Isolation and molecular characterization of biosurfactant producing yeasts from the soil samples contaminated with petroleum derivatives.
In this study, 65 yeast strains were isolated from different environmental samples contaminated with various petroleum hydrocarbons such as activated sludges and soil samples from automobile workshops. The yeast isolates were tested for biosurfactant production using various screening methods such as parafilm M test, oil displacement assay, drop collapse assay, determination of surface tension reduction, and emulsification index. Nineteen of the isolates were found positive for biosurfactant production and their molecular characterizations were carried out by sequencing analysis of the ITS1-5.8S-ITS2 region and D1/D2 domain of 26S rDNA. The results indicated that these strains were from a wide range of yeast genera including Rhodotorula, Candida, Yarrowia, Geotrichum, Galactomyces, and Cystobasidium. The studies to determine the emulsification index revealed that the biosurfactants produced by Yarrowia lipolytica strains (TEMGS33, TEMOS12, and TEMOS14) and Apiotrichum loubieri strain (TEMOS16) were the most potent and capable of forming stable emulsions with emulsion index (E24 ) up to 68%. In addition, quantitative measurements of the surface tension reduction of the biosurfactants produced by these strains were carried out by Du Noüy ring method. Biosurfactants produced from Yarrowia lipolytica strain TEMGS33 and Apiotrichum loubieri strain TEMOS16 gave the best results reducing the surface tension to 34.7 ± 1.15 and 35.3 ± 0.55 mN m-1 , respectively. Based on these data, biosurfactants from Yarrawia lipolytica strains (TEMGS33, TEMOS12, and TEMOS14) and Apiotrichum loubieri strain (TEMOS16) showed promising results and might be implemented in numerous industrial fields such as bioremediation and food industry.


Strategies for saving and improving children's lives.
At the Child Abuse Recognition, Research, and Education Translation (CARRET) Conference, national child abuse experts representing different disciplines discussed and developed new strategies that would address the barriers to reporting suspected child abuse and improve the protection of children. This article describes the experts' analysis of the barriers to and strategies for improving the outcome for abused children, in addition to the steps planned to facilitate continued action.


Results of a Phase 1/2 Trial of Chemoradiotherapy With Simultaneous Integrated Boost of Radiotherapy Dose in Unresectable Locally Advanced Esophageal Cancer.
Effective treatment options for locally advanced esophageal cancer are limited, and rates of local recurrence after standard chemoradiotherapy remain high. To evaluate toxic effects, local control, and overall survival rates after chemoradiotherapy with a simultaneous integrated boost of radiotherapy dose to the gross tumor and nodal disease for patients with unresectable locally advanced esophageal cancer. A phase 1/2, single-arm trial was conducted in 46 patients from April 28, 2010, to April 9, 2015 (median follow-up, 52 months [range, 2-86 months]), at a tertiary academic cancer center. Outcomes of the study patients were compared with those of 97 similar patients treated at the same institution from January 10, 2010, to December 5, 2014, as part of the interim analysis. Statistical analysis was performed from December 15, 2018, to February 12, 2019. Chemoradiotherapy with a simultaneous integrated boost of radiotherapy dose (50.4 Gy to subclinical areas at risk and 63.0 Gy to the gross tumor and involved nodes, all given in 28 fractions) with concurrent docetaxel and capecitabine or fluorouracil. Toxic effects, local (in-field) control, and overall survival rates. All 46 patients (11 women and 35 men; median age, 65.5 years [range, 37.3-84.4 years]) received per-protocol therapy, as intensity-modulated photon therapy (39 [85%]) or intensity-modulated proton therapy (7 [15%]); 11 patients (24%) ultimately underwent resection. No patients experienced grade 4 or 5 toxic effects; the 10 acute grade 3 toxic events were esophagitis (4), dysphagia (3), and anorexia (3) and the 3 late grade 3 toxic events were all esophageal strictures. The actuarial local recurrence rates were 22% (95% CI, 11%-35%) at 6 months, 30% (95% CI, 18%-44%) at 1 year, and 33% (95% CI, 20%-46%) at 2 years. Overall, 15 patients (33%) experienced local failure, at a median interval of 5 months (range, 1-24 months). The median overall survival time was 21.5 months (range, 2.3-86.4 months). Exploratory comparison with a 97-patient contemporaneous institutional cohort receiving standard-dose (non-simultaneous integrated boost) chemoradiotherapy showed superior local control (hazard ratio, 0.49; 95% CI, 0.26-0.92; P = .03) and overall survival (hazard ratio, 0.66; 95% CI, 0.47-0.94; P = .02) in the group that received chemoradiotherapy with a simultaneous integrated boost. These findings suggest that chemoradiotherapy with a simultaneous integrated boost of radiotherapy dose for locally advanced esophageal cancer is well tolerated, with encouraging local control, and thus warrants further study. ClinicalTrials.gov identifier: NCT01102088.


Activity of ofloxacin against Mycobacterium leprae in the mouse.
Mice inoculated with 4800 Mycobacterium leprae in the left hind foot pad were treated from day 62 to day 150 after infection with 50 mg or 150 mg of ofloxacin per kg body weight, 150 mg pefloxacin per kg, or 50 mg prothionamide per kg. These drugs were administered by esophageal cannula 5 days weekly with dapsone (0.01 g per 100 g diet). Multiplication of M. leprae in the treated and in untreated control mice was assessed by monthly harvests. The treatment of mice with the smaller dosage ofloxacin, with pefloxacin, prothionamide, or dapsone uniformly resulted in a delay of multiplication of 4 months, compared to the multiplication of M. leprae in the untreated controls. The delay of multiplication (4 months) being 1 month longer than the duration of drug administration (3 months), all of the treatments may be considered as bacteriopausal or moderately bactericidal. In contast with these results, treatment of mice with 150 mg ofloxacin per kg resulted in no growth of the organisms whatever as late as 18 months after inoculation, strongly suggesting that, in that dosage, ofloxacin had killed all of the M. leprae. Such a profound killing activity has been observed only with rifampin. Although the pharmacokinetic characteristics of ofloxacin are different in man from those in the mouse, the daily dosage of 150 mg ofloxacin per kg body weight in the mouse is equivalent to 400 mg per day in man which is the usual therapeutic dosage; thus, the results obtained in the mouse may be extrapolated to man. Therefore, ofloxacin appears a very promising drug for the chemotherapy of leprosy.


Pancreatic hemolymphangioma.
Hemolymphangioma of pancreas is a tumor has its origins on vascular and lymphatic vessels malformation. At this time, only eight cases have been reported (PubMed). A 52-year-old woman with history of abdominal pain and early satiety was admitted to our external consultation. Laboratory data were normal. CT initially showed a high vascularized solid tumor, apparently arising from the right hepatic lobe, and it was considered to be a hemangioma. Two sessions of CT guided embolizations were performed. Control CT scan revealed a reduction in tumor´s size and location confined to pancreatic head. With this diagnosis studies and suspicion of neoplastic tumor, it was performed a pylorus preserving pancreatoduodenectomy. Pathology report was to be a pancreatic head hemolymphangioma. Diagnosis and management of cystic pancreatic tumors can be challenging. Cystectomy or even surgical procedures as pancreatoduodenectomy should be performed when is possible. We report a case of pancreatic hemolymphangioma, a benign cystic tumor with a rare incidence.


A clinicopathologic case report on macular hole associated with von Hippel-Lindau disease: a novel ultrastructural finding of wormlike, wavy tangles of filaments.
We describe a novel ultrastructural finding observed in an epiretinal membrane excised from a patient with von Hippel-Lindau disease. This interventional case report presents a 45-year-old woman who noted decreased vision in her right eye and was referred for treatment of a macular hole secondary to von Hippel-Lindau disease. Blindness had occurred previously in the left eye because of exudative retinal detachment. Funduscopic examination revealed a macular hole associated with a delicate epiretinal membrane, multiple retinal angiomas, and multiple old laser scars. Vitrectomy was performed in her right eye. The epiretinal membrane was peeled off and processed for light and electron microscopy. Postoperatively the macular hole was successfully closed, and vision recovered to 20/20 from 20/40. In the excised epiretinal membrane, flattened glial cells and extracellular matrix containing fibrous elements formed a multilayered pattern. Ultrastructurally, the fibrous elements appeared as wormlike, wavy tangles of filaments (WWTF) with an orientation parallel to the surface of the epiretinal membrane. Just above the WWTF, flattened glial cells frequently extended thin cytoplasmic processes with pinocytotic vesicles. The ultrastructure suggested that retinal glial cells had induced a remodeling of the collagenous stroma in the posterior vitreous cortex, resulting in tangential macular traction.


Heterogeneity of endothelial function within the circulation.
As our understanding of endothelial function continues to evolve, it has become increasingly clear that the peripheral vasculature exhibits striking regional and segmental heterogeneity in the influence of the endothelial cell layer on vascular tone. This heterogeneity encompasses not only the normal interactions between endothelium-derived factors and vascular smooth muscle, but also the way in which these interactions can change during juvenile growth or in disease states such as hypertension. The underlying causes of this heterogeneity are multifactorial and include intrinsic differences among endothelial cell populations and differences in the endothelial cell microenvironment.


Electronic structure of neighboring extein residue modulates intein C-terminal cleavage activity.
Protein splicing is an autocatalytic reaction where an intervening element (intein) is excised and the remaining two flanking sequences (exteins) are joined. The reaction requires specific conserved residues, and activity may be affected by both the intein and the extein sequence. Predicting how sequence will affect activity is a challenging task. Based on first-principles density functional theory and multiscale quantum mechanics/molecular mechanics, we report C-terminal cleavage reaction rates for five mutations at the first residue of the C-extein (+1), and describe molecular properties that may be used as predictors for future mutations. Independently, we report on experimental characterization of the same set of mutations at the +1 residue resulting in a wide range of C-terminal cleavage activities. With some exceptions, there is general agreement between computational rates and experimental cleavage, giving molecular insight into previous claims that the +1 extein residue affects intein catalysis. These data suggest utilization of attenuating +1 mutants for intein-mediated protein manipulations because they facilitate precursor accumulation in vivo for standard purification schemes. A more detailed analysis of the "+1 effect" will also help to predict sequence-defined effects on insertion points of the intein into proteins of interest.


Mutant p63 Affects Epidermal Cell Identity through Rewiring the Enhancer Landscape.
Transcription factor p63 is a key regulator of epidermal keratinocyte proliferation and differentiation. Mutations in the p63 DNA-binding domain are associated with ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC) syndrome. However, the underlying molecular mechanism of these mutations remains unclear. Here, we characterized the transcriptome and epigenome of p63 mutant keratinocytes derived from EEC patients. The transcriptome of p63 mutant keratinocytes deviated from the normal epidermal cell identity. Epigenomic analyses showed an altered enhancer landscape in p63 mutant keratinocytes contributed by loss of p63-bound active enhancers and unexpected gain of enhancers. The gained enhancers were frequently bound by deregulated transcription factors such as RUNX1. Reversing RUNX1 overexpression partially rescued deregulated gene expression and the altered enhancer landscape. Our findings identify a disease mechanism whereby mutant p63 rewires the enhancer landscape and affects epidermal cell identity, consolidating the pivotal role of p63 in controlling the enhancer landscape of epidermal keratinocytes.


[The significance of motor activity in regulating the cholinergic sensitivity of cat muscle spindles].
Following a complete transection of the spinal cord at the Th12-L1, an augmented chemosensitivity of the nuclear bag and nuclear chain fibres was observed. The supersensitivity of the intrafusal fibres to subecholine was higher than to acetylcholine. The supersensitivity of the intrafusal muscle fibres against the background of intact anatomical projections suggests that the motor activity rather than axonal transport plays the leading role in regulation of the cholinergic sensitivity of intrafusal muscle fibres.


[Effect of thymectomy on activity of key enzymes of gluconeogenesis in the rat liver].
Activities of key enzymes of gluconeogenesis--phosphoenolpyruvate carboxykinase, fructose-1,6-diphosphatase, glucose-6-phosphatase as well as the content of glycogen were studied in liver tissue of thymectomized rats. Gluconeogenesis was inhibited in liver tissue of these rats. As thymus and adrenal cortex are firmly related, the inhibition of gluconeogenesis in liver tissue of thymectomized rats appears to occur due to a decrease in the glucocorticoid activating effect followed the inhibition of adrenal cortex functions and absence of thymus hormones directly responsible for carbohydrate metabolism.


Coexistent chlamydial infections related to natural history of human papillomavirus lesions in uterine cervix.
To assess the role of Chlamydia trachomatis in the development of cervical intraepithelial neoplasia (CIN) and to evaluate possible synergism between chlamydiae and human papillomavirus (HPV) in this process, 418 women who had been prospectively followed up for cervical HPV infections at our clinic since 1981 were tested for chlamydiae. At each visit the patients were examined by colposcopy, and other investigations, such as Papanicolaou (Pap) smears, punch biopsies, urethral, and cervical swabs, were undertaken as indicated. In biopsy specimens the cytopathic changes of HPV, concomitant CIN, and the local immunocompetent cell infiltrates were analysed. The latter were measured and further identified using an alpha naphthyl acetate esterase (ANAE) technique to define B cells, macrophages, and T cells and using monoclonal antibodies to define T cell subsets, NK (natural killer cells), and Langerhans cells. Chlamydial isolation (4.1% in the cervix, and 3.6% in the urethra) did not positively correlate with the degree of cytological atypia in PAP smears or with the degree of CIN lesions associated with HPV. Chlamydial cervicitis did not affect the ANAE definable cell composition of the immunocompetent cell infiltrates in HPV lesions, or that of the immunocompetent cell subsets, including the ratios of T helper to T suppressor cells and the numbers of NK cells. Chlamydial infection did not alter the natural history of HPV lesions, of which 30% regressed, 53% persisted, and 17% progressed during follow up. The present results do not provide evidence to substantiate the hypothesis that chlamydiae and HPV might act synergistically in cervical carcinogenesis, or the view that C trachomatis may be a major aetiological agent of CIN lesions. Chlamydiae and HPV are covariables of sexual behaviour, and their concomitant appearance in sexually promiscuous women is best explained by this fact. As we do not have more direct evidence for the oncogenic potential of C trachomatis (as we have of HPV), it seems reasonable to consider that this agent is not a major cause of CIN, but rather a sexually transmitted agent commonly found in women with CIN because of their promiscuous sexual behaviour.


Developmental aspects of the renal responses to hemorrhage during converting-enzyme inhibition in fetal lambs.
The role of the renin-angiotensin system in modulating the renal hemodynamic and functional responses to reductions of fetoplacental blood volume (8.8-35.5%) was studied in two groups of fetal lambs (less than 120 days and greater than 130 days gestation; term 145 days) during infusion of either captopril (experimental fetuses) or dextrose 5% in water (control fetuses). At high hemorrhage levels (level III), renal blood flow decreased and renal vascular resistance increased significantly in both groups of fetuses (less than 120 days and greater than 130 days), either treated or not treated with captopril. However, at low hemorrhage levels (levels I and II), and contrary to what was observed in young fetuses (less than 120 days), near-term fetuses (greater than 130 days) receiving captopril showed neither significant decreases in renal blood flow nor increases in renal vascular resistance, whereas untreated fetuses of the same gestational ages demonstrated significant decreases in renal blood flow and increases in renal vascular resistance. It was found in both less than 120 day and greater than 130 day fetuses that hemorrhage is associated with a decrease in urinary flow rate and free water clearance accompanied by an increase in urine osmolality and sodium reabsorption. It was shown that captopril does not modify this response. The present study also demonstrated that the blood pressure response to hemorrhage was characterized by a similar decrease in less than 120 day fetuses, whether treated or untreated with captopril. On the other hand, blood pressure did not change in control fetuses greater than 130 days, but decreased slightly in captopril-treated fetuses during hemorrhage. Taken together, the present results tend to suggest that the renin-angiotensin system may be an important modulator of the renal hemodynamic response to low level hemorrhage as fetuses approach term, and may be more important in controlling blood pressure in near-term than in young fetuses.


Group V Secreted Phospholipase A2 Induces the Release of Proangiogenic and Antiangiogenic Factors by Human Neutrophils.
Secreted phospholipases A2 (sPLA2s) are extracellular enzymes that catalyze the release of free fatty acids and lysophospholipids from membrane phospholipids and also bind to different receptors (e.g., PLA2R1 or integrins). To date, 12 mammalian sPLA2s have been identified, which play a critical role in pathophysiological processes including inflammation and cancer. sPLA2s activate immune cells such as human neutrophils (PMNs) by enzymatic activity- or receptor-mediated mechanisms. In addition, human PMNs synthesize and store human group V (hGV) and human group X (hGX) sPLA2s in their granules, but only the former is released upon cellular activation. We investigated the effects of sPLA2s on the release of proangiogenic and antiangiogenic factors by PMNs. We found that exogenous hGV and hGX sPLA2s induce the release of vascular endothelial growth factor (VEGF)-A, angiopoietin 1 (Ang1), and CXCL8/IL-8. Only hGV induces the secretion of the antiangiogenic isoform of VEGF-A, namely, VEGF-A165b. While the release of VEGF-A, Ang1, and CXCL8/IL-8 was likely mediated by hGV enzymatic activity and/or binding to PLA2R1 and heparan sulfate proteoglycans, the release of VEGF-A165b requires the interaction with αVβ3 and α4β1 integrins. We also provide evidence that endogenous hGV released by N-formyl-met-leu-phe (fMLF)-activated PMNs is involved in the release of angiogenic factors. The translational relevance of these data is supported by our findings that hGV expression is increased in human samples of lung cancer which are infiltrated by PMNs. Overall, our results suggest that the hGV-neutrophil axis may play a relevant role in the modulation of cancer-related inflammation and angiogenesis.


[Influence of voluntary military service on the sexual behavior of a population of young adults].
To determine if having done the voluntary military service is related to the sexual behavior of a population of young adults. A cross-sectional study was carried out, which involved cadets enrolled in the Peruvian Air Force Sub Officer Academy of Peru, in 2010. For this study, civilians, as well as personnel who had performed voluntary military service, anonymously answered a self-administered questionnaire about their knowledge regarding HIV transmission and sexual risk behaviors. 124 male participants took part in the study. 19.4% had performed voluntary military service and 80.6% were civilians. Those cadets who had performed voluntary military service knew more about HIV transmission than the civilians (p=0.04). Likewise, the former also had more occasional sexual partners in the last 12 months (p=0.04), number that doubled that of the civil personnel. Cadets with a record of voluntary military service informed to have consumed three times as much alcohol before their last sexual contact in comparison to the civilians (p=0.06). According to UNAIDS's definition, having performed voluntary military services was not a predictor of sexual risk behavior. Having performed voluntary military service was associated with having a better knowledge of HIV transmission. On the other hand, it seems to be related to having a higher number of occasional sexual partners. Finally, it was not found to be related to sexual risk behaviors.


Relative saliency model over multiple images with an application to yarn surface evaluation.
Saliency models have been developed and widely demonstrated to benefit applications in computer vision and image understanding. In most of existing models, saliency is evaluated within an individual image. That is, saliency value of an item (object/region/pixel) represents the conspicuity of it as compared with the remaining items in the same image. We call this saliency as absolute saliency, which is uncomparable among images. However, saliency should be determined in the context of multiple images for some visual inspection tasks. For example, in yarn surface evaluation, saliency of a yarn image should be measured with regard to a set of graded standard images. We call this saliency the relative saliency, which is comparable among images. In this paper, a study of visual attention model for comparison of multiple images is explored, and a relative saliency model of multiple images is proposed based on a combination of bottom-up and top-down mechanisms, to enable relative saliency evaluation for the cases where other image contents are involved. To fully characterize the differences among multiple images, a structural feature extraction strategy is proposed, where two levels of feature (high-level, low-level) and three types of feature (global, local-local, local-global) are extracted. Mapping functions between features and saliency values are constructed and their outputs reflect relative saliency for multiimage contents instead of single image content. The performance of the proposed relative saliency model is well demonstrated in a yarn surface evaluation. Furthermore, the eye tracking technique is employed to verify the proposed concept of relative saliency for multiple images.


Characterization of hybrid bilayer membranes on silver electrodes as biocompatible SERS substrates to study membrane-protein interactions.
Hybrid bilayer lipid membranes (HBMs) were built on roughened silver electrodes exhibiting surface-enhanced Raman scattering (SERS) activity. The HBM consisted of a first layer of octadecanethiol (ODT) directly bound to the electrode surface, on which a second layer of 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC) was obtained by self-assembled phospholipid vesicle fusion. The electrochemical properties of the HBM were investigated in situ by cyclic voltammetry (CV), AC voltammetry and electrochemical impedance spectroscopy (EIS). The results indicate that our HBMs are well-formed, and their insulating properties are comparable to those observed for HBM supported by smooth metal substrates. The interaction between the bilayer and the human enzyme cytochrome P450 2D6 (CYP2D6) was investigated. Surface-enhanced resonance Raman scattering (SERRS) measurements in combination with AC and EIS, performed on the same electrode sample, proved that the CYP2D6 is immobilized on the HBM without evident alterations of its active site and without significant perturbations of the bilayer architecture. This study yields novel insights into the properties of HBMs built on roughened surfaces, providing in situ electrochemical characterization of a substrate which is suitable for studying peripheral membrane proteins with SERRS spectroscopy.


Targeting human 8-oxoguanine DNA glycosylase to mitochondria protects cells from 2-methoxyestradiol-induced-mitochondria-dependent apoptosis.
2-Methoxyestradiol (2-ME), an endogenous estrogen metabolite of 17beta-estradiol, is known to induce mitochondria-mediated apoptosis through several mechanisms. We sought to study the effect of mitochondrialy targeted hOGG1 (MTS-hOGG1) on HeLa cells exposed to 2-ME. MTS-hOGG1-expressing cells exposed to 2-ME showed increased cellular survival and had significantly less G(2)/M cell cycle arrest compared to vector-only-transfected cells. In addition, 2-ME exposure resulted in an increase in mitochondrial membrane potential, increased apoptosis, accompanied by higher activation of caspase-3, -9, cleavage of Bid to tBid and protein poly(ADP-ribose) polymerase (PARP) cleavage in HeLa cells lacking MTS-hOGG1. Fas inhibitors cerulenin or C75 inhibited 2-ME-induced caspase activation, PARP cleavage, apoptosis and reversed mitochondrial membrane hyperpolarization, thereby recapitulating the increased expression of MTS-hOGG1. Hence, MTS-hOGG1 plays an important protective role against 2-ME-mediated mitochondrial damage by blocking apoptosis induced through the Fas pathway.


Gunslingers, poker players, and chickens 1: Decision making under physical performance pressure in elite athletes.
The cognitive skills required during sport are highly demanding; accurate decisions based on the processing of dynamic environments are made in a fraction of a second (Walsh, 2014). Optimal decision-making abilities are crucial for success in sporting competition (Bar-Eli et al., 2011; Kaya, 2014). Moreover, for the elite athlete, decision making is required under conditions of intense mental and physical pressure (Anshel and Wells, 2000), yet much of the work in this area has largely ignored the highly stressful context in which athletes operate. A number of studies have shown that conditions of elevated pressure influence athletes' decision quality (Kinrade et al., 2015; Smith et al., 2016), response times (Hepler, 2015; Smith et al., 2016) and risk taking (Pighin et al., 2015). However, almost all of this work has been undertaken in nonelite athletes and participants who do not routinely operate under conditions of high stress. Thus, there is very little known about the influence of pressure on decision making in elite athletes. This study investigated the influence of physical performance pressure on decision making in a sample of world-class elite athletes. This allowed an examination of whether findings from the previous work in nonelite athletes extend to those who routinely operate under conditions of high stress. How this work could be applied to improve insight and understanding of decision making among sport professionals is examined. We sought to introduce a categorization of decision making useful to practitioners in sport: gunslingers, poker players, and chickens. Twenty-three elite athletes who compete and have frequent success at an international level (including six Olympic medal winners) performed tasks relating to three categories of decision making under conditions of low and high physical pressure. Decision making under risk was measured with performance on the Cambridge Gambling Task (CGT; Rogers et al., 1999), decision making under uncertainty with the Balloon Analogue Risk Task (BART; Lejuez et al., 2002), and fast reactive responses and interference with the Stroop Task (Stroop, 1935). Performance pressures of physical exhaustion was induced via an exercise protocol consisting of intervals of maximal exertion undertaken on a watt bike. At a group level, under physical pressure elite athletes were faster to respond to control trials on the Stroop Task and to simple probabilistic choices on the CGT. Physical pressure was also found to increase risk taking for decisions where probability outcomes were explicit (on the CGT), but did not affect risk taking when probability outcomes were unknown (on the BART). There were no significant correlations in the degree to which individuals' responses changed under pressure across the three tasks, suggesting that elite athletes did not show consistent responses to physical pressure across measures of decision making. When assessing the applicability of results based on group averages to individual athletes, none of the sample showed an "average" response (within 1 SD of the mean) to pressure across all three decision-making tasks. There are three points of conclusion. First, an immediate scientific point that highlights a failure of transfer of work reported from nonelite athletes to elite athletes in the area of decision making under pressure. Second, a practical conclusion with respect to the application of this work to the elite sporting environment, which highlights the limitations of statistical approaches based on group averages and thus the beneficial use of individualized profiling in feedback sessions. Third, the application of this work in a sports setting is described, in particular the development and implementation of a decision-making taxonomy as a framework to conceptualize and communicate psychological skills among elite sporting professionals.


Doppler ultrasound facilitates renal vein dissection during distal splenorenal shunt.
We have found that the use of intraoperative Doppler ultrasound greatly facilitates the performance of the selective distal splenorenal shunt by precisely identifying the retroperitoneal location of the renal vein. The amount of dissection and tissue injury required for performing this operation was, thereby, minimized. This may theoretically result in a lowered incidence of postoperative ascites and complications after the Warren shunt.


Morphometric and molecular analyses of the sand fly species Lutzomyia shannoni (Diptera: Psychodidae: Phlebotominae) collected from seven different geographical areas in the southeastern United States.
A morphometric and molecular study of adult male and female Lutzomyia shannoni (Dyar 1929) collected at seven different locations within the southeastern United States was conducted to assess the degree of divergence between the grouped specimens from each location. The collection locations were as follows: Fort Bragg, NC; Fort Campbell, KY; Fort Rucker, AL; Ossabaw Island, GA; Patuxent National Wildlife Research Refuge, MD; Suwannee National Wildlife Refuge, FL; and Baton Rouge, LA. Forty males and forty females from each location were analyzed morphometrically from 54 and 49 character measurements, respectively. In addition, the molecular markers consisting of the partial cytochrome c oxidase subunit I (from 105 sand flies: 15 specimens/collection site) and the partial internal transcribed spacer 2 (from 42 sand flies: six specimens/collection site) were compared. Multivariate analyses indicate that the low degree of variation between the grouped specimens from each collection site prevents the separation of any collection site into an entity that could be interpreted as a distinct population. The molecular analyses were in concordance with the morphometric study as no collection location grouped into a separate population based on the two partial markers. The grouped specimens from each collection site appear to be within the normal variance of the species, indicating a single population in the southeast United States. It is recommended that additional character analyses of L. shannoni based on more molecular markers, behavioral, ecological, and physiological characteristics, be conducted before ruling out the possibility of populations or a cryptic species complex within the southeastern United States.


Hypothalamic-pituitary-adrenal (HPA) axis functioning as predictor of antidepressant response-Meta-analysis.
Although antidepressants are effective, around 50% of depressed patients are non-responsive. At the same time, some patients show alterations in the hypothalamic-pituitary-adrenal (HPA) axis. Due to interactions with central monoaminergic systems, these may profit less from antidepressants. To determine whether non-responders and responders differed in pre-treatment HPA axis functioning, the Cochrane Library, EMBASE, MEDLINE, and PsycINFO were searched. Studies using patients with depression being treated with antidepressants, and including both a pre-treatment HPA and a post-treatment response measure were included. Standardised mean differences were calculated for meta-analysis. Thirty-nine studies were included. Non-responders and responders did not differ in pre-treatment corticotropin-releasing hormone or adrenocorticotropic hormone. Meta-regression showed non-responders had comparably higher pre-treatment cortisol in studies measuring cortisol non-invasively, not reporting sample storage, failing to control for age, and excluding patients with comorbidities. Only studies with a specific methodological profile seem to be able to show that the more marked depressed patients' alterations in the HPA axis, the less likely they are to profit from antidepressants.


Amino acid and catecholamine markers of metabolic abnormalities in human focal epilepsy.
Studies of various parameters of amino acid and catecholamine metabolism in human cerebral cortex have provided a number of biochemical markers that appear to delineate areas of focal epileptic activity. These observations have been consolidated further by investigations of a number of experimental models of epilepsy in animals. In appraising this data, it is important to take into consideration whether the tissue samples were obtained during an actual seizure state or in an interictal period. It is also important when possible to assess the extent of astrogliosis and neuronal loss. Sites of spontaneously active epileptic spiking in the cerebral neocortex have a somewhat different amino acid profile when compared to gray matter obtained from surrounding nonspiking gyri several centimeters away. There is an elevation in glycine content, a relative diminution in taurine, and a trend towards lowered glutamic acid levels. However, the concentrations of the eight amino acids measured appear in both the foci and surround to still be within the general range for normal tissue. Measurements of key enzymes involved in the synthesis and regulation of neurotransmitters provide a complementary method of evaluating functional changes in epileptic brain as they are generally less labile than their substrates. There is a moderate increase in the activity of glutamic acid dehydrogenase, an enzyme that plays an important role in the synthesis of glutamic acid from glucose. In some patients a decrease in glutamic acid decarboxylase has also been reported: this enzyme forms gamma-aminobutyric acid (GABA) from glutamic acid and is thus important for inhibition in the central nervous system. Moreover, there is a striking increase in the activity of tyrosine hydroxylase, the rate-limiting enzyme responsible for catecholamine synthesis. The possibility of a focal abnormality in catecholamine metabolism is reinforced by the simultaneous finding of a relative decrease in the number of alpha-1 postsynaptic receptor sites. An important marker of energy metabolism in neural tissue, Na+,K+-ATPase activity, has also been found to be decreased in actively spiking human cerebral cortex. Data from experimental animal foci produced by topical application of convulsant agents show a consistent drop in glutamic acid tissue content. This can be matched to an efflux of glutamic acid from the cortical surface, which in turn is proportional to the electrographic activity of the spike focus. In addition, there is often also a decrease in taurine and GABA in such foci, as well as an increase in the levels of a number of neutral amino acids.(ABSTRACT TRUNCATED AT 400 WORDS)


[The peculiarities of defining the psychological and information characteristics of individuals in non-standard situations].
In some situations (e.g. long-duration experiments with human subjects, accidents and catastrophes) assessment of individual's ability to work or even continue functioning by objective criteria may have practical implications. The authors propose complementing the common methods of examination with a number of semantic, self-awareness, associative and symbolic (sign) questionnaires. Thrice-repeated questioning was found to provide adequate results reducing the dispersion of data. The proposed approach was positively validated in an accident and showed good consistency when compared with the objective examination data.


Screening African-American elderly for the presence of depressive symptoms: a preliminary investigation.
Several authors have reported that older African-Americans with multiple medical problems and decreased activities of daily living are at an increased risk of reporting symptoms of depression. African-Americans were more likely to report symptoms of anger, irritability, denial of illness, and to spontaneously report symptoms that did not reflect a change in mood, but rather forbearance of a difficult time or somatic complaints. This paper describes the results of a study to assess the presence of depressive symptoms in older African-American community residents. A new instrument, the Baker Belief Scale, is compared with the Center for Epidemiologic Studies-Depression Scale (CES-D) and the association of medical illnesses, social network, and level of physical function in activities of daily living (ADL). Ninety-six African-American men and women, aged 60 years or older, with equal representation from urban and rural counties in western Tennessee comprised the sample. The sample was stratified, in each of the two counties, into three age categories; 60-69, 70-79, and 80 years and older. A screening battery consisting of the Short Portable Mental Status Questionnaire, the CES-D, the Lubben Social Network Scale, and the Katz ADL were administered to the sample. Current medical illnesses were recorded with demographic data. There was a significant association between the CES-D score and the BBS score for those who screened positive for symptoms of depression. In addition there was a significant relationship between CES-D score and specific medical illnesses, social network, physical function in ADL, and residence (urban vs. rural). Residents who screened positive (N = 19) for depressive symptomatology with CES-D scores of 16 or higher exhibited a higher frequency of hypertension, arteriosclerosis, and circulatory problems than those who tested negative (N = 77). More urban residents (N = 13) than rural residents (N = 6) screened positive for symptoms of depression. Approximately 21% (N = 20) of the 96 respondents had scores of 20 or less on the Lubben Social Network Scale, suggesting a group of "at risk" for social isolation.


Accessory liver lobe attached to the wall of the gallbladder: a cadaveric case report.
Accessory liver lobe is found incidentally during laparoscopy, laparotomy or autopsy performed for unrelated reasons. The occurrence of accessory liver lobe attached to the gallbladder is reported rarely in the literature. During regular dissection classes, we came across an accessory liver lobe in the wall of the gallbladder in an adult male cadaver. On its left, it was connected to the quadrate lobe by a short fold of peritoneum. On the right, it was attached to the wall of the gallbladder. The fragment was triangular in shape, and was 20 mm in length, 11 mm in width and 6 mm thick. The histology of the fragment revealed the unusual architecture of hepatic tissue with the absence of the classical hexagonal lobule pattern. Cords of hepatocytes surrounding the central vein, with an absence of portal canals, were observed. There were branches of hepatic artery, portal vein and hepatic duct in its peritoneal fold. Smooth muscle fibers were also observed along its attachment on the wall of the gallbladder. Awareness of the incidence of accessory liver lobe in the wall of the gallbladder is of clinical importance during the diagnosis and treatment of gallstones.


A double-blind, randomized, vehicle-controlled clinical study to evaluate the efficacy and safety of MAS063DP (ATOPICLAIR) in the management of atopic dermatitis in paediatric patients.
A multicenter, randomized, double-blind, vehicle-controlled clinical study was conducted to evaluate the efficacy and safety of MAS063DP in 60 paediatric patients affected by atopic dermatitis (AD), aged between 2 and 17 years. Using the Investigator's Global Assessment (IGA) score for AD, patients with a score of 2 (mild) or 3 (moderate) were enrolled in the study. Patients were randomly selected to receive MAS063DP (20 patients), MAS060 (20 patients, a similar formulation with lower key ingredients' concentration and no preservatives) or vehicle (20 patients).The study consisted in a treatment period of 43 days, with clinical evaluations at baseline (day 1), days 8, 15, 22, 29 and 43, at which time the treatment was stopped. MAS063DP showed nearly 80% improvement in IGA score at day 22, compared with 16.6% and 26.3% with the MAS060 and vehicle respectively. A statistically significant difference was found by comparing MAS063DP with MAS060 (p < 0.0001); a similar result was evidenced comparing MAS063DP and vehicle (p = 0.001). By contrast, no significant difference was found between MAS060 and vehicle. A statistically significant difference was sustained until the end of the study. MAS063DP may therefore be considered as one of the available regimens effective in the treatment of mild-to-moderate AD in children and adolescents.


Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2.
The mammalian target of rapamycin (mTOR) regulates cell growth and survival by integrating nutrient and hormonal signals. These signaling functions are distributed between at least two distinct mTOR protein complexes: mTORC1 and mTORC2. mTORC1 is sensitive to the selective inhibitor rapamycin and activated by growth factor stimulation via the canonical phosphoinositide 3-kinase (PI3K)-->Akt-->mTOR pathway. Activated mTORC1 kinase up-regulates protein synthesis by phosphorylating key regulators of mRNA translation. By contrast, mTORC2 is resistant to rapamycin. Genetic studies have suggested that mTORC2 may phosphorylate Akt at S473, one of two phosphorylation sites required for Akt activation; this has been controversial, in part because RNA interference and gene knockouts produce distinct Akt phospho-isoforms. The central role of mTOR in controlling key cellular growth and survival pathways has sparked interest in discovering mTOR inhibitors that bind to the ATP site and therefore target both mTORC2 and mTORC1. We investigated mTOR signaling in cells and animals with two novel and specific mTOR kinase domain inhibitors (TORKinibs). Unlike rapamycin, these TORKinibs (PP242 and PP30) inhibit mTORC2, and we use them to show that pharmacological inhibition of mTOR blocks the phosphorylation of Akt at S473 and prevents its full activation. Furthermore, we show that TORKinibs inhibit proliferation of primary cells more completely than rapamycin. Surprisingly, we find that mTORC2 is not the basis for this enhanced activity, and we show that the TORKinib PP242 is a more effective mTORC1 inhibitor than rapamycin. Importantly, at the molecular level, PP242 inhibits cap-dependent translation under conditions in which rapamycin has no effect. Our findings identify new functional features of mTORC1 that are resistant to rapamycin but are effectively targeted by TORKinibs. These potent new pharmacological agents complement rapamycin in the study of mTOR and its role in normal physiology and human disease.


Anxiety and depression in end-stage COPD.
Although feelings of anxiety and depression are common in patients with chronic obstructive pulmonary disease (COPD), estimates of their prevalence vary considerably. This probably reflects the variety of scales and methods used to measure such symptoms. Regardless of whether anxiety and depression are considered separately or as a single construct, their impact on COPD patients is important. A heightened experience of dyspnoea is likely to be a contributing factor to anxiety. Feelings of depression may be precipitated by the loss and grief associated with the disability of COPD. Smoking has been associated with nicotine addiction, and the factors that contribute to smoking may also predispose to anxiety and depressive disorders. Randomised controlled trials indicate that exercise training and carefully selected pharmacological therapy are often effective in ameliorating anxiety and depression. Most medical illnesses are influenced by the psychological responses and coping mechanisms that patients use. However, anxiety and depression are associated with dyspnoea, fatigue and altered sleep, all of which also occur in COPD. An understanding of the psychological history and coping mechanisms of patients and the role of anxiety and depressive reactions to illness may enable clinicians to reduce these symptoms and improve quality of life among patients with chronic obstructive pulmonary disease.


A diagnostic algorithm for pulmonary hypertension due to left heart disease in resource-limited settings: can busy clinicians adopt a simple, practical approach?
Pulmonary hypertension (PH) has progressively moved from an orphan disease to a significant global health problem with a major disease burden in limited7hyphen;resource countries, where over 97% of patients live. The aetiologies of PH differ between high- and low-income nations, but PH due to left heart disease is credited to be the most frequent contemporary form. Although a straightforward diagnosis of PH requires the use of right heart catheterisation (RHC), access to equipment for RHC is a deterrent. Furthermore, the risk associated with RHC limits its uptake to a selection of specialised centres. Moreover, the rigour and clinical reasoning for diagnosis in clinical medicine is rapidly changing and revealing that PH can complicate a diverse range of medical conditions needing other explorations. In this article, we provide for the busy clinician, a simplified diagnostic algorithm for PH that is relevant for making a correct early diagnosis and limiting the impact of PH.


Dietary Fisetin Supplementation Protects Against Alcohol-Induced Liver Injury in Mice.
Overproduction of reactive oxygen species is associated with the development of alcoholic liver disease (ALD). Plant polyphenols have been used as dietary interventions for multiple diseases including ALD. The objective of this study was to determine whether dietary supplementation with fisetin, a novel flavonoid, exerts beneficial effect on alcohol-induced liver injury. C57BL/6J mice were pair-fed with the Lieber-DeCarli control or ethanol (EtOH) diet for 4 weeks with or without fisetin supplementation at 10 mg/kg/d. Alcohol feeding induced lipid accumulation in the liver and increased plasma alanine aminotransferase and aspartate aminotransferase activities, which were attenuated by fisetin supplementation. The EtOH concentrations in the plasma and liver were significantly elevated by alcohol exposure but were reduced by fisetin supplementation. Although fisetin did not affect the protein expression of alcohol metabolism enzymes, the aldehyde dehydrogenase activities were significantly increased by fisetin compared to the alcohol alone group. In addition, fisetin supplementation remarkably reduced hepatic NADPH oxidase 4 levels along with decreased plasma hydrogen peroxide and hepatic superoxide and 4-hydroxynonenal levels after alcohol exposure. Alcohol-induced apoptosis and up-regulation of Fas and cleaved caspase-3 in the liver were prevented by fisetin. Moreover, fisetin supplementation attenuated alcohol-induced hepatic steatosis through increasing plasma adiponectin levels and hepatic protein levels of p-AMPK, ACOX1, CYP4A, and MTTP. This study demonstrated that the protective effect of fisetin on ALD is achieved by accelerating EtOH clearance and inhibition of oxidative stress. The data suggest that fisetin has a therapeutical potential for treating ALD.


Positron emission tomography and stage migration in head and neck cancer.
Since 2001, there has been a rapid adoption of positron emission tomography (PET) for diagnosis and American Joint Committee on Cancer (AJCC) staging of head and neck cancer (HNC) without data describing improved clinical outcomes. To determine the association between increased use of PET and stage and/or survival for patients with HNC in the managed care environment. Adult patients diagnosed as having HNC (n = 958) from 2000 to 2008 at 4 integrated health systems were identified via tumor registries linked to administrative data. The AJCC stage distribution, patient and treatment characteristics, and survival between pre-PET era (2000-2004) vs PET era (2005-2008) and use of PET vs no use of PET during the PET era were compared. The AJCC stages were categorized to represent localized (stage I or II), locally advanced (stage III, IVA, or IVB), and metastatic (stage IVC) disease. Treatments were determined by billing codes for surgery, radiation treatment, and chemotherapy. The primary outcome for this study was the use of PET. Secondary outcomes included treatment received and 2-year survival. A logit model estimated the effects of PET on diagnosis of locally advanced disease. Kaplan-Meier estimates described overall survival differences between PET and non-PET. Cox regression evaluated the association of PET on survival in patients with locally advanced disease. An association between PET and locally advanced disease was found (odds ratio, 2.86 [95% CI, 1.90-4.29) (P < .001). Two-year overall survival for patients with locally advanced disease with and without PET was 52% and 32%, respectively (P = .004), but there was no difference for all stages (P = .69). On Cox proportional hazard regression, PET had no association with survival in patients with locally advanced disease (hazard ratio, 1.208 [95% CI, 0.778-1.877]) (P = .40). The increasing use of PET among patients with HNC is associated with a greater number of patients with higher-stage disease and a dilution of the population with higher-stage disease with patients who have a better prognosis. Thus, the improved survival in patients with locally advanced disease likely reflects selection bias and stage migration. Further research on PET use among patients with HNC is necessary to determine if it results in improved treatment for individual patients.


Gene expression modules in primary breast cancers as risk factors for organotropic patterns of first metastatic spread: a case control study.
Metastases from primary breast cancers can involve single or multiple organs at metastatic disease diagnosis. Molecular risk factors for particular patterns of metastastic spread in a clinical population are limited. A case-control design including 1357 primary breast cancers was used to study three distinct clinical patterns of metastasis, which occur within the first six months of metastatic disease: bone and visceral metasynchronous spread, bone-only, and visceral-only metastasis. Whole-genome expression profiles were obtained using whole genome (WG)-DASL assays from formalin-fixed paraffin-embedded (FFPE) samples. A systematic protocol was developed for handling FFPE samples together with stringent data quality controls to identify robust expression profiling data. A panel of published and novel gene sets were tested for association with these specific patterns of metastatic spread and odds ratios (ORs) were calculated. Metasynchronous metastasis to bone and viscera was found in all intrinsic breast cancer subtypes, while immunohistochemically (IHC)-defined receptor status and specific IntClust subgroups were risk factors for visceral-only or bone-only first metastases. Among gene modules, those related to proliferation increased the risk of metasynchronous metastasis (OR (95% CI) = 2.3 (1.1-4.8)) and visceral-only first metastasis (OR (95% CI) = 2.5 (1.2-5.1)) but not bone-only metastasis (OR (95% CI) = 0.97 (0.56-1.7)). A 21-gene module (BV) was identified in estrogen-receptor-positive breast cancers with metasynchronous metastasis to bone and viscera (area under the curve = 0.77), and its expression increased the risk of bone and visceral metasynchronous spread in this population. BV was further orthogonally validated with NanoString nCounter in primary breast cancers, and was reproducible in their matched lymph nodes metastases and an external cohort. This case-control study of WG-DASL global expression profiles from FFPE tumour samples, after careful quality control and RNA selection, revealed that gene modules in the primary tumour have differing risks for clinical patterns of metasynchronous first metastases. Moreover, a novel gene module was identified as a putative risk factor for metasynchronous bone and visceral first metastatic spread, with potential implications for disease monitoring and treatment planning.


CLIMATE MODELING OF A POTENTIAL EXOVENUS.
The planetary mass and radius sensitivity of exoplanet discovery capabilities has reached into the terrestrial regime. The focus of such investigations is to search within the Habitable Zone where a modern Earth-like atmosphere may be a viable comparison. However, the detection bias of the transit and radial velocity methods lies close to the host star where the received flux at the planet may push the atmosphere into a runaway greenhouse state. One such exoplanet discovery, Kepler-1649b, receives a similar flux from its star as modern Venus does from the Sun, and so was categorized as a possible exoVenus. Here we discuss the planetary parameters of Kepler-1649b with relation to Venus to establish its potential as a Venus analog. We utilize the general circulation model ROCKE-3D to simulate the evolution of the surface temperature of Kepler-1649b under various assumptions, including relative atmospheric abundances. We show that in all our simulations the atmospheric model rapidly diverges from temperate surface conditions towards a runaway greenhouse with rapidly escalating surface temperatures. We calculate transmission spectra for the evolved atmosphere and discuss these spectra within the context of the James Webb Space Telescope (JWST) Near-Infrared Spectrograph (NIRSpec) capabilities. We thus demonstrate the detectability of the key atmospheric signatures of possible runaway greenhouse transition states and outline the future prospects of characterizing potential Venus analogs.


Evaluation of a Hypersensitivity Inhibitor Containing a Novel Monomer That Induces Remineralization-A Case Series in Pediatric Patients.
Recently, tooth deformities have been frequently encountered by pediatric dentists. Severe enamel hypomineralization sometimes induces pain such as hyperesthesia, but composite resin restoration is difficult because it often detaches without any cavity preparation. Resin-based hypersensitivity inhibitors for tooth physically seal the dentinal tubules. It was reported that hypersensitivity inhibitor containing novel adhesive monomers forms apatite and induces remineralization in vitro. Therefore, these case series assessed the clinical effects of remineralization and the suppression of hypersensitivity by Bio Coat Ca (Sun Medical, Shiga, Japan). After mechanical tooth cleaning was performed, the hypersensitivity inhibitors were applied and cured by light exposure. Changes in hypersensitivity were determined by visual analog scale (VAS). The improvement of hypomineralization was evaluated by the change in color tone based on the digital images of intraoral photographs. After repeated monthly treatments, these cases showed decreased hypersensitivity after the fourth application, while the opaque white and brownish color improved on the seventh application. This novel hypersensitivity inhibitor with calcium salt of 4-methacryloxyethyl trimellitic acid (C-MET) and 10-methacryloyloxydecyl dihydrogen calcium phosphate (MDCP) not only suppressed hypersensitivity but also improved cloudiness and brown spots in recently erupted permanent teeth in presented cases.


Filamentous Fungi Producing l-Asparaginase with Low Glutaminase Activity Isolated from Brazilian Savanna Soil.
l-asparaginase is an enzyme used as treatment for acute lymphoblastic leukemia (ALL) due to its ability to hydrolyze l-asparagine, an essential amino acid synthesized by normal cells unlike neoplastic cells. The adverse effects of l-asparaginase formulations are associated with its glutaminase activity and bacterial origin; therefore, it is important to find new sources of l-asparaginase-producing eukaryotic microorganisms with low glutaminase activity. This work evaluated the biotechnological potential of filamentous fungi isolated from Brazilian Savanna soil and plants for l-asparaginase production. Thirty-nine isolates were screened for enzyme production using the plate assay, followed by measuring enzymatic activity in cells after submerged fermentation. The variables influencing l-asparaginase production were evaluated using Plackett-Burman design. Cell disruption methods were evaluated for l-asparaginase release. Penicillium sizovae 2DSST1 and Fusarium proliferatum DCFS10 showed the highest l-asparaginase activity levels and the lowest glutaminase activity levels. Penicillium sizovae l-asparaginase was repressed by carbon sources, whereas higher carbon concentrations enhanced l-asparaginase by F. proliferatum. Maximum enzyme productivity, specific enzyme yield and the biomass conversion factor in the enzyme increased after Plackett-Burman design. Freeze-grinding released 5-fold more l-asparaginase from cells than sonication. This study shows two species, which have not yet been reported, as sources of l-asparaginase with possible reduced immunogenicity for ALL therapy.


[Helicobacter pylori infection is carcinogenic for humans].
International Agency for Research on Cancer recognized as sufficient the evidence of Helicobacter pylori (HP) infection carcinogenicity and placed it into the 1st group of carcinogens. The results of the studies performed during last years are discussed. They showed the involvement of HP in the development of stomach cancer. HP enhances mitogenesis of epithelium with translocation of immature cells on the surface of stomach mucous membrane and thus forms the targets for mutagenic and carcinogenic influences. HP takes part in the formation of mutagens, primarily of free oxygen radicals. Achlorohydria is the outcome of HP-gastritis and results in the bacterial growth in the stomach which participate in the formation of N-nitrosocompounds-well known carcinogens. Antitumor stomach defense is weakened by the decrease in the stomach of ascorbic acid, carotin and tocopherol resulting from HP-infection.


Why do you play? The development of the motives for online gaming questionnaire (MOGQ).
Although the majority of research focuses on the risks and disadvantages of online gaming, the present authors suggest that online games also represent new ways of satisfying basic human needs within the conditions of modern society. The aim of our present study was to reveal and operationalize the components of the motivational basis of online gaming. A total 3,818 persons (90.6% males; mean age 20.9 years, SD = 5.81) were recruited through websites providing online games. A combined method of exploratory and confirmatory factor analysis was applied. The results confirmed our preliminary model as we identified seven motivational factors (social, escape, competition, coping, skill development, fantasy, and recreation), which were used to develop the 27-item Motives for Online Gaming Questionnaire (MOGQ). The seven dimensions identified seem to cover the full range of possible motives for gaming, and the MOGQ proved to be an adequate measurement tool to assess these motives.


Placental metastasis from maternal carcinoma of the lung.
A case of large cell undifferentiated carcinoma of the lung metastatic to the placenta and a review of the literature are presented. This is the 44th documented case of placental and/or fetal metastasis from maternal cancer in the past 113 years. Fifty percent of these cases are either malignant melanomas or hematopoietic malignancies. Evidence indicates that these 2 malignancies are more likely to metastasize to the products of conception than are other malignancies.


Feasibility of titrating PEEP to minimum elastance for mechanically ventilated patients.
Selecting positive end-expiratory pressure (PEEP) during mechanical ventilation is important, as it can influence disease progression and outcome of acute respiratory distress syndrome (ARDS) patients. However, there are no well-established methods for optimizing PEEP selection due to the heterogeneity of ARDS. This research investigates the viability of titrating PEEP to minimum elastance for mechanically ventilated ARDS patients. Ten mechanically ventilated ARDS patients from the Christchurch Hospital Intensive Care Unit were included in this study. Each patient underwent a stepwise PEEP recruitment manoeuvre. Airway pressure and flow data were recorded using a pneumotachometer. Patient-specific respiratory elastance (Ers ) and dynamic functional residual capacity (dFRC) at each PEEP level were calculated and compared. Optimal PEEP for each patient was identified by finding the minima of the PEEP-Ers profile. Median Ers and dFRC over all patients and PEEP values were 32.2 cmH2O/l [interquartile range (IQR) 25.0-45.9] and 0.42 l [IQR 0.11-0.87]. These wide ranges reflect patient heterogeneity and variable response to PEEP. The level of PEEP associated with minimum Ers corresponds to a high change of functional residual capacity, representing the balance between recruitment and minimizing the risk of overdistension. Monitoring patient-specific Ers can provide clinical insight to patient-specific condition and response to PEEP settings. The level of PEEP associated with minimum-Ers can be identified for each patient using a stepwise PEEP recruitment manoeuvre. This 'minimum elastance PEEP' may represent a patient-specific optimal setting during mechanical ventilation. Australian New Zealand Clinical Trials Registry: ACTRN12611001179921.


Augmented expression of normal c-myc is sufficient for cotransformation of rat embryo cells with a mutant ras gene.
We studied the effect of altered c-myc structure and expression upon the ability of c-myc to promote the transformation of normal rat embryo cells when it was supplemented by EJras (the mutant c-H-ras1 gene from EJ/T24 bladder carcinoma cells). We tested several c-myc alleles cloned from normal and tumor tissues of chicken and human origin and found that only LL4myc (derived from a bursal lymphoma in which an avian leukosis virus long terminal repeat resides within the first c-myc intron in the same transcriptional orientation) had cotransforming activity. No activity was observed with normal chicken and human c-myc alleles, two other bursal lymphoma c-myc alleles (LL3myc and LL6myc), and two human c-myc genes (HSRmyc and DMmyc) from human neuroectodermal tumor cell line COLO320, in which c-myc is amplified. Some of these inactive alleles had the following alterations that are frequently found in tumor-derived c-myc: point mutations affecting the encoded protein (LL3myc); a truncated structure with loss of the first, noncoding exon (LL3myc and DMmyc); and proviral integration within or near the myc locus (LL3myc and LL6myc). The following two experimental approaches indicated that cotransforming activity was directly related to the transcriptional activity of the alleles in cultured rat cells: when cotransfected into Rat-2 cells, LL4myc was more highly expressed than the other (inactive) alleles; and augmented expression of HSRmyc, DMmyc, or normal human or normal chicken c-myc placed under the transcriptional control of retroviral long terminal repeats or increased expression of normal human c-myc under the influence of a retroviral enhancer element was accompanied by cotransformation activity. We concluded that augmented expression of even a normal c-myc gene is sufficient for cotransforming activity and that additional structural alterations frequently found in tumor-derived alleles are neither necessary nor sufficient for the gene to acquire rat embryo cell cotransforming properties.


Chromatin dynamics during the cell cycle at centromeres.
Centromeric chromatin undergoes major changes in composition and architecture during each cell cycle. These changes in specialized chromatin facilitate kinetochore formation in mitosis to ensure proper chromosome segregation. Thus, proper orchestration of centromeric chromatin dynamics during interphase, including replication in S phase, is crucial. We provide the current view concerning the centromeric architecture associated with satellite repeat sequences in mammals and its dynamics during the cell cycle. We summarize the contributions of deposited histone variants and their chaperones, other centromeric components - including proteins and their post-translational modifications, and RNAs - and we link the expression and deposition timing of each component during the cell cycle. Because neocentromeres occur at ectopic sites, we highlight how cell cycle processes can go wrong, leading to neocentromere formation and potentially disease.


Intra-species tranduction with Proteus mirabilis high frequency transducing phages.
The properties of three additional Proteus mirabilis hosts for the high frequency transducing (HET) phages 5006MHFTkappa and 5006MHFTak are described. The phages transduce resistance to kanamycin and to ampicillin plus kanamycin, respectively, and were produced by ultraviolet induction of derivatives of P. mirabilis strain PM5006. Strain PM804 could not be shown to adsorb the phages although it yielded a few transductants. All transductants, even those produced at low multiplicities of phage input were lysogenic and segregated markers at high frequency. Ultraviolet induced phage lysates of these transductants transduced PM804 at higher frequencies and PM5006 at lower frequencies than the original phages. Strain PM804 or its derivatives did not adsorb phage from these lysates. Tranmission experiments through PM5006 of phage in the transductant lysates confirmed that PM804 had a host-controlled modification system which modified HFT phage from PM5006. That PM804 also possessed a restriction system was inferred from the greater numbers of transductants obtained with page which bore a compatible modification pattern. Strain N and a restrictionless mutant of it named NHI, adsorbed the HET phages avidly and failed to modify their host range. Transduction frequencies of the phage markers were about 10(-4)/p.f.u. adsorbed to strain NHI and only about tenfold lower to strain N which did not plate the phages. Tranductants also had the features of heterogenotes and those obtained at low multiplicites of infection were non-lysogenic. The latter transductants adsorbed homolgous phage while NHI transductants also plated the HFT lysates. Strain NHI, lysogenized by the parent phage 5006M, did not adsorb the HFT phages. These findings suggest that the HFT phages were most likely defective for lysogenic conversion to homologous phage non-adsorption. The postulated restriction enzymes of PM804 and strain N could not be shown to be thermolabile.


Retrospective analysis of liraglutide and basal insulin combination therapy in Japanese type 2 diabetes patients: The association between remaining β-cell function and the achievement of the glycated hemoglobin target 1 year after initiation.
The glucose-lowering effects of the glucagon-like peptide-1 receptor agonist, liraglutide, have been shown to rely on remaining β-cell function. However, the possible associations of remaining β-cell function with the glucose-lowering effects of liraglutide in combination with basal insulin remain unknown and warrant investigation. This was a single-center, retrospective, observational study carried out in a private hospital in Osaka, Japan. Type 2 diabetes patients who received a prescription change from insulin therapy, both multiple-dose insulin and basal insulin-supported oral therapy, to liraglutide and basal insulin combination and continued the therapy for 54 weeks without additional oral antidiabetic drugs or bolus insulin were retrospectively analyzed. Among the 72 participants who received a prescription change from multiple-dose insulin and basal insulin-supported oral therapy to liraglutide and basal insulin combination, 57 continued the therapy for 54 weeks. Of those who continued the therapy without receiving additional oral antidiabetic drugs or bolus insulin, seven participants achieved glycated hemoglobin < 7.0% at 54 weeks, but 30 participants did not. The participants who achieved glycated hemoglobin < 7.0% at 54 weeks had a significantly higher C-peptide immunoreactivity index, a β-cell function-related index frequently used in Japanese clinical settings. The receiver operating curve analysis showed that the C-peptide immunoreactivity index cut-off value for the achievement of glycated hemoglobin <7.0% at 54 weeks is 1.103. The current findings show that the glucose-lowering effects of liraglutide rely on remaining β-cell function, even when used with basal insulin; and suggest that liraglutide and basal insulin combination might require additional bolus insulin to fully compensate insulin insufficiency in individuals with reduced β-cell function.


Multiple positive and negative elements involved in the regulation of expression of GSY1 in Saccharomyces cerevisiae.
GSY1 is one of the two genes encoding glycogen synthase in Saccharomyces cerevisiae. Both the GSY1 message and the protein levels increased as cells approached stationary phase. A combination of deletion analysis and site-directed mutagenesis revealed a complex promoter containing multiple positive and negative regulatory elements. Expression of GSY1 was dependent upon the presence of a TATA box and two stress response elements (STREs). Expression was repressed by Mig1, which mediates responses to glucose, and Rox1, which mediates responses to oxygen. Characterization of the GSY1 promoter also revealed a novel negative element. This element, N1, can repress expression driven by either an STRE or a heterologous element, the UAS of CYC1. Repression by N1 is dependent on the number of these elements that are present, but is independent of their orientation. N1 repressed expression when placed either upstream or downstream of the UAS, although the latter position is more effective. Gel shift analysis detected a factor that appears to bind to the N1 element. The complexity of the GSY1 promoter, which includes two STREs and three distinct negative elements, was surprising. This complexity may allow GSY1 to respond to a wide range of environmental stresses.


Compulsive Internet and Prevalence Substance Use among Spanish Adolescents.
This paper analyses compulsive Internet use among Spanish adolescents as measured by the Compulsive Internet Use Scale (CIUS) of the ESTUDES 2016 survey (national survey on drug use in secondary schools), which was recently added to the statistical programme of the Spanish National Plan on Drugs. We examined two subsamples of Spanish adolescents (those who suffer from compulsive Internet use and those who do not) while taking into account gender and age. Our general hypothesis was that adolescents who suffer from compulsive Internet use have a greater prevalence of alcohol, tobacco, cannabis, sedative, and new substance consumption as well as a greater prevalence of modes of consumption such as getting drunk, drinking with friends in public places (botellón), and binge drinking. While our results confirm these assumptions, they also suggest that gender and age play an ambivalent role in these associations.


Computation of the lattice Green function for a dislocation.
Modeling isolated dislocations is challenging due to their long-ranged strain fields. Flexible boundary condition methods capture the correct long-range strain field of a defect by coupling the defect core to an infinite harmonic bulk through the lattice Green function (LGF). To improve the accuracy and efficiency of flexible boundary condition methods, we develop a numerical method to compute the LGF specifically for a dislocation geometry; in contrast to previous methods, where the LGF was computed for the perfect bulk as an approximation for the dislocation. Our approach directly accounts for the topology of a dislocation, and the errors in the LGF computation converge rapidly for edge dislocations in a simple cubic model system as well as in BCC Fe with an empirical potential. When used within the flexible boundary condition approach, the dislocation LGF relaxes dislocation core geometries in fewer iterations than when the perfect bulk LGF is used as an approximation for the dislocation, making a flexible boundary condition approach more efficient.


A memory of chirality approach to the stereoselective synthesis of 4-hydroxy-alpha-methylprolines.
To extend the memory of chirality (MOC) methodology to structurally more diverse compounds, the synthesis of 4-hydroxy-alpha-methylprolines was undertaken. Yield and selectivity were very good, with an unexpected reversal in selectivity observed for the cyclization of one adduct with an unprotected hydroxyl.


Delayed recognition of excess mortality in West Timor.
In September 1999, militia-initiated violence in East Timor forced the displacement of approximately 290,000 persons to West Timor in Indonesia. Whereas the security and health status of the East Timorese in East Timor had been well-monitored, by contrast, the health status of 150,000 refugees in approximately 200 camps in West Timor was essentially unknown. The death of a child during transfer from a refugee camp there to a United Nations transit camp prompted further investigation. The present study population was the largest West Timorese camp of 14,088 refugees. Despite security constraints, a rapid epidemiological assessment was undertaken. Retrospective analysis of camp mortality data, key informant interviews and environmental assessment were included. A crude mortality rate of 2.3/10,000/day and an under 5 year mortality rate of 10.3/10,000/day were found. Environmental sanitation, personal hygiene, water quality and vector control were inadequate. International aid agencies provided medical care with variable case definitions, no treatment protocols, non-standard treatment practices, inappropriate antibiotic use, variable referral practices and no secondary prevention. Syndromic diagnoses of causes of dealth guided recommendations for interventions. Follow-up reports indicated that excess camp mortality was eliminated within a month. All conflict-affected populations must have an ongoing examination of essential health data to identify urgent unmet needs, guide appropriate health interventions and monitor progress. Sentinel health events must be promptly reported and investigated. Syndromic diagnoses are useful in targeting life-saving public health interventions. All humanitarian health assistance must have transparency, technical supervision and peer review to ensure compliance with minimum standards.


Mitochondrial DNA mutations in focal segmental glomerulosclerosis lesions.
Glomerular epithelial cells are primary pathogenic sites in focal segmental glomerulosclerosis (FGS) lesions. Glomerular epithelial cells are regarded as terminally differentiated cells that do not proliferate. These characteristics are also noted for neurons and muscular cells, which are major sites of mitochondrial DNA (mtDNA) mutation accumulation. Screening for mtDNA mutations was performed with renal biopsy specimens from patients with primary FGS and patients with IgA nephropathy (as subjects with secondary FGS and as control subjects). mtDNA extracted from kidney biopsy specimens was amplified with appropriate primer pairs for study of the mtDNA point mutations 3243A-->G, 3271T-->C, 8344A-->G, and 8993T-->G/C, as well as the common deletion (a 4977-bp deletion spanning mtDNA nucleotide pairs 8469 to 13447). In situ amplification of both total mtDNA and the common deletion was also performed. Two patients with FGS demonstrated the 3243A-->G point mutation; 12 patients with FGS and seven patients with IgA nephropathy accompanied by glomerulosclerotic lesions exhibited the common deletion in their kidney tissue. No patient demonstrated the mtDNA mutations 3271T-->C, 8344A-->G, or 8993T-->G/C. The degree of heteroplasmy for the 3243A-->G point mutation was >85%; however, the heteroplasmy for the common deletion was <1%. As determined with in situ PCR, normal mtDNA was mainly distributed in the tubular epithelium and mtDNA with the common deletion was mainly distributed among glomerular epithelial cells. In conclusion, it is suggested that mtDNA mutations are distributed in glomerular epithelial cells among some patients with primary FGS or secondary FGS with IgA nephropathy. These mutations may be related to glomerular epithelial cell damage.


CRISPRa-Mediated Upregulation of scn1laa During Early Development Causes Epileptiform Activity and dCas9-Associated Toxicity.
Dravet syndrome (DS) is a monogenic epileptic encephalopathy caused by loss-of-function mutations in the voltage-gated sodium channel (VGSC) gene SCN1A. DS has an age of onset within the first year of life and severe disease prognosis. In the past years, it has been shown that upregulation of endogenous SCN1A can be beneficial in animal models for DS, but a complete rescue was not observed. We hypothesized that upregulation during early development that precedes onset of first symptoms might improve disease outcome. To test this hypothesis, we first evaluated the CRISPR activating method for early upregulation of voltage gated sodium channels during early development. We injected CRISPRa components, which target the proximal or distal promoter region of the VGSC gene scn1Laa in the yolk of one-cell stage zebrafish embryos. The effect of both dCas9-VPR and dCas9-VP64 was evaluated. Both CRISPRa fusions showed toxicity in the majority of embryos, with or without guide RNAs. The few embryos that survived developed normally, and dCas9-VPR induces an upregulation of scn1Laa mRNA until 24 hours after fertilization. At 5 days post fertilization, CRISPRa-injected embryos showed an epileptic phenotype, including locomotor burst movements, hyperactivity, and epileptiform activity originating from the brain. In addition to previously published scn1Laa and scn1Lab loss-of-function models, we conclude that gain of scn1Laa function can have an equally severe phenotype. Upregulation of scn1Laa in the current zebrafish model for DS, scn1Lab-KO, aggravated the disease phenotype, highlighting that early-stage upregulation using CRISPRa can lead to both toxicity and a worsening of the disease phenotype.


The Utility of Muscle-Sparing Axillar Skin Crease Incision with Thoracoscopic Surgery in Children.
Thoracoscopic surgery for pediatric benign tumors is a common procedure. However, a large incision is needed to remove large tumors from the thoracic cavity. And, for intrapulmonary sequestration in lower lobe, it sometimes needs a large incision to ligate the aberrant vessels. A muscle-sparing axillar skin crease incision (MSASCI) has been introduced for thoracic open surgery, resulting in excellent aesthetic outcomes compared with a standard incision. We herein report the utility of this MSASCI technique in thoracoscopic surgery to remove large tumors from the thoracic cavity and to ligate the aberrant vessels in intrapulmonary sequestration in lower lobe. From 2014 April to 2016 March, we performed the MSASCI technique in thoracoscopic surgeries for 5 children. Five cases were diagnosed as mediastinal masses (mature teratoma for 1 case, ganglioneuroblastoma for 2 cases, and extrapulmonary sequestration and intrapulmonary sequestration for 1 case each). The age at surgery was 32.0 ± 25.0 months (range 5-58 months). The size of the mediastinal mass was 9 × 5 × 5 cm, 4 × 3 × 3 cm, 5 × 5 × 2.5 cm, and 3 × 2.5 × 2 cm. For 4 other cases, except for the intrapulmonary sequestration case, the mass was resected under thoracoscopic surgery using only three or four 5-mm trocars and the mass was removed from the thoracic cavity using the MSASCI technique. For the intrapulmonary sequestration case, the aberrant vessels were resected under thoracoscopic surgery using only two 5-mm and one 12-mm trocars and the left lower lobectomy was performed using the MSASCI technique. All lesions were resected completely. No cases had surgical complications, none showed recurrence, and all cases demonstrated good cosmetic outcomes. Performing thoracoscopic surgery using a MSASCI technique is associated with good cosmetic outcome.


[Effect of gamma-aminobutyric acid on peripheral mechanisms regulating autonomic functions].
Experiments with cats ascertained the potentiating action of GABA (100,300,500 mg/kg) on the pressor reactions of the small intestine vessels, the systemic arterial pressure, depressing (100 mg/kg) and facilitating (500 mg/kg) effect upon the reactions of inhibition of the small intestine motor activity evoked by the efferent stimulation of the celiac nerve. Adrenolytics (dihydroergotoxin, inderal) abolished the facilitating effects of GABA. The latter (0.01 solution) inhibited spontaneous contractions of isolated small intestine lengths. As proved histochemically GABA (500 mg/kg) reduces the catecholamines content in the suprarenals, in the solar plexus ganglia and in vessles "in vivo". It also increases the catecholamines content in the small intestine wall in experiments in vivo and reduces in vitro tests. The potentiating action of GABA on the vegetative reactions in efferent stimulation of the ciliac nerve occurs, apparently, due to an increased ejection of catecholamines by suprarenals and lowered the content of catecholamines in the solar plexus ganglia, which causes facilitated conduction of excitation in the ganglia.


Perspectives of African and Brazilian immigrant women on sexual and reproductive health.
To explore attitudes and experiences related to sexual and reproductive health (SRH) of African and Brazilian immigrant women in Portugal. Focus groups were conducted with 35 immigrant women with low income living in Lisbon, chosen through purposive sampling. Discussions were audio-taped and transcribed, and analysed through content analysis procedure. Compared to the Brazilian women, most Africans lacked knowledge and had more negative attitudes toward contraceptive methods, which adversely affected their proper use. African women were also less knowledgeable on sexually transmitted infections (STIs); some of them considered that their vulnerability to STIs was related to their partners' sexual risk behaviours. Nevertheless, a few Africans held less traditional attitudes toward condom use and appeared to have greater control over their sexual behaviour and STI prevention. Focus group discussions brought to light that cultural background often shapes women's desires concerning maternity. The participants' statements highlight the interaction between economic and social factors that affect immigrants and play an important role in their reproductive health. This study illustrates the importance of developing holistic and tailored interventions for SRH promotion among immigrant women, whereby the differences and specific needs of each group need to be taken into consideration.


Financial Capability and Economic Security among Low-Income Older Asian Immigrants: Lessons from Qualitative Interviews.
This article examines financial capability among low-income older Asian immigrants, using data from in-depth interviews with 13 participants in a subsidized employment program in Los Angeles. Overall, respondents present a portrait of economic insecurity. Qualitative analyses indicate that respondents perceived little need to improve their financial knowledge and management skills because they had "no money to manage." Most respondents lacked either financial knowledge or financial management skills, which resulted in substantial financial losses among some respondents. Mistrust of financial institutions ("Banks are always vampires") and other financial barriers (for example, lack of credit history) blocked respondents' access to formal financial services. In some cases, ethnic financial resources (for example, ethnic banks) reduced the effects of such barriers. There is evidence that respondent financial knowledge and management skills may improve after opening a bank account, suggesting a potential role for financial access in expanding financial capability. Findings demonstrate the importance of financial capability-building interventions for low-income older Asian immigrants. Social workers should be equipped with financial literacy and in-depth understanding of financial needs, perceptions, values, behaviors, and resources of this population.


Anti-inflammatory effect of resveratrol by inhibition of IL-8 production in LPS-induced THP-1 cells.
Resveratrol is a polyphenol compound and prominent anti-inflammatory agent found in plants, including the fruits of Morus alba. However, the therapeutic mechanisms of resveratrol remain largely unclear. To gain insight into the biological effects of resveratrol, we examined its influence on LPS-induced IL-8 production in the human monocytic cell line, THP-1. In inflammatory diseases, IL-8 plays a central role in the initiation and maintenance of inflammatory response. In the present study, IL-8 production was measured by ELISA and RT-PCR, while MAPK activation, IkappaBalpha degradation, nuclear factor (NF)-kappaB activation and cyclooxygenase (COX)-2 expression were determined by Western blot analysis. Resveratrol inhibited LPS-induced IL-8 production in a dose-dependent manner. Furthermore, resveratrol inhibited extracellular signal-regulated kinase (ERK) and p38 MAPK phosphorylation, IkappaBalpha degradation, NF-kappaB activation and cyclooxygenase (COX)-2 expression, which suggest that resveratrol inhibits IL-8 secretion by blocking MAPK phosphorylation and NF-kappaB activation. Taken together, these findings may help elucidate the mechanism by which resveratrol modulates THP-1 cell activation under inflammatory conditions.


Diffusion tensor imaging of left ventricular remodeling in response to myocardial infarction in the mouse.
The cardiac muscle architecture lies at the basis of the mechanical and electrical properties of the heart, and dynamic alterations in fiber structure are known to be of prime importance in healing and remodeling after myocardial infarction. In this study, left ventricular remodeling was characterized using diffusion tensor imaging (DTI) in a mouse model of myocardial infarction. Myocardial infarction was induced in mice by permanent ligation of the left anterior descending coronary artery. Serial ex vivo DTI measurements were performed 7, 14, 28, and 60 days after ligation. Apparent diffusion coefficient, fractional anisotropy, the three eigenvalues of the diffusion tensor, and the myofiber disarray served as readout parameters. After myocardial infarction, the mouse hearts displayed extreme wall thinning in the infarcted area, which covered large parts of the apex and extended into the free wall up to the equator. Average heart mass increased by 70% 7-60 days after infarction. Histological analysis showed that the infarct at 7 days consisted of unstructured tissue with residual necrosis and infiltration of macrophages and myofibroblasts. At 14 days after infarction, the necrotic tissue had disappeared and collagen fibers were starting to appear. From 28 to 60 days, the infarct had fully developed into a mature scar. DTI parameters showed dynamic changes as a function of time after infarction. The apparent diffusion coefficient in the infarcted region was lower than in remote regions and increased as a function of time after infarction. The fractional anisotropy was higher in the infarcted region and was maximum at 28 days, which was attributed to the development of structured collagen fibers. Myofiber disarray, which was analyzed by considering the alignment of fibers in neighboring voxels, was significantly higher in infarcted regions. DTI provides a valuable non-destructive tool for characterizing structural remodeling in diseased myocardium.


Draft Genome Sequence of Aspergillus persii NIBRFGC000004109, Which Has Antibacterial Activity against Plant-Pathogenic Bacteria.
The fungus Aspergillus persii strain NIBRFGC000004109 is capable of producing penicillic acid and showed antibacterial activity against various plant-pathogenic bacteria, including Xanthomonas arboricola pv. pruni. Here, we report the first draft whole-genome sequence of A. persii The assembly comprises 38,414,373 bp, with 12 scaffolds.


Surgical Treatment of Epiphrenic Diverticulum: Technique and Controversies.
The goal of this article is to illustrate the current minimal invasive approaches to patients with epiphrenic diverticulum in terms of preoperative evaluation, surgical technique, and outcomes. Two techniques will be presented: a laparoscopic and a video-assisted thoracic repair. Indications for each technique will be discussed as well as proper patient selection and management. Current controversies in the treatment of patients with this rare disease will be addressed.


Uptake and efficacy of bilateral risk reducing surgery in unaffected female BRCA1 and BRCA2 carriers.
Women testing positive for BRCA1/2 pathogenic variants have high lifetime risks of breast cancer (BC) and ovarian cancer. The effectiveness of risk reducing surgery (RRS) has been demonstrated in numerous previous studies. We evaluated long-term uptake, timing and effectiveness of risk reducing mastectomy (RRM) and bilateral salpingo-oophorectomy (RRSO) in healthy BRCA1/2 carriers. Women were prospectively followed up from positive genetic test (GT) result to censor date. χ² testing compared categorical variables; Cox regression model estimated HRs and 95% CI for BC/ovarian cancer cases associated with RRS, and impact on all-cause mortality; Kaplan-Meier curves estimated cumulative RRS uptake. The annual cancer incidence was estimated by women-years at risk. In total, 887 women were included in this analysis. Mean follow-up was 6.26 years (range=0.01-24.3; total=4685.4 women-years). RRS was performed in 512 women, 73 before GT. Overall RRM uptake was 57.9% and RRSO uptake was 78.6%. The median time from GT to RRM was 18.4 months, and from GT to RRSO-10.0 months. Annual BC incidence in the study population was 1.28%. Relative BC risk reduction (RRM versus non-RRM) was 94%. Risk reduction of ovarian cancer (RRSO versus non-RRSO) was 100%. Over a 24-year period, we observed an increasing number of women opting for RRS. We showed that the timing of RRS remains suboptimal, especially in women undergoing RRSO. Both RRM and RRSO showed a significant effect on relevant cancer risk reduction. However, there was no statistically significant RRSO protective effect on BC.


A statistical model for the determination of the optimal metric in factor analysis of medical image sequences (FAMIS).
A statistical model is added to the conventional physical model underlying factor analysis of medical image sequences (FAMIS). It allows a derivation of the optimal metric to be used for the orthogonal decomposition involved in FAMIS. The oblique analysis of FAMIS is extended to take this optimal metric into account. The case of scintigraphic image sequences is used. We derive in this case that the optimal decomposition is obtained by correspondence analysis. A scintigraphic dynamic study illustrates the practical consequences of the use of the optimal metric in FAMIS.


Improving hospital death certification in Vietnam: results of a pilot study of injury-related fatalities.
Vietnam has prioritised the establishment of a civil registration system for deaths but as yet is unable to report accurate national statistics for the population of 93.5 million people due to inadequate mortality data. Verbal autopsy data suggest that injury is a third leading cause of death (by International Statistical Classification of Diseases and Related Health Problems 10th Revision chapters) in Vietnam, with road traffic injuries in particular a significant and increasing challenge. The study aims to present a more accurate profile of the number and probable causes of these deaths based on data collected hospitals using a version of the WHO death certificate modified for the Vietnamese context. Death data collected from Viet Duc Surgical and Trauma Hospital in Vietnam between 1 March 2013 to 31 March 2015 was analysed to explore the number and probable causes of deaths for deaths resulting from an injury. A total of 1616 deaths were recorded for Viet Duc Hospital, of which 73% (1181/1616) were associated with an injury. Most (83%; n=871/1049) injury-related deaths for which immediate cause of death was documented were as a result of head/brain injuries. Injury-related deaths were most commonly caused by from traffic accidents (72%, 853/1181). The majority of patients suffering injury-related deaths were discharged home to die (93%, 1097/1181). The study confirms some findings from previous studies about deaths from injuries, while disagreeing with others, highlighting the challenge for Vietnam in collecting these data. Gathering detailed death data provides essential evidence on which to base decisions about allocation of government funding and policy for injury prevention and treatment.


Association of crescentic glomerulonephritis with membranous glomerulonephropathy: a report of three cases.
Association of membranous glomerulonephropathy with crescentic glomerulonephritis is apparently extremely rare. We report three patients who had this combination. One patient had biopsy-proven membranous glomerulonephropathy thirteen months prior to sudden and rapid decline in renal function necessitating hemodialysis. A repeat renal biopsy showed a superimposed crescentic nephritis and antiglomerular (GBM) antibodies were demonstrable in the serum. A second patient had proteinuria of unknown duration and then developed renal failure. Renal biopsy showed crescentic nephritis with a fine granular glomerular immunofluorescence for IgG typical of membranous glomerulonephropathy. Anti-GBM antibodies were present in this patient's serum. The third patient presented with acute renal failure of moderate severity. A renal biopsy revealed crescentic nephritis, granular deposits of immunoglobulins, and epimembranous electron-dense deposits typical of membranous glomerulonephropathy. Although his creatinine clearance improved spontaneously, nephrotic syndrome has persisted and a repeat renal biopsy showed a progression of the membranous glomerulonephropathy with the disappearance of the crescentic lesions. The reason for this peculiar association of membranous glomerulonephropathy and crescentic glomerulonephritis is unclear. It is possible that deposition of immune-complexes along glomerular basement membrane may render the glomerulus more susceptible to additional injury from a variety of other agents. Alternatively, depostis formed in one disease could initiate release of normal or altered basement membrane material and lead to formation of anti-GBM antibodies and subsequent development.


Connexin-43 can delay early recurrence and metastasis in patients with hepatitis B-related hepatocellular carcinoma and low serum alpha-fetoprotein after radical hepatectomy.
We studied the relationships among Cx43, CD105, and VEGF in specimens of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) with different serum AFP levels with respect to recurrence and metastasis. Expressions of Cx43, CD105, and VEGF in 234 HCC tissue specimens were examined using tissue microarray and immunohistochemistry. Cx43 mRNA expression was examined in 38 frozen HCC specimens using RT-PCR. Correlations between these expressions and tumor recurrence, metastasis, and prognosis were analyzed using Kaplan-Meier and Cox regression analyses. Cx43 expression correlated with early tumor recurrence (P = 0.001), disease-free survival (P = 0.026), and overall survival (P = 0.000) in patients with serum AFP < 400 ng/ml, but not in those with serum AFP ≥ 400 μg/L. Cx43 expression is an independent predictor of later recurrence and longer overall survival and is inversely correlated with expression of CD105 and VEGF (P = 0.018 and 0.023, respectively), histological differentiation (P = 0.002), vessel tumor embolism (P = 0.029), and focal number (P = 0.017). Immunohistochemistry showed that Cx43 expression in patients with low AFP was lower in patients with distant metastases than in those with no metastasis or those with liver metastasis. Patients with early recurrence expressed less Cx43 mRNA than did those with no recurrence (χ2 = 9.827, P = 0.002). Cx43 expression can delay early HCC recurrence, metastasis, and poor prognosis after radical hepatectomy in patients with HBV-related HCC and low AFP.


Unilateral closed lip schizencephaly with septo-optic dysplasia.
Schizencephaly is a rare malformation of the central nervous system. Both genetic and non-genetic etiologies like prenatal infections or ischemia have been postulated. Clinical manifestations most often include varying degrees of developmental delay, motor impairment and seizures. It can be associated with septo-optic dysplasia (SOD), optic nerve hypoplasia and absence of septum pellucidum, pachygyria, polymicrogyria, heterotopia and arachnoid cysts. We report a case of unilateral closed lip schizencephaly with SOD.