The plant sterol brassicasterol as additional CSF biomarker in Alzheimer's disease.
Plant sterols (sitosterol, campesterol, stigmasterol and brassicasterol) are solely dietary-derivable sterols that are structurally very similar to cholesterol. In contrast to peripheral cholesterol, plant sterols can cross the blood-brain barrier and accumulate within mammalian brain. As an impaired function of the cerebrospinal fluid (CSF)-blood barrier is linked to neurodegenerative disorders, i.e. Alzheimer's disease (AD), we investigated whether this results in altered plant sterol concentrations in CSF. Applying gas chromatography/mass spectrometry analysis, plant sterol concentrations were measured in plasma and CSF of patients with AD (n = 67) and controls (n = 29). Age, gender, plasma-to-CSF albumin ratio, CSF Aβ(42) , CSF pTau, APOE4 genotype, and serum creatinine were applied as covariates in the statistical analysis for individual plant sterols in order to compare plasma and CSF plant sterol concentrations between patients with AD and controls. Albumin quotient was a consistent predictor in CSF for cholesterol and methyl plant sterols campesterol and brassicasterol. Comparison of lipid parameters per diagnosis based on relevant predictors revealed significantly lower concentrations of brassicasterol (P < 0.001) in CSF of patients with AD. Binary logistic regression analysis revealed that brassicasterol improved the predictive value when added to pTau and Aβ42 in a biomarker model. Brassicasterol might be a relevant additional biomarker in AD.


Phenolic compounds from Origanum vulgare and their antioxidant and antiviral activities.
In the present study, six new phenolic compounds (1-6) along with five known ones were isolated from the ethanol extract of the whole plants of Origanum vulgare. The structures of the new compounds were identified on the basis of extensive spectroscopic analyses (UV, IR, NMR, and HRESIMS) and acid hydrolysis. Twenty-one phenolic compounds isolated from O. vulgare in our previous and present studies were evaluated for their in vitro antioxidant activity using 2,2-diphenyl-1-picryhydrazyl (DPPH) radical-scavenging and ferric-reducing antioxidant power (FRAP) assays; twelve of them including two new compounds exhibited significant antioxidant activity comparable to that of ascorbic acid. In addition, the antiviral effects against respiratory syncytial virus (RSV), Coxsackie virus B3 (CVB3) and herpes simplex virus type 1 (HSV-1) were tested by cytopathic effect (CPE) reduction assay.


Children's Fruit "Juice" Drinks and FDA Regulations: Opportunities to Increase Transparency and Support Public Health.
Objectives. To compare children's drink products that contain or purport to contain juice and evaluate labels in light of US Food and Drug Administration (FDA) regulations.Methods. In 2019, we analyzed federal law for drinks that contain or purport to contain juice by using LexisNexis and FDA's Web site, identified top-selling children's "juice" drinks in fruit punch flavors, gathered labels in store and online, and extracted data from the principal display and information panels.Results. FDA regulations permit a wide range of names, claims, and fruit vignettes on drinks that contain or purport to contain juice, reflecting the product's flavor and not necessarily its ingredients. We identified 39 brands of children's drinks, including 100% juice (n = 7), diluted juices (n = 11), juice drinks (n = 8), fruit-flavored drinks (n = 8), and flavored waters (n = 5), with nonuniform statements of identity; vitamin C and low-sugar claims; and fruit vignettes representing 19 fruits. Many products contained added sugar and nonnutritive sweeteners but little to no juice.Conclusions. Principal display panels rendered it difficult to differentiate among product types, identify those with added sweeteners, and distinguish healthier products. Revised labeling regulations are warranted to support public health.


[Variations in the distribution of bronchial arteries. Apropos of 72 arteriographies].
Anatomic distribution of bronchial arteries was studied by arteriography, and evaluation conducted of 72 images considered as being complete. Seven frequent types of distribution were note and findings compared with those of previous studies. Frequency of collateral circulation and of anastomosis was comparable with that reported in the literature. One new distribution pattern was observed: common lower trunk, right upper intercostobronchial trunk, left upper trunk.


Hematopoietic Cell Transplantation in the Treatment of Adult Acute Lymphoblastic Leukemia: Updated 2019 Evidence-Based Review from the American Society for Transplantation and Cellular Therapy.
The role of hematopoietic cell transplantation (HCT) in adults with acute lymphoblastic leukemia (ALL) is reviewed and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the recommendations. A panel of ALL experts developed consensus on the treatment recommendations based on the evidence. Allogeneic HCT offers a survival benefit in selected patients with ALL, and this review summarizes the standard indications as well as the areas of controversy. There is now greater experience with pediatric-inspired chemotherapy regimens that has transformed upfront therapy for adult ALL, resulting in higher remission rates and overall survival. This in turn has increased the equipoise around decision making for ALL in first complete remission (CR1) when there is no measurable residual disease (MRD) at the end of induction and/or consolidation. Randomized studies are needed for adults with ALL to compare allogeneic HCT in CR1 with pediatric-inspired chemotherapy alone. Indications for transplantation in the evolving landscape of MRD assessments and novel targeted and immune therapeutics remain important areas of investigation.


Molecular cytogenetic analysis of durum wheat x tritordeum hybrids.
Southern and in situ hybridization were used to examine the chromosome constitution, genomic relationships, repetitive DNA sequences, and nuclear architecture in durum wheat x tritordeum hybrids (2n = 5x = 35), where tritordeum is the fertile amphiploid (2n = 6x = 42) between Hordeum chilense and durum wheat. Using in situ hybridization, H. chilense total genomic DNA hybridized strongly to the H. chilense chromosomes and weakly to the wheat chromosomes, which showed some strongly labelled bands. pHcKB6, a cloned repetitive sequence isolated from H. chilense, enabled the unequivocal identification of each H. chilense chromosome at metaphase. Analysis of chromosome disposition in prophase nuclei, using the same probes, showed that the chromosomes of H. chilense origin were in individual domains with only limited intermixing with chromosomes of wheat origin. Six major sites of 18S-26S rDNA genes were detected on the chromosomes of the hybrids. Hybridization to Southern transfers of restriction enzyme digests using genomic DNA showed some variants of tandem repeats, perhaps owing to methylation. Both techniques gave complementary information, extending that available from phenotypic, chromosome morphology, or isozyme analysis, and perhaps are useful for following chromosomes or chromosome segments during further crossing of the lines in plant breeding programs.


Cavity-Based Reservoir Engineering for Floquet-Engineered Superconducting Circuits.
Considering the example of superconducting circuits, we show how Floquet engineering can be combined with reservoir engineering for the controlled preparation of target states. Floquet engineering refers to the control of a quantum system by means of time-periodic forcing, typically in the high-frequency regime, so that the system is governed effectively by a time-independent Floquet Hamiltonian with novel interesting properties. Reservoir engineering, on the other hand, can be achieved in superconducting circuits by coupling a system of artificial atoms (or qubits) dispersively to pumped leaky cavities, so that the induced dissipation guides the system into a desired target state. It is not obvious that the two approaches can be combined, since reaching the dispersive regime, in which system and cavities exchange excitations only virtually, can be spoiled by driving-induced resonant transitions. However, working in the extended Floquet space and treating both system-cavity coupling as well as driving-induced excitation processes on the same footing perturbatively, we identify regimes, where reservoir engineering of targeted Floquet states is possible and accurately described by an effective time-independent master equation. We successfully benchmark our approach for the preparation of the ground state in a system of interacting bosons subjected to Floquet-engineered magnetic fields in different lattice geometries.


The relation between neuroimaging and visual impairment in children and adolescents with cerebral palsy: A systematic review.
The structure-function relation between magnetic resonance imaging (MRI) and visual impairment (VI) in children with cerebral palsy (CP) has not been fully unravelled. The present systematic review aims to summarize the relation between brain lesions on MRI and VI in children and adolescents with CP. PubMed, Embase, Web of Science Core Collection, and Cochrane Database were systematically searched according to the PRISMA checklist. A total of 45 articles met the inclusion criteria. White matter lesions were most frequently associated with VI. Only 25 studies described lesions within specific structures, mainly in the optic radiations. Only four studies reported on the thalamus. 8.4% of children with CP showed no brain abnormalities on MRI. Diffusion-weighted MRI studies showed that decreased structural connectivity in the optic radiations, superior longitudinal fasciculus, posterior limb of the internal capsule, and occipital lobe is associated with more severe VI. All types of brain lesions lead to visual dysfunctions, arguing for a comprehensive visual assessment in all children with CP. Whereas white matter damage is a well-known contributor, the exact contribution of specific visual structures requires further investigation, to enable early prediction, detection, and intervention.


The Complexities of "Minding the Gap": Perceived Discrepancies Between Values and Behavior Affect Well-Being.
Research on self-determination theory and clinical models such as acceptance and commitment therapy has shown that behaving in line with our values is a key to maintaining healthy well-being. Combining work on values and experimental studies on moral hypocrisy and well-being, we experimentally tested how behaving incongruently with values affects well-being. We hypothesized that discrepancies between how one thinks one should have behaved and how one reported one did behave would be more detrimental to well-being when the behaviors were value-expressive and motivationally coherent compared to a control condition; greater perceived gaps between how participants feel they should have acted and how they report they did act would be associated with more negative well-being outcomes; the relationship between value manipulation and well-being would be mediated by perceived behavioral gap; and that personal values would interact with value manipulation to produce differential effects on well-being. One-hundred and fifty-eight first-year psychology students participated in an experiment designed to highlight discrepancies between how participants have behaved in accordance with a certain value and how they think they should have behaved, before reporting their well-being. As hypothesized, greater discrepancies between reported past behavior and how participants thought they should have behaved was associated with negative affect and decreased reports of positive well-being. We found no evidence for differential effects of manipulated value-expressive behaviors on well-being, or for our hypothesis that personal values and manipulated value-expressive behaviors interact. Nevertheless, value content mattered in terms of inducing perceived behavioral gaps. Our study suggests that perceived discrepancies between any value and reported past behavior can have a negative impact on some aspects of well-being. We discuss how the application of our methodology can be used in further studies to disentangle the value-behavior nexus.


Chiral recognition and separation of beta2-amino acids using non-covalently molecularly imprinted polymers.
Non-covalently molecularly imprinted polymers (MIPs) for beta2-amino acids were prepared for the first time. N-(2-chlorobenzyloxycarbonyl)-(R)-beta2-homophenylalanine (N-2-ClZ-(R)-beta2-HPhe) was imprinted with methacrylic acid (MAA) and/or 4-vinylpyridine (4-VPy) as the functional monomers, with ethylene glycol dimethacrylate (EDMA) as the cross-linker. The MIPs made with different ratios of MAA:4-VPy were studied in HPLC mode. The results show that MIPs made with 4-VPy yielded the best chiral separation factor (alpha= 1.86) for the template molecule. The importance for an efficient separation of pi-stacking interactions between the MIPs and the template molecule is demonstrated. Racemates of Z-alpha-amino acids and beta-amino acid analogues of the template were either not or poorly resolved by the MIPs, thus demonstrating the close three-dimensional complementarity of the MIPs' recognition sites with the template.


Quantitative analysis of three-dimensional conformal radiotherapy techniques for posterior fossa treatment in children.
Numerous beam directions using 3-D conformal techniques can be employed in treating tumors in the posterior fossa, each with characteristic normal tissue exposure along the entrance and exit trajectory. A representative variety of beam configurations were modeled in a modern computer planning system initially with the entire posterior fossa as the target. These beams were quantitatively scored using criteria based on integral doses for both low dose and high dose effects encompassing a variety of critical normal structures, thus identifying strengths and weaknesses of each beam. By blocking portions of a particular beam accounting for unfavorable scores, a map of "zones" within the posterior fossa ideally treated by a certain beam or beams could be constructed. No universally ideal photon beam arrangement for the entire posterior fossa target could be identified. However, using single beam analysis, the strengths and weaknesses of particular strategies could be quantified. For example, vertex beams treating the cerebellar hemispheres allow the greatest sparing of cochlea and hypothalamus but at the cost of increased low to moderate dose to the supratentorial brain. Using the constructed maps identifying "zones" appropriately treated by a given beam or beams, three-dimensional conformal treatment plans with favorable dose-volume statistics can be designed based on previously defined normal tissue tolerance considerations. It is shown how this approach can be individualized based on specific patient characteristics (e.g., age). We conclude that radiotherapy directed to the posterior fossa can be optimized based on systematic assessment of individual beam contributions to normal tissues. This technique allows fast selection of treatment beams based on known normal tissue anatomical and tolerance information. Further studies will be required regarding long term effects of various radiation doses on specific volumes of normal tissue in order to individualize beam selection. When treating children, knowledgeable consideration of these beam characteristics can help avoid late effects.


Experimental Infection of Mid-Gestation Pregnant Female and Intact Male Sheep with Zika Virus.
Zika virus (ZIKV) is an arbovirus that causes birth defects, persistent male infection, and sexual transmission in humans. The purpose of this study was to continue the development of an ovine ZIKV infection model; thus, two experiments were undertaken. In the first experiment, we built on previous pregnant sheep experiments by developing a mid-gestation model of ZIKV infection. Four pregnant sheep were challenged with ZIKV at 57-64 days gestation; two animals served as controls. After 13-15 days (corresponding with 70-79 days of gestation), one control and two infected animals were euthanized; the remaining animals were euthanized at 20-22 days post-infection (corresponding with 77-86 days of gestation). In the second experiment, six sexually mature, intact, male sheep were challenged with ZIKV and two animals served as controls. Infected animals were serially euthanized on days 2-6 and day 9 post-infection with the goal of isolating ZIKV from the male reproductive tract. In the mid-gestation study, virus was detected in maternal placenta and spleen, and in fetal organs, including the brains, spleens/liver, and umbilicus of infected fetuses. Fetuses from infected animals had visibly misshapen heads and morphometrics revealed significantly smaller head sizes in infected fetuses when compared to controls. Placental pathology was evident in infected dams. In the male experiment, ZIKV was detected in the spleen, liver, testes/epididymides, and accessory sex glands of infected animals. Results from both experiments indicate that mid-gestation ewes can be infected with ZIKV with subsequent disruption of fetal development and that intact male sheep are susceptible to ZIKV infection and viral dissemination and replication occurs in highly vascular tissues (including those of the male reproductive tract).


Fingerprints of bonding motifs in DNA duplexes of adenine and thymine revealed from circular dichroism: synchrotron radiation experiments and TDDFT calculations.
Synchrotron radiation circular dichroism (SRCD) spectra were recorded for a family of 12 DNA duplexes that all contain nine adenines (A) and nine thymines (T) in each strand but in different combinations. The total number of AT Watson-Crick (WC) base pairs is constant (18), but the number of cross-strand (CS) hydrogen bonds between A and T varies between 0 and 16, the maximum possible. Eleven of the duplexes have one or more A tracts, and one duplex has T tracts. The signals due to hybridization were found from subtraction of spectra of single strands from spectra of the duplexes. The residual spectrum of the T-tract duplex T(9)A(9):A(9)T(9) (5'-3':3'-5') significantly differs from that of the A-tract duplex A(9)T(9):T(9)A(9), but only below 210 nm, which suggests that the signal in this region depends on the superhelicity of the duplex. A principal component analysis of all residual spectra reveals that spectra of A-tract duplexes can be obtained to a good approximation as a linear combination of just two basis spectra. The first component is assigned to the spectrum of 18 WC and 8 CS pairs, whereas the second component is that of 8 CS pairs. This interpretation is supported by separate experiments on duplexes of varying lengths but with similar arrangements of the A and T's and by experiments on two other duplex families of 14 and 30 base pairs. The best correlation is obtained by the assumption that cross-strand interactions occur as long as there are two adenine neighbors in a strand. Our data indicate that a circular dichroism spectrum of a duplex containing only A and T can simply be inferred from the number of WC base pairs and the number of CS interactions, and we provide reference spectra for these two interactions. Finally, time dependent density functional theory calculations of the circular dichroism spectra for an isolated WC base pair and two different CS base pairs (between adenine N-6 amine and thymine O-4 or between adenine C-2-H and thymine O-2) were performed to provide some additional support for the interpretation of the experimental spectra. We find large differences between the two calculated CS spectra. However, there is a reasonable qualitative agreement between the calculated WC and the C-2-H...O-2 CS spectra and those deduced from the experimental data.


An experimental comparison of composite and grab sampling of stream water for metagenetic analysis of environmental DNA.
Use of environmental DNA (eDNA) to assess distributions of aquatic and semi-aquatic macroorganisms is promising, but sampling schemes may need to be tailored to specific objectives. Given the potentially high variance in aquatic eDNA among replicate grab samples, compositing smaller water volumes collected over a period of time may be more effective for some applications. In this study, we compared eDNA profiles from composite water samples aggregated over three hours with grab water samples. Both sampling patterns were performed with identical autosamplers paired at two different sites in a headwater stream environment, augmented with exogenous fish eDNA from an upstream rearing facility. Samples were filtered through 0.8 μm cellulose nitrate filters and DNA was extracted with a cetyl trimethylammonium bromide procedure. Eukaryotic and bacterial community profiles were derived by amplicon sequencing of 12S ribosomal, 16S ribosomal, and cytochrome oxidase I loci. Operational taxa were assigned to genus with a lowest common ancestor approach for eukaryotes and to family with the RDP Classifier software for prokaryotes. Eukaryotic community profiles were more consistent with composite sampling than grab sampling. Downstream, rarefaction curves suggested faster taxon accumulation for composite samples, and estimated richness was higher for composite samples as a set than for grab samples. Upstream, composite sampling produced lower estimated richness than grab samples, but with overlapping standard errors. Furthermore, a bimodal pattern of richness as a function of sequence counts suggested the impact of clumped particles on upstream samples. Bacterial profiles were insensitive to sample method, consistent with the more even dispersion expected for bacteria compared with eukaryotic eDNA. Overall, samples composited over 3 h performed equal to or better than triplicate grab sampling for quantitative community metrics, despite the higher total sequencing effort provided to grab replicates. On the other hand, taxon-specific detection rates did not differ appreciably and the two methods gave similar estimates of the ratio of the common fish genera Salmo and Coregonus at each site. Unexpectedly, Salmo eDNA dropped out substantially faster than Coregonus eDNA between the two sites regardless of sampling method, suggesting that differential settling affects the estimation of relative abundance. We identified bacterial patterns that were associated with eukaryotic diversity, suggesting potential roles as biomarkers of sample representativeness.


Mechanism of activation of renal Na+-K+-ATPase in the rat: effects of reduction of renal mass.
The mechanism of activation of renal Na+-K+-ATPase was studied in rats 2 wk after unilateral nephrectomy. The increase in enzyme specific activity was confined to the outer medulla and occurred without changes in the cellular contents of RNA or protein. Enzyme activation was accompanied by increases in the levels of the phosphorylated intermediate with little or no change in the apparent turnover numbers of the reaction. The specific activity of the ouabain-sensitive p-nitrophenylphosphatase also increased by uninephrectomy but to a larger extent than did Na+-K+-ATPase. Kinetic studies demonstrated an increase in Vmax for ATP, sodium, and potassium, and small increases in Km for ATP and K1/2 for potassium. There was no change in the activation energies or phase transition temperature to indicate alterations in the membrane environment of Na+-K+-ATPase. Adrenalectomy did not adversely affect activation. These results indicate that activation of renal Na+-K+-ATPase after reduction of renal mass occurs mainly by an increase in the number of sodium pump sites.


Vancomycin resistance in staphylococci.
Vancomycin resistance has been reported in clinical isolates of both coagulase-negative staphylococci and Staphylococcus aureus. The emerging threat of widespread vancomycin resistance poses a serious public health concern given the fact that vancomycin has long been the preferred treatment of antibiotic-resistant gram-positive organisms. Though major efforts are now being focused on improving our understanding of vancomycin resistance, there is much that remains unknown at this time. This article reviews the major epidemiologic, microbiologic, and clinical characteristics of vancomycin resistance in both coagulase-negative staphylococci and S. aureus. The review begins with a discussion of issues common to both coagulase-negative staphylococci and S. aureus, such as definitions, laboratory detection of vancomycin resistance, and infection control issues related to vancomycin-resistant staphylococci. The rest of the article is then devoted to a discussion of issues unique to each organism, including epidemiology, risk factors for infection, mechanisms of resistance, and management options.


[Isolated tuberculosis of the sternum].
Isolated tuberculous foci of the sternum are rare. In a period of 26 years (1955 to 1981) we have treated ten sternal lesions surgically in our clinic. Eight of these were tuberculous. The clinical material (three females, five males) is described, including diagnostic and therapeutic details. The frequency, localisation, clinical features, diagnosis, treatment, prognosis and differential diagnosis of specific sternal infections are discussed and the relevant literature is reviewed.


Metaplastic Carcinoma Breast: A Clinical Analysis of Nine Cases.
Metaplastic Breast Carcinoma (MBC) is a rare heterogeneous group of primary breast malignancies with different subgroups; exhibits a variety of histopathologic patterns and appears to be both epithelial and mesenchymal in origin. The ideal treatment for MBC remains unknown, due to its low incidence and pathological variability. Owing to its rarity, MBC has been treated as a variant of Invasive Duct Carcinoma (IDC). But it has poorer prognosis as compared to IDC. This is a case series to evaluate clinicopathologic characteristics and the multi-disciplinary treatment of nine MBC patients treated in a single institute.


Gender inequalities in COPD decision-making in primary care.
COPD is a frequent severe illness that increasingly affects females. Gender inequalities have been reported in COPD care. To analyze decision-making in primary care for men and women with identical COPD as a function of the gender of the family physician (FP). Cross-sectional, multicenter study in 457 Andalusian FPs, using a self-administered vignette-based questionnaire on COPD featuring a male or female patient, with four variables on clinical reasoning: "tobacco as most important risk factor (RF)", "ordering of spirometry", "COPD as most likely diagnosis", and "referral". Multilevel logistic regression analysis. Response rate was 67.4% (308/457). In analysis of the four FP gender-patient gender dyads, tobacco was more frequently considered as priority RF for the man than for the woman in the vignette by female (95.6%vs.67.1%) and male (79.8%vs.62.5%) FPs. COPD was more frequently the most likely diagnosis for the man versus woman by female (84.4%vs.49.9%) and male (78.5%vs.57.8%) FPs. Male FPs more frequently ordered spirometry for the man versus woman (68.1%vs.46.8%). There were no differences in referral between male and female patients. Male FPs were more likely than female FPs to consider tobacco as priority RF for the man (p = 002). Female FPs were more likely than male FPs to refer the man (22.5%vs.8%). There may be gender inequalities in primary care for COPD in our setting. Diagnostic and therapeutic efforts appear lower in female patients. Male and female FPs only differed in care of the male patient, indicating FP gender-patient gender interaction.


[Modification of meatoglanuloplasty (MAGPI-Duckett) for treatment of balanic and coronal forms of hypospadia in children].
14 boys with balanic hypospadia (BH) and 23 boys with coronal hypospadia (CH) aged 9 months to 15 years were operated in 1997-2000. For 13 boys this operation was meatoglanuloplasty (MAGPI) by J. Duckett. Complications occurred in 4 boys: retraction (downwards) of the meatus (n = 2), urethral stenosis and urinary fistula (n = 2). 24 boys have undergone modified MAGPI operation. The modification consists in extended mobilization of the lateral parts of the head with longitudinal consecutive incisions along the head margin into the spongy bodies. The head is closed by suturing its mobilized margins with two rows of interrupted monofilamentous (PDS, prolene) sutures above the urethra. A variant of saving foreskin is possible when partial separation of the internal and external layers is made bilaterally with consecutive circular closure of the preputial sac. Phimosis is prevented by a relief longitudinal incision along the internal foreskin and transverse suturing. The patients were followed up for 2 months to 1.5 years. The original operation MAGPI provided good cosmetic and functional results in 9 boys(69.2%), satisfactory in 2 boys(15.4%), unsatisfactory also in 2 boys(15.4%). The modified MAGPI operation provided only good cosmetic and functional results. Thus, the proposed modification (MAGPI-Duckett) ensures a more reliable variant of meatoglanuloplasty in balanic and coronal hypospadia irrespective of the size and shape of the head, presence of the scaphoid fossa or meatostenosis. These additional procedures helped to reduce the number of postoperative complications and improved cosmetic and functional results.


Delamination and dissection of arteriovenous grafts: A multicenter report of four cases.
Arteriovenous (AV) grafts are an alternative vascular access for chronic hemodialysis. AV graft failure is often due to stenosis of the feeding artery, graft, or draining vein. We report four cases of AV graft dysfunction and failure rarely caused by graft delamination and dissection. Two males and two females aged 47-67 years had been on chronic hemodialysis. Ultrasound examination detected graft delamination and dissection between 1 and 33 months after Acuseal AV graft implantation. Two cases were successfully treated with stenting and partial graft replacement, respectively. False lumen volume reduction by fluid withdrawal failed to salvage the delaminated graft in one of the patients. The delamination and dissection of another case spontaneously resolved 5 months later. Graft delamination and dissection should be considered as a possible cause for AV graft dysfunction and failure. Stenting and graft replacement may be recommended to treat AV graft dissection and delamination.


Minimally Invasive Adenocarcinoma of the Lung as Second Malignant Neoplasm Following Pediatric Rhabdomyosarcoma.
Primary pulmonary tumors are extremely rare in the pediatric population; however, sporadic cases of invasive pulmonary adenocarcinoma as a second malignant neoplasm (SMN) have been described in survivors of pediatric cancers. Pediatric patients with rhabdomyosarcoma (RMS) have a particularly increased risk of developing a SMN when compared to the general population, though pulmonary adenocarcinoma has not been previously described in a RMS patient. A 12-year-old female previously treated for stage IV pelvic RMS was found to have a left pulmonary nodule on surveillance computed tomography. The nodule was detected 4.25 years after the completion of treatment, which included resection, chemotherapy, and radiation to the abdomen and pelvis. Wedge resection of the pulmonary lesion was performed with negative margins. Histopathological examination revealed minimally invasive adenocarcinoma. Pulmonary adenocarcinoma may rarely present as a SMN in pediatric cancer survivors. The pathogenesis of this association is not yet entirely clear, but may include chemotherapy-induced mutagenesis and/or genetic predisposition. As pulmonary adenocarcinoma may present as a lung lesion radiographically indistinguishable from metastatic RMS, it should be considered in the differential diagnosis of any pediatric RMS survivor presenting with a new pulmonary nodule, especially in cases with late recurrence.


Object-oriented developmental environment for image-analysis applications: implementation for 2D gel electrophoretogram analysis.
The principal motivation was to design an environment for the development of image-analysis applications which would allow the integration of independent modules into one frame and make available tools for their build-up, running, management and mutual communication. The system was designed as modular, consisting of the core and work modules. The system core focuses on overall management and provides a library of classes for build-up of the work modules, their user interface and data communication. The work modules carry practical implementation of algorithms and data structures for the solution of a particular problem, and were implemented as dynamic-link libraries. They are mutually independent and run as individual threads, communicating with each other via a unified mechanism. The environment was designed to simplify the development and testing of new algorithms or applications. An example of implementation for the particular problem of the analysis of two-dimensional (2D) gel electrophoretograms is presented. The environment was designed for the Windows NT operating system with the use of Microsoft Foundation Class Library employing the possibilities of C++ programming language. Available on request from the authors.


β-Blockers in Hepatosplenic Schistosomiasis: A Narrative Review.
Hepatosplenic schistosomiasis (HSS) is a serious complication of chronic schistosomiasis that can result in portal hypertension and variceal bleeding. β-blockers, a class of medications commonly used to treat hypertension and other cardiovascular conditions, have been investigated for their potential use in preventing variceal bleeding in HSS. Several studies have shown that β-blockers can reduce portal pressure and prevent variceal bleeding effectively in these patients. However, there are limited data on the long-term efficacy and safety of β-blockers in this setting, and further research is needed to determine the optimal use of these medications. This review summarizes the evidence supporting current recommendations of β-blocker use in patients with HSS.


A new member of the psittacosis-lymphogranuloma group of viruses that causes infection in calves.
From portions of intestine and feces of apparently normal calves, a virus that produces elementary bodies was procured in guinea pigs and in embryonated eggs. Morphologically and tinctorially this virus closely resembled members of the psittacosis-lymphogranuloma group of viruses and it shared a common antigen or antigens with them. Comparison of serological, pathogenic, and other properties indicated that this virus from calves is a new member of the psittacosis-lymphogranuloma group and in keeping with classification practices it is provisionally named Miyagawanella bovis. Miyagawanella bovis when fed to experimental calves established an infection in the intestinal tract that resembled the inapparent infection seen in natural cases but failed to produce evident disease. Ability of the virus to infect experimental animals by feeding, and its presence in feces of infected animals indicate its natural mode of spread. This method of dissemination and persistence of virus for long periods of time in infected animals suggested the virus should be widespread and more than 60 per cent of the calves in the vicinity of lthaca were found to be infected.


Effects of Ayahuasca on Personality: Results of Two Randomized, Placebo-Controlled Trials in Healthy Volunteers.
Rationale: Previous studies with the serotonergic hallucinogens LSD and psilocybin showed that these drugs induced changes in personality traits, such as increases in Openness. However, results are inconsistent, and the effects of ayahuasca on personality were never investigated in a controlled trial. Objectives: To assess the effects of ayahuasca on personality in two randomized, placebo-controlled trials in healthy volunteers. Methods: Data from two parallel-group, randomized, placebo-controlled trials in healthy volunteers were included. In the first trial, 15 volunteers ingested ayahuasca or placebo, while in the second trial 15 volunteers received placebo+ayahuasca or cannabidiol (CBD)+ayahuasca. Personality was assessed with the NEO-Five Factor Inventory (NEO-FFI) at baseline and 21 days post-treatment. Results: There were significant differences between groups in baseline Openness scores, but not on day 21. A significant increase in Openness scores was observed in the placebo + ayahuasca group in study 2. No other within-group differences were observed for any other domain. Conclusions: Ayahuasca produced inconsistent effects on personality since it induced significant increase in Openness 21 days post-drug intake only in one of the trials. The absence of significant differences in the other ayahuasca groups could be due to small sample sizes and baseline differences among groups. The effects of ayahuasca and other serotonergic hallucinogens on personality should be further investigated in clinical samples.


Interexaminer difference in infarct volume measurements on MRI: a source of variance in stroke research.
The measurement of ischemic lesion volume on diffusion- (DWI) and perfusion-weighted MRI (PWI) is examiner dependent. We sought to quantify the variance imposed by measurement error in DWI and PWI lesion volume measurements in ischemic stroke. Fifty-eight consecutive patients with DWI and PWI within 12 hours of symptom onset and follow-up MRI on >or= day-5 were studied. Two radiologists blinded to each other measured lesion volumes by manual outlining on each image. Interexaminer reliability was evaluated by intraclass correlation coefficients (ICC) and relative paired difference or RPD (ratio of difference between 2 measurements to their mean). The ratio of between-examiner variability to between-subject variability (variance ratio) was calculated for each imaging parameter. The correlation (ICC) between examiners ranged from 0.93 to 0.99. The median RPD was 10.0% for DWI, 14.1% for mean transit time, 18.9% for cerebral blood flow, 21.0% for cerebral blood volume, 16.8% for DWI/MTT mismatch, and 6.3% for chronic T2-weighted images. There was negative correlation between RPD and lesion volume in all but chronic T2-weighted images. The variance ratio ranged between 0.02 and 0.10. Despite high correlation between volume measurements of abnormal regions on DWI and PWI by different examiners, substantial differences in individual measurements can still occur. The magnitude of variance from measurement error is primarily determined by the type of imaging and lesion volume. Minimizing this source of variance will better enable imaging to deliver on its promise of smaller sample size.


[Mechanical thrombolysis of the basilar artery. Report of one case].
We report a 40 year-old male presenting in the emergency room with headache, vertigo and left hemiparesis. A magnetic resonante imaging reported a left cerebellar infarction with occlusion of the basilar artery and a dissection of the right vertebral artery. The patient experienced a clinical deterioration with the appearance of a right hemiparesis. Therefore a brain angiography was performed along with a mechanical thrombolysis using a Solitaire FR® revascularization device. A thrombus located in the distal third of the artery was eliminated obtaining a complete perfusión of the artery. The patient had a satisfactory evolution.


Real time visualization of 13N-translocation in rice under different environmental conditions using positron emitting Ttacer imaging system.
The ammonium ion is an indispensable nitrogen source for crops, especially paddy rice (Oryza sativa L. cv Nipponbare). Until now, it has been impossible to measure ammonium uptake and nitrogen movement in plants in real time. Using the new technologies of PETIS (positron emitting tracer imaging system) and PMPS (positron multi-probe system), we were able to visualize the real time translocation of nitrogen and water in rice plants. We used positron-emitting 13N-labeled ammonium (13NH4+) and 15O-water to monitor the movement. In plants cultured under normal conditions, 13NH4+ supplied to roots was taken up, and a 13N signal was detected at the discrimination center, the basal part of the shoots, within 2 minutes. This rapid translocation of (13)N was almost completely inhibited by a glutamine synthetase inhibitor, methionine sulfoximine. In general, nitrogen deficiency enhanced 13N translocation to the discrimination center. In the dark, 13N translocation to the discrimination center was suppressed to 40% of control levels, whereas 15O-water flow from the root to the discrimination center stopped completely in the dark. In abscisic acid-treated rice, 13N translocation to the discrimination center was doubled, whereas translocation to leaves decreased to 40% of control levels. Pretreatment with NO3- for 36 hours increased 13N translocation from the roots to the discrimination center to 5 times of control levels. These results suggest that ammonium assimilation (from the roots to the discrimination center) depends passively on water flow, but actively on NH4+-transporter(s) or glutamine synthetase(s).


Breast and torso characteristics of female contact football players: implications for the design of sports bras and breast protection.
This study aimed to provide normative data characterising the breast size, breast position and torso size of female contact football players. 117 AFL, Rugby League, Rugby Union and Rugby 7s players attended a single testing session where a three-dimensional scan was taken of their naked breasts and torso. Dimensions relevant to the design of sports bras and breast protective equipment were then calculated from the scans. Several breast and torso characteristics of female contact football athletes differed to measurements reported for females in the general population and amongst the contact football codes. Designers and manufacturers of sports bras or breast protective equipment should consider the specific breast and torso dimensions of female contact football players to maximise the fit, comfort and efficacy of these garments. Practitioner summary: Using three-dimensional scanning, this study characterised the breast and torso size and shape of 117 female contact football players. These normative data should be used to improve the fit and comfort of sports bras and breast protective equipment for female contact football players.


Inhibitory effects of extracts from Cinnamomum camphora fallen leaves on algae.
Natural allelochemicals are considered as a source of algaecides. To uncover the anti-algal activity of Cinnamomum camphora fallen leaves and promote their usage as algaecides, the composition of their water and methanol extracts was analyzed, and the inhibitory effects of extracts on the growth of Microcystis aeruginosa and Chlamydomonas reinhardtii, and chlorophyll (Chl) content and photosynthetic abilities in C. reinhardtii were investigated. Twenty-five compounds were detected in the water extracts, mainly including terpenoids, esters, alcohols, and ketones. Compared to water extracts, there were more compounds and higher concentration in methanol extracts. Both water and methanol extracts inhibited the growth of the two algae, and 15 mg·ml-1 methanol extracts killed the algal cells after 48 h. The levels of Chl a and Chl b, as well as maximum quantum yield of photosystem II photochemistry (Fv/Fm) in C. reinhardtii cells reduced gradually with increasing the concentration of extracts, while the maximum quantum yield of non-photochemical de-excitation (φDO) increased gradually. At the same concentration, methanol extracts showed stronger inhibitory effects than water extracts, due to their higher number of compounds and higher concentration. Therefore, C. camphora fallen leaves have a potential value as an algaecide.


Cooperation and deception: from evolution to mechanisms.
Nature is full of struggle, as predicted by the theory of evolution through natural selection, yet there are also paramount examples where individuals help each other. These instances of helping have been difficult to reconcile with Darwin's theory because it is not always obvious how individuals are working for their own direct benefit. Consequently, initial publications that offered solutions to subsets of the observed cases of helping, such as kin selection or reciprocity, are among the most influential and most cited papers in evolution/behavioural ecology. During the last few years, a wave of new studies and concepts has considerably advanced our understanding of the conditions under which individuals are selected to help others. On the empirical side, advances are due to stronger incorporation of the natural history of each study species and an emphasis on proximate questions regarding decision-making processes. In parallel, theorists have provided more realistic models together with an increased exploration of the importance of life history and ecology in understanding cooperation. The ideas presented by the authors of this volume represent, in many ways, the revolutionary new approach to studying behaviour which is currently underway.


Radiolytic mapping of solvent-contact surfaces in Photosystem II of higher plants: experimental identification of putative water channels within the photosystem.
Photosystem II uses water as an enzymatic substrate. It has been hypothesized that this water is vectored to the active site for water oxidation via water channels that lead from the surface of the protein complex to the Mn4O5Ca metal cluster. The radiolysis of water by synchrotron radiation produces amino acid residue-modifying OH(•) and is a powerful technique to identify regions of proteins that are in contact with water. In this study, we have used this technique to oxidatively modify buried amino acid residues in higher plant Photosystem II membranes. Fourier transform ion cyclotron resonance mass spectrometry was then used to identify these oxidized amino acid residues that were located in several core Photosystem II subunits (D1, D2, CP43, and CP47). While, as expected, the majority of the identified oxidized residues (≈75%) are located on the solvent-exposed surface of the complex, a number of buried residues on these proteins were also modified. These residues form groups which appear to lead from the surface of the complex to the Mn4O5Ca cluster. These residues may be in contact with putative water channels in the photosystem. These results are discussed within the context of a number of largely computational studies that have identified putative water channels in Photosystem II.


MiR-9 inhibits Schwann cell migration by targeting Cthrc1 following sciatic nerve injury.
The regulative effects of microRNAs (miRNAs) on responses of Schwann cells to a nerve injury stimulus are not yet clear. In this study, we noted that the expression of eight miRNAs was downregulated at different time points following rat sciatic nerve transection, and found that 368 potential targets of these eight miRNAs were mainly involved in phenotypic modulation of Schwann cells. Of these miRNAs, miR-9 was identified as an important functional regulator of Schwann cell migration that was a crucial regenerative response of Schwann cells to nerve injury. In vitro, upregulated expression of miR-9 inhibited Schwann cell migration, whereas silencing of miR-9 promoted Schwann cell migration. Intriguingly, miR-9 exerted this regulative function by directly targeting collagen triple helix repeat containing protein 1 (CTHRC1), which in turn inactivated downstream Rac1 GTPase. Rac1 inhibitor reduced the promotive effects of anti-miR-9 on Schwann cell migration. In vivo, high expression of miR-9 reduced Schwann cell migration within a regenerative nerve microenvironment. Collectively, our results confirmed the role of miR-9 in regulating Schwann cell migration after nerve injury, thus offering a new approach to peripheral nerve repair.


Watertightness of wound closure in lumbar spine-a comparison of different techniques.
Since a primary watertight dural suture after incidental durotomies has a failure rate of 5-10%, a watertight closure technique of the overlying layers (fascia, subcutis and skin) is essential. The purpose of this cadaveric study was to find the most watertight closure technique for fascia, subcutis and skin. Different suturing techniques were tested for each layer in a sheep cadaveric model by measuring the leakage pressure. The specimens were mounted on a pressure chamber connected to a manometer and a water tube system. Subsequently, the leakage was over-sewed with a cross stitch and the experiment was repeated. Cross stitch suturing [median =180 mbar (43; 660)] performed best compared to continuous [median =16 mbar (6; 52)] (P=0.003) but not to single knot [median =118 mbar (21; 387)] (P=1.0) or locking stitch suturing [median =109 mbar (3; 149)] (P=0.93) for fascia closure. Continuous suture [median =9 mbar (3; 14)] resulted in a higher leakage pressure than single knot [median =1 mbar (1; 6)] (P=0.017) for subcutaneous closure. No significant differences were found between intracutaneous, Donati-continuous, single knot and locking stitch for skin closures (P=0.075). However, the Donati-continuous stitch closure resulted in higher pressures in tendency. Over-sewing increased median leakage pressure from 8.0 to 11.0 mbar (P=0.068) and from 4.0 to 13.0 mbar (P=0.042) for single knot and for locking stitch skin closures, respectively. Cross stitches for the fascia, continuous suturing technique for the subcutis and Donati-continuous stitch for the skin resulted in the most watertight closure within this experimental setting. If leakage occurs, over-sewing might relevantly improve the watertightness of the wound.


Exendin-4 alleviates angiotensin II-induced senescence in vascular smooth muscle cells by inhibiting Rac1 activation via a cAMP/PKA-dependent pathway.
Vascular aging has been implicated in the progression of diabetes and age-related cardiovascular disorders. Glucagon-like peptide-1 (GLP-1) is an incretin hormone capable of cytoprotective actions in addition to its glucose-lowering effect. The present study was undertaken to examine whether Exendin-4, a specific ligand for the GLP-1 receptor, could prevent angiotensin (ANG) II-induced premature senescence in vascular smooth muscle cells (VSMCs) and to determine the underlying mechanism involved. Senescence-associated β-galactosidase (SA β-gal) assay showed that ANG II induced premature senescence of VSMCs. Pretreatment with Exendin-4 significantly attenuated ANG II-induced generation of H2O2 and the subsequent VSMC senescence. These effects were, however, reversed in the presence of exendin fragment 9-39, a GLP-1 receptor antagonist, or PKI14-22. Moreover, a marked increase in the levels of p53 and p21 induced by ANG II was blunted by the treatment with Exendin-4. Nevertheless, Exendin-4 failed to decrease ANG II-induced expression of NAD(P)H oxidase 1 (Nox1), NAD(P)H oxidase 4 (Nox4), p22(phox), or p47(phox) in VSMCs. Mechanistically, Exendin-4 blocked ANG II-induced Rac1 activation through the cAMP/PKA signaling cascade. Specifically, NSC23766, a Rac1 inhibitor, abrogated the suppressive effects of Exendin-4 on ANG II-induced premature senescence and H2O2 generation, respectively. Thus Exendin-4 confers resistance to ANG II-induced superoxide anion generation from NAD(P)H oxidase and the resultant VSMC senescence by inhibiting Rac1 activation via a cAMP/PKA-dependent pathway. These findings demonstrate that GLP-1 as well as its analogs (GLP-1-related reagents) may hold therapeutic potential in the treatment of diabetes with cardiovascular disease.


Caring for patients with kidney disease: shifting the paradigm from evidence-based medicine to patient-centered care.
The last several decades have witnessed the emergence of evidence-based medicine as the dominant paradigm for medical teaching, research and practice. Under an evidence-based approach, populations rather than individuals become the primary focus of investigation. Treatment priorities are largely shaped by the availability, relevance and quality of evidence and study outcomes and results are assumed to have more or less universal significance based on their implications at the population level. However, population-level treatment goals do not always align with what matters the most to individual patients-who may weigh the risks, benefits and harms of recommended treatments quite differently. In this article we describe the rise of evidence-based medicine in historical context. We discuss limitations of this approach for supporting real-world treatment decisions-especially in older adults with confluent comorbidity, functional impairment and/or limited life expectancy-and we describe the emergence of more patient-centered paradigms to address these limitations. We explain how the principles of evidence-based medicine have helped to shape contemporary approaches to defining, classifying and managing patients with chronic kidney disease. We discuss the limitations of this approach and the potential value of a more patient-centered paradigm, with a particular focus on the care of older adults with this condition. We conclude by outlining ways in which the evidence-base might be reconfigured to better support real-world treatment decisions in individual patients and summarize relevant ongoing initiatives.


Databases for biomass and waste biorefinery - a mini-review and SWOT analysis.
The world is facing problems of the increasing amount of resources wasted as the world population grows. Biowaste streams form a significant part of the overall waste generation, and a circular economy utilizing this biowaste will significantly reduce waste whilst lowering the anthropogenic carbon footprint. Due to their energy content and high concentration of hydrocarbon molecules, bio-based waste streams have the potential to be transformed into valorized products (energy, fuels, and chemicals) using biorefinery technologies. In this work, a mini-review has been conducted on available, mostly European databases on existing biomass types and biorefinery technologies to provide a framework for a desirable, comprehensive database connecting bio-based waste streams, biorefinery technologies and bioproducts, as well as the geographical distribution of feedstocks and biorefineries. The database assessment utilized the SWOT (strengths, weakness, opportunities, threats) methodology to support benchmark analysis and to identify critical gaps in underlying data structures that could be included in a single database. The results show that current databases are useful but insufficient for waste biorefineries due to limited quality and quantity as well as the usability of data. A comprehensive database or improved database cluster would be necessary, not only for technology development but for better investment and policy decisions. The development of the new database architecture would need to incorporate the aspects: expansion of database scope and content depth, improved usability, accessibility, applicability, update frequency, openness to new contributions, process descriptions and parameters, and technology readiness level.


ELF4 Is a Target of miR-124 and Promotes Neuroblastoma Proliferation and Undifferentiated State.
13-Cis-retinoic acid (RA) is typically used in postremission maintenance therapy in patients with neuroblastoma. However, side effects and recurrence are often observed. We investigated the use of miRNAs as a strategy to replace RA as promoters of differentiation. miR-124 was identified as the top candidate in a functional screen. Genomic target analysis indicated that repression of a network of transcription factors (TF) could be mediating most of miR-124's effect in driving differentiation. To advance miR-124 mimic use in therapy and better define its mechanism of action, a high-throughput siRNA morphologic screen focusing on its TF targets was conducted and ELF4 was identified as a leading candidate for miR-124 repression. By altering its expression levels, we showed that ELF4 maintains neuroblastoma in an undifferentiated state and promotes proliferation. Moreover, ELF4 transgenic expression was able to counteract the neurogenic effect of miR-124 in neuroblastoma cells. With RNA sequencing, we established the main role of ELF4 to be regulation of cell-cycle progression, specifically through the DREAM complex. Interestingly, several cell-cycle genes activated by ELF4 are repressed by miR-124, suggesting that they might form a TF-miRNA regulatory loop. Finally, we showed that high ELF4 expression is often observed in neuroblastomas and is associated with poor survival. IMPLICATIONS: miR-124 induces neuroblastoma differentiation partially through the downregulation of TF ELF4, which drives neuroblastoma proliferation and its undifferentiated phenotype.


An updated review of the genus Rhododendron since 2010: Traditional uses, phytochemistry, and pharmacology.
Rhododendron, the largest genus of Ericaceae, consists of approximately 1000 species that are widely distributed in Europe, Asia, and North America but mainly exist in Asia. Rhododendron plants have not only good ornamental and economic value but also significant medicinal potential. In China, many Rhododendron plants are used as traditional Chinese medicine or ethnic medicine for the treatment of respiratory diseases, pain, bleeding and inflammation. Rhododendron is known for its abundant metabolites, especially diterpenoids. In the past 13 years, a total of 610 chemical constituents were reported from Rhododendron plants, including 222 diterpenoids, 122 triterpenoids, 103 meroterpenoids, 71 flavonoids and 92 other constituents (lignans, phenylpropanoids, phenolic acids, monoterpenoids, sesquiterpenoids, coumarins, steroids, fatty acids). Moreover, the bioactivities of various extracts and isolates, both in vitro and in vivo, were also investigated. Our review summarized the research progress of Rhododendron regarding traditional uses, phytochemistry and pharmacology in the past 13 years (2010 to December 2022), which will provide new insight for prompting further research on Rhododendron application and drug development.


Bottled water contaminant exposures and potential human effects.
Bottled water (BW) consumption in the United States and globally has increased amidst heightened concern about environmental contaminant exposures and health risks in drinking water supplies, despite a paucity of directly comparable, environmentally-relevant contaminant exposure data for BW. This study provides insight into exposures and cumulative risks to human health from inorganic/organic/microbial contaminants in BW. BW from 30 total domestic US (23) and imported (7) sources, including purified tapwater (7) and spring water (23), were analyzed for 3 field parameters, 53 inorganics, 465 organics, 14 microbial metrics, and in vitro estrogen receptor (ER) bioactivity. Health-benchmark-weighted cumulative hazard indices and ratios of organic-contaminant in vitro exposure-activity cutoffs were assessed for detected regulated and unregulated inorganic and organic contaminants. 48 inorganics and 45 organics were detected in sampled BW. No enforceable chemical quality standards were exceeded, but several inorganic and organic contaminants with maximum contaminant level goal(s) (MCLG) of zero (no known safe level of exposure to vulnerable sub-populations) were detected. Among these, arsenic, lead, and uranium were detected in 67 %, 17 %, and 57 % of BW, respectively, almost exclusively in spring-sourced samples not treated by advanced filtration. Organic MCLG exceedances included frequent detections of disinfection byproducts (DBP) in tapwater-sourced BW and sporadic detections of DBP and volatile organic chemicals in BW sourced from tapwater and springs. Precautionary health-based screening levels were exceeded frequently and attributed primarily to DBP in tapwater-sourced BW and co-occurring inorganic and organic contaminants in spring-sourced BW. The results indicate that simultaneous exposures to multiple drinking-water contaminants of potential human-health concern are common in BW. Improved understandings of human exposures based on more environmentally realistic and directly comparable point-of-use exposure characterizations, like this BW study, are essential to public health because drinking water is a biological necessity and, consequently, a high-vulnerability vector for human contaminant exposures.


Nociceptive afferent phenotyping reveals that transient receptor potential ankyrin 1 promotes cold pain through neurogenic inflammation upstream of the neurotrophic factor receptor GFRα3 and the menthol receptor transient receptor potential melastatin 8.
The proper detection and behavioral response to painfully cold temperatures is critical for avoiding potentially harmful tissue damage. Cold allodynia and hyperalgesia, pain associated with innocuous cooling and exaggerated pain with noxious cold, respectively, are common in patients with chronic pain. In peripheral somatosensory afferents, the ion channels transient receptor potential melastatin 8 (TRPM8) and transient receptor potential ankyrin 1 (TRPA1) are candidate receptors for innocuous and noxious cold temperatures, respectively. However, the role of TRPA1 as a cold sensor has remained controversial, and recent evidence suggests that TRPM8 channels and afferents mediate the detection of both pleasant and painful cold. To determine the role of TRPA1 afferents in cold-induced mouse behaviors in vivo, we used functional phenotyping by targeted nerve conduction block with the cell-impermeant lidocaine derivative QX-314. Surprisingly, we find that injection of QX-314 with TRPA1 agonists reduces cold-induced behaviors in mice, but does so in a TRPM8-dependent manner. Moreover, this effect is sexually dimorphic and requires the glial cell line-derived neurotrophic factor receptor GFRα3, as does cold hypersensitivity produced by the activation of TRPA1 channels. Taken together, these results suggest that under conditions of neurogenic inflammation, TRPA1 works upstream of GFRα3 and TRPM8 to produce cold hypersensitivity, providing novel insights into the role of TRPA1 channels in cold pain.


Strong Backreaction Regime in Axion Inflation.
We study the nonlinear dynamics of axion inflation, capturing for the first time the inhomogeneity and full dynamical range during strong backreaction, till the end of inflation. Accounting for inhomogeneous effects leads to a number of new relevant results, compared to spatially homogeneous studies: (i) the number of extra efoldings beyond slow-roll inflation increases very rapidly with the coupling, (ii) oscillations of the inflaton velocity are attenuated, (iii) the tachyonic gauge field helicity spectrum is smoothed out (i.e., the spectral oscillatory features disappear), broadened, and shifted to smaller scales, and (iv) the nontachyonic helicity is excited, reducing the chiral asymmetry, now scale dependent. Our results are expected to impact strongly on the phenomenology and observability of axion inflation, including gravitational wave generation and primordial black hole production.


Crystal structure of the HIV-2 neutralizing Fab fragment 7C8 with high specificity to the V3 region of gp125.
7C8 is a mouse monoclonal antibody specific for the third hypervariable region (V3) of the human immunodeficiency virus type 2 (HIV-2)-associated protein gp125. The three-dimensional crystal structure of the Fab fragment of 7C8, determined to 2.7 Å resolution, reveals a deep and narrow antigen-binding cleft with architecture appropriate for an elongated epitope. The highly hydrophobic cleft is bordered on one side by the negatively charged second complementarity determining region (CDR2) and the unusually long positively charged CDR3 of the heavy chain and, on the other side, by the CDR1 of the light chain. Analysis of 7C8 in complex with molecular models of monomeric and trimeric gp125 highlights the importance of a conserved stretch of residues FHSQ that is localized centrally on the V3 region of gp125. Furthermore, modeling also indicates that the Fab fragment neutralizes the virus by sterically impairing subsequent engagement of the gp125 trimer with the co-receptor on the target cell.


Long-term results of kidney transplantation between HLA-identical siblings.
Long-term data on HLA-identical renal transplants are scarce, and the advantages of using cyclosporine (CsA) over azathioprine (AZA) have yet to be elucidated. In 68 recipients from HLA-identical donors (37 under AZA-steroids and 31 under CsA-steroids), we estimated the graft and patient survival to posttransplant 120 months, and compared the results between patients on different protocols. Episodes of rejection, causes of graft loss or patient death, and longterm complications were also compared retrospectively. The 10-year patient/graft survivals were comparable: 82.7/67.6% for the AZA and 78.4/63.5% for the CsA patients. The incidence of acute rejection during the first year after transplant was also comparable. We lost 25 grafts. The major causes of graft loss were patient death (7/13 in AZA and 5/12 in CsA patients) and chronic rejection (3/13 in AZA and 3/12 in CsA patients). Four grafts were lost due to poor compliance. We lost 12 patients due mostly to cerebrovascular disease and infections. There was no difference in the prevalence of complications between patients. In conclusion, the long-term outcome was excellent in this subgroup of transplant patients. We could not find any advantages of using CsA over AZA in these patients after a long-term follow-up. To achieve better results, continued attention should be paid to the prevention of poor compliance and complications.


Whose social capital matters? The case of U.S. urban public hospital closures and conversions to private ownership.
Prior literature on social capital and health has predominantly focused on health outcomes and individual access to healthcare services. It is not known to what degree, if any, community social capital influences the performance or behaviors of public hospitals, a key source of healthcare for disadvantaged communities in the United States. In this study we developed measures of community bridging social capital - horizontal social networks between heterogeneous groups of similar social position - and linking social capital - vertical networks across the status hierarchy - relevant to public hospitals. We examined associations between social capital, and U.S. urban public hospital closures and conversions to private ownership from 1987 to 2007. We found that higher voting participation was associated with a greater hazard of public hospital closure over time (p < 0.01), whereas the number of business, professional and political organizations per 10,000 residents was associated a greater hazard of conversion (p < 0.05). Additional measures of bridging and linking social capital were not associated with either outcome. Taken together, our findings suggest that, at least historically, horizontal forms of social capital among more privileged groups (e.g., business, professional, and political associations) bear influence on public hospital outcomes. Specific efforts to increase engagement of disadvantaged groups and connect them with decision-makers may be needed to fully realize the potential of linking social capital to influence local healthcare policy promoting social protection.


Folding similarity of the outer pore region in prokaryotic and eukaryotic sodium channels revealed by docking of conotoxins GIIIA, PIIIA, and KIIIA in a NavAb-based model of Nav1.4.
Voltage-gated sodium channels are targets for many drugs and toxins. However, the rational design of medically relevant channel modulators is hampered by the lack of x-ray structures of eukaryotic channels. Here, we used a homology model based on the x-ray structure of the NavAb prokaryotic sodium channel together with published experimental data to analyze interactions of the μ-conotoxins GIIIA, PIIIA, and KIIIA with the Nav1.4 eukaryotic channel. Using Monte Carlo energy minimizations and published experimentally defined pairwise contacts as distance constraints, we developed a model in which specific contacts between GIIIA and Nav1.4 were readily reproduced without deformation of the channel or toxin backbones. Computed energies of specific interactions between individual residues of GIIIA and the channel correlated with experimental estimates. The predicted complexes of PIIIA and KIIIA with Nav1.4 are consistent with a large body of experimental data. In particular, a model of Nav1.4 interactions with KIIIA and tetrodotoxin (TTX) indicated that TTX can pass between Nav1.4 and channel-bound KIIIA to reach its binding site at the selectivity filter. Our models also allowed us to explain experimental data that currently lack structural interpretations. For instance, consistent with the incomplete block observed with KIIIA and some GIIIA and PIIIA mutants, our computations predict an uninterrupted pathway for sodium ions between the extracellular space and the selectivity filter if at least one of the four outer carboxylates is not bound to the toxin. We found a good correlation between computational and experimental data on complete and incomplete channel block by native and mutant toxins. Thus, our study suggests similar folding of the outer pore region in eukaryotic and prokaryotic sodium channels.


Quantitative assessment of the time course of infarct signal intensity on diffusion-weighted images.
Diffusion-weighted (DW) MR imaging is important in evaluating acute stroke, and knowledge of the signal intensity changes associated with acute stroke is valuable. Our purpose was to model the time course of the signal intensity of infarcts and to characterize the apparent diffusion coefficient (ADC) and T2 effects on total signal intensity. Ninety-two patients were included in this prospective cross-sectional study. Signal intensity in infarcts (4 hours to 417 days) and control regions were recorded on DW images (b = 0 and 1000 s/mm(2)), ADC maps, and ratio images (image with b = 1000 s/mm(2) divided by image with b = 0 s/mm(2)). Cubic spline functions were used for polynomial fitting. The time courses of log signal intensity with log time were modeled. The independent contributions of T2 and ADC to the total signal intensity were retrospectively compared at 0-63 hours, 3-10 days, 11-57 days, and 57 days onward. Mean signal intensity on DW images was maximal at 40 hours after infarction and normalized at 57 days. At 0-63 hours, the positive effect of ADC on signal intensity was greater than that of T2 (log value,13 +/- 0.04 vs 0.11 +/- 0.05; P =.04). At days 3-10, the positive T2 effect predominated (0.13 +/- 0.08 vs 0.08 +/- 0.04; P =.12). At 10-57 days, the positive T2 effect was greater than the negative ADC effect. After day 57, the negative ADC effect predominated. The signal intensity of infarcts on DW images normalizes at 57 days, which is substantially later than previously suggested. T2 (shine-through) effect contributes largely to the total infarct signal intensity.


Nature's green revolution: the remarkable evolutionary rise of C4 plants.
Plants with the C4 photosynthetic pathway dominate today's tropical savannahs and grasslands, and account for some 30% of global terrestrial carbon fixation. Their success stems from a physiological CO2-concentrating pump, which leads to high photosynthetic efficiency in warm climates and low atmospheric CO2 concentrations. Remarkably, their dominance of tropical environments was achieved in only the past 10 million years (Myr), less than 3% of the time that terrestrial plants have existed on Earth. We critically review the proposal that declining atmospheric CO2 triggered this tropical revolution via its effects on the photosynthetic efficiency of leaves. Our synthesis of the latest geological evidence from South Asia and North America suggests that this emphasis is misplaced. Instead, we find important roles for regional climate change and fire in South Asia, but no obvious environmental trigger for C4 success in North America. CO2-starvation is implicated in the origins of C4 plants 25-32 Myr ago, raising the possibility that the pathway evolved under more extreme atmospheric conditions experienced 10 times earlier. However, our geochemical analyses provide no evidence of the C4 mechanism at this time, although possible ancestral components of the C4 pathway are identified in ancient plant lineages. We suggest that future research must redress the substantial imbalance between experimental investigations and analyses of the geological record.


Effect of hepatitis C infection on the quality of life.
To assess the quality of life (QoL) of patients with hepatitis C infection (HCI) and its correlations with demographic and clinical variables. QoL and depressive symptoms were evaluated with the validated rating instruments of the 36-item short form (SF-36) generic health survey and the second version of the self-rated Beck depression inventory (BDI-II) in a cross-sectional design and correlated with basic demographic and clinical variables, including the Fibroscan score, which indicates the severity of liver impairment. A cohort of 60 HCI patients who participated in the study scored lower than the general population on all domains of the SF-36. In the multivariate correlation analysis, only the physical functioning domain of the SF-36 showed a significant correlation with age, gender, and BD-II and Fibroscan scores. QoL is lower for patients who are older, female, and have depressive symptoms. Progression of hepatic cirrhosis is associated with lower QoL in the physical domain.


Resident-to-resident physical aggression leading to injury in nursing homes: a systematic review.
resident-to-resident aggression (RRA) is an understudied form of elder abuse in nursing homes. the purpose of this systematic review was to examine the published research on the frequency, nature, contributing factors and outcomes of RRA in nursing homes. in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement, this review examined all original, peer-reviewed research published in English, French, German, Italian or Spanish between 1st January 1949 and 31st December 2013 describing incidents of RRA in nursing homes. The following information was extracted for analysis: study and population characteristics; main findings (including prevalence, predisposing factors, triggers, nature of incidents, outcomes and interventions). eighteen studies were identified, 12 quantitative and 6 qualitative. The frequency of RRA ranged from 1 to 122 incidents, with insufficient information across the studies to calculate prevalence. RRA commonly occurred between exhibitors with higher levels of cognitive awareness and physical functionality and a history of aggressive behaviours, and female targets who were cognitively impaired with a history of behavioural issues including wandering. RRA most commonly took place in the afternoon in communal settings, was often triggered by communication issues and invasion of space, or was unprovoked. Limited information exists on organisational factors contributing to RRA and the outcomes for targets of aggression. we must continue to grow our knowledge base on the nature and circumstances of RRA to prevent harm to an increasing vulnerable population of nursing home residents and ensure a safe working environment for staff.


Improving the career decisions of deaf seniors in residential and day high schools.
Career development interventions can have positive effects on the career decisions that deaf seniors make before graduating from high school. Interviews with 189 seniors from 16 residential and day high schools revealed their career decisions and their experiences with career development activities. School staff evaluated the seniors' career decisions, career decision-making skills, and probable post-high school placements. The results indicated that seniors who had vocational training were more knowledgeable about their vocational aptitudes than were seniors who had no vocational training. Seniors with vocational training were also more likely to have considered other careers prior to making career decisions. Seniors who had received career counseling were more knowledgeable than those who had not about the skills needed to enter their chosen careers and were more interested in their career choices. More importantly, the amount of interest in one's career choice was determined to be related to ratings of motivation, readiness, and prospects for completing the postsecondary placement. The implications of these results are discussed below for professionals in education and rehabilitation.


Clinical Application of Six Current Classification Systems for Iatrogenic Bile Duct Injuries after Cholecystectomy.
Due to being a severe complication, iatrogenic bile duct injury is still a challenging issue for surgeons in gallbladder surgery. However, a commonly accepted classification describing the type of injury has not been available yet. This study aims to evaluate ability of six current classification systems to discriminate bile duct injury patterns. Twelve patients, who were referred to our clinic because of iatrogenic bile duct injury after laparoscopic cholecystectomy were reviewed retrospectively. We described type of injury for each patient according to current six different classifications. 9 patients underwent definitive biliary reconstruction. Bismuth, Strasberg-Bismuth, Stewart-Way and Neuhaus classifications do not consider vascular involvement, Siewert system does, but only for the tangential lesions without structural loss of duct and lesion with a structural defect of hepatic or common bile duct. Siewert, Neuhaus and Stewart-Way systems do not discriminate between lesions at or above bifurcation of the hepatic duct. The Hannover classification may resolve the missing aspects of other systems by describing additional vascular involvement and location of the lesion at or above bifurcation.


How did welfare reform affect the health insurance coverage of women and children?
To measure the change in U.S. women and children's health insurance coverage as a result of welfare reform (i.e. the creation of Temporary Assistance for Needy Families or TANF) in 1996. 1992-1999 longitudinal data from the Survey of Income and Program Participation (SIPP) merged with data on the timing of state implementation of welfare reform after 1996. Two key advantages of the SIPP data are that they permit matching type of insurance coverage to the welfare policy environment in each state in each month, and permit controlling for individual-level fixed effects. We measure how much insurance coverage changed after welfare reform using a difference in differences method that eliminates the influence of time-invariant unobserved individual heterogeneity and of statewide trends in insurance coverage. Models also control for individual, state, and year fixed effects, individual-level characteristics such as education, age, and number of children, plus state-level variables such as real per capita income, real minimum wage, and Medicaid eligibility. We limit our analysis to the SIPP data specific to the month just completed prior to the interview; as a result, we have up to twelve observations for each individual in the SIPP. This paper uses pooled data from the 1992-1996 panels of the SIPP covering the period 1992-1999. Publicly available state identifiers permit the merger of state policies and macroeconomic variables with the SIPP. TANF implementation is associated with an 8.1 percent increase in the probability that a welfare-eligible woman was uninsured. Welfare reform had less of an impact on the health insurance coverage of children. For example, TANF implementation was associated with a 3.0 percent increase in the probability that a welfare-eligible child lacked health insurance. An unintended consequence of welfare reform was to adversely impact the health insurance coverage of economically vulnerable women and children, and that this impact was several times larger than the previous literature implies.


The legume-specific transcription factor E1 controls leaf morphology in soybean.
The leaf is a determinate organ essential for photosynthesis, whose size and shape determine plant architecture and strongly affect agronomic traits. In soybean, the molecular mechanism of leaf development is not well understood. The flowering repressor gene E1, which encodes a legume-specific B3-like protein, is known to be the gene with the largest influence on soybean flowering and maturity. However, knowledge of its potential other functions remains poor. Here, we identified a novel function of E1 protein in leaf development. Unifoliolate leaves of E1-overexpression (E1-OE) lines were smaller and curlier than those of wild type DongNong 50 (DN50) and Williams 82 (W82). Transverse histological sections showed disorganized cells and significantly elevated palisade tissue number, spongy tissue number, and bulliform cell number in E1-OE lines. Our results indicate that E1 binds to the promoters of the leaf- development-related CINCINNATA (CIN)-like TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP) transcription factor genes to negatively regulate their expression. Our findings identify E1 as an important new factor in soybean leaf development.


Transcriptomic approach for assessment of the impact on microalga and macrophyte of in-situ exposure in river sites contaminated by chlor-alkali plant effluents.
Water quality degradation is a worldwide problem, but risk evaluation of chronic pollution in-situ is still a challenge. The present study aimed to evaluate the potential of transcriptomic analyses in representative aquatic primary producers to assess the impact of environmental pollution in-situ: the microalga Chlamydomonas reinhardtii and the macrophyte Elodea nuttallii were exposed 2 h in the Babeni Reservoir of the Olt River impacted by chlor-alkali plant effluent release resulting in increased concentrations of Hg and NaCl in receiving water. The response at the transcriptomic level was strong, resulting in up to 5485, and 8700 dysregulated genes (DG) for the microalga and for the macrophyte exposed in the most contaminated site, respectively. Transcriptomic response was congruent with the concentrations of Hg and NaCl in the water of the impacted reservoir. Genes involved in development, energy metabolism, lipid metabolism, nutrition, and RedOx homeostasis were dysregulated during in-situ exposure of both organisms. In addition, genes involved in the cell motility of C. reinhardtii and development of the cell wall of E. nuttallii were affected. DG were in line with adverse outcome pathways and transcriptomic studies reported after exposure to high concentrations of Hg and NaCl under controlled conditions in the laboratory. Transcriptomic response provided a sensitive measurement of the exposure as well as hints on the tolerance mechanisms of environmental pollution, and is thus promising as an early-warning tool to assess water quality degradation.


The Correlation Between Computed Tomography Volumetry and Prognosis of Advanced Gastric Cancer Treated with Neoadjuvant Chemotherapy.
To investigate the feasibility and utility of computer tomography (CT) volumetry in evaluating the tumor response to neoadjuvant chemotherapy (NAC) in advanced gastric cancer (AGC) patients. One hundred and seventeen Patients with AGC who received NAC followed by R0 resection between January 2006 and December 2012 were included. Tumor volumes were quantified using OsiriX software. The volume reduction rate (VRR) was calculated as follows: VRR = [(pre-chemotherapy total volume) - (post-chemotherapy total volume)]/(pre-chemotherapy total volume) × 100%. The optimal cut-off VRR for differentiating favorable from unfavorable prognosis was determined by receiver operating characteristic (ROC) analysis. Overall survival was calculated using Kaplan-Meier analysis and values were compared using the Log-rank test. Multivariate analysis was determined by the Cox proportional regression model. The optimal cut-off VRR was 31.95% according to ROC analysis, with a sensitivity of 70.4% and a specificity of 71.7%. Based on the cut-off VRR, patients were divided into the VRR-High (VRR ≥ 31.95%, n = 63) and VRR-Low (VRR < 31.95%, n = 54) groups. The VRR-Low group exhibited a worse prognosis than that of the VRR-High group (HR, 2.85; 95% CI, 1.69-4.82, P < 0.001), with 3-year survival rates of 40.7% and 79.4%, and 5-year survival rates of 31.5% and 63.5%, respectively. CT volumetry is a feasible and reliable method for assessing the tumor response to NAC in patients with AGC.


Polyuria and inappropriate secretion of arginine vasopressin in hypothalamic sarcoidosis.
Inappropriate arginine vasopressin release and polyuria with excessive thirst were found in a patient with hypothalamic sarcoidosis subsequently confirmed at autopsy. He became intensely thirsty during a 5% saline infusion at a plasma osmolality of 274 mosmol/liter. The normal thirst threshold under these conditions is 294 +/- 3 mosmol/liter (+/- SD). An increase in radioimmunoassayable arginine vasopressin was detected at an inappropriately low plasma osmolality, and free water clearance was negative despite a plasma osmolality of 265 +/- 5 mosmol/liter with ad libitum fluid intake. The syndrome of inappropriate antidiuresis has not been described previously in combination with hypothalamic sarcoidosis. Demeclocycline therapy was associated with an exacerbation of the patient's polyuria. Propranolol administration, however, was associated with a reduction of urine output and an increase in plasma osmolality to 279 mosmol/liter on one and 299 mosmol/liter on another occasion.


Synthesis of omega-agatoxin IVA and its related peptides.
A potent and selective P type calcium channel blocker isolated from the venom of the funnel web spider Agelenopsis aperta, omega-agatoxin IVA, and its related peptides were synthesized by the solution procedure. Synthetic omega-agatoxin IVA was found to block high-threshold P-type calcium current in rat Purkinje neuron with the same potency as that reported for the natural product. Its disulfide structure was determined by amino acid analysis, gas-phase sequencing and mass spectrometry of the proteolytic fragments. The N-terminus biotinylated and truncated peptides showed the same disulfide-bond-forming profile and the same activities as those of omega-agatoxin IVA, indicating that the N-terminal basic tripeptide, Lys-Lys-Lys, is not important for both the folding and the expression of the biological activity. However, the Trp residue in the molecule might be essential for the toxin to bind tightly with the channel pores.


Association of pericardial adipose tissue with left ventricular structure and function: a region-specific effect?
The independent role of pericardial adipose tissue (PAT) as an ectopic fat associated with cardiovascular disease (CVD) remains controversial. This study aimed to determine whether PAT is associated with left ventricular (LV) structure and function independent of other markers of general obesity. We studied 2471 participants (50.9 % women) without known CVD from the Korean Genome Epidemiology Study, who underwent 2D-echocardiography with tissue Doppler imaging (TDI) and computed tomography measurement for PAT. Study participants with more PAT were more likely to be men and had higher cardiometabolic indices, including blood pressure, glucose, and cholesterol levels (all P < 0.001). Greater pericardial fat levels across quartiles of PAT were associated with increased LV mass index and left atrial volume index (all P < 0.001) and decreased systolic (P = 0.015) and early diastolic (P < 0.001) TDI velocities, except for LV ejection fraction. These associations remained after a multivariable-adjusted model for traditional CV risk factors and persisted even after additional adjustment for general adiposity measures, such as waist circumference and body mass index. PAT was also the only obesity index independently associated with systolic TDI velocity (P < 0.001). PAT was associated with subclinical LV structural and functional deterioration, and these associations were independent of and stronger than with general and abdominal obesity measures.


Management of sexuality in a mental health setting.
Clients with long term mental health problems can be particularly vulnerable to sexually transmitted diseases, but nurses and other staff find it difficult to address the issues of sex and sexuality. More training courses would help to address this, but the attitudes of health professionals to these issues also need to be examined.


Behavioral and neurochemical effects of the dopamine transporter ligand 4-chlorobenztropine alone and in combination with cocaine in vivo.
The current studies evaluated the novel diphenylmethoxytropane analog 4-chlorobenztropine (4-Cl-BZT), cocaine, and combinations of the two drugs for their abilities to stimulate locomotor activity, produce cocaine-like discriminative stimulus effects, and elevate extracellular dopamine (DA) in the nucleus accumbens (NAc) as measured by in vivo microdialysis. Peripherally administered cocaine was approximately twice as efficacious as 4-Cl-BZT as a locomotor stimulant and was behaviorally active at a lower dose than was 4-Cl-BZT. Cocaine also was more efficacious than 4-Cl-BZT in producing discriminative-stimulus effects in rats trained to discriminate i.p. injections of 10 mg/kg cocaine from saline. The time course of behavioral activation differed markedly between the two drugs, with much shorter onset and duration of locomotor stimulant effects for cocaine relative to 4-Cl-BZT. Similarly, i.p. cocaine (10 and 40 mg/kg) induced a pronounced, rapid, and short-lived increase in DA in the NAc, whereas i.p. 4-Cl-BZT was effective only at the higher dose and produced a more gradual, modest, and sustained (>/=2 h) elevation in accumbens DA. In contrast to i.p. administration, local infusion of 4-Cl-BZT (1-100 microM) into the NAc through the microdialysis probe elevated extracellular DA to a much greater extent than did local cocaine (nearly 2000% of baseline maximally for 4-Cl-BZT versus 400% of baseline for cocaine) and displayed a much longer duration of action than cocaine. However, when microinjected bilaterally into the NAc at 30 or 300 nmol/side, cocaine remained a more efficacious locomotor stimulant than 4-Cl-BZT. Finally, pretreatment with i.p. 4-Cl-BZT dose dependently enhanced the locomotor stimulant, discriminative stimulus effects, and NAc DA response to a subsequent low-dose i.p. cocaine challenge. The diphenylmethoxytropane analog also facilitated the emergence of stereotyped behavior and convulsions induced by high-dose cocaine. The current results demonstrate that DA transporter ligands that do not share the neurochemical and behavioral profiles of cocaine nevertheless may enhance the effects of cocaine in vivo.


Wear behavior of different materials used for pit and fissure sealing.
To evaluate the wear of different materials used for pit and fissure sealing applied with non-invasive and invasive preparation techniques. A total of 170 molar teeth were divided into two main preparation groups (non-invasive and invasive), each consisting of eight subgroups after a control group was separated for wear standardization. Eight subgroups included: nano-filled flowable composite (Filtek Ultimate Flow), nanohybrid flowable composite (GrandioSo Flow), micro-hybrid flowable composite (Majesty Flow), resin-based unfilled fissure sealant (ClinPro Sealant), resin-based filled fissure sealant (Fissurit FX), resin-based highly filled fissure sealant (GrandioSeal), giomer-based fissure sealant (BeautiSealant), and glass-ionomer-based fissure sealant (Fuji Triage) (n= 10). The materials were applied according to the manufacturers' instructions. The initial data were obtained for wear analysis. The specimens were subjected to 2-year thermocycling and brushing simulations. Final data were obtained, and the wear characteristics were evaluated digitally. Data were statistically analyzed (P< 0.05). There were no significant differences in wear between the non-invasive and invasive application groups (P< 0.05). In comparison of the materials, flowable composites presented the lowest wear (0.15 P± 0.13), and glass-ionomer-based fissure sealant presented the highest wear (0.66 P± 0.32). The present study reported that the invasive preparation technique, which slightly abrades the enamel surfaces, did not adversely affect the wear of the sealant materials. Although the application of flowable composites as fissure sealants with a bonding agent is time-consuming and costly, it yielded better results in terms of wear.


Gain of oncogenic function of p53 mutants induces invasive phenotypes in human breast cancer cells by silencing CCN5/WISP-2.
CCN5/WISP-2 is overexpressed in noninvasive breast cancer cells and tissue samples, whereas its expression is minimal or undetected in invasive conditions. CCN5/WISP-2 has been considered as an antiinvasive gene because CCN5/WISP-2 silencing augments the invasive phenotypes in vitro. However, the mechanism of silencing of CCN5 during the progression of the disease has been elusive. Because p53 mutations are associated with breast cancer progression and have been shown to correlate inversely with CCN5/WISP-2 expression in other cancer cell types, the objective of this study was to explore whether p53 mutants suppress CCN5 expression in breast tumor cells resulting in the progression of this disease. We found CCN5 expression is inversely correlated with the mutational activation of p53 in human breast tumor cells. The ectopic expression of p53 mutants in ER-positive noninvasive breast tumor cells silenced the CCN5/WISP-2 expression and enhanced invasive phenotypes, including the induction of morphologic changes from the epithelial-to-mesenchymal type along with the alterations of hallmark proteins of these cell types and an augmentation of the migration of these cells. The suppression of CCN5 by the p53 mutants can be nullified by estrogen signaling in these cells through the transcriptional activation of the CCN5 gene. Moreover, the invasive changes can be imitated by blocking the CCN5/WISP-2 expression through RNA interference or can be reversed by the addition of CCN5/WISP-2 recombinant protein in the culture. Thus, these studies suggest that CCN5 inactivation could be an essential molecular event for p53 mutant-induced invasive phenotypes.


Rapid Detection of Tobacco Rattle Tobravirus in Viruliferous Paratrichodorus allius from Greenhouse and Field Specimens.
The stubby root nematode, Paratrichodorus allius, is important to the potato industry in the Pacific Northwest of USA, because it vectors Tobacco rattle virus (TRV), the causal agent of corky ringspot disease. The current method for determining if nematodes are viruliferous for TRV takes several weeks, requiring a glasshouse bioassay followed by a serological test. To overcome this drawback, a rapid and affordable molecular test was developed using reverse transcription polymerase chain reaction (RT-PCR) to identify viruliferous P. allius nematodes within 48 hours. Primers from the 16 kDa gene of TRV were used to detect TRV in both greenhouse-reared and field collected P. allius. TRV RNA can be detected consistently in nucleic acids equivalent to one quarter of a viruliferous adult nematode reared in the greenhouse. In order to reduce the time and expense of processing individual nematodes from field samples, viral RNA was consistently and affordably detected in extracts from 5 field-collected adult P. allius.


[Interpretation of hand injuries: 10 tips].
The treatment of hand injuries is an important part of the daily practice of healthcare professionals in primary, secondary and tertiary care. The complex anatomy and the specific physical examination required may make it difficult for a healthcare professional to establish a proper diagnosis. Based on the literature and our personal experience in hand surgery, we will describe 10 practical tips. These 10 tips will contribute to the detection of small lesions in daily practice.


Hippocampal volume and verbal memory performance in late-stage bipolar disorder.
Studies about changes in hippocampal volumes in subjects with bipolar disorder (BD) have been contradictory. Since the number of manic episodes and hospitalization has been associated with brain changes and poor cognitive outcomes among BD patients, we have hypothesized that these variables could clarify this issue. We stratified subjects with BD in early (BD-Early), intermediate (BD-intermediate) and late (BD-Late) stages as a function of number of manic episodes and prior hospitalization. Then, we compared their hippocampal volumes and California Verbal Learning Test-II (CVLT-II) scores with healthy controls (HC) using the general linear model. A total of 173 subjects were included in the study (112 HC, 15 BD-Early, 30 BD-Intermediate, and 16 BD-Late). We found a significant group effect on hippocampus volume (F(3,167) = 3.227, p = 0.024). Post-hoc analysis showed that BD-Late subjects had smaller hippocampus than HC (p = 0.017). BD-Early and BD-Intermediate subjects showed no significant difference in hippocampus volume compared to HC and BD-Late subjects. The CVLT trial 1 to 5 scores were significantly different across the groups (F(3,167) = 6.371, p < 0.001). Post-hoc analysis showed that BD-Intermediate (p = 0.006) and BD-Late (p = 0.017) subjects had worse memory performance during immediate recall than HC, while the performance difference between BD-Early subjects and HC was not significant (p = 0.208). These findings add to the notion that BD is a neuroprogressive disorder with brain changes and cognitive impairment according to prior morbidity (number of manic episodes and hospitalization). Also, they suggest that hippocampus is a brain marker and a potential therapeutic target for patients at late stage.