n)C(n)) and a synthetic rapeseed. To construct the synthetic Brassica napus, hexaploid plants (2n=54, A(r)A(r)B(c)B(c)C(c)C(c)) were first obtained through chromosome doubling of trigenomic hybrids (2n=27, A(r)B(c)C(c)) between Brassica carinata (2n=34) and B. rapa (2n=20). Pentaploid hybrids (2n=46, A(r)A(n)B(c)C(c)C(n)) were then produced by crossing the hexaploid with the pollen of natural B. napus (2n=38). Chromosomes with dual and single B(c) genomes were observed in somatic cells of hexaploid and pentaploid plants. About 80% of pollen mother cells of pentaploid hybrids had 19 or more bivalents, indicating that the bivalents from A(r)/A(n) and C(c)/C(n) chromosomes were normally formed. The occurrence of trivalents and quadrivalents at diakinesis suggested that B(c), A(n) and A(r) or B(c), C(n) and C(c) homologous pairing and exchange might happen. The variable number of laggards, 3 and 4 in most cases, were observed in the majority of PMCs at anaphase. Results from genomic in situ hybridization showed that the laggards belonged mainly to the B(c) genome, suggesting that the B(c) genome could be eliminated in the gametes of pentaploid hybrids. 16.15% of seeds derived from self-pollinated pentaploids have 38 chromosomes, and 90% of 38-chromosome seeds were completely excluded B(c) genome. The cytological results of this experiment suggested that it is possible to obtain new materials with genome composition of A(r)A(r)C(c)C(c) for rapeseed breeding.


Engineering Drought Resistance in Forest Trees.
Climatic stresses limit plant growth and productivity. In the past decade, tree improvement programs were mainly focused on yield but it is obvious that enhanced stress resistance is also required. In this review we highlight important drought avoidance and tolerance mechanisms in forest trees. Genomes of economically important trees species with divergent resistance mechanisms can now be exploited to uncover the mechanistic basis of long-term drought adaptation at the whole plant level. Molecular tree physiology indicates that osmotic adjustment, antioxidative defense and increased water use efficiency are important targets for enhanced drought tolerance at the cellular and tissue level. Recent biotechnological approaches focused on overexpression of genes involved in stress sensing and signaling, such as the abscisic acid core pathway, and down-stream transcription factors. By this strategy, a suite of defense systems was recruited, generally enhancing drought and salt stress tolerance under laboratory conditions. However, field studies are still scarce. Under field conditions trees are exposed to combinations of stresses that vary in duration and magnitude. Variable stresses may overrule the positive effect achieved by engineering an individual defense pathway. To assess the usability of distinct modifications, large-scale experimental field studies in different environments are necessary. To optimize the balance between growth and defense, the use of stress-inducible promoters may be useful. Future improvement programs for drought resistance will benefit from a better understanding of the intricate networks that ameliorate molecular and ecological traits of forest trees.


BRMCF: Binary Relevance and MLSMOTE Based Computational Framework to Predict Drug Functions From Chemical and Biological Properties of Drugs.
In silico machine learning based prediction of drug functions considering the drug properties would substantially enhance the speed and reduce the cost of identifying promising drug leads. The drug function prediction capability of different drug properties happens to be different. So assessing these is advantageous in drug discovery. The task of drug function prediction is multi-label in nature reason being, in case of several drugs, multiple functions are associated with a drug. A number of existing works have ignored this inherent multi-label nature of the problem in context of addressing the issue of class imbalance. In the present work, a computational framework named as BRMCF has been proposed for analysing the prediction capability of chemical and biological properties of drugs toward drug functions in view of multi-label nature of problem. It employs Binary Relevance (BR) approach along with five base classifiers for handling the multi-label prediction task and MLSMOTE for addressing the issue of class imbalance. The proposed framework has been validated and compared with BR, Classifier Chains (CC) and Deep Neural Network (DNN) method on four drug properties datasets: SMILES Strings (SS) dataset, 17 Molecular Descriptors (17MD) dataset, Protein Sequences (PS) dataset and drug perturbed Gene EXpression Profiles (GEX) dataset. The analysis of results shows that the proposed framework BRMCF has outperformed BR, CC and DNN method in terms of exact match ratio, precision, recall, F1-score, ROC-AUC which signifies the effectiveness of MLSMOTE. Further, assessment of prediction capability of different drug properties is done and they are ranked as SS GEX PS 17MD. Additionally, the visualization and analysis of drug function co-occurrences signify the appropriateness of the proposed framework for drug function co-occurrence detection and in signaling the new possible drug leads where the detection rate varies from 94.34% to 99.61%.


[Doctor reports of a neurological clinic in the view of permanent resident neurologists and nerve doctors].
Eight discharge reports involving five diagnoses (anterior territory ischemic stroke, epilepsy, Parkinson's syndrome, multiple sclerosis, polyneuropathy) from five neurological departments were peer-reviewed by five neurologists working in out-patient (private) practice. The review considered the diagnosis, case history, clinical status, laboratory investigation, differential diagnosis and treatment. Criticism mainly involved the quality of the clinical assessment, lack of clinical status at discharge, narrow or incomplete differential diagnosis and the quality of the neurophysiological investigations for epilepsy and polyneuropathy. Improvement potential was seen for the speed of reporting, better comprehensibility, omission of irrelevant information, greater participation of experienced neurologists in report writing, and standardization.


Comparison of tethered star and linear poly(ethylene oxide) for control of biomaterials surface properties.
Four different poly(ethylene oxide) [PEO] molecules were compared as grafted polymer layers for biomaterials' substrates: two linear polymers and two star polymers. Conditions maximizing surface coverage for each molecule were employed with the aim of inhibiting protein adsorption and increasing the density of end groups. Neutron reflectivities of the grafted layers immersed in deuterium oxide (heavy water) were measured and used to calculate volume fraction profiles of the polymer as a function of distance from the surface. These density profiles were combined with protein adsorption data on the grafted layers to compare with recent theoretical and experimental studies of protein resistance by PEO at surfaces. We found that the grafting density is maximized by coupling the linear PEO from a K2SO4 salt buffer, which is a poor solvent for PEO. However, the grafting density of star PEO was maximized when no K2SO4 was used and the stars were dissolved near the overlap concentration. Concentration profiles obtained from the reflectivity data show that the hydrated polymers swell to approximately 10 times the dried layer thickness and exhibit a low density (maximum volume fractions < 0.4 PEO) throughout the layer. The PEO surfaces obtained with both the star and linear polymers resisted adsorption of cytochrome-c and albumin except for a small amount of cytochrome-c adsorption on the short, many-armed star polymer surface. A hypothesis of adsorption on the star polymer layer is presented and criteria for controlling receptor-mediated cell-substrate interactions by ligand-modified chain ends are discussed.


[AGE receptor: a novel pro-inflammatory pathway for chronic respiratory disorders?].
Interstitial pneumonites represent a heterogeneous group of respiratory disorders with known causes or idiopathic, in which alveolar injury is followed by defense and repair mechanisms either with pro- and anti-inflammatory properties. It is hypothetised that common factors would orchestrate such events, and RAGE is one of possible such candidates. Implications connected to RAGE pathway in varying interstitial pneumonites are discussed.


ModulAR: eye-controlled vision augmentations for head mounted displays.
In the last few years, the advancement of head mounted display technology and optics has opened up many new possibilities for the field of Augmented Reality. However, many commercial and prototype systems often have a single display modality, fixed field of view, or inflexible form factor. In this paper, we introduce Modular Augmented Reality (ModulAR), a hardware and software framework designed to improve flexibility and hands-free control of video see-through augmented reality displays and augmentative functionality. To accomplish this goal, we introduce the use of integrated eye tracking for on-demand control of vision augmentations such as optical zoom or field of view expansion. Physical modification of the device's configuration can be accomplished on the fly using interchangeable camera-lens modules that provide different types of vision enhancements. We implement and test functionality for several primary configurations using telescopic and fisheye camera-lens systems, though many other customizations are possible. We also implement a number of eye-based interactions in order to engage and control the vision augmentations in real time, and explore different methods for merging streams of augmented vision into the user's normal field of view. In a series of experiments, we conduct an in depth analysis of visual acuity and head and eye movement during search and recognition tasks. Results show that methods with larger field of view that utilize binary on/off and gradual zoom mechanisms outperform snapshot and sub-windowed methods and that type of eye engagement has little effect on performance.


Reward system and temporal pole contributions to affective evaluation during a first person shooter video game.
Violent content in video games evokes many concerns but there is little research concerning its rewarding aspects. It was demonstrated that playing a video game leads to striatal dopamine release. It is unclear, however, which aspects of the game cause this reward system activation and if violent content contributes to it. We combined functional Magnetic Resonance Imaging (fMRI) with individual affect measures to address the neuronal correlates of violence in a video game. Thirteen male German volunteers played a first-person shooter game (Tactical Ops: Assault on Terror) during fMRI measurement. We defined success as eliminating opponents, and failure as being eliminated themselves. Affect was measured directly before and after game play using the Positive and Negative Affect Schedule (PANAS). Failure and success events evoked increased activity in visual cortex but only failure decreased activity in orbitofrontal cortex and caudate nucleus. A negative correlation between negative affect and responses to failure was evident in the right temporal pole (rTP). The deactivation of the caudate nucleus during failure is in accordance with its role in reward-prediction error: it occurred whenever subject missed an expected reward (being eliminated rather than eliminating the opponent). We found no indication that violence events were directly rewarding for the players. We addressed subjective evaluations of affect change due to gameplay to study the reward system. Subjects reporting greater negative affect after playing the game had less rTP activity associated with failure. The rTP may therefore be involved in evaluating the failure events in a social context, to regulate the players' mood.


Prevalence of fatigue in patients 3 months after stroke and association with early motor activity: a prospective study comparing stroke patients with a matched general population cohort.
Fatigue is a common complaint after stroke. Reasons for higher prevalence are still unclear. This study aimed to determine if fatigue prevalence in stroke patients is different to that of age and gender matched general population controls, and to explore whether early motor activity was associated with reduced likelihood of fatigue three months after stroke. This was a prospective multicenter cohort study of stroke patients admitted to eleven regional Norwegian hospitals, within 14 days after stroke. Stroke patients (n = 257) were age and gender matched to participants in a general population health survey (HUNT3-survey) carried out in a regional county of central Norway. The single-item fatigue questionnaire from the HUNT3-survey was administered to both groups to compare prevalence. The association between early motor activity (time in bed, time sitting out of bed, and time upright) and fatigue at three months after stroke (Fatigue Severity Scale) was tested with logistic regression. Simple models including each activity outcome, with adjustment for stroke severity and pre-stroke function, were tested, as well as a comprehensive model that included additional independent variables of depression, pain, pre-stroke fatigue, age and gender. Prevalence was higher after stroke compared with the general population: 31.1% versus 10.9%. In the simple regression models, none of the early motor activity categories were associated with fatigue three months after stroke. In the comprehensive model, depression, pain and pre-stroke fatigue were significantly associated with post-stroke fatigue. Time in bed through the daytime during hospital stay approached statistical significance (p = 0.058) with an odds ratio for experiencing fatigue of 1.02 (95% CI 1.00-1.04) for each additional 5.4 minutes in bed. Stroke patients had higher prevalence of fatigue three months after stroke than the age and gender matched general population sample, which may be partly explained by the stroke population being in poorer health overall. The relationship between early motor activity (and inactivity) and fatigue remains unclear. Further research, which may help drive development of new treatments to target this challenging condition, is needed.


Successful management of spontaneous intracranial hypotension with epidural blood patch.
Spontaneous intracranial hypotension (SIH) is characterised by postural headache and a cerebrospinal fluid (CSF) pressure of ≤6 cmH20 measured with the patient in the lateral decubitus position. Other symptoms include tinnitus, altered hearing, diplopia, photophobia, nausea and neck stiffness, and must not have occurred within a month of dural puncture. Symptoms typically remit after normalisation of CSF pressure or successful sealing of the CSF leak. An epidural blood patch (EBP) is a treatment option in those who have not responded to bed rest, fluids, non-steroidal anti-inflammatories or caffeine. We present a case of SIH successfully treated with both conservative measures and EBP. We compare our case with similar cases in the literature and summarise what is known about EBP for SIH to help clinicians take a more informed approach to managing such patients.


Roughness induced backscattering in optical silicon waveguides.
We report on the direct observation of backscattering induced by sidewall roughness in high-index-contrast optical waveguides based on total internal reflection. Our results demonstrate that backscattering is one of the most severe limiting factors in state-of-the art silicon on insulator nanowires employed in densely integrated photonics. We also derive the general relationship between backscattering and geometrical and optical parameters of the waveguide. Further, the role of roughness in polarization rotation and coupling with higher-order modes is pointed out.


RNAi screening identifies Trypanosoma brucei stress response protein kinases required for survival in the mouse.
Protein kinases (PKs) are a class of druggable targets in Trypanosoma brucei, the causative agent of Human African Trypanosomiasis (sleeping sickness), yet little is known about which PKs are essential for survival in mammals. A recent kinome-wide RNAi screen with 176 individual bloodstream form Trypanosoma brucei lines identified PKs required for proliferation in culture. In order to assess which PKs are also potential virulence factors essential in vivo, lines were pooled, inoculated into mice, and screened for loss of fitness after 48 h RNAi. The presence of trypanosomes in the bloodstream was assessed using RNAi target sequencing (RITseq) and compared to growth in culture. We identified 49 PKs with a significant loss of fitness in vivo in two independent experiments, and a strong correlation between in vitro and in vivo loss of fitness for the majority. Nine PKs had a more pronounced growth defect in vivo, than in vitro. Amongst these PKs were several with putative functions related to stress responses mediated through the PI3K/TOR or MAPK signaling cascades, which act to protect the parasite from complement-mediated and osmotic lysis. Identification of these virulence-associated PKs provides new insights into T. brucei-host interaction and reveals novel potential protein kinase drug targets.


Clinical Validation of the Surface Volume Coefficient for Minimally Invasive Treatment of the Temple
Objective: The aim of the present study is to compare the temporal surface volume coefficient obtained in the cadaveric model from subdermal and supraperiosteal injections to the clinical setting when treating temporal hollowing. Material and Methods: A total of 36 subjects were included in this investigation, 17 patients (16 females, 1 male; 46.3 ± 8.9 years; 25.5 ± 2.8 kg/m2) and 19 cadaveric specimens (11 females, 8 males; 76.4 ± 11.5 years; 24.0 ± 5.1 kg/m2). Subdermal and supraperiosteal injections were performed and live subjects were evaluated and followed for 12 months. The surface volume coefficients were calculated using 3D surface volume scanning and compared for validity. Results: No statistically significant difference was detected between the clinical outcome scores of the subdermal vs supraperiosteal injection technique. The supraperiosteal injection technique utilized significantly more product 1.20 ± 0.5 cc [range: 0.50 – 2.6 cc] compared to the subdermal 0.71 ± 0.2 cc [range: 0.30 – 1.20 cc] vs with P< 0.001. This difference was consistent with the different values of the cadaveric surface volume coefficient (subdermal vs supraperiosteal): 1.00 ± 0.2 vs 0.70 ± 0.2. At 12-month follow-up, the product loss was 19% for the subdermal injection and 21% for patients treated with supraperiosteal injections. Conclusion: The results of the study support the clinical validity of the surface volume coefficient. They demonstrate that the different injection volumes necessary to deliver aesthetically appealing results when utilizing the subdermal vs the supraperiosteal technique can be explained by the region-specific surface volume coefficient. J Drugs Dermatol. 2019;18(6):533-540.


Natural Products as Modulators of CES1 Activity.
Carboxylesterase (CES) 1 is the predominant esterase expressed in the human liver and is capable of catalyzing the hydrolysis of a wide range of therapeutic agents, toxins, and endogenous compounds. Accumulating studies have demonstrated associations between the expression and activity of CES1 and the pharmacokinetics and/or pharmacodynamics of CES1 substrate medications (e.g., methylphenidate, clopidogrel, oseltamivir). Therefore, any perturbation of CES1 by coingested xenobiotics could potentially compromise treatment. Natural products are known to alter drug disposition by modulating cytochrome P450 and UDP-glucuronosyltransferase enzymes, but this issue is less thoroughly explored with CES1. We report the results of a systematic literature search and discuss natural products as potential modulators of CES1 activity. The majority of research reports reviewed were in vitro investigations that require further confirmation through clinical study. Cannabis products (Δ 9-tetrahydrocannabinol, cannabidiol, cannabinol); supplements from various plant sources containing naringenin, quercetin, luteolin, oleanolic acid, and asiatic acid; and certain traditional medicines (danshen and zhizhuwan) appear to pose the highest inhibition potential. In addition, ursolic acid, gambogic acid, and glycyrrhetic acid, if delivered intravenously, may attain high enough systemic concentrations to significantly inhibit CES1. The provision of a translational interpretation of in vitro assessments of natural product actions and interactions is limited by the dearth of basic pharmacokinetic data of the natural compounds exhibiting potent in vitro influences on CES1 activity. This is a major impediment to assigning even potential clinical significance. The modulatory effects on CES1 expression after chronic exposure to natural products warrants further investigation. SIGNIFICANCE STATEMENT: Modulation of CES1 activity by natural products may alter the course of treatment and clinical outcome. In this review, we have summarized the natural products that can potentially interact with CES1 substrate medications. We have also noted the limitations of existing reports and outlined challenges and future directions in this field.


Isolation and transcriptional analysis of a cellulase gene (cell) from the basidiomycete Irpex lacteus.
A gene (named cell) homologous to the cellobiohydrolase I gene (cbhl) of Trichoderma reesei was isolated and sequenced from the white rot basidiomycete Irpex lacteus MC-2. The cell open reading frame consists of 1551 bp, which is interrupted by two introns, encoding a polypeptide of 517 amino acid residues with a calculated molecular mass of 54,522 Da. The deduced amino acid sequence showed that CEL1 (the protein encoded by cell) has a modular structure consisting of a catalytic domain of 449 amino acids and a C-terminal cellulose-binding domain (CBD) of 36 amino acids separated by a proline-, serine-, threonine-rich linker region of 32 amino acids. The CEL1 catalytic domain is homologous with fungal cellobiohydrolases (CBHs) belonging to family 7 of the glycosyl hydrolases. The transcription of cell was induced in the presence of various cellulosic substrates and repressed by glucose. It was therefore concluded that the reported sequence represents the first cellulase gene isolated from the basidiomycete Irpex.


Modulation of human Niemann-Pick C1-like 1 gene expression by sterol: Role of sterol regulatory element binding protein 2.
Niemann-Pick C1-like 1 (NPC1L1) is an essential intestinal component of cholesterol absorption. However, little is known about the molecular regulation of intestinal NPC1L1 expression and promoter activity. We demonstrated that human NPC1L1 mRNA expression was significantly decreased by 25-hydroxycholesterol but increased in response to cellular cholesterol depletion achieved by incubation with Mevinolin (an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase) in human intestinal Caco-2 cells. We also showed that a -1741/+56 fragment of the NPC1L1 gene demonstrated high promoter activity in Caco-2 cells that was reduced by 25-hydroxycholesterol and stimulated by cholesterol depletion. Interestingly, we showed that the NPC1L1 promoter is remarkably transactivated by the overexpression of sterol regulatory element (SRE) binding protein (SREBP)-2, suggesting its involvement in the sterol-induced alteration in NPC1L1 promoter activity. Finally, we identified two putative SREs in the human NPC1L1 promoter and established their essential roles in mediating the effects of cholesterol on promoter activity. Our study demonstrated the modulation of human NPC1L1 expression and promoter activity by cholesterol in a SREBP-2-dependent mechanism.


Management of pancreatic walled-off necrosis using an ultrasonic pneumatic lithotripsy system and double-catheter aspirated lavage performed through drainage tract: a case report.
Patients with pancreatic walled-off necrosis (WON) treated by minimally invasive approaches often require repeated necrosectomy instead of conventional open necrosectomy. A 55-year-old woman with lateral infected pancreatic WON was successfully treated by an infrequently used technique involving an ultrasonic pneumatic lithotripsy system (UPLS) and double-catheter aspirated lavage through a percutaneous drainage tract. No perioperative complications occurred. The mean operating time of the repeated procedures was 35 minutes (range, 25-48 minutes). The total hospitalization stay was 46 days, and no recurrence of the fluid collection was observed during the 15-month follow-up period. UPLS-assisted necrosectomy and double-catheter aspirated lavage is an alternative technique for lateral WON that fails to improve by percutaneous drainage. It efficiently combines disintegration and aspiration procedures and can be safely repeated under total intravenous anesthesia through sinus tracts.


Collaborating for Community Health.
The Greensboro Housing Coalition was founded 27 years ago to advocate for fair, safe, decent, and affordable housing for low- to moderate-income individuals. We advocate in 4 primary service areas: foreclosure prevention/homeowner counseling, homelessness prevention/ rental housing counseling, healthy homes, and our Community Centered Health Initiative.


Biochemical characterization and 1H NMR based metabolomics revealed Melicope lunu-ankenda leaf extract a potent anti-diabetic agent in rats.
Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by continuous hyperglycemia associated with insulin resistance and /or reduced insulin secretion. There is an emerging trend regarding the use of medicinal plants for the treatment of diabetes mellitus. Melicope lunu-ankenda (ML) is one of the Melicope species belonging to the family Rutaceae. In traditional medicines, its leaves and flowers are known to exhibit prodigious health benefits. The present study aimed at investigating anti-diabetic effect of Melicope lunu-ankenda (ML) leaves extract. In this study, anti-diabetic effect of ML extract is investigated in vivo to evaluate the biochemical changes, potential serum biomarkers and alterations in metabolic pathways pertaining to the treatment of HFD/STZ induced diabetic rats with ML extract using 1H NMR based metabolomics approach. Type 2 diabetic rats were treated with different doses (200 and 400 mg/kg BW) of Melicope lunu-ankenda leaf extract for 8 weeks, and serum samples were examined for clinical biochemistry. The metabolomics study of serum was also carried out using 1H NMR spectroscopy in combination with multivariate data analysis to explore differentiating serum metabolites and altered metabolic pathways. The ML leaf extract (400 mg/kg BW) treatment significantly increased insulin level and insulin sensitivity of obese diabetic rats, with concomitant decrease in glucose level and insulin resistance. Significant reduction in total triglyceride, cholesterol and low density lipoprotein was also observed after treatment. Interestingly, there was a significant increase in high density lipoprotein of the treated rats. A decrease in renal injury markers and activities of liver enzymes was also observed. Moreover, metabolomics studies clearly demonstrated that, ML extract significantly ameliorated the disturbance in glucose metabolism, tricarboxylic acid cycle, lipid metabolism, and amino acid metabolism. ML leaf extract exhibits potent antidiabetic properties, hence could be a useful and affordable alternative option for the management of T2DM.


State-Specific Prevalence of Severe Obesity Among Adults in the US Using Bias Correction of Self-Reported Body Mass Index.
Adults with severe obesity are at increased risk for poor metabolic health and may need more intensive clinical and community supports. The prevalence of severe obesity is underestimated from self-reported weight and height data. We examined severe obesity prevalence among US adults by sociodemographic characteristics and by state after adjusting for self-report bias. Using a validated bias-correction method, we adjusted self-reported body mass index (BMI) data from the 2020 Behavioral Risk Factor Surveillance System (BRFSS) by using measured data from the National Health and Nutrition Examination Survey. We compared bias-corrected prevalence of severe obesity (BMI ≥40) with self-reported estimates by sociodemographic characteristics and state. Self-reported BRFSS data significantly underestimated the prevalence of severe obesity compared with bias-corrected estimates. In 2020, 8.8% of adults had severe obesity based on the bias-corrected estimates, whereas 5.3% of adults had severe obesity based on self-reported data. Women had a significantly higher prevalence of bias-corrected severe obesity (11.1%) than men (6.5%). State-level prevalence of bias-corrected severe obesity ranged from 5.5% (Massachusetts) to 13.2% (West Virginia). Based on bias-corrected estimates, 16 states had a prevalence of severe obesity greater than 10%, a level not seen in the self-reported estimates. Self-reported BRFSS data underestimated the overall prevalence of severe obesity by 40% (5.3% vs 8.8%). Accurate state-level estimates of severe obesity can help public health and health care decision makers prioritize and plan to implement effective prevention and treatment strategies for people who are at high risk for poor metabolic health.


Isolation and Characterization of Stress-Tolerant Priestia Species from Cowpea Rhizosphere Under Drought and Nutrient Deficit Conditions.
This study aimed to isolate stress-tolerant phytobeneficial bacteria as bio-inoculants for cowpea's sustainable growth under drought and nutrient deficiency conditions. However, the application successful of phytobeneficial bacteria is subject to effective in vitro screening under different physiological conditions. We isolated several Priestia species from cowpea rhizosphere that tolerates polyethylene glycol (PEG6000)-induced drought and nutrient deficiency. Of them, C8 (Priestia filamentosa; basonym: Bacillus filamentosus), followed by C29 (Priestia aryabhattai; basonym: Bacillus aryabhattai), tolerated up to 20% PEG in a low-nutrient medium. In the presence of PEG, Priestia filamentosa and Bacillus aryabhattai exhibited optimal growth in different temperatures and pH but failed to survive at extreme temperatures of 45 °C and pH 11. Priestia filamentosa preferred L-proline and L-glutamate, while L-tryptophan and L-tyrosine were the least utilized. Interestingly, Priestia filamentosa and Bacillus aryabhattai used more complex nitrogen sources, peptone, and yeast extract, than inorganic nitrogen for growth. Most importantly, under drought and nutrient deficiency, Priestia filamentosa exhibited multiple plant growth-promoting traits and more amylase and protease production than C29. Our results indicate that Priestia filamentosa is a potential bacterium to enhance the growth of cowpea plants under stressful conditions.


The development of random DNA probes specific for Aeromonas salmonicida.
RAPD-PCR has been used to produce DNA probes for Aeromonas salmonicida. DNA hybridization studies showed that RAPD-PCR fragments of the same size did not necessarily hybridize to each other and therefore these sequences were not always homologous. However, a single RAPD-PCR fragment (designated 15e) was identified as being common to Aer. salmonicida. Subsequently, 15e was found to comprise five DNA fragments of similar size which differed in their nucleotide sequences. All five fragments were evaluated as DNA probes for the specific detection of Aer. salmonicida DNA: two hybridized specifically to DNA of all Aer. salmonicida isolates tested, including the four current subspecies and atypical isolates; one hybridized to subspecies salmonicida, achromogenes and masoucida, but not subspecies smithia; one hybridized to subspecies salmonicida and achromogenes, but not subspecies masoucida or smithia; and one hybridized to subspecies salmonicida, achromogenes and smithia, but not subspecies masoucida. It is believed that these fragments could be useful as non-radioactive probes for the safe and rapid diagnosis of these fish pathogens.


Hyperlipasemia in 6 dogs with pancreatic or hepatic neoplasia: evidence for tumor lipase production.
Amarked increase in serum pancreatic lipase (PL) activity with minimal concurrent increase in serum alpha-amylase activity was observed in 6 dogs with pancreatic or hepatic neoplasia. Serum PL activity ranged from 5410 U/L to 42,900 U/L, 11 to 93 times the upper reference limit for our laboratory. Neoplasms included pancreatic adenocarcinoma (n=3), endocrine carcinoma (n=2), and hepatic carcinoma of unknown origin (n=1). Tumor tissue and normal canine pancreatic tissue were stained histochemically with diastase periodic acid-Schiff to demonstrate zymogen granule content, and immunohistochemically with human monoclonal antibody for PL. Normal canine pancreatic tissue stained positive for both zymogen granule content and PL. Five of the 6 tumors stained positive for zymogen granule content, and 2 of the 6 tumors stained positive for PL. Together, the histochemical and immunohistochemical staining patterns suggested tumor PL production in 5 of the 6 dogs. Marked, unexplained hyperlipasemia may be a noninvasive indicator and biochemical marker for neoplasia of the pancreas and liver in dogs.


Long-term survival after a favorable response to anti-EGFR antibody plus chemotherapy to treat bone marrow metastasis: a case report of KRAS-wildtype rectal cancer.
Bone marrow metastasis is a rare consequence of colorectal cancer that results in a poor prognosis; few reports describe a favorable response to doublet chemotherapy combined with targeted therapy, which is currently the standard treatment. We experienced a case where anti-epidermal growth factor receptor (EGFR) antibody produced a marked anti-tumor response to bone marrow metastasis that led to long-term survival. A 51-year-old man was diagnosed with a primary KRAS-wildtype rectal cancer with multiple metastases, including the bone marrow. Disease control was achieved for 10.8 months following chemotherapy with a modified FOLFOX6 regimen combined with an anti-EGFR antibody. He died of cancer 22.7 and 16.6 months after disease onset and first-line chemotherapy, respectively. This case shows that early tumor shrinkage and deepness of response to the anti-EGFR antibody were observed even in a patient with bone marrow metastasis. Anti-EGFR antibody therapy should therefore be considered even when a patient's medical condition appears to be poor owing to bone marrow metastasis. Moreover, tumors that are likely to be sensitive to chemotherapy, such as RAS-wildtype colorectal cancers, can be considered for anti-EGFR antibody therapy even if the patient is considered unfit for chemotherapy.


Molecular changes in Trypanosoma evansi after treatment against trypanosomosis.
Neither physiological nor pathological changes following treatments explained why trypanosomes in the same group of experimentally treated animals correlated in virulence. Also, they behaved like each other but not similar to other groups despite the same T. evansi injected strain. The current study aims to discuss whether molecular changes might occur to Trypanosoma evansi isolates followed treatments are responsible for that difference or not. Ten preserved isolates from T. evansi after previous treatments besides the original strain of T. evansi that injected before treatments were used in the present study. These isolates were intraperitoneally inoculated in 11 groups of male Wister Albino rats with equal doses. Parasitological findings and the molecular changes accompanied were discussed along with the experiment based on PCR-TR3/TR4 specific-primers. The study also achieved alignments, gene sequence and phylogenetic analysis for submitted and reference strains belong to T. evansi, T. brucei, T. b. brucei, and T. b. gambiense deposited in GenBank. The present results assessed molecularly the effectiveness and highly antitrypanosomal activity of human plasmas O+ and A+ on T. evansi than others, and how their strains drifted from its original sequence to the nearest form of T. brucei. At the same time, T. evansi in other plant extract groups multiplied progressively like cancer cells and became more virulent and close to reference strains of T. evansi. Our data further indicated that T. evansi after treatment was a paraphyletic group. It also corroborated the antitrypanosomal activityspecificity and the molecular changes occurring were correlated to the type of treatment.


Human placenta mesenchymal stem cells suppress airway inflammation in asthmatic rats by modulating Notch signaling.
Neurogenic locus notch homolog protein (Notch) signaling mediates intracellular communication and may regulate cell fate decisions, including cell proliferation, differentiation, and apoptosis. Mesenchymal stem cells (MSCs) possess immunomodulatory properties and the potential for use in stem cell replacement treatments. The aim of the present study was to evaluate the therapeutic effects of human placenta‑deviated MSCs (hPMSCs) in asthma and to investigate the mechanisms of Notch signaling mediated by transplanted MSCs. A Sprague‑Dawley rat ovalbumin (OVA)‑sensitized acute asthma model was established and challenged. MSCs derived from human placenta (hPMSCs) were transplanted into the asthmatic rats. Transplantation resulted in reduced Notch‑1, Notch‑2 and jagged‑1, and increased Notch‑3, Notch‑4 and delta‑like ligand (delta)‑4 expression in lung, blood, and lymph samples. Notch‑1, Notch‑2, and jagged‑1 expression in OVA‑treated rats was significantly decreased compared with controls and hPMSC‑treated rats; however, Notch‑3, Notch‑4 and delta‑4 expression was significantly increased. Serum interferon‑γ significantly increased after hPMSCs transplantation, whereas interleukin‑4 and immunoglobulin E decreased. In OVA‑treated rats, Notch‑1, Notch‑2 and jagged‑1 levels were increased in the lymph compared with the blood, although Notch‑4 and delta‑4 levels were decreased. Peribronchial infiltration of cells and goblet cell hyperplasia were markedly decreased in the OVA + hPMSCs group compared with those in the OVA‑treated and control groups. Alterations in Notch signaling pathway expression were accompanied by decreased inflammatory cell infiltration, goblet cell hyperplasia and mucus production in lung tissues. The results of the present study are consistent with hPMSC suppression of asthma symptoms and inflammation by regulating the Notch signaling pathway in the rat asthma model.


Vascular Development and Regeneration in the Mammalian Heart.
Cardiovascular diseases including coronary artery disease are the leading cause of death worldwide. Unraveling the developmental origin of coronary vessels could offer important therapeutic implications for treatment of cardiovascular diseases. The recent identification of the endocardial source of coronary vessels reveals a heterogeneous origin of coronary arteries in the adult heart. In this review, we will highlight recent advances in finding the sources of coronary vessels in the mammalian heart from lineage-tracing models as well as differentiation studies using pluripotent stem cells. Moreover, we will also discuss how we induce neovascularization in the damaged heart through transient yet highly efficient expression of VEGF-modified mRNAs as a potentially therapeutic delivery platform.


Characterization of monoclonal antibodies specific to bovine renal vitamin D hydroxylases.
Monoclonal antibodies (MAbs) have been produced which recognize specific epitopes on bovine renal mitochondrial vitamin D3 1 alpha- and 24-hydroxylases. Renal mitochondria cytochrome P-450s were partially purified to 0.5-2 nmol/mg by Emulgen 911 and cholate solubilization, followed by chromatography on a 2-(4,6-dichloro-O-biphenyloxy)ethylamine HBR affinity column. Reduced carbon monoxide difference spectra determined that this preparation contained 0.5-2 nmol P-450/mg protein. This preparation contained both 1 alpha- and 24-hydroxylase activities, and Eadie-Hofstee plots of product formation as a function of substrate concentrations have maximum velocities of 1.4 and 4 pmol product/30 min.mg protein and Km values of 690 and 1300 nM, respectively. Bovine renal hydroxylases were isolated by immunoprecipitation from this partially purified P-450 preparation with a polyclonal antibody specific for rat liver microsomal cytochrome P-450 RLM5. This polyclonal antibody immunoprecipitated both 1 alpha- and 24-hydroxylase activities as well as renal mitochondrial cytochrome P-450, as determined by reduced CO spectra. Bovine renal mitochondrial components were immunoisolated and used to immunize BALB/c mouse spleen cells in vitro. MAbs then produced were screened for 1) immunoisolation of renal mitochondrial hydroxylase activity from a partially purified preparation, 2) immunohistochemical detection of antigen in renal proximal tubule cells, and 3) immunoquantitation of renal hydroxylases in a solid phase sandwich (enzyme-linked immunosorbent assay) and by 4) Western blot analysis. MAbs were isolated with specifically immunoprecipitated 1 alpha-hydroxylase activity, 24-hydroxylase activity, or both. In 10 micron sections of bovine kidney, antibodies detected antigen only in proximal tubule cells on the basal surface, which is rich in mitochondria. No antigen was detected in sections of pancreas or liver. In the solid phase sandwich enzyme-linked immunosorbent assay, MAbs detected 1 alpha and 24-hydroxylases only in renal mitochondria and not in liver microsomes or adrenal gland mitochondria. In a Western blot, MAbs specific for epitopes expressed on both hydroxylases detected a single band(s) at 52,000-53,000 daltons. Apparently it is not possible to discriminate between hydroxylases by sodium dodecyl sulfate-polyacrylamide gel electrophoresis Western blots. By these criteria, MAbs have been generated which are specific to epitopes expressed on bovine renal mitochondrial 1 alpha- and 24-hydroxylases.


Bifidobacterium lactis in Treatment of Children with Acute Diarrhea. A Randomized Double Blind Controlled Trial.
Probiotics are becoming increasingly popular treatment for children diarrhea. Although there are several probiotic strains potentially useful, researches were often limited to certain strains. To test Bifidobacterium lactis on morbidity of acute diarrhea in children less than 2 years. A randomized double-blind controlled clinical trial was conducted in 50 children (1 - 23 months) admitted with acute diarrhea to the Pediatric Hospital, Cairo University and were randomly assigned to receive in addition to usual treatment of diarrhea according to WHO guidelines; one of two treatments either milk formula non-supplemented (n = 25) or supplemented (n = 25) with Bifidobacterium lactis 14.5 × 10(6) CFU/100 ml daily for one week. Primary outcomes were frequency and duration of diarrhea and hospital stay. Secondary outcomes were duration of fever and vomiting episodes. Safety and tolerance were also recorded. On admission, patients' characteristics of both groups (50 cases) were similar. For children who received the probiotics for one week; mean duration of diarrhoea was shorter than in controls (3.12 ± 0.92 vs. 4.10 ± 0.94 days) (P = 0.02), number of motions per day was less than in controls (3.96 ± 0.62 vs. 4.46 ± 0.85) (P = 0.04) and discharge from hospital <2 days was more frequent than in controls (72% vs. 44%) (P = 0.048). There was no effect on fever (P = 0.63) or vomiting (P = 0.54). Bifidobacterium lactis probiotics in supplemented milk formula decreased significantly frequency, duration of diarrhea, and hospital stay than usual treatment alone in children with acute diarrhea. Additional researches on other uncommon local probiotic species should be encouraged.


Efficiency in extracorporeal membrane oxygenation-cellular deposits on polymethylpentene membranes increase resistance to blood flow and reduce gas exchange capacity.
Bioline-coated polymethylpentene (PMP) membrane oxygenators (MO) are used for extracorporeal membrane oxygenation (ECMO) to improve gas exchange in patients with severe acute respiratory distress syndrome (ARDS). However, in some patients, long-term durability is limited due to fibrous and cellular accumulations on the gas exchange surface which can increase resistance to blood flow and diffusion path. These surface deposits of PMP MO after removal were studied with scanning electron and fluorescence microscopy techniques. Three of 31 patients supported by a PMP MO in an ECMO setting required a replacement of the oxygenator after a mean support interval of 11 +/- 7 days due to an increase in flow resistance and an impairment of the gas exchange capacity. The membrane surface of the MO was covered with a fibrous network with imbedded platelets and red blood cells. A membranous structure composed of single cells and clusters of cells covered large areas of the PMP fibers. We assume that these cellular deposits lower the efficacy of ECMO. The identification of these cells could be a key for future therapeutic interventions and improvements in the development of MO.


MORPHOLOGICAL EVOLUTION MEDIATED BY BEHAVIOR IN THE DAMSELFLIES OF TWO COMMUNITIES.
Behavior can play a mediating role in determining the selective pressures that influence the evolution of morphological structures. To examine this, I quantified patterns of morphological variation among larvae of Enallagma damselfly species (Odonata: Coenagrionidae) that use different behaviors to avoid the major predators found in each of two communities, lakes with and without fish. Specifically, I quantified the sizes and shapes of the abdomens and caudal lamellae (used for swimming) and legs for three species from fishless lakes and six species from lakes with fish. A preliminary cladistic analysis indicates that species within each lake type are not members of a single clade, which supports the conclusions of previous odonate taxonomists. Previous studies have shown that species in fishless lakes are very active, running and swimming frequently and at high rates of speed in the absence of predators, and they avoid their primary predators, large dragonflies, by swimming. These species have the widest abdomens, the largest caudal lamellae relative to overall body size, and the longest legs of the species studied, which should make them powerful swimmers and runners. Furthermore, species in fishless lakes are morphologically very similar to one another and differ greatly from fish-lake species, although each is more closely related to species in fish lakes. In contrast, species from lakes with fish move very slowly and infrequently in the absence of predators and do not attempt to evade attacking predators. However, despite their behavioral similarity, large interspecific variation in morphology exists among the fish-lake species, and the only morphological patterns were differences associated with membership in the two primary clades identified in the cladistic analysis. A modification of Felsenstein's (1985) method of evolutionary contrasts which allows character change to be isolated along single branches is introduced and is used to reconstruct the evolutionary histories of these characters. This analysis suggests that large increases in caudal lamella size, abdominal segment lengths and widths, and leg length accompany speciation events associated with habitat shifts from fish-lakes to fishless lakes. Following habitat shifts selection pressures exerted by dragonfly predation apparently favored swimming as an escape tactic, which mediated selection pressures onto morphologies used in swimming to increase swimming performance; morphological patterns in extant species reflect this adaptation to a new environment. Mechanisms by which behaviorally mediated selection could have accelerated evolutionary dynamics following founder events are discussed.


Enhancing care for transfusion patients.
Frequent hospital attendance and excessive waiting times for treatments are often part of haematological patient care. Home platelet transfusions reduced hospital visits for patients. Hospital waiting times decreased and the quality of care improved.


Alternative Splicing of the Flip/Flop Cassette and TARP Auxiliary Subunits Engage in a Privileged Relationship That Fine-Tunes AMPA Receptor Gating.
Alternative splicing of AMPA-type glutamate receptors (AMPARs) and allosteric modulation by auxiliary subunits, such as transmembrane AMPAR regulatory proteins (TARPs), are two important mechanisms that regulate the time course of glutamatergic neurotransmission. Prior work has shown that alternative splicing of the flip/flop cassette profoundly regulates TARP γ2 modulation, where flip receptor gating exhibits robust sensitivity to TARPs while flop isoforms are relatively insensitive to TARP modulation. Whether this splice variant-specific regulation extends to other auxiliary subunit families, such as cornichons (CNIHs), GSG1L, or CKAMPs, remains unknown. Here, we demonstrate that CNIH-3 modulation is unaffected by AMPAR alternative splicing due to inherent differences in how CNIH-3 and TARP γ2 modify channel gating. CNIH-3 slows receptor deactivation from the outset of current decay, consistent with structural evidence showing its point of contact at the level of the pore. In contrast, TARP γ2 acts via the KGK site of the ligand-binding domain (LBD) to slow the onset of desensitization. Although GSG1L and CKAMP44 primarily slow recovery from desensitization, their effects on channel gating are unaffected by alternative splicing, further underlining that structural events leading to the onset and recovery from desensitization are separable. Together, this work establishes that alternative splicing and TARP auxiliary subunits form a unique partnership that governs fast glutamatergic signaling at central synapses. Since proteomic studies suggest that all native AMPARs co-assemble with at least two TARPs, allosteric coupling between the flip/flop cassette and TARPs may represent a common design element in all AMPAR complexes of the mammalian brain.SIGNIFICANCE STATEMENT All fast excitatory neurotransmission in the mammalian brain is mediated by AMPA-type glutamate receptors (AMPARs). The time course of AMPAR gating can be regulated by two distinct mechanisms: alternative splicing of the flip/flop cassette and association with auxiliary subunits. Although these regulatory mechanisms have been well studied individually, it is not clear whether alternative splicing impacts auxiliary protein modulation of AMPARs. Here, we compare the four main families of AMPAR auxiliary subunits, transmembrane AMPAR regulatory proteins (TARPs; γ2), cornichons (CNIH-3), GSG1L and CKAMPs (CKAMP44), and find a privileged relationship between TARPs and the flip/flop cassette that is not shared by others. The flop cassette acts as a master switch to override TARP action, and this coupling represents a way to fine-tune AMPAR signaling.


Magnetic-field dependence of the anomalous noise behavior in a two-dimensional electron system in silicon.
Studies of low-frequency resistance noise show that the dramatic change in the dynamics of the two-dimensional electron system (2DES) in Si that occurs near the metal-insulator transition (MIT) persists in high parallel magnetic fields B such that the 2DES is fully spin polarized. This strongly suggests that charge, as opposed to spin, degrees of freedom are responsible for this effect. In the metallic phase, however, noise is suppressed by a parallel B, pointing to the role of spins. At low B, the temperature dependence of conductivity in the metallic phase provides evidence for a MIT.


Mosaicism or pseudomosaicism: the problem of hypermodal cells in amniotic fluid cell culture.
A series of 2029 consecutive amniotic fluid specimens studied for prenatal genetic diagnosis were reviewed and reassessed so as to evaluate the frequency and clinical significance of hypermodal cells in amniotic fluid cell cultures. Hypermodal cells were defined as those with more than 46 chromosomes, and were characterized by an additional structurally normal or structurally abnormal chromosome. Of 2029 specimens, 47 (2.31 per cent) contained a total of 167 hypermodal cells. True fetal mosaicism was detected in three cases (0.14 per cent). All had hypermodal cells in more than one culture flask or colony which contained the same aberrant chromosome complement. In all but one case the babies were normal when only one cell was hypermodal, or when several cells were hypermodal but present in only one colony or one culture vessel. One case had an extra No. 20 chromosome in one cell. Although the child had multiple anomalies, they were not characteristic of trisomy 20, and subsequent chromosomal study on the baby postnatally revealed a 46,XX karyotype. The in situ coverslip technique is recommended as the preferred method for prenatal diagnosis, and it is useful as an aid in differentiating true mosaicism from pseudomosaicism.


Yet more knots in the radial artery, unravelling purely by counter clockwise rotation.
We describe here two more radial knots that could be unravelled by counter-clockwise rotation alone. We and others have previously described radial knots that occur when trying to engage the right coronary artery (RCA). Here, we show two knots that were unravelled purely by counter-clockwise rotation. One occurred during RCA catheterisation and the other occurred during left coronary angiography via the radial route. In one of the patients, severe pain occurred in the right shoulder. This occurred even though the artery was not in spasm. We were able to move the catheter. Therefore it is possible that pain combined with the ability to move the catheter may be a marker of an intravascular knot.


RCAS1 decidual immunoreactivity during stillbirth: immune cell presence and activity.
Alterations in RCAS1 (a receptor-binding cancer antigen expressed on SiSo cells) expression in the placenta and decidua may be related to the regulation of the process of maternal immune tolerance against fetal antigens. Moreover, it has been demonstrated that the occurrence of the spontaneous beginning of stillbirth is related to a decrease in the placental expression of RCAS1. There are no data currently available on the immune processes in decidua during stillbirth. The aim of this study was to evaluate the RCAS1 immunoreactivity level in decidua and to identify the cytotoxic immune cells present during labor, induced after intrauterine fetal death either with a combination of oxytocin (OT) and prostaglandins or with OT alone; a further objective was to assess the potential impact of these molecular alterations on the effectiveness of stillbirth induction. The immunoreactivity of RCAS1, CD3, CD56, CD69, and CD25 was assessed by immunohistochemistry in 31 decidual samples derived from patients in whom the stillbirth occurred before the onset of labor. The RCAS1 immunoreactivity level was higher in a statistically significant manner in decidual tissue samples derived from patients in whom OT alone proved insufficient to induce labor after the diagnosis of intrauterine fetal death but required additionally the use of prostaglandins when compared with samples from women in whom stillbirth was induced successfully with OT alone. However, we did not observe any differences either in CD56 and CD3 positive cell presence or in CD25 and CD69 antigen immunoreactivity in the respective decidua of these two groups of patients. The level of RCAS1 in decidua seems to influence the effectiveness of stillbirth induction.


Modulation of motor cortex excitability by physical similarity with an observed hand action.
The passive observation of hand actions is associated with increased motor cortex excitability, presumably reflecting activity within the human mirror neuron system (MNS). Recent data show that in-group ethnic membership increases motor cortex excitability during observation of culturally relevant hand gestures, suggesting that physical similarity with an observed body part may modulate MNS responses. Here, we ask whether the MNS is preferentially activated by passive observation of hand actions that are similar or dissimilar to self in terms of sex and skin color. Transcranial magnetic stimulation-induced motor evoked potentials were recorded from the first dorsal interosseus muscle while participants viewed videos depicting index finger movements made by female or male participants with black or white skin color. Forty-eight participants equally distributed in terms of sex and skin color participated in the study. Results show an interaction between self-attributes and physical attributes of the observed hand in the right motor cortex of female participants, where corticospinal excitability is increased during observation of hand actions in a different skin color than that of the observer. Our data show that specific physical properties of an observed action modulate motor cortex excitability and we hypothesize that in-group/out-group membership and self-related processes underlie these effects.


Prevalence, economic analysis and chemotherapeutic control of small ruminant fasciolosis in the Sargodha district of Punjab, Pakistan.
This study describes the epidemiology, the economic significance of small ruminant fasciolosis in animals slaughtered in the abattoirs of the Sargodha district, Punjab, Pakistan between January and June 2012. In vivo fasciolicidal efficacy of commercially available compounds was examined using a randomised complete block design. Microscopically screened faecal samples revealed 40.51% positive animals for fasciolosis. The prevalent species included Fasciola hepatica (35.64%) and Fasciola gigantica (8.21%). Mixed infections were noted in 3.33% subjects. Prevalence rates were significantly higher in females (42.25%) than in males (39.52%), and in adults (51.20%) compared to younger animals (33.98%). The disease was recorded more often in emaciated animals (63.63%) followed in order by average (43.45%), thin (43.22%), and fat (32.12%) animals. Between January and June 2012, fasciolosis in Sargodha district, Punjab, Pakistan, was estimated to incur US$0.036 million and US$0.177 million direct (liver condemnation) and indirect (carcass depreciation) economic losses, respectively. In vivo fasciolicidal efficacy of oxyclozanide proved to be the most effective method of control, compared to triclabendazole, and levamisole. Results provide useful information on the frequency distribution of fasciolosis and its economic significance. Finally, data on in vivo fasciolicidal trials show that oxyclozanide is the most efficacious compound for the treatment of the disease in the district Sargodha, Punjab, Pakistan.


A Study Looking at the Teaching of Peripheral Arterial Disease to Medical Personnel in Nepal: How well are we doing and how might we be able to improve?
Background There is currently no data showing the prevalence of peripheral arterial disease in Nepal, although they have a high incidence of risk factors in their population such as diabetes, hypertension, and high volume of smoke inhalation. Objective To quantify a gap in medical education curriculum in Nepal as it pertains to medical trainees that have a lack of exposure to peripheral arterial disease (PAD) in a clinical setting as well as improve lecture quality on peripheral arterial disease. Method A survey was sent out to 615 medical trainees in Nepal with a survey completion rate of 44%. The results indicate that both medical students and intern doctors feel most confident in their ability to diagnose peripheral arterial disease and comfortable ordering a workup for peripheral arterial disease when their education includes both a dedicated lecture and care of a patient. Result The self-reported ability to diagnose peripheral arterial disease increased in medical students from 21.9% in the lecture only group to 44.4% in the group who had both lecture and cared for a patient. The current curriculum at the Kathmandu University School of Medical Sciences only allows two hours in the medical school to cover all vascular topics and is taught with a traditional PowerPoint method. Conclusion To improve this area of curriculum, we recommend increasing the allotted time for lectures as well as demonstrate on live patients the evaluation for peripheral arterial disease.


Do nociceptive stimulation intensity and temporal predictability influence pain-induced corticospinal excitability modulation?
Temporal predictability and intensity of an impending nociceptive input both shape pain experience and modulate laser-evoked potentials (LEPs) amplitude. However, it remains unclear whether and how these two factors could influence pain-induced corticospinal excitability modulation. The current study investigated the influence of nociceptive stimulation intensity and temporal predictability on motor-evoked potentials (MEPs) modulation, in parallel to their effect on pain perception and LEPs amplitude. Twenty participants completed electroencephalographic and transcranial magnetic stimulation experiments during which two laser nociceptive stimulation intensities (high and low) were either unpredictably delivered (random delay) or preceded by a fixed-timing cue (fixed delay). The amplitude of the conditioned MEPs was significantly reduced only for the high nociceptive stimulation and was not affected by the temporal predictability of pain (despite the fact that temporal predictability modulated the amplitude of P2 LEP component amplitude). However, a posteriori analyses based on patterns of pain-induced MEPs modulation revealed that participants in which nociceptive stimulation resulted in an increase in corticospinal excitability were more affected by the predictability of pain (i.e. increasing corticospinal excitability even more when pain occurrence was predictable), regardless of the nociceptive stimulation intensity; whereas participants in which nociceptive stimulation resulted in a decrease in corticospinal excitability were sensitive to the intensity of the stimulation but not its predictability. These results suggest a potential influence of cognitive factors such as temporal predictability on the response of the motor system in the presence of pain for some participants, contributing to explain, at least in part, the high variability highlighted in a number of previous studies.


Hypervolemia increases release of atrial natriuretic peptide and shedding of the endothelial glycocalyx.
Acute normovolemic hemodilution (ANH) and volume loading (VL) are standard blood-sparing procedures. However, VL is associated with hypervolemia, which may cause tissue edema, cardiopulmonary complications and a prolonged hospital stay. The body reacts to hypervolemia with release of atrial natriuretic peptide (ANP) from the heart. ANP has been shown to deteriorate the endothelial glycocalyx, a vital part of the vascular permeability barrier. The aim of the present study was to evaluate and compare ANP release and damage to the glycocalyx during ANH and VL. ANH or VL with 6% hydroxyethyl starch 130/0.4 was administered prior to elective surgery in patients of good cardiopulmonary health (n =9 in each group). We measured concentrations of ANP in plasma and of three main constituent parts of the glycocalyx (hyaluronan, heparan sulfate and syndecan 1) in serum before and after ANH or VL. Heparan sulfate and syndecan 1 levels in urine were also determined. In contrast to ANH, VL (20 ml/kg) induced a significant release of ANP (approximately +100%, P <0.05) and increased the serum concentration of two glycocalyx constituents, hyaluronan and syndecan 1 (both by about 80%, P <0.05). Elevation of syndecan 1 was also detected in the urine of patients undergoing VL, but no increase was found in patients undergoing ANH. Heparan sulfate levels were not influenced by either procedure. These data suggest that hypervolemia increases the release of ANP and causes enhanced shedding of the endothelial glycocalyx. This perturbation must be expected to impair the vascular barrier, implying that VL may not be as safe as generally assumed and that it should be critically evaluated.


Overexpression of regucalcin suppresses apoptotic cell death in the cloned rat hepatoma H4-II-E cells induced by a naturally occurring isothiocyanate sulforaphane.
The effect of regucalcin, a regulatory protein in intracellular signaling system, on cell death and apoptosis was investigated. Sulforaphane, a naturally occurring isothiocyanate, is known to induce cell cycle arrest and apoptosis in cancer cells, although its effect has not been clarified in the cloned rat hepatoma H4-II-E cells. Hepatoma H4-II-E cells (wild-type) and stable regucalcin/pCXN2-transfected cells were cultured for 72 h in a medium containing 10% fetal bovine serum (FBS). Cells with subconfluency were changed to a medium containing either vehicle or sulforaphane (10(-7) or 10(-6) M) in the absence of FBS. After medium change, cells were cultured for 24, 48, or 72 h. The number of wild-type cells was significantly decreased in the presence of sulforaphane (10(-7) or 10(-6) M). Agarose gel electrophoresis showed the presence of low-molecular-weight deoxyribonucleic acid (DNA) fragments of adherent wild-type cells cultured with sulforaphane (10(-7) or 10(-6) M) for 24 h. Sulforaphane (10(-7) or 10(-6) M)-induced cell number and DNA fragmentation was significantly suppressed in transfectants. The effect of sulforaphane (10(-6) M) in decreasing the number of wild-type cells was significantly prevented in the presence of caspase-3 inhibitor (10(-9) M), while the presence of Nomega-nitro-L-arginine methylester (NAME), an inhibitor of nitric oxide synthase, did not prevent sulforaphane-induced death of wild-type cells. Sulforaphane (10(-6) M) did not have a significant effect on cell number of transfectants in the presence of caspase-3 inhibitor or NAME. This study demonstrates that sulforaphane induces cell death and apoptosis in the cloned rat hepatoma H4-II-E cells, and that overexpression of regucalcin suppresses sulforaphane-induced apoptotic cell death which is partly mediated through caspase-3..