Transcriptional response of the terpenoid indole alkaloid pathway to the overexpression of ORCA3 along with jasmonic acid elicitation of Catharanthus roseus hairy roots over time.
Jasmonic acid (JA) activates the transcriptional regulator ORCA3, which has a role in regulating the terpenoid indole alkaloid (TIA) pathway within Catharanthus roseus. The TIA pathway leads to the production of the anticancer drugs vinblastine and vincristine. This work explores the transient effects of overexpressing ORCA3 under the control of a glucocorticoid-inducible promoter system in C. roseus hairy roots along with the simultaneous feeding of JA. The changes in TIA metabolites and in mRNA transcripts of pathway genes and regulators were tracked for 72h. Upon induction of ORCA3 expression and elicitation with JA, ORCA3 transcripts increased 170-fold whereas ORCA3 expression caused an 89-fold increase and JA elicitation caused a 5-fold increase in ORCA3 transcripts. JA treatment caused the largest increase in TIA metabolites and transcripts of pathway genes. These transcripts displayed a transient response with the maximum expression reached between 12 and 24h. In the samples overexpressing ORCA3, the largest increase in the transcripts of ZCT1 and ZCT2 (ZCT-zinc finger-binding protein), TIA transcriptional repressors, coincided with the largest increase in ORCA3 transcripts. This counter response of transcriptional repressors may explain why the large increase in ORCA3 transcripts do not correspond with larger increases in transcripts of TIA pathway genes.


Epidemiology, microbiology, and treatment considerations for bacterial pneumonia complicating influenza.
Post-influenza bacterial pneumonia is a major cause of morbidity and mortality associated with both seasonal and pandemic influenza virus illness. However, despite much interest in influenza and its complications in recent years, good clinical trial data to inform clinicians in their assessment of treatment options are scant. This paucity of evidence needs to be addressed urgently in order to improve guidance on the management of post-influenza bacterial pneumonia. The objectives of the current article are to evaluate the emergence of the 2009 H1N1 influenza pandemic and use this information as background for an in-depth review of the epidemiology of bacterial pneumonia complicating influenza, to review the bacterial pathogens most likely to be associated with post-influenza bacterial pneumonia, and to discuss treatment considerations in these patients. When determining optimal management approaches, both antiviral and antibacterial agents should be considered, and their selection should be based upon a clear understanding of how their mechanisms of action intervene in the pathogenesis of post-influenza acute bacterial pneumonia.


Sin Nombre hantavirus nucleocapsid protein exhibits a metal-dependent DNA-specific endonucleolytic activity.
We demonstrate that the nucleocapsid protein of Sin Nombre hantavirus (SNV-N) has a DNA-specific endonuclease activity. Upon incubation of SNV-N with DNA in the presence of magnesium or manganese, we observed DNA digestion in sequence-unspecific manner. In contrast, RNA was not affected under the same conditions. Moreover, pre-treatment of SNV-N with RNase before DNA cleavage increased the endonucleolytic activity. Structure-based protein fold prediction using known structures from the PDB database revealed that Asp residues in positions 88 and 103 of SNV-N show sequence similarity with the active site of the restriction endonuclease HindIII. Crystal structure of HindIII predicts that residues Asp93 and Asp108 are essential for coordination of the metal ions required for HindIII DNA cleavage. Therefore, we hypothesized that homologous residues in SNV-N, Asp88 and Asp103, may have a similar function. Replacing Asp88 and Asp103 by alanine led to an SNV-N protein almost completely abrogated for endonuclease activity.


Population Genetic-Based Pharmacokinetic Modeling of Methadone and its Relationship with the QTc Interval in Opioid-Dependent Patients.
Methadone is a μ-opioid agonist widely used for the treatment of pain, and for detoxification or maintenance treatment in opioid addiction. It has been shown to exhibit large pharmacokinetic variability and concentration-QTc relationships. In this study we investigated the relative influence of genetic polymorphism and other variables on the dose concentration-QTc relationship. A population model for methadone enantiomers in 251 opioid-dependent patients was developed using non-linear mixed effect modeling (NONMEM®). Various models were tested to characterize the pharmacokinetics of (R)- and (S)-methadone and the pharmacokinetic-pharmacodynamic relationship, while including demographics, physiological conditions, co-medications, and genetic variants as covariates. Model-based simulations were performed to assess the relative increase in QTc with dose upon stratification according to genetic polymorphisms involved in methadone disposition. A two-compartment model with first-order absorption and lag time provided the best model fit for (R)- and (S)-methadone pharmacokinetics. (S)-methadone clearance was influenced by cytochrome P450 (CYP) 2B6 activity, ABCB1 3435C>T, and α-1 acid glycoprotein level, while (R)-methadone clearance was influenced by CYP2B6 activity, POR*28, and CYP3A4*22. A linear model described the methadone concentration-QTc relationship, with a mean QTc increase of 9.9 ms and 19.2 ms per 1000 ng/ml of (R)- and (S)-methadone, respectively. Simulations with different methadone doses up to 240 mg/day showed that <8 % of patients presented with a QTc interval above 450 ms; however, this might reach 12 to 18 % for (R)- and (S)-methadone, respectively, in patients with a genetic status associated with a decreased methadone elimination at doses exceeding 240 mg/day. Risk factor assessment, electrocardiogram monitoring, and therapeutic drug monitoring are beneficial to optimize treatment in methadone patients, especially for those who have low levels despite high methadone doses, or who are at risk of overdosing.


Teratogenic study of phenobarbital and levamisole on mouse fetus liver tissue using biospectroscopy.
Biospectroscopic investigations have attracted attention of both the clinicians and basic sciences researchers in recent years. Scientists are discovering new areas for FTIR biospectroscopy applications in medicine. The aim of this study was to measure the possibility of FTIR-MSP application for the recognition and detection of fetus abnormalities after exposure of pregnant mouse to phenobarbital (PB) and levamisole (LEV) alone or in combination. PB is one of the most widely used antiepileptic drugs (AEDs), with sedative and hypnotic effects. When used by pregnant women, it is known to be a teratogenic agent. LEV is an antihelminthic drug with some applications in immune-deficiency as well as colon cancer therapy. Four groups of ten pregnant mice were selected for the experiments as follows: one control group received only standard diet, one group was injected with 120mg/kg of BP, one group was injected with 10mg/kg of LEV, and the last group was treated simultaneously with both BP and LEV at the above mentioned doses. Drugs administration was performed on gestation day 9 and fetuses were dissected on pregnancy day 15. Each dissected fetus was fixed, dehydrated and embedded in paraffin. Sections of liver (10μm) were prepared from control and treated groups by microtome and deparaffinized with xylene. The spectra were taken by FTIR-MSP in the region of 4000-400cm(-1). All the spectra were normalized based on amide II band (1545cm(-1)) after baseline correction of the entire spectrum, followed by classification using PCA, ANN and SVM. Both morphological and spectral changes were shown in the treated fetuses as compared to the fetuses in the control group. While cleft palate and C-R elongation were seen in PB injected fetuses, developmental retardation was mostly seen in the LEV injected group. Biospectroscopy revealed that both drugs mainly affected the cellular lipids and proteins, with LEV causing more changes in amide I and lipid regions than PB. Application of PCA, ANN and SVM methods were able to successfully classify these FTIR spectroscopic data and discriminate between control and treated groups of fetuses, making it a new potential tool for drugs teratogenic investigations.


Radiotherapy for nasopharyngeal cancer.
Nasopharyngeal cancers are a rarity in France. Radiotherapy is the cornerstone of treatment, frequently combined with chemotherapy. The technical modality of radiotherapy is complex in this disease, which is located in the vicinity of numerous organs at risk. In this article, we will present the updated guidelines of the French society for radiation oncology (Société française de radiothérapie oncologique, SFRO) on the indications, and technical details of radiotherapy in nasopharyngeal cancers.


Poly(ethylene glycol) shell-sheddable magnetic nanomicelle as the carrier of doxorubicin with enhanced cellular uptake.
This research is aimed to develop a kind of poly(ethylene glycol) shell-sheddable magnetic nanomicelle as the carrier of doxorubicin (Dox) in order to enhance its cellular uptake ability, and achieve synchronous magnetic resonance imaging (MRI)-visible function. Firstly, the five-member rings in poly (L-succinimide) (PSI) were successively opened by the amino terminated disulfide-linked poly(ethylene glycol) monomethyl ether (mPEG-SS-NH2) and dopamine (DA) to produce the graft copolymer of mPEG-SS-NH-graft-PAsp-DA. And then, drug-loaded magnetic nanomicelles of firstname.lastname@example.com were obtained by the Fe3O4 nanoparticle-induced self-assembly of mPEG-SS-NH-graft-PAsp-DA. These magnetic nanomicelles showed spherical shapes with average particle size of about 120 nm measured by dynamic light scattering (DLS). Due to the detachment of PEG shell in the presence of dithiothreitol (DTT), the magnetic nanomicelles showed accelerated in vitro release of Dox, and enhanced cellular uptake ability. Compared with free Dox, the Dox-loaded magnetic nanomicelles showed essential decreased cytotoxicity against Bel-7402 cell line. If its high r2 relaxation rate (221 mM(-1) s(-1)) and good negative contrast effect for magnetic resonance imaging (MRI) were taken into account, firstname.lastname@example.com could be used as MRI-detectable drug carrier of Dox with enhanced cellular uptake ability.


Less is more: the influence of traffic count on drinking and driving behaviour.
Drinking and driving road checks are often organized with either a clear prevention or repression objective in mind. The objective of a prevention strategy is to make as many people as possible believe that police officers are enforcing drinking and driving laws and that drinking drivers will most likely be caught. As such, targeting high traffic count road sites with high-visibility road checks is a priority because it serves to increase awareness of the enforcement activity. An alternative to this prevention approach is the "repression" approach that involves targeting times and places where the highest number of drinking drivers are to be expected. Rather than attempting to affect the subjective chance of getting caught, this approach seeks to increase the objective likelihood of getting caught; the aim is to apprehend as many drinking drivers as possible. Regardless of the chosen strategy, there is a need to understand how traffic count influences drinking and driving behaviour as traffic count may play a role in a police officer's choice of sites for a road check. The objective of this paper is to shed some light on this relationship between drinking and driving behaviour and traffic count. In this paper, data from a roadside survey, carried out in British Columbia in 2003, are used. A two-level logistic regression analysis was carried out with data from 2627 drivers coming from 48 different road sites to replicate a model that was previously obtained with comparable data from a Belgian roadside survey, also carried out in 2003. The present study successfully replicated the findings of the Belgian model, substantiating that the probability for drivers to be drinking and driving significantly decreases with an increasing level of traffic count. This supports the suggestion that drinking drivers avoid high traffic count road sites. The relevance of these findings with respect to organizing preventive or repressive road checks and possible confounding variables are discussed at the end of this paper.


Aquaporin 6 is permeable to glycerol and urea.
The passive water permeability ( L(p)) of AQP6 is activated by Hg(2+). Our aim was to test if L(p) was associated with a permeability to small hydrophilic molecules such as glycerol and urea. AQP6 was expressed in Xenopus laevis oocytes and activated by 0.3 mM of HgCl(2) in the bathing solution. HgCl(2) caused the oocytes to swell at a rate of about 0.3% min(-1). The L(p) of AQP6 was determined from brief additions or removals of mannitol from the bathing solution, and compared to the L(p) obtained from adding glycerol or urea. In paired experiments, L(p (mannitol)) was 2.4+/-0.1, L(p (glycerol)) 1.5+/-0.2, and L(p (urea)) 0.7+/-0.1 (units: 10(-5) cm s(-1) osmol(-1); 14 oocytes); the latter was not different from L(p)s obtained for native oocytes. The L(p)s were independent of the Hg(2+)-induced swelling and of the magnitude of the osmotic challenge (-75 to +100 mosmol). Hg(2+) stimulated the uptake of [(14)C]glycerol fivefold and [(14)C]urea twofold in AQP6-expressing oocytes. There were no significant uptakes in native oocytes nor in AQP1-expressing oocytes whether these were treated with HgCl(2) or not. We conclude that water, glycerol and urea share an aqueous pathway in AQP6.


[Effect of theo-polyphenols on oxygen free radicals and hemorrheology in patients with essential hypertension].
To observe the effect of theo-polyphenols (TP) on oxygen free radicals and hemorrheology in patients with essential hypertension. Hemorheology as well as oxygen free radical of 38 patients were determined before and after TP treatment. TP markedly increased RBC-SOD activity, reduced the level of serum MDA, the whole blood viscosity, plasma viscosity and the level of plasma fibrinogen. The efficacy of TP was higher than that of aspirin. The TP had remarkable effects of anti-oxygen free radicals, and could improve hemorheology.


Inactivation of an acceptor RNA splice site by a short deletion in beta-thalassemia.
The cloned beta-globin gene of an Indian patient with beta-thalassemia revealed a 25-nucleotide deletion at the 3'-end of the first intervening sequence, including the acceptor RNA splicing site. RNA transcripts of this mutant gene produced following transfection into HeLa cells remained unspliced at both the first intervening sequence donor and acceptor sites. This beta-thalassemic gene is the first in which critical sequences of an acceptor splice junction are mutated and associated with abnormal RNA processing.


[Intracameral and lenticular penetration of locally applied deuterium-labeled vitamin E in rats].
To confirm the intraocular dynamics of 1% deuterium (D)-labeled alpha-tocopherol acetate (VEA) solution. The concentrations of D3-VEA and D3-alpha-tocopherol (VE) derived from D3-VEA in the aqueous humor and lens were measured after instilling 1% D3-VEA continuously into the cul-de-sac of rat eyes for one and three weeks. D3-VEA and D3-VE concentrations were determined by gas chromatograph/mass spectrometry. D3-VEA and D3-VE concentrations in the aqueous humor after one and three weeks of continuous administration were 93.1 and 498.9, and 9.4 and 21.5 ng/ml, respectively. The concentrations in the lens were 15.0 and 6.1, and 9.8 and 4.8 ng/g, respectively. The penetration of VEA into the aqueous humor and lens by eyedrop application was confirmed.


Proteomic studies on protective effects of salvianolic acids, notoginsengnosides and combination of salvianolic acids and notoginsengnosides against cardiac ischemic-reperfusion injury.
Salvia miltiorrhiza and Panax notoginseng are popularly used traditional Chinese medicine for cardiovascular disorders and they are often used in the form of combination. However, mechanisms of their cardioprotective effects were still not clear. In the present study, the protective effects of salvianolic acids (SA), notoginsengnosides (NG) and combination of SA and NG (CSN) against rat cardiac ischemia-reperfusion injury were checked and the protein expression profiles of heart tissues were examined to search their possible protein targets. The cardioprotective effects of SA, NG and CSN were checked in a rat model of ischemia-reperfusion (IR) by temporarily occluding coronary artery for 20 min followed by reperfusion. Rats were grouped into sham-operation group, IR group, IR+SA group, IR+NG group and IR+CSN group. The plasma creatine kinase (CK) activities were measured using commercial kit and the percentages of infarcted area in total ventricle tissue were calculated after nitroblue-tetrazolium (N-BT) staining of heart tissue slices. Two-dimensional protein electrophoresis (2-DE) was used to check the protein expression profiles of heart tissues. Then, proteins differentially expressed between IR group and sham-operation group were identified using matrix assisted laser desorption ionization-time of flight-mass spectrometry/mass spectrometry (MALDI-TOF MS/MS). The regulative effects of SA, NG and CSN on these IR-related proteins were analyzed. Treatments including SA, NG and CSN all showed cardioprotective effects against ischemia-reperfusion injury and CSN exhibited to be the best. Eighteen proteins involved in IR injury were found. These proteins are involved in pathways including energy metabolism, lipid metabolism, muscle contraction, heat shock stress, cell survival and proliferation. The regulation of these proteins by SA, NG or CSN suggested possible protein targets in their cardioprotective effects. SA and NG showed both similarity and difference in their protein targets involved in cardioprotective effects. The capability of CSN to regulate both protein targets of SA and NG might be the basis of CSN to show cardioprotective effects better than that of SA or NG.


Characterization of the roles of NikR, a nickel-responsive pleiotropic autoregulator of Helicobacter pylori.
The Helicobacter pylori genome contains a gene (hp1338 or nikR) that encodes a nickel-dependent regulator that is homologous to the Escherichia coli nickel-responsive regulator, NikR. The H. pylori nikR product acts as a pleiotropic metal-dependent regulator. We constructed a non-polar isogenic mutant deleted for the nikR gene. NikR was essential for the survival of H. pylori in the presence of high nickel and cobalt ion concentrations in vitro. We screened a DNA macroarray for genes that were differentially expressed in parental and nikR-deficient H. pylori strains grown in the presence of excess nickel. We found that H. pylori NikR mediates the expression of nickel-activated and -repressed genes. In the presence of excess nickel, NikR activated the transcription of ureA-ureB (hp72-73), nixA (hp1077 ), copA2 (hp1072), hpn (hp1427 ) and hpn-like (hp1432) genes and repressed the expression of genes encoding proteins involved in ferric iron uptake and storage [pfr (hp0653), fur (hp1027 ), frpB4 (hp1512), exbB/exbD (hp1339-1340), ceuE (hp1561)], motility [cheV (hp616), flaA (hp0601), flaB (hp0115 )], stress responses [hrcA-grpE-dnaK (hp111-110-109)] and encoding outer-membrane proteins [omp11(hp0472), omp31 (hp1469), omp32 (hp1501)]. Slot blot DNA/RNA hybridization experiments using RNA from three independent bacterial cultures confirmed the transcriptome data for 10 selected genes. The results of gel shift experiments using purified native NikR, beta-galactosidase assays with the region between nikR and the exbB/exbD divergent operon, and the study of exbB gene expression using a gentamicin/apramycin reporter gene in H. pylori indicated that NikR is an autorepressor that binds to this intergenic region and also controls the expression of the exbB/exbD/tonB operon, which provides energy for ferric iron uptake. Thus, as previously suggested for Fur in H. pylori, NikR appears to be a global regulator of the metabolism of some divalent cations within a highly complex regulated network.


Left ventricular synchronization by biventricular pacing in Becker muscular dystrophy as assessed by tissue Doppler imaging.
Biventricular (BiV) pacing is a promising therapy for severe heart failure. The effect of BiV pacing is cardiac resynchronization of both ventricles. Asynchrony of the ventricular contraction and restoration of cardiac synchronization can be assessed by tissue Doppler imaging. Here we describe a patient with Becker muscular dystrophy with heart failure caused by dilated cardiomyopathy in whom a BiV pacemaker was implanted.


Understanding the impact of the Canada Prenatal Nutrition Program: a quantitative evaluation.
The objectives of this study were to assess whether high exposure to the Canada Prenatal Nutrition Program (CPNP) improved 1) the personal health practices, such as smoking and breastfeeding, of participants and 2) birth outcomes, such as low birth weight and preterm birth. The CPNP is a population-level health intervention that aims to contribute to improved health outcomes for pregnant women and their newborn children facing conditions of risk. The program, which is jointly managed by the federal and provincial governments, serves more than 45,000 Canadian women annually. Participants were women who entered the program prenatally in 2002-2006 and were socially, demographically and geographically diverse. Almost 12% were adolescents, and almost 10% were over 34 years of age; 5% were recent immigrants (in Canada <10 years), and close to one quarter were Aboriginal. This comprised a broad range of community-based projects in 2,000 communities. Descriptive statistics showed that the CPNP is reaching the women for which it is intended. Participants with high CPNP exposure were more likely to reduce the number of cigarettes they smoked, to cease drinking, to breastfeed their infants and to breastfeed for longer, and to increase their use of vitamin/mineral supplements from never to daily. Furthermore, they were less likely to give birth to an infant that was preterm, had low birth weight, was small for gestational age or had poor neonatal health. Unexpectedly, participants were more likely to give birth to a large-for-gestational-age infant. Our stratified "equity" analyses showed some variation by social group, indicating that the benefits were not consistently shared by all. High CPNP exposure improved the health behaviours and birth outcomes of women and their newborn children facing conditions of risk. Furthermore, our equity analysis found that the associations between higher CPNP exposure and healthy behaviour changes, and even more so, better birth outcomes, were generally found across many social groups. In the absence of a control group, the study used an innovative approach to estimating the impact of the CPNP by comparing those who received a higher "dose" with those receiving a lower dose of CPNP services.


A bilirubin-conjugated chitosan nanotheranostics system as a platform for reactive oxygen species stimuli-responsive hepatic fibrosis therapy.
The development of nanoparticles that can be used as stimuli-responsive drug carriers for the treatment of different diseases has been an emerging area of research. In this study, we designed a chitosan-bilirubin micelle (ChiBil) carrying losartan, which is responsive to intrinsic reactive oxygen species (ROS), for the treatment of hepatic fibrosis. Because bilirubin is hydrophobic in nature, its carboxyl group was conjugated to an amine group from chitosan using EDC-NHS chemistry to form an amphiphilic conjugate, ChiBil. Losartan is an angiotensin receptor blocker that reduces hepatic fibrosis, and it was used as the therapeutic payload in this study to form ChiBil-losartan micelles. The release characteristics of ChiBil-losartan were tested by ROS generation to confirm losartan release. Human hepatic stellate cell line LX2 was found to be the best in vitro model for the study. The reduction of hepatic stellate cell activation after treatment with ChiBil-losartan was analyzed based on the expression of alpha-smooth muscle actin (α-SMA) in both in vitro and in vivo studies. Advanced liver fibrosis was induced in C3H/HeN mice using a thioacetamide (TAA) via intraperitoneal injection and 10% ethanol (EtOH) in their drinking water. In addition, the hydroxyproline levels, histopathological evaluation, and mRNA quantification in the liver showed a decreased collagen content in the treated groups compared to that in the untreated control group. Macrophage infiltration studies and qPCR studies of inflammatory markers also proved the reduction of hepatic fibrosis in the treatment group. The intravenous administration of ChiBil-losartan resulted in decreased fibrosis in a TAA/EtOH-induced liver fibrosis mouse model. The in vitro and in vivo results suggest that the ROS stimuli-responsive ChiBil nanoparticles carrying losartan may be a potent therapeutic option for the treatment of hepatic fibrosis. The combined effect of losartan and bilirubin exhibited a decreased hepatic fibrosis both in vitro and in vivo.


The contributions of Jin H. Kinoshita to aldose reductase research.
Sorbitol is a sugar alcohol formed from the aldose reductase catalyzed reduction of glucose. Mounting experimental evidence links the abnormal intracellular accumulation of sorbitol to the onset and severity of diabetes-associated pathology which results in a variety of tissue and/or functional changes in the cornea, lens, retina, iris, peripheral nerves, and kidney. Animal studies indicate that aldose reductase inhibitors, by inhibiting the formation of sorbitol in target tissues affected by diabetes, can either prevent or significantly delay the onset of many of these diabetes-associated changes. The pioneering studies of Dr Jin Kinoshita have been instrumental in defining the pathophysiological role of aldose reductase and excess sorbitol production under diabetic conditions. These studies provide a firm scientific groundwork for investigating the premise that inhibition of sorbitol formation is a new, pharmacologically direct treatment for diabetic complications that is independent of the control of blood sugar levels.


The development of ADAM10 endocytosis inhibitors for the treatment of Alzheimer's disease.
The development of new therapeutic avenues that target the early stages of Alzheimer's disease (AD) is urgently necessary. A disintegrin and metalloproteinase domain 10 (ADAM10) is a sheddase that is involved in dendritic spine shaping and limits the generation of amyloid-β. ADAM10 endocytosis increases in the hippocampus of AD patients, resulting in the decreased postsynaptic localization of the enzyme. To restore this altered pathway, we developed a cell-permeable peptide (PEP3) with a strong safety profile that is able to interfere with ADAM10 endocytosis, upregulating the postsynaptic localization and activity of ADAM10. After extensive validation, experiments in a relevant animal model clarified the optimal timing of the treatment window. PEP3 administration was effective for the rescue of cognitive defects in APP/PS1 mice only if administered at an early disease stage. Increased ADAM10 activity promoted synaptic plasticity, as revealed by changes in the molecular compositions of synapses and the spine morphology. Even though further studies are required to evaluate efficacy and safety issues of long-term administration of PEP3, these results provide preclinical evidence to support the therapeutic potential of PEP3 in AD.


Tekicihila Unpo (Love One Another): Confronting Human Trafficking With the Guidance of Traditional Lakota Wisdom in Nursing Practice.
Human trafficking emerged as a serious social issue in North Dakota during the Bakken oil field boom in the western part of the state. The oil industry has seen a dramatic decrease in production in recent years. However, the presence of human trafficking continues to dominate the scene in the state. As the RN Case Manager and Community Outreach Nurse for a Healthcare for the Homeless grantee clinic in Fargo, the author is the only nurse outside of a traditional environment who works with victims of trafficking in the largest metropolitan area of North Dakota. The majority of the current targets for this heinous industry are young Native American women. The author, a Lakota woman, employs an approach with trafficking victims that seeks to reestablish the view of self as a being with significant value and ability to contribute to the world in a way that no other being can. In advocacy, she teaches professionals about the Lakota view of the Earth as a living being whose destruction may be correlated with the increased violence against women.


Use of gamma-linolenic acid in the treatment of schizophrenia and tardive dyskinesia.
There is good background evidence to suggest that essential fatty acids and their eicosanoid derivatives may play a role in schizophrenia and in with tardive dyskinesia. Trials involving treatment with essential fatty acids, or eicosanoids or drugs which stimulate eicosanoid synthesis have shown modestly promising results. Particularly favourable outcomes in both schizophrenia and tardive dyskinesia were associated with combined treatment using essential fatty acids and nutritional supplements.


A one-layer recurrent neural network for nonsmooth pseudoconvex optimization with quasiconvex inequality and affine equality constraints.
As two important types of generalized convex functions, pseudoconvex and quasiconvex functions appear in many practical optimization problems. The lack of convexity poses some difficulties in solving pseudoconvex optimization with quasiconvex constraint functions. In this paper, we propose a one-layer recurrent neural network for solving such problems. We prove that the state of the proposed neural network is convergent from the feasible region to an optimal solution of the given optimization problem. We show that the proposed neural network has several advantages over the existing neural networks for pseudoconvex optimization. Specifically, the proposed neural network is applicable to optimization problems with quasiconvex inequality constraints as well as affine equality constraints. In addition, parameter matrix inversion is avoided and some assumptions on the objective function and inequality constraints in existing results are relaxed. We demonstrate the superior performance and characteristics of the proposed neural network with simulation results in three numerical examples.


Cell-to-cell adhesion modulates Stat3 activity in normal and breast carcinoma cells.
Stat3 (signal transducer and activator of transcription-3) activity is required for transformation by a number of oncogenes, while a constitutively active form of Stat3 alone is sufficient to induce neoplastic transformation. Although in most instances Stat3 is growth-promoting, the impact of cell density on Stat3 activation status and the biological importance of Stat3 during growth arrest have not been characterized. Previous results indicated that cell density alters tyrosine phosphorylation levels of cultured cells. Since signalling through Stat3 is determined by a key phosphorylation at tyr705, we examined the effects of cell density upon Stat3 activity in normal breast epithelial cells, breast carcinoma lines and normal mouse fibroblasts. Intriguingly, the results revealed a dramatic increase in Stat3, tyr705 phosphorylation and activity with cell density, which gradually declined at later stages. This activation was dependent upon cell-cell contact, since it was eliminated if cell adhesion was disrupted through calcium chelation, while it was reinstated through cell aggregation. Furthermore, this activation was suppressed following inhibition of JAKs (Janus kinases) but not inhibition of Fer, IGF1-R, or kinases of the c-Src family. On the other hand, constitutively active Stat3 in carcinoma lines, known to harbor activated Src, was blocked by pharmacological inhibitors of Src as well as JAKs. These results point to the existence of two distinct pathways of Stat3 activation in breast carcinomas, based on Src dependence. More importantly, our results suggest that Stat3 activity is upregulated during the confluence-mediated growth arrest by a signalling mechanism that requires JAKs.


Tissue-infiltrating immune cells as prognostic markers in oral squamous cell carcinoma: a systematic review and meta-analysis.
Various immune cells have been suggested as prognostic markers for cancer patients. In this article, we present a systematic review and meta-analysis of studies assessing the prognostic value of tissue-infiltrating immune cells in oral cancer and discuss the reporting quality of these studies. We performed a systematic literature search and included studies using immunohistochemistry and survival analysis to assess the prognostic value of tumour-infiltrating T cells, B cells, macrophages, dendritic cells, mast cells and natural killer cells in oral cancer. We performed meta-analysis of studies providing necessary statistical data and investigated the studies' adherence to the REporting recommendations for tumour MARKer prognostic studies (REMARK) guidelines. Of the 1960 articles identified, 33 were eligible for this systematic review and 8 were included in the meta-analysis. CD163+ M2 macrophages and CD57+ natural killer cells were the most promising predictors of survival in oral cancer patients. Many studies lacked important information on their design and conduct. Deficiencies in the reporting of study design and conduct make it difficult to draw reliable conclusions about the suggested markers. The prognostic value of CD163+ M2 macrophages and CD57+ natural killer cells should be validated in large, standardised studies.


Effects of health-oriented descriptors on combustible cigarette and electronic cigarette packaging: an experiment among adult smokers in the United States.
Certain tobacco companies use health-oriented descriptors (eg, 100% organic) on product packaging and advertising of combustible cigarettes or electronic cigarettes (e-cigarettes) that create a 'health halo' around smoking and vaping. Previous observational research suggests that such language may be associated with more favourable attitudes and reduced risk perceptions toward these brands compared with others. This study aimed to determine the effects of health-oriented descriptors on smokers' attitude toward the brand, perception of packaging information, comparative harm versus other brands and intention to purchase either combustible cigarettes or e-cigarettes. US adult smokers were randomly assigned to view either a health-oriented language package ('100% organic,' 'all natural' or 'no additives'), traditional marketing language package ('fine quality,' 'premium blend' or '100% original') or a no-language package of a combustible cigarette brand (Study 1, n=405) or an e-cigarette brand (Study 2, n=396) in an experimental design. Study 1: Participants in the health-oriented condition reported more favourable perceptions toward the package information, lower comparative harm and higher intention to purchase combustible cigarettes versus the no language control. In addition, participants in the health-oriented condition reported more positive attitude toward the brand and lower comparative harm versus the traditional marketing condition. Study 2: Compared with the traditional marketing condition, participants in the health-oriented condition reported greater intention to purchase Absolute e-cigarettes. There were no significant differences in attitude toward the brand, perception of packaging information and comparative harm versus other brands across conditions. The effect of health-oriented language was significant for combustible cigarettesand e-cigarette packages. Policies to restrict health-oriented language on cigarette and e-cigarette packaging are recommended.


Prevention of neuroma formation by Neodym Yag laser--experimental observations.
The influence of Laser radiation on neuroma formation was investigated in rat sciatic nerves. Peripheral nerve trunks were divided by focused Neodym Yag Laser and compared with those transected by microscissors. The nerves were re-exposed at different time intervals up to 240 days after initial operation. True neuroma formation could not be observed after laser transection. Sharp division resulted in widespread amputation neuromas consisting of regenerating axons and connective tissue. Neodym Yag laser radiation by its scattering effect may cause deep coagulation necrosis and thrombosis of vasa nervorum thus sealing the dome of the divided nerve trunk. The formation of amputation neuromas may be suppressed by laser application.


Multifaceted Effects of Intermittent Fasting on the Treatment and Prevention of Diabetes, Cancer, Obesity or Other Chronic Diseases.
Obesity and diabetes are global epidemics resulting in a range of comorbidities. Both have been linked to an increased risk of hormonal imbalance, cancer, and other significant disorders, which are a concerning trend for cancer rates in the backdrop of rising obesity and diabetes rates worldwide. Around 1 in 10 persons in the United States and Canada have serious illnesses correlated to type 2 diabetes and early death. It is believed that the US economy alone spends $245 billion annually due to this health burden. Lifestyle modification with intermittent fasting protocol and proper diet helps lower blood glucose level, maintain the body mass index, and reduce inflammation, which is the main cause of all chronic diseases. We searched case series and clinical trials on type 2 diabetes, insulin resistance, cancer, thyroid, cardiovascular disease, or other inflammatory diseases in response to intermittent fasting in the PubMed, MEDLINE, and Google Scholar databases. In this review, we have focused on intermittent fasting-based approaches that are becoming more widely accepted for improving health and reducing unwanted effects in patients with type 2 diabetes, cancer, cardiovascular disease, neurodegenerative disease, obesity, thyroid, and hormonal imbalance; it is also contemplated whether intermittent fasting can be considered as a non-medicinal therapeutic option for persons suffering from chronic diseases. Intermittent fasting successfully reversed diabetes, thyroid, and high blood pressure, elevated lipid levels, and maintained the body mass index; also, studies have shown that it has been instructed to be followed for the treatment and prevention of cancer and neurodegenerative diseases.


Prevalence and factors associated with intergenerational sexual partnerships among undergraduate health science students in Eswatini.
Intergenerational sexual partnerships (IGSPs) put young people at an increased risk of sexually transmitted infections (STIs) including HIV and AIDS. However, their burden and predictors remain poorly understood. To describe the prevalence and factors associated with IGSPs among undergraduate health science students at a selected tertiary institution in Eswatini (formerly Swaziland). Data were collected through a cross-sectional survey of 148 conveniently sampled undergraduate health science students at the University of Eswatini. Multiple logistic regression analysis was performed to determine predictors of IGSPs (i.e. a 10-year or greater age disparity between heterosexual partners). There was equal participation of males and females in this study (50%, n=74). The prevalence of IGSPs among the sample was 31.8% (n=47). Females (adjusted odds ratio, AOR = 0.08, 95% CI: 0.03-0.24) and those who received money from sexual partners (AOR = 0.08, 95% CI: 0.01-0.62) had lower odds of being in IGSPs. Being female and being a recipient of money from a sexual partner were negatively associated with IGSPs. The relatively high prevalene of IGSPs calls for health education campaigns targeting university students on the negative consequences associated with IGSPs, especially among young women.


Increasing SARS-CoV-2 RT-qPCR testing capacity by sample pooling.
Limited testing capacity has characterized the ongoing coronavirus disease 2019 (COVID-19) pandemic in Spain, hampering timely control of outbreaks and opportunities to reduce the escalation of community transmission. This study investigated the potential to use sample pooling, followed by one-step retrotranscription and real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) to increase testing capacity for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Various pool sizes (five, 10 and 15 samples) were evaluated prior to RNA extraction followed by standard RT-qPCR for the diagnosis of COVID-19. The pool size achieving reproducible results with individual sample testing was subsequently used to assess nasopharyngeal samples in a tertiary hospital in August 2020. A pool size of five samples had higher sensitivity compared with pool sizes of 10 and 15 samples, showing a mean cycle threshold (Ct) shift of 3.5 [standard deviation (SD) 2.2] between the pooled test and positive samples in the pool. Next, a pool size of five was used to test a total of 895 pools (4475 prospective samples) using two different RT-qPCR kits. The Real Accurate Quadruplex corona-plus PCR Kit (PathoFinder) reported the lowest mean Ct shift [2.2 (SD 2.4)] between the pool and individual samples. This strategy enables detection of individual positive samples in positive pools with Ct of 16.7-39.4. Grouping samples into pools of five for RT-qPCR resulted in an increase in SARS-CoV-2 testing capacity with minimal loss of sensitivity compared with testing each sample individually.


[Biocompatibility study of polylactic/glycolic acid and Schwann cell].
To examine the biocompatibility of polylactic/glycolic acid (PLGA) and Schwann cells. Schwann cells were harvested from rat brachial and sciatic nerves. Schwann cells were cultured with PLGA, observed by phase-contrast microscopy and electron microscopy. Schwann cells could attach and proliferate on the surface of the PLGA. The PLGA has good cellular biocompatibility. It can be used as biomaterial for tissue engineering.


Insulin regulation of solute carrier family 2 member 1 (glucose transporter 1) expression and glucose uptake in decidualizing human endometrial stromal cells: an in vitro study.
Solute carrier family 2 member 1 (SLC2A1; previously known as glucose transporter 1), is the most abundant glucose transporter in human endometrium and is up-regulated during decidualization, whereas high insulin may have a negative impact on this process. The present study aimed to investigate the effect of insulin on the expression of SLC2A1 and glucose uptake in decidualizing human endometrial stromal cells. We induced in vitro decidualization of endometrial stromal cells obtained from regularly menstruating healthy non-obese women. The cells were treated with increasing concentrations of insulin, and the involvement of the transcription factor forkhead box O1 (FOXO1) was evaluated using a FOXO1 inhibitor. SLC2A1 mRNA levels were measured by Real-Time PCR and protein levels were evaluated by immunocytochemistry. Glucose uptake was estimated by an assay quantifying the cellular uptake of radioactive glucose. One-way ANOVA, Dunnett's multiple comparisons test and paired t-test were used to determine the statistical significance of the results. We found that insulin dose-dependently decreased SLC2A1 mRNA levels and decreased protein levels of SLC2A1 in decidualizing human endometrial stromal cells. Transcriptional inactivation of FOXO1 seems to explain at least partly the down-regulation of SLC2A1 by insulin. Glucose uptake increased upon decidualization, whereas insulin treatment resulted in a slight inhibition of the glucose uptake, although not significant for all insulin concentrations. These results indicate an impairment of decidualization by high concentrations of insulin. Future studies will determine the clinical significance of our results for endometrial function and decidualization in women with insulin resistance and hyperinsulinemia.


Characteristics of U.S. Mental Health Facilities That Offer Suicide Prevention Services.
This study characterized mental health facilities that offer suicide prevention services or outcome follow-up after discharge. The study analyzed data from 8,459 U.S. mental health facilities that participated in the 2010 National Mental Health Services Survey. Logistic regression analyses were used to compare facilities that offered neither of the prevention services with those that offered both or either service. About one-fifth of mental health facilities reported offering neither suicide prevention services nor outcome follow-up. Approximately one-third offered both, 25% offered suicide prevention services only, and 21% offered only outcome follow-up after discharge. Facilities that offered neither service were less likely than facilities that offered either to offer comprehensive support services or special programs for veterans; to offer substance abuse services; and to be accredited, licensed, or certified. Further examination of facilitators and barriers in implementing suicide prevention services in mental health facilities is warranted.


Inhibition of lncRNA-UCA1 suppresses pituitary cancer cell growth and prolactin (PRL) secretion via attenuating glycolysis pathway.
Pituitary tumor is one type of endocrine tumor with high incidence and mortality rates. Long non-coding RNAs (lncRNAs) are a family of non-coding RNAs with longer than 200 nucleotides. Among them, lncRNA-UCA1 is highly expressed in multiple cancers and plays critically oncogenic roles in tumor progressions. However, the potential roles of UCA1 in human pituitary tumor have not been elucidated. In this study, the expressions of lncRNA-UCA1 were analyzed in thirty pituitary tumor samples and thirty normal pituitary tissues. Cancer cell glycolysis rate was examined by glucose uptake and lactate production. The lncRNA-UCA1 expression was detected by qRT-PCR. Glycolysis enzyme expressions were measured by Western blot and qRT-PCR. Consistent with other cancers, lncRNA-UCA1 was highly expressed in pituitary tumors. Meanwhile, we found glycolysis of pituitary tumors was higher than normal pituitary tissues. Overexpression of lncRNA-UCA1 in rat pituitary cancer cell lines, GH3 and MMQ, significantly promoted glucose uptake and lactate production. In addition, expressions of the glycolysis key enzymes, HK2 and LDHA, were significantly upregulated by exogenous overexpression of lncRNA-UCA1. Importantly, silencing lncRNA-UCA1 obviously inhibited pituitary cancer cells growth and prolactin (PRL) secretion. We report higher lncRNA-UCA1 expression is associated with higher serum PRL level in pituitary patients. Finally, by blocking the lncRNA-UCA1-promoted glycolysis of pituitary cancer cells by glycolysis inhibitor, 2-DG, we obtained recovery of cell growth rate and PRL secretion from an in vitro model. Taken together, our investigation revealed an oncogenic role of lncRNA-UCA1 through upregulating glycolysis of pituitary tumors. This study contributes to underlying molecular mechanisms of the tumorigenesis of pituitary tumors.


Hepatocellular carcinoma in Peru: A molecular description of an unconventional clinical presentation.
Hepatocellular carcinoma (HCC) is the third most frequent cancer of digestive tract tumors in Peru, with a high mortality rate of 17.7 per 100,000 inhabitants. A significant number of HCC cases in Peru do not follow the classic clinical epidemiology of the disease described in other parts of the world. Those patients present with a distinct transcriptome profile and a singular tumor process, suggesting a particular type of hepatocarcinogenesis in a portion of the Peruvian population. Our aim was to understand the clinical and biologic involvement of the epigenetic profile (methylation) and gene expression (transcriptome) of HCC in Peruvian patients. HCC and liver transcriptome and DNA methylation profiles were evaluated in 74 Peruvian patients. When grouped by age, there was greater DNA methylation in younger patients with HCC but no differences with respect to the transcriptomic profile. A high prevalence of the hepatitis B virus (HBV) (>90%) was also observed in the younger patients with HCC. Enrichment analyses in both molecular profiles pinpointed PRC2 as an important molecular effector of that liver tumor process in Peruvian patients. HCC in Peruvian patients has a unique molecular profile, associated with the presence of HBV, as well as overall DNA hypermethylation related to undifferentiated liver cells or cellular reprogramming.


Intimacy and mental disorder in late middle age. Report of the TURVA project.
This study, which was carried out as part of the TURVA project on psychosocial adaptation in old age, is concerned with the significance of social support to people approaching retirement age. The population consisted of 200 urban dwellers and 189 rural dwellers, who were studied at the age of 62. The subjects were either about to retire in the near future or had already retired, and it was assumed that this event causes a certain amount of stress, which may lead to mental disturbance regardless of the amount of social support available to the individual. Intimate relationship and close friendship served as the measures of social support. Mental disturbances were assessed on the basis of the General Health Questionnaire (36-item version) and the number of psychic and especially depressive symptoms. The prevalence of mental disturbance and depressive symptoms was lowest in those people who lived in a close marital relationship and who also described their spouse as empathic. Psychic symptoms were most common in those people who said their relationship to their spouse was distant and who described them as unempathic. The subjects who were not married fell in-between these 2 groups regardless of whether they had an intimate relationship with someone of the opposite sex. A positive marital relationship seemed to provide a shield against depression, while a negative marital relationship tended to make the individual more vulnerable to depression. The role of a close non-marital friendship depended on the respondent's sex. In women, it was associated with a high prevalence of depressive symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)


Immunologically cross-reactive and redox-competent cytochrome b6/f-complexes in the chlorophyll-free plasma membrane of cyanobacteria.
Plasma and thylakoid membranes were separated and purified from cell-free extracts of the cyanobacteria Anacystis nidulans, Synechocystis 6714, Anabaena variabilis and Nostoc sp. strain Mac. Immunoblots of the membrane proteins using antisera raised against subunits I-IV of the chloroplast b6/f-complex gave evidence for the presence of a homologous complex in both plasma and thylakoid membranes from the four species of cyanobacteria investigated. Both plasma and thylakoid membranes catalyzed the electron transfer from (exogenous) plastoquinol-9 and NADH to horse heart ferricytochrome c. However, while with plasma membranes these reactions were severely inhibited by low concentrations of antimycin A and rotenone, respectively, the inhibitors were without major effect on thylakoid membranes. The results will be discussed in terms of a possible similarity (analogy and/or homology?) of cyanobacterial plasma membranes to the inner mitochondrial membrane.


Growth performance, haematology and serum biochemistry of African catfish (Clarias gariepinus) fingerlings fed graded levels of dietary fumonisin B1.
Fingerlings of Clarias gariepinus were used to evaluate the effect of dietary fumonisin B1 (FB1), a mycotoxin produced by Fusarium verticillioides, on growth, haematological and serum biochemical parameters. The fingerlings were sorted, weighed and randomly stocked in 16 plastic tanks at the rate of 20 fingerlings per tank. Fusarium-cultured maize grains containing FB1 were used to formulate three diets containing approximately 5.0, 10.0 and 15.0 mg FB1/kg, constituting diets 2, 3, and 4 respectively. These three diets, plus diet 1, which contained non-Fusarium cultured maize grains that served as the control, were used in a 6-week feeding trial. The final weight gains by the fingerlings were significantly (P < 0.05) influenced by FB1. The final weights of the fingerlings fed diets 2, 3 and 4 ranged from 70.07 to 87.10% of the controls. The haematocrit, erythrocytes, haemoglobin, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and the serum protein constituents (total protein, albumin and globulin) values significantly (P < 0.05) decreased, while the leucocytes, MCV and MCH increased significantly (P < 0.05) with increase in the dietary FB1. The total serum protein values of the fingerlings fed diets 2, 3 and 4 were 34.53, 39.42 and 50.17% lower than the total serum protein values of those fed the control diet. These results indicate that Fusarium-contaminated diets containing about 5.0 mg or more FB1/kg reduced weight gain and significantly altered haematological parameters and serum protein constituents in the fingerlings. These may have a significant impact on physiological activities and may be vital in immunosuppression in the fingerlings with a strong negative impact on subsequent performance of the fish.


Effect of focal adhesion kinase (FAK) downregulation with FAK antisense oligonucleotides and 5-fluorouracil on the viability of melanoma cell lines.
Inhibition of focal adhesion kinase (FAK), a non-receptor tyrosine kinase linked to tumour cell survival, causes cell rounding, loss of adhesion and apoptosis in human cancer cell lines. In this study, we tested antisense oligonucleotide inhibitors of FAK, in combination with 5-fluorouracil (5-FU), to increase its sensitivity in human melanoma cell lines. Antisense oligonucleotides directed to the 5' mRNA sequence of FAK and missense control oligonucleotides were used. In BL melanoma cells, treatment with FAK antisense oligonucleotide was associated with a 2.5-fold increase in cell death compared with treatment with control oligonucleotide (33+/-2% vs. 13+/-3%, P<0.0001). 5-FU alone had no effect on BL cells (4.4% cell death, P=0.15). The addition of 5-FU after antisense oligonucleotide resulted in a significant synergistic increase in cell death equal to 69+/-2% compared with treatments with antisense oligonucleotide alone, 5-FU alone and control oligonucleotide (P<0.0001). Similar results were found in the C8161 melanoma cell line. In both cell lines, reduction in cell viability was accompanied by an increased loss of adhesion and increased apoptosis that was proportional to the decrease in viability. Treatment with antisense oligonucleotide plus 5-FU resulted in significantly decreased p125FAK expression in both C8161 and BL melanoma cell lines, demonstrated by Western blot analyses. These data show that the downregulation of FAK by antisense oligonucleotide combined with 5-FU chemotherapy results in a greater loss of adhesion and greater apoptosis in melanoma cells than treatment with either agent alone, suggesting that the combination may be a potential therapeutic agent for human melanoma in vivo.


Prenatal ultrasound-assisted identification of multiple malformations caused by a deletion in the long-arm end of chromosome 7 and review of the literature.
Clinical cases of chromosome 7 long-arm end deletion are rare. Generally, 7q terminal deletion syndrome results in complex clinical phenotypes, such as microcephaly, growth and development retardation, holoprosencephaly, and sacral hypoplasia. Herein, we report the genetic and clinical features of a fetus with multiple malformations observed by prenatal ultrasound. The results showed that there was a large fragment deletion of approximately 27.7 Mb in 7q32.3-qter. The induced fetus showed facial abnormalities of cleft lip and palate, and some organ structural abnormalities (such as diaphragmatic hernia and polycystic renal dysplasia) were observed by autopsy and pathology. To provide more reliable information for disease diagnosis and genetic counseling, we reviewed and analyzed the reported cases of isolated 7q terminal syndrome.


Conformation Dependent Architectures of Assembled Antimicrobial Peptides with Enhanced Antimicrobial Ability.
Antimicrobial peptides (AMPs) are a developing class of natural and synthetic oligopeptides with host defense mechanisms against a broad spectrum of microorganisms. With in-depth research on the structural conformations of AMPs, synthesis or modification of peptides has shown great potential in effectively obtaining new therapeutic agents with improved physicochemical and biological properties. Notably, AMPs with self-assembled properties have gradually become a hot research topic for various biomedical applications. Compared to monomeric peptides, these peptides can exist in diverse forms (e.g., nanoparticles, nanorods, and nanofibers) and possess several advantages, such as high stability, good biocompatibility, and potent biological functions, after forming aggregates under specific conditions. In particular, the stability and antibacterial property of these AMPs can be modulated by rationally regulating the peptide sequences to promote self-assembly, leading to the reconstruction of molecular structure and spatial orientation while introducing some peptide fragments into the scaffolds. In this work, four self-assembled AMPs are developed, and the relationship between their chemical structures and antibacterial activity is explored extensively through different experiments. Importantly, the evaluation of antibacterial performance in both in vitro and in vivo studies has provided a general guide for using self-assembled AMPs in subsequent treatments for combating bacterial infections.


Optimized Whole Transcriptome Profiling of Motor Axons.
In highly polarized cells such as neurons, most RNA molecules are not randomly distributed but sorted into different compartments. So far, methods to analyze the transcriptome in distinct subcellular compartments are not well established. Here, we first describe the culturing of primary motoneurons in compartmentalized chambers to separate the axons from the somatodendritic compartment. Second, we introduce a method for whole transcriptome amplification followed by high-throughput sequencing to analyze the RNA composition of these two different compartments in neuronal cells.


Effects of temperature, pH, water activity and CO2 concentration on growth of Rhizopus oligosporus NRRL 2710.
To investigate the effects of temperature, pH, water activity (aw) and CO2 concentration on the growth of Rhizopus oligosporus NRRL 2710. Hyphal extension rates from mycelial and spore inocula were measured on media with different aw (approximately 1.0, 0.98 and 0.96) and pH (3.5, 5.5 and 7.5) incubated at 30, 37 or 42 degrees C in atmospheres containing 0.03, 12.5 or 25% (v/v) CO2. The effects of environmental conditions on hyphal extension rate were modelled using surface response methodology. The rate of hyphal extension was very sensitive to pH, exhibiting a pronounced optimum at pH 5.5-5.8. The hyphal extension rate was less sensitive to temperature, aw or CO2, exhibiting maximum rates at 42 degrees C, a(w) approximately 1.0 and 0.03% (v/v) CO2. The fastest hyphal extension rate (1.7 mm h(-1)) was predicted to occur at 42 degrees C, pH 5.85, a(w) approximately 1.0 and 0.03% CO2. The present work is the first to model the simultaneous effects of temperature, pH, aw and CO2 concentration on mould growth. The information relates to tempe fermentation and to possible control of the microflora in Tanzanian cassava heap fermentations.


Normal neuroanatomical variation due to age: the major lobes and a parcellation of the temporal region.
We used high-resolution MRI to investigate gray and white matter aging in the major lobes of the cerebrum (frontal, parietal, temporal, occipital) and the major sectors of the temporal lobe (temporal pole, superior temporal gyrus, infero-temporal region, parahippocampal gyrus, amygdala, hippocampus). Subjects included 87 adults between the ages of 22 and 88 years. Regions of interest were hand-traced on contiguous 1.5mm coronal slices. For the cerebrum in general, gray matter decreased linearly with age, resulting in a decline of about 9.1-9.8% between the ages of 30 and 70 years, and a decline of 11.3-12.3% by the age of 80. In contrast, white matter volume increased until the mid-50s, after which it declined at an accelerated rate. At 70 years, white matter volume was only 5.6-6.4% less than at 30 years, but by age 80, a cubic regression model predicted that the decrease would be 21.6-25.0%. Multivariate analyses indicate that the frontal gray matter was most strongly associated with age, while occipital gray and white matter were least associated. Reduction in volume in the hippocampus was best modeled by a cubic regression model rather than a linear model. No sex differences in aging were found for any regions of interest.


FKBP12.6 disruption impairs glucose-induced insulin secretion.
Cyclic ADP-ribose (cADPR), accumulated in pancreatic beta-cells in response to elevated ATP levels after glucose stimulation, mobilizes Ca(2+) from the endoplasmic reticulum through the ryanodine receptor (RyR) and thereby induces insulin secretion. We have recently demonstrated in an in vitro study that cADPR activates RyR through binding to FK506-binding protein 12.6 (FKBP12.6), an accessory protein of RyR. Here we generated FKBP12.6-deficient (FKBP12.6(-/-)) mice by homologous recombination. FKBP12.6(-/-) mice showed glucose intolerance coupled to insufficient insulin secretion upon a glucose challenge. Insulin secretion in response to glucose was markedly impaired in FKBP12.6(-/-) islets, while sulfonylurea- or KCl-induced insulin secretion was unaffected. No difference was found in the glucose oxidation rate between FKBP12.6(-/-) and wild-type islets. These results indicate that FKBP12.6 plays a role in glucose-induced insulin secretion downstream of ATP production, independently of ATP-sensitive K(+) channels, in pancreatic beta-cells.


Close Patient Follow-up Among Patients Receiving Outpatient Parenteral Antimicrobial Therapy.
Outpatient parenteral antimicrobial therapy (OPAT) programs allow patients to receive intravenous treatment in the outpatient setting. We developed a predictive model of 30-day readmission among hospitalized patients discharged on OPAT from 2 academic medical centers with a dedicated OPAT clinic for management. A retrospective medical records review was performed and logistic regression was used to assess OPAT and other outpatient clinic follow-up in conjunction with age, sex, pathogen, diagnosis, discharge medication, planned length of therapy, and Charlson comorbidity score. We hypothesized that at least 1 follow-up visit at the Emory OPAT clinic would reduce the risk for hospital readmission within 30 days. Among 755 patients, 137 (18%) were readmitted within 30 days. Most patients (73%) received outpatient follow-up care at Emory Healthcare within 30 days of discharge or prior to readmission, including 52% of patients visiting the OPAT clinic. The multivariate logistic regression model indicated that a follow-up OPAT clinic visit was associated with lower readmission compared to those who had no follow-up visit (odds ratio, 0.10 [95% confidence interval, .06-.17]) after adjusting for infection with enterococci, Charlson score, discharge location, and county of residence. These results can inform potential interventions to prevent readmissions through OPAT clinic follow-up and to further assess factors associated with successful care transitions from the inpatient to outpatient setting.


SCLERAL BUCKLING WITH WIDE-ANGLED ENDOILLUMINATION AS A SURGICAL EDUCATIONAL TOOL.
To describe a technique of wide-angle viewing as an educational tool in scleral buckling for rhegmatogenous retinal detachment. Retrospective comparative study of the reported technique was performed. Fourteen consecutive patients each who underwent Chandelier-assisted scleral buckling (CSB) or standard scleral buckling (SSB) using indirect ophthalmoscope were included. The primary outcome measure was the proportion of eyes that had successful reattachment of retina. Mean study eye baseline visual acuity was 20/160 in the CSB group and 20/320 in SSB group. The primary reattachment rate was similar, with 13 of 14 eyes (92.85%) successfully attached in the CSB group and 12 of 14 eyes (85.71%) in the SSB group. The mean visual acuity improved from 20 of 160 to 20 of 80 in the CSB group, and 20 of 320 to 20 of 160 in the SSB group. The surgical time was significantly less in the CSB group (77.85 ± 16.37 minutes) compared with the SSB group (95.71 ± 26.59 minutes, P = 0.037). Chandelier-assisted buckling had similar outcomes compared with standard buckling. It could be used as a valuable educational tool for teaching fellows by allowing them to simultaneously view the operative steps along with the surgeon.


Adaptive down-regulation of the serotonin transporter in the 6-hydroxydopamine-induced rat model of preclinical stages of Parkinson's disease and after chronic pramipexole treatment.
Our recent study has indicated that a moderate lesion induced by bilateral 6-hydroxydopamine (6-OHDA) injections into the ventrolateral region of the caudate-putamen (CP) in rats, modeling preclinical stages of Parkinson's disease, induces a "depressive-like" behavior which is reversed by chronic treatment with pramipexole (PRA). The aim of the present study was to examine the influence of the above lesion and chronic PRA treatment on binding to the serotonin transporter (SERT) in different brain regions. As before, 6-OHDA (15 μg/2.5 μl) was administered bilaterally into the CP. PRA (1mg/kg) was injected subcutaneously twice a day for 2 weeks. Serotonergic and dopaminergic neurons of the dorsal raphe (DR) were immunostained for tryptophan hydroxylase and tyrosine hydroxylase, respectively, and were counted stereologically. Binding of [(3)H]GBR 12,935 to the dopamine transporter (DAT) and [(3)H]citalopram to SERT was analyzed autoradiographically. Intrastriatal 6-OHDA injections decreased the number of dopaminergic, but not serotonergic neurons in the DR. 6-OHDA reduced the DAT binding in the CP, and SERT binding in the nigrostriatal system (CP, substantia nigra (SN)), limbic system (ventral tegmental area (VTA), nucleus accumbens (NAC), amygdala, prefrontal cortex (PFCX), habenula, hippocampus) and DR. A significant positive correlation was found between DAT and SERT binding in the CP. Chronic PRA did not influence DAT binding but reduced SERT binding in the above structures, and deepened the lesion-induced losses in the core region of the NAC, SN, VTA and PFCX. The present study indicates that both the lesion of dopaminergic neurons and chronic PRA administration induce adaptive down-regulation of SERT binding. Moreover, although involvement of stimulation of dopaminergic transmission by chronic PRA in its "antidepressant" effect seems to be prevalent, additional contribution of SERT inhibition cannot be excluded.


Comparison of the Isolator 1.5 Microbial Tube with a conventional blood culture broth system for detection of bacteremia in children.
A lysis direct plating technique, utilizing the Isolator 1.5 Microbial Tube (Du Pont Company) was compared to a conventional two-bottle culture system during a prospective study conducted in a children's hospital. Specimens were processed so that the amounts of blood allocated to each conventional blood culture bottle and the Isolator tube were as equivalent as possible. Of the 1,823 specimens enrolled, 93 (5.1%) yielded growth of 102 clinically significant isolates. Lysis direct plating and conventional blood culture bottles detected 85 and 89 of the isolates, respectively. No statistically significant differences were observed between the two methods in the overall efficiency of organism recovery or in the detection of any specific organism. Contamination rates during the entire study were 14.1% and 3.6% for lysis direct plating and conventional blood culture bottles, respectively. The mean time to availability of colonies of clinically significant isolates from specimens positive by both methods was 29 hr and 35 hr for lysis direct plating and conventional blood culture bottles, respectively. We conclude that lysis direct plating offers an attractive alternative to conventional blood culture bottles for the processing of blood cultures from pediatric patients.


Reproductive and neurobehavioral effects of dinotefuran in an F1 -generation toxicity study in mice.
Few studies were found for neurobehavioral toxicity of dinotefuran in mammals. This study was designed to evaluate the reproductive and neurobehavioral effects of dinotefuran exposure in mice. Dinotefuran was given in the diet to provide levels of 0% (control), 0.015%, 0.03%, and 0.06% from 5 weeks of age of the F0 generation to 11 weeks of age of the F1 generation in mice. Selected reproductive and neurobehavioral parameters were measured. Movement time increased with a significant dose-related trend, and the related variables of rearing time decreased in significant dose-related trends in adult males in the F0 generation. Litter size and weight increased in significant dose-related trends, and sex ratio decreased in a significant dose-related trend. The average body weight of offspring increased in a significant dose-related trend on postnatal day (PND) 21 in both sexes. In the olfactory orientation on PND 14 in female offspring, the time required lengthened in a significant dose-related trend. In male offspring, total distance and the average speed decreased in significant dose-related trends, and the average time of rearing, number of defecations, and frequencies of mice with urination increased in a significant dose-related trend. In female offspring, the related variables of rearing increased in significant dose-related trends. In spontaneous behavior of males, the parallel lines during the control and treatment groups indicated a significant distance in the number of horizontal activities. The dose levels of dinotefuran in the present study produced several adverse effects on reproductive and neurobehavioral parameters in mice.


Microplastic contamination in brown shrimp (Crangon crangon, Linnaeus 1758) from coastal waters of the Southern North Sea and Channel area.
This study assessed the capability of Crangon crangon (L.), an ecologically and commercially important crustacean, of consuming plastics as an opportunistic feeder. We therefore determined the microplastic content of shrimp in shallow water habitats of the Channel area and Southern part of the North Sea. Synthetic fibers ranging from 200μm up to 1000μm size were detected in 63% of the assessed shrimp and an average value of 0.68±0.55microplastics/g w. w. (1.23±0.99microplastics/shrimp) was obtained for shrimp in the sampled area. The assessment revealed no spatial patterns in plastic ingestion, but temporal differences were reported. The microplastic uptake was significantly higher in October compared to March. The results suggest that microplastics >20μm are not able to translocate into the tissues.


Construction of three contiguous stereocenters through amine-catalyzed asymmetric aldol reactions.
Three contiguous stereocenters were constructed by an amino acid-catalyzed asymmetric aldol reaction of α-siloxyketones with racemizable α-haloaldehydes via dynamic kinetic resolution. One-pot catalytic asymmetric synthesis of the highly functionalized products could also be accomplished by the α-bromination of simple aldehydes and the subsequent asymmetric aldol reaction.


COPD and the metabolic syndrome: an intriguing association.
Chronic Obstructive Pulmonary Disease (COPD) has been recently recognized as a condition involving more than the lungs. The presence of common factors in COPD and in other chronic extra-pulmonary diseases, as well as the co-existence of these conditions in the same adult individual, supports the hypothesis of a shared pathogenetic pathway. We will here review the interplay between coexisting COPD and the metabolic syndrome (MS), based on the most updated knowledge. We will discuss this clinical condition from the definition, to the pathophysiology and to the clinical implications. Basically, MS is more likely to be present in a COPD patients, and increased levels of circulatory pro-inflammatory proteins from both the lung and adipose tissue coincide in these patients. The relative impact of the coexisting COPD and MS may depend on several factors: the presence of physical inactivity and of systemic inflammation related to a smoking habit, sedentary lifestyle, airway inflammation and obstruction, adipose tissue and inflammatory marker activation. More studies will be required to elucidate the association between COPD and MS and to formulate individualized management approaches for this specific disease phenotype.


A single session of EUS directed transgastric ERCP and EUS FNB in a patient with RYGB, pancreatic head tumor and biliary obstruction.
The alteration of the gastrointestinal anatomy represents a challenge for the performance of endoscopic procedures in case of bile duct obstruction. Follow we present the technique used in a patient with altered anatomy and a mass in the head of the pancreas with obstruction of the bile duct through endoscopic ultrasound-guided trans gastric retrograde cholangiopancreatography.


Compact localized states in magnonic Lieb lattices.
Lieb lattice is one of the simplest bipartite lattices, where compact localized states (CLS) are observed. This type of localization is induced by the peculiar topology of the unit cell, where the modes are localized only on selected sublattices due to the destructive interference of partial waves. We demonstrate the possibility of magnonic Lieb lattice realization, where flat bands and CLS can be observed in the planar structure of sub-micron in-plane sizes. Using forward volume configuration, the Ga-doped YIG layer with cylindrical inclusions (without Ga content) arranged in a Lieb lattice with 250 nm period was investigated numerically (finite-element method). The structure was tailored to observe, for a lowest magnonic bands, the oscillatory and evanescent spin waves in inclusions and matrix, respectively. Such a design reproduces the Lieb lattice of nodes (inclusions) coupled to each other by the matrix with the CLS in flat bands.


When less is more--microRNAs and psychiatric disorders.
MicroRNAs are small non-coding RNA molecules that regulate gene expression, including genes involved in neuronal function and plasticity that have relevance for brain function and mental health. We therefore performed a systematic review of miRNAs in general adult psychiatric disorders. Systematic searches in PubMed/MEDLINE and Web of Science were conducted to identify published clinical articles on microRNAs in general adult psychiatric disorders. We also reviewed references from included articles. There is mounting evidence of microRNAs' regulatory roles in a number of central nervous system processes, including neurogenesis and synaptic plasticity. The majority of clinical studies of microRNAs in psychiatric disorders are in schizophrenia, where a number of specific microRNAs have been identified in separate studies. There is some evidence of marked downregulation of some microRNAs in affective disorders. Treatment with antidepressants appears to upregulate microRNA levels. There is currently little evidence from human studies in anxiety, addiction or other psychiatric disorders. MicroRNA research in psychiatry is currently in a nascent period, but represents an emerging and exciting area, with the potential to clarify molecular mechanisms of disease and identify novel biomarkers and therapeutic agents.


BRAF mutation and anaplasia may be predictive factors of progression-free survival in adult pleomorphic xanthoastrocytoma.
Pleomorphic xanthoastrocytoma (PXA) is a rare, low-grade glioma that frequently occurs in pediatric patients. To analyze adult patients diagnosed with PXA and to search for pathological and molecular markers of diagnosis and prognosis. We retrospectively included patients older than 16 years with PXA who were referred to our institution between October 2003 and September 2013. All pathological diagnoses were reviewed by a neuropathologist. Histological characteristics and immunostaining of GFAP, OLIG2, neurofilament, CD34, Ki67, p53, p16, and IDH1 R132H were analyzed. The following molecular alterations were analyzed: mutations of IDH1/2, BRAF and the histone H3.3 and the EGFR amplification. Clinical data, treatment modalities, and patient outcome were recorded. We identified 16 adult patients with reviewed PXA diagnosis. No IDH neither histone H3.3 mutations were found; BRAF V600E mutation was recorded in six patients. Ten patients presented with anaplastic features. BRAF mutations were associated with lower Ki67, OLIG2 expression, and lack of p16 expression. Median PFS and OS were 41.5 months (95% CI: 11.4-71.6) and 71.4 months (95% CI: 15.5-127.3), respectively. BRAF mutation tended to be associated with greater PFS (p = 0.051), whereas anaplastic features were associated with minimal PFS (p = 0.042). PXA in adults PXA may present features distinct from pediatric PXA. Anaplastic features and BRAF mutation may potentially identify specific subgroups with distinct prognoses.


Positron emission tomography for staging and management of malignant melanoma.
The incidence of malignant melanoma is rising; it now has an incidence of ten per 100 000 per annum in the UK. The development of metastases is unpredictable, but prognosis is linked directly to the initial stage at diagnosis. Positron emission tomography (PET) can allow the detection of malignant cells at a relatively early stage. A review of the literature was undertaken by searching the Medline database for the period 1980-2000 without any language restrictions. The overall sensitivity and specificity of PET are 74-100 and 67-100 per cent respectively. PET has a reduced sensitivity and specificity for thinner lesions (less than 1 x 5 mm). Comparison with computed tomography and magnetic resonance imaging has shown a higher sensitivity and specificity for PET in all regions of the body except the thorax. Currently the accepted indication for PET is recurrent melanoma when surgical intervention is being considered. However, other potential indications include the detection of occult or distant metastasis at initial presentation and the clarification of abnormal radiological findings at follow-up. The routine use of PET for American Joint Commission on Cancer stage I or II disease is of uncertain benefit and is not indicated at present.


Shape from shading in different frames of reference.
It has often been reported that, in the absence of information about the direction of illumination, people interpret surface convexities and concavities in accordance with the assumption that illumination comes from above. However, 'above' could mean with reference to gravity, the head or the retina. Yonas et al reported that four-year-old infants use the head more than gravity as the frame of reference in interpreting surface relief but that seven-year-olds make about equal use of the two frames of reference. The potency of these two frames of reference when acting separately and when pitted against each other was measured on adult subjects. For all subjects the 'assumption' about the direction of illumination was predominantly with respect to the head. The gravitational frame was used only when the headcentric frame was irrelevant, and then not consistently.


Why do people go to the doctor? Sex differences in the correlates of GP consultation.
This study explores the variables associated with consultation behaviour within the NHS of 256 men and women aged 16-45 and registered with one GP. The focus is on long term effects rather than on the immediate precipitants of a consultation and hence the dependent variable is the one year consultation rate. The predictor variables include predisposing, enabling and need factors. It is found that not only do women consult more often than men but also the correlates of primary care utilisation differ between the sexes. Health status (need) and social role factors (including parenthood and marital status) are found to be more important for men, while psychological predisposition is of greater significance among women in this setting. The implications of the findings are discussed.


Management and outcomes of non-small cell lung cancer patients with rapid progression under second-or-more-line immune checkpoint inhibitors: ERORECI study (GFPC 2016-04).
Immune checkpoint inhibitors (ICIs) have been approved as second-line therapy for advanced non-small cell lung cancers (NSCLCs) progressing after platinum-based chemotherapy. However, some patients' disease progressed rapidly and sometimes exhibited explosive tumor progression. This descriptive, prospective study aimed to assess the characteristics of nonresponders with rapid progression (RP), defined as progression-free survival (PFS) ≤2 or 2-4 months under ICIs. This analysis included all consecutive ICI-treated (second-or-more line) patients with RP ≤4 months from 1 September 2016 to 31 August 2017 and compared the clinical characteristics, treatments, and outcomes (overall survival [OS]; responses; PFS, according to treatment line) of NSCLCs that progressed after ≤2 vs 2-4 months on ICIs. Comparisons of the 224 (70.2%) patients with ≤2-month and 95 (29.8%) with 2- to 4-month RP revealed the former had less frequent nonsmokers and ECOG PS = 0, more frequent stage IV disease and higher neutrophil/lymphocyte ratio. Their respective ICI PFS rates were: 1.6 [95% CI: 0.1-2] and 2.7 [2.0-4.2] months, with 16.5% and 11.6% having partial responses to first- and second-line therapies post-ICI chemotherapy. Their respective median OS rates were 6.0 and 9.0 months (P ≤ .009). Multivariate analysis retained only PFS of the first-line therapy pre-ICI and neutrophil/lymphocyte ratio at ICI onset as being significantly associated with ≤2-month RP. In the real-life setting, NSCLC RP on ICI remains a challenge. New descriptive and analytic studies are needed to identify factors predictive of RP.


[Predictors of clinical response in patients with ulcerative colitis treated with granulocyte-monocyte apheresis: analysis of the apheresis registry data].
We analyzed predictors of clinical response after a cycle of granulocytemonocyte apheresis in 173 patients with ulcerative colitis. Hemoglobin levels independently predicted good clinical outcome.


The application of fourier transform infrared transmission spectroscopy to the study of model and natural membranes.
Fourier transform infrared transmission spectroscopy is presented as a technique with great potential for the study of aqueous membrane preparations. The methodology of sample preparation, spectra recording and data reduction is outlined. Spectral parameters are derived from FT-IR difference spectra which provide an extremely sensitive means to monitor the temperature-dependent behavior of individual vibrational modes in model and natural membranes.


Endoscopic variceal ligation vs. propranolol for prevention of first variceal bleeding: a randomized controlled trial.
Data in the literature regarding the role of endoscopic variceal ligation for the prevention of first variceal bleeding in cirrhotic patients are controversial. To further explore this issue we have compared ligation and propranolol treatment in a prospective randomized study. Sixty patients with cirrhosis and oesophageal varices with no history but at high risk of bleeding were randomized to ligation treatment (30 patients) or propranolol (30 patients). Patients were followed for approximately 27.5 months. Variceal obliteration was achieved in 28 patients (93.3%) after 3+/-1 sessions. The mean daily dose of propranolol was 60.3+/-13.3 mg. Two patients (6.7%) in the ligation group and nine patients (30%) in the propranolol group developed variceal bleeding (P = 0.043). The actuarial risks of variceal bleeding at 2 years were 6.7% and 25%, respectively. On multivariate analysis, propranolol treatment and grade III varices turned out to be predictive factors for the risk of variceal bleeding. Mortality was not different between the two groups. There were no serious complications due to ligation. Propranolol treatment was discontinued in four patients because of side effects. Variceal ligation is a safe and more effective method than propranolol treatment for the prevention of first variceal bleeding in cirrhotic patients with high-risk varices.


Hysteroscopy with directed biopsy versus dilatation and curettage for the diagnosis of endometrial hyperplasia and cancer in perimenopausal women.
The present study was undertaken to compare the effectiveness of dilatation and curretage (D&C) with hysteroscopy and guided biopsy (H+B) for the collection of endometrial samples adequate for histological examination in perimenopausal women at risk of endometrial hyperplasia or cancer. We performed hysteroscopy and biopsy followed by dilatation and curettage in 734 patients with abnormal perimenopausal bleeding or sonographically revealed endometrial pathology. Two hundred and ninety-two patients in whom lesions were totally removed during hysteroscopy were excluded from further study. Using both methods we disclosed 64 cases of endometrial polyps, 60 cases of endometrial hyperplasia, and 49 cases of endometrial cancer. Hysteroscopy left just four cases of endometrial pathology undiagnosed as opposed to 21 cases using dilatation and curettage. Histology could not be performed on material obtained with hysteroscopy in four cases and with curettage in 23 cases. 1) Hysteroscopy with directed biopsy is more sensitive in disclosing all types of uterine lesions than dilatation and curettage. 2) Curettage done after hysteroscopy and directed biopsy does not improve the detection of endometrial cancer.


Effects of adenoviral up-regulation of bcl-2 on oxidative stress and graft coronary artery disease in rat heart transplants.
Bcl-2 has been shown to have antioxidant properties. Early oxidative stress is an important antigen-independent factor that contributes to the development of graft coronary artery disease (GCAD). We hypothesized that adenoviral up-regulation of bcl-2 would decrease early oxidative stress and inhibit GCAD after heart transplantation. PVG rat hearts were treated with adenovirus carrying the human bcl-2 gene (AdvBcl-2) or null adenovirus (AdvNull) then transplanted into the abdomens of PVG recipients. After 4 days of reperfusion to allow adenoviral gene expression, grafts were retransplanted into ACI rat recipients and reperfused for 4 or 8 hours or 90 days (cyclosporine A 7.5 mg/kg on postoperative day [POD] 0-9). Production of tumor necrosis factor (TNF)-alpha after 4 hours and oxidized glutathione (GSSG) after 8 hours indicated development of oxidative stress. 90-day allografts were assessed for GCAD by way of computerized morphometry. Over-expression of bcl-2 at the time of allograft reperfusion was confirmed by Western blotting. Whereas AdvNull-treated hearts demonstrated elevated TNF-alpha levels after 4 hours and increased GSSG after 8 hours of reperfusion, AdvBcl-2-treated hearts were no different from nontransplanted hearts. AdvBcl-2 treatment also resulted in decreased luminal narrowing and intima-to-media ratio at POD 90. Bcl-2 over-expression interrupts the development of oxidative stress in reperfused rat-heart allografts. Early up-regulation of bcl-2 also decreases GCAD, indicating the importance of early oxidative stress and the role that bcl-2 may play in the long-term function of heart transplants.


Pigment changes of the retina in chronic progressive external ophthalmoplegia (CPEO).
A study was made of the retinal functions in 4 patients with chronic progressive external ophthalmoplegia, general myopathy, EEG anomalies and pigment changes of the fundus oculi (ophthalmoplegia-plus). Three of them exhibited typical, granular pigmentations in a linear or reticular arrangement at the periphery. All four showed slight to moderate pigment epithelial defects in the maculae, mostly only discernible with fluorescence angiography. In all 4 cases, a slight decrease of the visual acuity, a mildly abnormal ERG, mild concentric restriction of the field of vision and, in two cases, an abnormal dark-adaptation curve led to the conclusion of a mild diffuse, widely disseminated receptor affection of the retina (both rods and cones). The EOG appeared normal in 3, and at the lower limit of normal in 1 case. On the basis of a detailed study of the literature we can conclude that the retinal lesions in chronic progressive external ophthalmoplegia may vary from benign pigmentations without functional impairment to genuine 'retinitis pigmentosa' with all gradations of rod-cone or cone-rod dystrophy. Emphasis is laid on the possibility of a correlation between the mitochondrial abnormalities encountered in ocular myopathy and ophthalmoplegia-plus on the one hand, and the retinal abnormalities on the other, with special reference to a possible disorder of the utilization of pyruvate in the citric-acid cycle and a loose coupling of the oxidative phosphorylation.


Correlations between radiological and cytological findings in early development of bronchopulmonary dysplasia.
Sequential chest radiographs from 40 newborn infants requiring assisted ventilation for respiratory distress syndrome or other conditions were evaluated with a new scoring system aiming at identifying abnormal expansion patterns and interstitial infiltrates representing an early stage of bronchopulmonary dysplasia (BPD). Age at examination ranged from 3 to 23 days. Tracheal effluent samples obtained from the babies during the same period of observation were examined cytologically for evidence of regenerating airway epithelium with squamous metaplasia, indicating BPD. According to the radiological scoring system 24 babies (60%) developed BPD, first diagnosed at a median age of 9 days. By cytological criteria 20 babies (50%) developed BPD, first diagnosed at a median age of 10.5 days. The results from radiological and cytological diagnosis of BPD were concordant in 16 babies (P < 0.05 by chi-square test). Using oxygen dependency at the age of 28 days as evidence of established BPD, the radiological scoring system alone had a sensitivity of 93% and a specificity of 53%. The corresponding figures for cytological assessment alone were 73% and 58%, respectively. By combining radiological and cytological findings, values for sensitivity and specificity were 67% and 68%, respectively.


The inequality of city-level energy efficiency for China.
This paper proposes a new methodology for measuring energy efficiency inequality based on the Shephard energy distance function and the "double" stochastic meta-frontier. To incorporate the regional inequality, we use three different grouping criteria, geography, city features, and strategic development goals. We also explore whether the different city grouping criteria can influence the energy efficiency. A panel data of 284 cities in China from 2003 to 2013 is used for empirical analysis. The results indicate that the regional heterogeneity has significant impact on the energy efficiency. We find that different grouping criteria affect energy efficiency, especially, the urban feature criteria. These results highlight the importance of choosing a proper grouping criteria in meta-frontier energy efficiency analysis.


Direct inhibitory action of EGTA-Ca complex on reverse-mode Na/Ca exchange in Myxicola giant axons.
Giant axons from the marine annelid Myxicola infundibulum were internally dialyzed with solutions containing 22Na ions as tracers of Na efflux. In experiments performed in Li-substituted seawater, Na efflux that is dependent on external Ca ion concentration, [Ca2+]o, was measured using dialysis to maintain [Na+]i at 100 mM, which enhances the [Ca2+]o-dependent Na efflux component, (i.e., reverse-mode Na/Ca exchange). When dialysis fluid contained EGTA (1 mM) to buffer the internal Ca concentration, [Ca2+]i, to desired levels, Na efflux lost its normal sensitivity to external calcium. The inhibition was not simply due to the Ca-chelating action of EGTA to produce insufficient [Ca2+]i to activate Na/Ca exchange. The addition of EGTA inhibited Cao-dependent Na efflux even when a large enough excess of [Ca2+]i was present to saturate the EGTA and still produce elevated values of [Ca2+]i. Control experiments showed that these high values of [Ca2+]i resulted in normal Na/Ca exchange in the absence of EGTA. It is concluded that the presence of EGTA itself interferes with the manifestation of reverse-mode Na/Ca exchange in Myxicola giant axons.


Is antibiotic prophylaxis mandatory in laparoscopic incisional hernia repair? Data from the herniamed registry.
Several meta-analyses showed that laparoscopic incisional hernia repair is associated with lower surgical site infection (SSI) rates compared to open repair. However, the efficiency of antibiotic prophylaxis (AP) in laparoscopic incisional hernia repair alone is unknown and needs evaluation. Due to increasing antimicrobial resistance, a major global health care problem, AP needs to be critically evaluated. The aim of this study was to investigate the impact of AP on the rate of SSI and complication-related reoperations in patients undergoing laparoscopic incisional hernia repair. Prospectively documented data from the Herniamed Hernia Registry from 2009 to 2017 were retrospectively analysed. Multivariable analyses were used to study the influence of AP as well as further patient and surgery-related risk factors on SSI and complication-related reoperation rates. This was verified in a sensitivity analysis using propensity-score matching. In the analysed time period 13'513 patients undergoing elective laparoscopic incisional hernia repair were recorded, of which 14.4% (n = 1949) did not receive AP. The overall SSI rate showed no significant difference when directly comparing patients with (0.74%) and without AP (0.97%; p = 0.262). In the multivariable analysis the presence of patient related risk factors (p = 0.015) and defect size >10 cm (p = 0.035) significantly increased the rates of SSI and complication-related reoperations. The propensity-score matching analysis verified that SSI rates are not significantly different between the two groups (p = 0.265). In cases of laparoscopic incisional hernia repair in patients without risk factors and moderate hernia diameter (<10 cm), routine administration of AP in laparoscopic incisional hernia repair does not seem to be justified.


The legacy effect of microplastics on aquatic animals in the depuration phase: Kinetic characteristics and recovery potential.
The prevalence of microplastics (MPs) in global aquatic environments has received considerable attention. Currently, concerns have been raised regarding reports that the adverse effect of MPs on aquatic animals in the exposure phase may not be (completely) reversed in the depuration phase. In order to provide insights into the legacy effect of MPs from the depuration phase, this study evaluated the kinetic characteristics and recovery potential of aquatic animals after the exposure to MPs. More specifically, a total of 68 depuration kinetic curves were highly fitted to estimate the retention time of MPs. It was shown that the retention time ranged from 1.26 to 3.01 days, corresponding to the egestion of 90 % to 99 % of ingested MPs. The retention time decreased with the increased retention rate. Furthermore, variables potentially affecting the retention time were ranked by the decision tree-based eXtreme Gradient Boosting (XGBoost) algorithm, suggesting that the particle size and tested species were of great importance for explaining the difference in retention time of MPs. Moreover, a biomarker profile was recompiled to determine the toxic changes. Results indicated that the MPs-induced toxicity significantly reduced in the depuration phase, evidenced by the recovery of energy reserves and metabolism, hepatotoxicity, immunotoxicity, hematological parameters, neurotoxicity and oxidative stress. However, the continuous detoxification and remarkable genotoxicity implied that the toxicity was not completely alleviated. In addition, the current knowledge gaps are also highlighted, with recommendations proposed for future research.


Abdominopelvic perivascular epithelioid cell tumor with overt malignancy: a case report.
Perivascular epithelioid cell tumor (PEComa) is a group of rare tumors composed of epithelioid cells with characteristic perivascular distribution and co-expression of the melanogenic marker HMB-45 and muscular markers. There are no documented parameters referring to the biologic behavior of PEComa. We report an abdominopelvic PEComa with overt malignancy in a 16-year-old girl. Histologically, the tumor showed the typical morphophenotypic characteristics of PEComa. Though the cytologic appearance of the tumor cells was relatively bland, the extensive necrosis, presence of lymph node metastases, and surrounding tissue invasion were all indicative of malignancy. Relapse of the tumor with multiple lymphadenopathy shortly after debulking surgery for the primary lesion, and postoperative adjuvant chemotherapy, further denoted its aggressive behavior.


Response surface optimization for xylanase with high volumetric productivity by indigenous alkali tolerant Aspergillus candidus under submerged cultivation.
In this study, a novel isolate Aspergillus candidus was employed for xylanase production using low cost agro residues. A Box-Behnken design matrix was used to optimize the influential parameters like carbon source, nitrogen source and incubation temperature for maximum xylanase production. Under optimized condition, enzyme titer level enhanced to 69 IU/ml at 48 h with volumetric productivity 1437 IU/l h. Growth and enzyme production were observed even at pH 11.0, indicating its ability to sustain at high alkaline environment. Little amount of cellulase was produced concomitantly with xylanase during the course of the process. Volumetric productivity of xylanase was found as a function of temperature. This fungal strain was emerged as a one among few strains having high xylanase productivity.