Is grit relevant to well-being and strengths? Evidence across the globe for separating perseverance of effort and consistency of interests.
Researchers conceptualize grit as the combination of two facets: perseverance of effort and consistency of interests toward long-term goals. We tested the reliability of grit facet scores across the globe and examined how differently each grit facet related to well-being and personality strengths. An international sample of 7,617 participants from six of the seven continents (excluding Antarctica) completed an online survey. Confirmatory factor analyses and omega reliability coefficients indicated that the 12 items from the original Grit Scale were multidimensional and reliably measured perseverance of effort and consistency of interests. Concurrent validity analyses showed that perseverance of effort was moderately to strongly related to subjective well-being, beliefs about well-being, and personality strengths, whereas consistency of interests had weak or negative correlations with these outcomes. The stronger relations with perseverance of effort were replicated across seven regions of the world. The presence of overall grit was supported in individualistic countries, but not collectivistic countries (i.e., those in Latin America and Asia). We discuss the multidimensionality of grit, including a conceptual understanding of overall grit and how it may differ across cultures. We suggest well-being and strengths researchers study grit facets separately due to their differential validity.


Uro-oncologic patient management during the COVID-19 pandemic: survey findings from an Italian oncologic hub.
Aim: Patient and worker satisfaction at an oncologic hub during the COVID-19 pandemic has never been reported. We addressed this topic. Methods: We conducted a survey to test the views of patients (n = 64) and healthcare professionals (n = 52) involved with our operative protocol. Results: A moderate/severe grade of concern due to the COVID-19 emergency was recorded in 63% of patients versus 75% of hospital staff. High/very high versus low satisfaction grade about preventive strategies to reduce the risk of SARS-CoV-2 contagion was identified in the patients compared with the hospital staff group. Conclusion: Surgical treatment at a hub center of uro-oncologic patients coming from spoke centers is well accepted and should, therefore, be recommended. Preventive strategies to reduce the risk of SARS-CoV-2 contagion in hospital staff members should be implemented.


A longitudinal assessment of early pubertal timing as a predictor of psychosocial changes in adolescent girls with and without spina bifida.
A longitudinal comparison of adolescent girls with and without spina bifida (SB), regarding the effects of early pubertal timing on girls' depressive symptoms, mother-daughter conflict, and emotional distancing. 62 mother-daughter dyads (31 with SB and 31 without) reported on psychosocial outcomes at 5 time points (ages 8/9 to 16/17 years). A pubertal timing × SB status interaction predicted emotional distancing (T2), conflict (T2, T5), and depressive symptoms (T4), such that early maturing girls without SB reported the greatest increase in each outcome. Main effects of pubertal timing predicted emotional distancing (T4), conflict (T4), and depressive symptoms (T2, T3, T5). Findings were not always consistent across reporters, assessments of pubertal timing, and time-points. Although early maturing girls in both groups may experience greater psychosocial difficulties, early maturing girls without SB may be most at-risk. The somewhat reduced impact of early pubertal timing in girls with SB is discussed.


Unusual presentation of Kikuchi-Fujimoto disease.
The authors report the case of a 13-year-old girl with Kikuchi-Fujimoto disease who presented with features of raised intracranial pressure due to subdural effusions. A biopsy revealed dural involvement in the disease process. The authors review the medical literature of this rare disease and highlight the paucity of documented cases with CNS involvement.


Reducing Delirium and Improving Patient Satisfaction With a Perioperative Mindfulness Intervention: A Mixed-Methods Pilot Study.
Postoperative delirium (incidence estimated up to 82%) can be ameliorated with nonpharmacologic methods. Mindfulness has not yet been incorporated into these methods, although mindfulness has been demonstrated to help patients adapt to illness and hospitalization. To reduce postoperative delirium incidence and increase patient satisfaction, this study employs a program of thought exercises based on Langerian mindfulness. Preoperatively, cardiac surgical patients listened to a mindfulness or informational audio; mindfulness subjects were also guided by the principal investigator through mindfulness exercises. Postoperatively, mindfulness subjects were visited twice daily for mindfulness exercises. For all patients, delirium screening was performed twice daily. Before discharge, affective status and satisfaction with hospital stay were assessed. No patients who completed the study screened positive for delirium. Trends include (1) lower (improved) median anxiety and depression scores postoperatively when considering both study groups together; (2) both groups rated the hospital more favorably on global satisfaction measures; (3) both groups shared generally positive comments regarding the audio files (qualitative data). Audio files and mindfulness exercises are associated with patient satisfaction among cardiothoracic surgery patients. The absence of delirium precludes determination of the effectiveness of the intervention in reducing delirium incidence.


Epithelial cell-substrate adhesion in the cornea: localization of actin, talin, integrin, and fibronection [corrected].
During corneal wound healing, epithelial cells migrate and spread over a basement membrane to cover the denuded area. We have initiated studies on the proteins involved in this cell-substrate interaction. In the present report, we show the distribution of actin, talin, integrin and fibronectin in the unwounded chicken corneal epithelium. Rhodamine-phalloidin and antibodies against talin, the beta-subunit of integrin, and fibronectin were used to fluorescently label semi-thin cryosections of chicken cornea. Phalloidin labeling indicated the presence of f-actin around the boundaries of all epithelial cells. Antitalin labeled the most basal aspect of the basal cells. Diffuse cytoplasmic labeling of the basal cells was also seen. Integrin was detected by the polyclonal anti-CSAT and monoclonal 30B6 antibodies. With both antibodies, the basal cells were outlined by label. These cells were similarly labeled by antifibronectin. Less distinct labeling of fibronectin was present around the boundaries of the outer epithelial cells. Our results indicate that many of the proteins associated with cell-substrate adherens junctions in other systems are also present in cell-substrate adhesion of the corneal epithelium. Details of the distribution of some of the proteins appear to be somewhat unusual, however.


Wnt gene expression in human trabecular meshwork cells.
The aim of this study was to examine the expression of genes related to the Wnt signaling pathway, such as beta-catenin (CTNNB1) and secreted frizzled-related protein-1 (sFRP1), in human trabecular meshwork (TM) cells. In addition, the effect of oxidative stress on Wnt signaling was evaluated. All experiments were conducted using second- or third-passaged human TM cells. cDNA was prepared from total RNA extracted from cells by means of reverse transcription. PCR was then performed to determine the presence of Wnt genes. For oxidative stress, TM cells were treated with 1 mM of H(2)O(2) for 30 min. Actin staining was carried out to verify cell response to oxidative stress. Western blotting was used to measure Wnt-related protein levels after H(2)O(2) treatment. Positive PCR products were detected for a total of 25 Wnt and Wnt-related genes in human TM cells. Most of the genes identified belonged to the Wnt/beta-catenin pathway. Members of the beta-catenin-independent noncanonical pathways were also found. Oxidative stress did not result in significant changes in beta-catenin and sFRP1 protein levels. Genes related to canonical and noncanonical Wnt pathways are expressed in human TM cells. It appears that all three Wnt pathways are operative in the TM system. Oxidative stress, while thought to play a role in the development of glaucoma, had little effect on the Wnt activity in TM cells.


Characterization of the hypertriglyceridemic waist phenotype in patients with type 2 diabetes mellitus in Spain: an epidemiological study.
In patients with type 2 diabetes mellitus (DM2), the presence of increased waist circumference and triglycerides is a reflection of increased visceral fat and insulin resistance. However, information about the prevalence and clinical characteristics of the hypertriglyceridemic waist (HTGW) phenotype in patients with DM2 is scarce. The aim of the present study was to analyze the prevalence and characteristics of DM2 patients with HTGW. We analyzed 4214 patients with DM2 in this epidemiological, cross-sectional study conducted in primary care centers across Spain between 2011 and 2012. The HTGW phenotype was defined as increased waist circumference according to the International Diabetes Federation criteria for Europids (≥ 94 cm for men and ≥ 80 cm for women) with the presence of triglyceride levels ≥ 150 mg/dL. We compared the demographic, clinical and analytical variables according to the presence or absence of the HTGW phenotype. Thirty-five percent of patients presented the HTGW phenotype. Patients with the HTGW phenotype had a higher body mass index (31.14 ± 4.88 vs. 29.2 ± 4.82 kg/m2; p < .001) and glycated hemoglobin levels (7.38 ± 1.2% vs. 7 ± 1.07%; p < .001). The presence of hypertension, peripheral arterial disease, cardiac insufficiency and microvascular complications were higher when compared with patients without the HTGW phenotype. Patients with the HTGW phenotype were less adherent to prescribed diet (69.8 vs. 81%; p < .001), exercise (44.6 vs. 58.2%; p < .001) and presented greater weight increase within the year prior to the study visit (29.4 vs. 22.5%; p < .001). The HTGW phenotype is prevalent in the Spanish DM2 population and identifies a subgroup of patients with higher cardiometabolic risk and prevalence of diabetic complications.


Pediatric stroke outcome measure: predictor of multiple impairments in childhood stroke.
The ability to anticipate deficits would help with implementation of interventions for children affected by stroke. The pediatric stroke outcome measure (measure) measures neurological impairment after stroke, but there has been little research examining the relationship between the measure and functional outcomes. We hypothesized the Measure correlates with cognitive and behavioral outcomes. Thirty-six children with stroke were assessed with the Measure, and tested for cognitive ability, problem behavior, adaptive behavior, and social participation. We examined the correlation between the total Measure and outcomes and determined how subscale scores associated with outcomes. Higher total Measure scores correlated with poorer outcomes in cognitive ability, problem behaviors, adaptive behaviors, and social participation. Specific subscale scores correlated with poorer outcomes in multiple domains. The total Measure can be used to anticipate poor outcomes in multiple domains after stroke and can help the clinician in the treatment of children as they recover.


[Development of urea, creatinine and creatinine clearance as a function of age and sex].
Serum urea and creatinine concentrations were determined in 150 healthy subjects. The formula of Cockcroft and Gault was used in order to calculate creatinine clearance. Such estimation of creatinine clearance is widely used as a parameter for individualization of dosage of drugs secreted primary via the kidneys. The effects of age and sex were then assessed on serum urea, serum creatinine and on creatinine clearance.


Noise performance of optical fiber transmission links that use non-degenerate cascaded phase-sensitive amplifiers.
Based on semi-classical theory, the noise performance of a multi-span fiber optical transmission system employing a cascaded phase-insensitive amplifier (PIA) and phase-sensitive amplifiers (PSAs) is investigated. Compared with the pure-PIA and pure-PSA based in-line amplification schemes, the copier + PSA scheme is found to improve the system NF by up to 6 and 3 dB, respectively, in an optimized long-haul fiber link. In addition, this cascaded configuration will significantly relax the requirement for accurate phase- and wavelength-locking which is rigorously needed in the pure-PSA configuration. This scheme is also modulation-format independent. As a proof of concept, the NF of a fiber parametric amplifier based copier + PSA cascade with inter-stage attenuation representing the fiber link is measured, which shows a 1.8-dB total NF improvement over the conventional EDFA cascade.


Detection of weak intramolecular interactions in Ru(3)(CO)(12) by topological analysis of charge density distributions.
The presence of weak intramolecular interactions among the axial carbon atoms in Ru(3)(CO)(12), previously detected by topological analysis of the 120 K X-ray derived charge density, has been here confirmed by theoretical calculations on the isolated, "gas-phase" molecule, using the all-electron B97D/3-21G approach, as well as by further experimental determinations of higher accuracy on data collected at 100 K. The importance of using density functional theory (DFT) approaches where dispersion terms are explicitly added to the usual Kohn-Sham energy to reproduce such weak intramolecular interactions has been evidenced. This result confirms the multipole approach as an efficient and sensitive tool to extract fine details of electron density distributions.


SHIFTING PERSPECTIVES: COGNITIVE CHANGES PARTIALLY MEDIATE THE IMPACT OF ROMANTIC RELATIONSHIPS ON DESISTANCE FROM CRIME.
Although research regarding the impact of marriage on desistance is important, most romantic relationships during early adulthoood, the period in the life course when involvement in criminal offending is relatively high, do not involve marriage. Using the internal moderator approach, we tested hypotheses regarding the impact of non-marital romantic relationships on desistance using longitudinal data from a sample of approximately 600 African American young adults. The results largely supported the study hypotheses. We found no significant association between simply being in a romantic relationship and desistance from offending. On the other hand, for both males and females quality of romantic relationship was rather strongly associated with desistance. Partner antisociality only influenced the offending of females. Much of the effect of quality of romantic relationship on desistance was mediated by a reduction in commitment to a criminogenic knowledge structure (a hostile view of people and relationships, concern with immediate gratification, and cynical view of conduct norms). The mediating effect of change in affiliation with deviant peers was not significant once the contribution of criminogenic knowledge structure was taken into account. The findings are discussed in terms of social control and cognitive accounts of the mechanisms whereby romantic relationships influence desistance.


Charting accuracy in Navy dental records.
Eighty-five Navy patients and their dental records were reviewed, to determine the accuracy of the recorded initial findings in the SF603 Dental Record, and any subsequent treatment recordings. These findings were compared to those of a similar study published in 1970, and comparisons were drawn between the two reviews as to the accuracy of the charting and usefulness for forensic dental identification. A possible future concern in forensic dental identification was identified and is discussed.


Efficient targeting of fatty-acid modified oligonucleotides to live cell membranes through stepwise assembly.
Lipid modifications provide efficient targeting of oligonucleotides to live cell membranes in a range of applications. Targeting efficiency is a function of the rate of lipid DNA insertion into the cell surface and its persistence over time. Here we show that increasing lipid hydrophobicity increases membrane persistence, but decreases the rate of membrane insertion due to the formation of nonproductive aggregates in solution. To ameliorate this effect, we split the net hydrophobicity of the membrane anchor between two complementary oligonucleotides. When prehybridized in solution, doubly anchored molecules also aggregate due to their elevated hydrophobicity. However, when added sequentially to cells, aggregation does not occur so membrane insertion is efficient. Hybridization between the two strands locks the complexes at the cell surface by increasing net hydrophobicity, increasing their total concentration and lifetime, and dramatically improving their utility in a variety of biomedical applications.


An ethical review of euthanasia web sites.
Euthanasia is an act of mercifully killing or letting die a sick or injured individual, and is an alternative to palliative care. As a healthcare related web site, a euthanasia site should satisfy standard ethical criteria such as the HONcode. In this paper, we report our preliminary review of euthanasia web sites for compliance with HONcode criteria.


Taxonomic circumscription of Adenomera martinezi (Bokermann, 1956) (Anura: Leptodactylidae: Leptodactylinae) with the recognition of a new cryptic taxon through a bioacoustic approach.
In this paper, we provide a taxonomic circumscription of Adenomera martinezi from its type locality (Cachimbo, southwestern State of Pará) since its description (57 years ago) based on a newly collected series of eleven adult topotypes, and through a bioacoustic approach, recognize an undescribed cryptic taxon under this nominal species, which is widely distributed in central and northern Brazil. Adenomera martinezi and Adenomera saci sp. nov. can be diagnosed from all congeners by their distinctive 4-6 symmetrically arranged rows of longitudinal dark-colored spots on dorsum. They differ from each other through advertisement call structure, pulsed in Adenomera martinezi (audibly pulsed to the human ear), and non-pulsed in Adenomera saci sp. nov. (a whistle to the human ear). The recognition of Adenomera saci sp. nov. has conservation implications. Based on our assumed distribution of A. martinezi and A denomera saci sp. nov., the IUCN conservation status of A. martinezi requires a reassessment, inasmuch as we herein reconsider this species, as far as we know, as endemic to Cachimbo, southwestern State of Pará, Brazil. The 2004 extinction risk assessment included both A. martinezi and Adenomera saci sp. nov., and the conservation status category of 'Least Concern' might only be applied to Adenomera saci sp. nov., a widely distributed and abundant species in central and northern Brazil.


Educational support during organizational transition: half-day workshops for nurses and leaders.
The integration of the Intensive Care Unit and Coronary Care Unit at the Brant Community Healthcare System (Brantford General Site) in Brantford, Ontario, Canada, was carefully planned. As part of the planning efforts, much attention was given to effective transition management. An educational program was designed to assist the nurses from these units to begin to disengage from old ways of planning and delivering care, provide support to help them through the period of uncertainty (neutral zone) associated with this type of transition, and help them adapt to the new realities that the integrated Critical Care Unit demanded. This article describes the workshops designed to assist nurses and leaders through this transition.


Intracellular elemental concentrations in resting and secreting rat parotid glands.
Electron probe x-ray micro-analysis was used to study the elemental concentration changes that occur during pilocarpine-stimulated saliva secretion. Quantitative x-ray micro-analysis of elemental concentrations in intracellular compartments of rat parotid glands stimulated in vivo with pilocarpine showed that Na concentration was significantly increased, while K concentration was significantly reduced. The magnitude of these changes was consistent with values obtained in other tissues with the x-ray micro-analysis method, and in the same tissue with other experimental methods. Comparisons with results from studies utilizing dispersed acini suggest that acinar dispersion procedures may affect intracellular elemental concentrations. Total electrolyte concentrations in cytoplasm and secretory granules were estimated to increase on a dry-weight basis following pilocarpine stimulation. The former change is consistent with the notion of a transcellular route of salivary fluid flow, while the latter change may be important in the exocytosis of secretory granules.


[Mitral valve disease with pulmonary hypertension: two surgical cases].
Two surgical cases of mitral valve disease with severe pulmonary hypertension were reported, in which pulmonary hypertensive crisis (PHC) was a really serious problem to be treated. The first case (60-year-old woman) had atrial fibrillation and her pulmonary artery pressure was 68/32 mmHg (Pp/Ps = 0.63) and mean pulmonary wedge pressure was 26 mmHg with a high v wave (46 mmHg). PHC developed immediately after the cessation of artificial cardiopulmonary bypass, and intraaortic balloon pumping was performed. However, it was difficult to wean from the assist circulation, and then PGE1 and isoproterenol were given into the pulmonary artery and epinephrine and norepinephrine were given into the left atrium, and we succeeded in weaning from the assist circulation. The second case (58-year-old woman) had high pulmonary artery pressure (86/37 mmHg) and the Pp/Ps was 0.73. According to the experience of the first case, prevention of PHC started during cardiopulmonary bypass, giving PGE1, nitroglycerin and torazoline into the pulmonary artery. This led to the easy weaning from cardiopulmonary bypass. PHC may be seen even in cases of acquired valvular disease, and the prevention is mandatory for uneventful surgery.


Correlates of concurrent partnerships and patterns of condom use among men who have sex with men and transgender women in Peru.
In Peru, there is an ongoing high-incidence HIV epidemic among men who have sex with men (MSM) and transgender women (TW). Sexual concurrency, or having sex with a partner in between two acts of sex with another partner, may be a key factor in onward HIV transmission. In this study, we quantify concurrency, evaluate factors associated with concurrency, and assess condom use with concurrent partners among MSM and TW in Peru. We conducted a secondary analysis of data from the 2011 Peruvian Biobehavioral Survey. Pearson's Chi-squared test was used to identify individual-level characteristics associated with concurrency. We estimated the association between participant characteristics, concurrent partnerships, partnership type (stable vs. non-stable), and CLAI within the context of concurrent partnerships using multivariate and repeated-measure Poisson regression. 3-month cumulative prevalence of concurrency was higher among TW compared to MSM (30.7% vs 25.2%, p = 0.014). Among those with concurrent stable and non-stable partners, 45% used condoms with both partners (95% CI: 40%-50%) and 30% preferentially had CLAI with the stable partner only (95%CI: 26%-35%). Factors associated with CLAI within the context of concurrent partnerships varied between MSM and TW. Although concurrency is common among TW and MSM in Peru, patterns of concurrency and differential condom use may vary between TW and MSM. Future research may explore differential condom use with stable and non-stable partners to better understand behavioral factors that may alter vulnerability to HIV in TW compared to MSM.


Short-time extracorporeal photochemotherapy in the treatment of drug-resistant autoimmune bullous diseases.
Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are potentially severe diseases. In drug-resistant PV and pemphigus foliaceus, long-term adjuvant treatment with extracorporeal photochemotherapy (photopheresis, ECP) has been reported to induce remission. Only limited numbers of patients have been reported so far. No information about the effectiveness in drug-resistant BP is available. Seven patients with drug-resistant autoimmune bullous diseases have been referred to the photopheresis center of Jena (3 x PV, 3 x BP, 1 x pemphigus foliaceus). The age ranged from 31 to 85 years. ECP was performed on 2 consecutive days once a month. Oral 8-methoxypsoralen was used as photosensitizer. Previous immunosuppressive treatment with either prednisolone or prednisolone/ azathioprine was continued. Complete remission (absence of skin or mucous membrane lesions) was achieved in the 6 patients with PV and BP after 1-4 cycles. In the patient suffering from pemphigus foliaceus, a partial remission (> 50% improvement) was observed; in all except this patient, the immunosuppressive treatment could be tapered. Long-term remission was achieved. No severe side effects were observed. The treatment was well tolerated. Short-time ECP is an effective and safe adjuvant treatment for patients with drug-resistant autoimmune bullous diseases. It can induce remission and allows dose tapering of the immunosuppressive drugs.


RNA-binding properties and translation repression in vitro by germ cell-specific MSY2 protein.
The large amount of MSY2 protein, a mouse germ cell-specific Y-box protein, in oocytes and its degradation by the late two-cell stage suggest that MSY2 may stabilize and/or regulate the translation of maternal mRNAs. We report here the ability of bacterially expressed recombinant MSY2 protein to bind to mRNA and repress translation in vitro. Although MSY2 displays some sequence specificity in binding to short RNA sequences derived from the 3' untranslated region (UTR) of the protamine 1 (Prm1) mRNA, as determined by both gel shift and filter binding assays, essentially no sequence specificity is observed when full-length Prm1 mRNA is used. The binding of MSY2 is approximately 10-fold greater to the full-length Prm1 mRNA than to a 37-nucleotide sequence derived from the 3' UTR, and gel shift assays indicate that multiple MSY2 molecules bind to a single Prm1 mRNA. MSY2 binding to luciferase mRNA at ratios of protein to mRNA that are likely to exist in the oocyte also leads to a moderate inhibition of protein synthesis in vitro. Given the abundance of MSY2 in mouse oocytes (2% of total oocyte protein), these data suggest that MSY2 packages mRNAs in vivo with relatively little sequence specificity, which may lead to both stabilization and translation repression of maternal mRNAs.


Cloning and Functional Characterization of Octβ2-Receptor and Tyr1-Receptor in the Chagas Disease Vector, Rhodnius prolixus.
Octopamine and tyramine, both biogenic amines, are bioactive chemicals important in diverse physiological processes in invertebrates. In insects, octopamine and tyramine operate analogously to epinephrine and norepinephrine in the vertebrates. Octopamine and tyramine bind to G-protein coupled receptors (GPCRs) leading to changes in second messenger levels and thereby modifying the function in target tissues and insect behavior. In this paper, we report the cDNA sequences of two GPCRs, RhoprOctβ2-R, and RhoprTyr1-R, have been cloned and functionally characterized from Rhodnius prolixus. Octopamine and tyramine each activate RhoprOctβ2-R and RhoprTyr1-R in a dose-dependent manner. Octopamine is one order of magnitude more potent than tyramine in activating RhoprOctβ2-R. Tyramine is two orders of magnitude more potent than octopamine in activating RhoprTyr1-R. Phentolamine and gramine significantly antagonize RhoprOctβ2-R, whereas yohimbine and phenoxybenzamine are effective blockers of RhoprTyr1-R. The transcripts of both receptors are enriched in the central nervous system (CNS) and are expressed throughout the adult female reproductive system. It has been shown in other insects that Octβ2-R is essential for processes such as ovulation and fertilization. We previously reported that octopamine and tyramine modulate oviducts and bursa contractions in R. prolixus. Our data confirm the importance of octopamine and tyramine signaling in the reproductive system of R. prolixus.


Three-dimensional quantitative structure-property relationship (3D-QSPR) models for prediction of thermodynamic properties of polychlorinated biphenyls (PCBs): enthalpy of vaporization.
Three-dimensional Quantitative Structure-Property Relationship (QSPR) models have been derived using Comparative Molecular Field Analysis (CoMFA) to correlate the vaporization enthalpies of a representative set of polychlorinated biphenyls (PCBs) at 298.15 K with their CoMFA-calculated physicochemical properties. Various alignment schemes, such as inertial, as is, and atom fit, were employed in this study. The CoMFA models were also developed using different partial charge formalisms, namely, electrostatic potential (ESP) charges and Gasteiger-Marsili (GM) charges. The most predictive model for vaporization enthalpy (Delta(vap)H(m)(298.15 K)), with atom fit alignment and Gasteiger-Marsili charges, yielded r2 values 0.852 (cross-validated) and 0.996 (conventional). The vaporization enthalpies of PCBs increased with the number of chlorine atoms and were found to be larger for the meta- and para-substituted isomers. This model was used to predict Delta(vap)H(m)(298.15 K) of the entire set of 209 PCB congeners.


CTX-M-type extended-spectrum β-lactamases present in Escherichia coli from the feces of cattle in Ohio, United States.
CTX-M extended-spectrum β-lactamases are enzymes produced by bacteria that are capable of inhibiting the antimicrobial effects of cephalosporin drugs. Recently, the first domestically acquired Salmonella in the United States expressing bla(CTX-M) was reported. This is a concern because expanded-spectrum cephalosporins are the treatment of choice for invasive Gram-negative infections, including salmonellosis in children. Because Salmonella transmission is primarily foodborne, there is also concern that resistant enteric bacteria from livestock can be transferred through the food supply chain to consumers. bla(CTX-M) has not been previously identified in bacterial isolates from food animal populations in the United States. We report the recovery of CTX-M-type extended-spectrum β-lactamases from fecal Escherichia coli of sick and healthy dairy cattle in Ohio. Four individual fecal samples yielded E. coli isolates representing three clonal strains that carried bla(CTX-M) on transferable plasmids. Two distinguishable plasmids were identified, each encoding bla(CTX-M-1) or bla(CTX-M-79). Transferrable bla(CTX-M) genes in bovine E. coli have the potential to serve as a reservoir of resistance for pathogens and may represent a public health concern.


Influence of the haemodynamic parameters on the repartition of the flow between an artery and its graft.
The aim of this study was to investigate the repartition of the flow between an artery and its graft for several values of the geometric and dynamic parameters (length and severity of the stenosis, Reynolds number and frequency pulse value). The model, fabricated in silicone, was included in an hydrodynamic test bench, allowing to reproduce physiological conditions. Our study showed that the severity of the stenosis was the most influent parameter on the repartition of the flow; in particular, a 75% severity was necessary to obtain a repartition 70-30% between the graft and the artery.


Advanced research on cis-Neonicotinoids.
cis-Neonicotinoids are a type of neonicotinoid, in which the nitro or the cyano group are in cis-configuration relative to heteroaromatic moiety, which show excellent activities against a range of insect species. This review covers cis-neonicotinoids with commercialization perspectives, structural optimization (phenylazoneonicotinoids and chlorothiazolyl analogues of Paichongding), modes of action studies, radiao-synthesis of Paichongding and Cycloxaprid, and photostability of neonicotinoids.


Graph Theoretical Analysis, In Silico Modeling, Synthesis, Anti-Microbial and Anti-TB Evaluation of Novel Quinoxaline Derivatives.
We designed to synthesize a number of 2-(2-(substituted benzylidene) hydrazinyl)-N-(4-((3-(phenyl imino)-3,4-dihydro quinoxalin-2(1 H)-ylidene)amino) phenyl) acetamide S1-S13: with the hope to obtain more active and less toxic anti-microbial and anti-TB agents. A series of novel quinoxaline Schiff bases S1-S13: were synthesized from o-phenylenediamine and oxalic acid by a multistep synthesis. In present work, we are introducing graph theoretical analysis to identify drug target. In the connection of graph theoretical analysis, we utilised KEGG database and Cytoscape software. All the title compounds were evaluated for their in-vitro anti-microbial activity by using agar well diffusion method at three different concentration levels (50, 100 and 150 µg/ml). The MIC of the compounds was also determined by agar streak dilution method. The identified study report through graph theoretical analysis were highlights that the key virulence factor for pathogenic mycobacteria is a eukaryotic-like serine/threonine protein kinase, termed PknG. All compounds were found to display significant activity against entire tested bacteria and fungi. In addition the synthesized scaffolds were screened for their in vitro antituberculosis (anti-TB) activity against Mycobacterium tuberculosis (Mtb) strain H37Ra using standard drug Rifampicin. A number of analogs found markedly potent anti-microbial and anti-TB activity. The relationship between the functional group variation and the biological activity of the evaluated compounds were well discussed. The observed study report was showing that the compound S6: (4-nitro substitution) exhibited most potent effective anti-microbial and anti-TB activity out of various tested compounds.


Progressive loss of E-cadherin immunoexpression during cervical carcinogenesis.
To investigate E-cadherin immunoexpression during cervical carcinogenesis. We assessed the immunohistochemical expression of E-cadherin in squamous intraepithelial lesions (SIL - 52 cases), squamous cell carcinoma (SCC) of the uterine cervix (23 cases) and also in eight cases of cervicitis. The results show very different E-cadherin membrane expression levels when cervicitis (88%), SILs (73%) and SCC (17%) were compared. In SILs, higher E-cadherin loss was seen in less differentiated cells in the basal third of the epithelium. This study suggests that the absence of E-cadherin expression in the membrane is a molecular event that is observed more often in SCC of the uterine cervix than in SILs or cervicitis. E-cadherin is an essential molecule during the process of cervical carcinogenesis and in this context exhibits a different expression pattern according to the epithelial thickness layer.


Effects of alcohol use and estrogen on bone.
In marked contrast with men who drink, women who drink alcohol are found, as a group, to have higher bone mass compared with women who abstain. Furthermore, the apparent beneficial effects of alcohol use are more apparent in postmenopausal women than women of reproductive age, suggesting that there might be an interaction between alcohol and estrogen. Estrogen deficiency accompanying menopause leads to bone loss, which in turn predisposes women to osteoporosis later in life. Estrogen deficiency accelerates bone remodeling, which is the process by which small areas of bone are destroyed and rebuilt, and leads to an imbalance whereby bone resorption--the part of remodeling consisting of breaking down and assimilating--exceeds bone formation. Alcohol might reduce bone loss in postmenopausal women by increasing the circulating levels of estrogen. Alternatively, alcohol might slow bone loss by acting on bone cells to reduce bone remodeling. Alcohol use has a negative effect on the immature skeleton but current understanding suggests that small quantities of alcohol may have beneficial effects on bone in older women.


Immunologic effects of human peripheral and intrathyroidal lymphocytes on xenotransplanted human thyroid tissue in athymic nude mice.
T cells are intimately involved in the etiology and pathogenesis of human autoimmune thyroid disease. In order to further elucidate the immunologic mechanisms leading to Graves' disease (GD), we investigated the effects of human lymphocytes derived from patients with autoimmune and nonautoimmune thyroid diseases on human thyroid tissue xenotransplanted into nude mice. Eight weeks after transplantation of thyroid tissue from 26 patients with nonautoimmune thyroid disease (nontoxic nodular goiter [NTG]) into nude mice, peripheral (PBL) and intrathyroidal lymphocytes (ITL) from 14 patients with NTG and 12 patients with GD were engrafted into the animals. ITL and PBL subsets were analyzed by flow cytometer before engraftment. Two days after lymphocyte engraftment, the thyroid transplants were examined histologically (HE) as well as immunohistologically by staining with monoclonal antibodies directed against CD3 (T-cell activation and signal transduction), immunoglobulin G (IgG), HLA class II and CD31 (human endothelium). After injection of GD lymphocytes, thyroid transplants contained significantly more CD3, HLA class II, and CD4 expressing cells. Engrafted PBL and especially ITL from patients with GD specifically migrated into human thyroid transplants but not into the mouse thyroids, induced expression of class II products and led to IgG production by plasma cells. Persistence of human endothelium has been proven by positive CD31 staining. In conclusion, our data demonstrate that an organ-specific immune response is induced only by GD lymphocytes that migrate specifically into the thyroid transplants. Persistence of human endothelial cells in the transplants suggests that homing in this in vivo model reflects the situation in GD patients.


Occurrence of 4 Dengue Virus Serotypes and Chikungunya Virus in Kilombero Valley, Tanzania, During the Dengue Outbreak in 2018.
Dengue and Chikungunya viruses can cause large-scale epidemics, with attack rates of up to 80%. In Tanzania, there have been repeated outbreaks of dengue fever, the most recent in 2018 and 2019, mostly affecting the coastal areas. Despite the importance of these viruses, there is limited knowledge on the epidemiology of dengue (DENV) and Chikungunya (CHIKV) in Tanzania. This study was conducted to investigate the prevalence of DENV and CHIKV in Kilombero Valley, Tanzania. A cross-sectional study was conducted at Kibaoni Health Center in Kilombero Valley, Southeastern Tanzania, in the rainy and dry seasons of 2018. Febrile patients of any age and gender were enrolled from the outpatient department. Blood samples were taken and screened for DENV and CHIKV viral RNA by real-time reverse transcription polymerase chain reaction assays. Overall, 294 patients were recruited. Most were females (65%), and one-third of patients were aged 14-25 years. DENV and CHIKV were detected in 29 (9.9%) and 3 (1.0%) patients, respectively. DENV was detected across all age groups during both the dry and rainy seasons. Although all 4 DENV serotypes were detected, serotypes 1 and 3 dominated and were present in 14 patients (42.4%) each. Additionally, the study showed DENV-1 and DENV-3 co-infections. This study reveals the co-circulation of all 4 DENV serotypes and CHIKV in Kilombero. Importantly, we report the first occurrence of DENV-4 in Tanzania. Unlike previous DENV outbreaks caused by DENV-2, the 2018 outbreak was dominated by DENV-1 and DENV-3. The occurrence of all serotypes suggests the possibility of severe clinical outcomes in future DENV epidemics in Tanzania.


Serum levels of leptin, insulin-like growth factor-I and insulin-like growth factor binding protein-3 in women with pre-eclampsia, and their relationship to insulin resistance.
The present study was carried out to compare serum levels of leptin, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3), homeostasis model assessment--(pancreatic beta-cell function) (HOMA-(%B)) and homeostasis model assessment--(tissue insulin sensitivity) (HOMA-(%S)) in women with mild and severe pre-eclampsia and normotensive pregnant women; and to evaluate the possible relationships between these parameters in the pathogenesis of pre-eclampsia. Seventy-three women were divided into three groups: group A consisted of 20 normotensive pregnant women (NPW); group B consisted of 25 women with mild pre-eclampsia (MPE); and group C consisted of 28 women with severe pre-eclampsia (SPE). Serum level of leptin was measured by enzyme immunoassay using a commercial kit. Serum levels of IGF-I and IGFBP-3 were measured with a two-site immunoradiometric assay. Serum level of insulin was measured by the electrochemiluminescence immunoassay method. HOMA used indices of pancreatic beta-cell function and tissue insulin sensitivity. Differences between groups were compared by one-way analyses of variance and the post hoc Tukey-HSD test for multiple comparisons; however, when a variable was not normally distributed, the Mann-Whitney U test was used. Associations between variables were tested using Pearson's coefficient of correlation. Birth weight was significantly lower (p < 0.001) in the MPE and SPE groups than in the NPW group. Serum levels of leptin and insulin in women with SPE and MPE were significantly higher (p < 0.001) than in NPW. Serum levels of IGF-I and IGFBP-3 were significantly lower in women with SPE and MPE compared with NPW (p < 0.001). The mean HOMA-(%B) level in women with SPE and MPE was significantly higher than in NPW (p < 0.001), whereas the mean HOMA-(%S) level in women with SPE and MPE was significantly lower than in NPW (p < 0.001). In the SPE group, systolic blood pressure correlated significantly with serum levels of IGF-I and leptin (r = 0.375, p < 0.05 and r = 0.495, p < 0.01, respectively). A negative correlation between mean HOMA-(%S) level and serum IGFBP-3 level was noted (r = -0.357, p < 0.05). There was a positive correlation between serum level of IGF-I and mean HOMA-(%B) level in mildly pre-eclamptic women (r = 0.541, p < 0.01). We conclude that pre-eclampsia is associated with insulin resistance; and that existing hyperinsulinemia and insulin resistance in women with pre-eclampsia seem not to correlate with leptin and birth weight, but may correlate positively with IGF-1 and IGFBP-3. Therefore we think that hyperleptinemia, low IGF-I or IGFBP-3, and insulin resistance may contribute to the pathogenesis of pre-eclampsia.


Pharmacogenomics: What the Doctor Ordered?
About half a million adverse drug reactions are reported in the US each year that result in disability, hospitalization or death. The efficacy or toxicity of a drug in a patient can be strongly influenced by their genetics as well as environment. Application of genomics to clinical pharmacology, "pharmacogenomics," promises to transform patient care and health resource utilization in the coming decade.


Large-scale expansion of rat CD4+ CD25+ T(reg) cells in the absence of T-cell receptor stimulation.
T-cell receptor (TCR) stimulation is both central to homeostatic maintenance of CD4(+) CD25(+) regulatory T cells (T(reg) cells) in vivo and a prerequisite for the initiation of suppression by T(reg) cells, both in vivo and in vitro. However, TCR-independent stimulation of T(reg) cells, e.g. with superagonistic CD28-specific monoclonal antibodies (CD28-SA), not only expands these cells in vivo but, as we show here, also mediates large-scale expansion of rat T(reg) cells in vitro. Interestingly, CD28-SA stimulation plus interleukin (IL)-2 was even superior to conventional costimulation plus IL-2 in promoting T(reg) cell growth in vitro. Despite their highly activated phenotype suppression by T(reg) cells expanded in the absence of TCR stimulation remained fully dependent on TCR-triggering for initiation and cell contact was required to exert suppression. With regard to the regulation of suppression by CD28 stimulation we observed that neither the presence of a conventional anti-CD28 monoclonal antibody nor a CD28-SA generally rendered conventional T cells resistant to suppression by preactivated T(reg) cells. Taken together, we provide a novel protocol for long-term propagation of T(reg) cells in vitro and our data are the first to reveal a difference in the signals required for activation and expansion of T(reg) cells and those, involving the TCR, necessary for the initiation of suppression.


Neuropsychiatric manifestations and their outcomes in chronic hypocalcaemia.
Hypocalcaemia is an established cause of neurological and psychiatric disease with numerous clinical manifestations. The aim of the study was to determine the outcome of severe neuropsychiatric manifestations of chronic hypocalcaemia after correction of calcium levels. Clinical and laboratory data of 22 patients seen between 1999 and 2009 were retrospectively analysed. Calcium, magnesium, phosphorus, albumin and parathormone values were measured in all cases. All patients except infants under one year of age had computed tomography (CT) scans of the head. Most patients (n = 19; 86%) presented with generalised tonic clonic convulsions while three had seizures with psychiatric manifestations. Movement disorders were present in 4 patients and one had candida meningitis. Nineteen of the 22 patients had primary hypoparathyroidism of which one had associated mucocutaneous candidiasis. One had pseudohypoparathyroidism and two had vitamin D deficiency. All patients improved with calcitriol and calcium treatment. Twelve of the 14 patients with convulsions could be taken off anticonvulsants. Hemiballismus disappeared in one patient and choreiform movements disappeared in one patient and dystonia in two patients. Psychiatric manifestations improved but did not disappear in the three patients who had them. Adult patients with seizures or neuropsychiatric manifestations should have calcium levels checked. Seizure disorders due to chronic hypocalcaemia had excellent prognosis on correction of serum calcium levels. Movement disorders improved markedly. Psychiatric manifestations did not improve substantially on correction of serum calcium levels.


Occupational exposure and cancer of the pancreas: a review.
Many hypotheses have been proposed about the aetiology of cancer of the pancreas, especially concerning the effects of tobacco, coffee, alcohol, diet, and pancreatic pathology. Results of numerous epidemiological studies are, however, inconsistent. Chemical carcinogens have been implicated as possible risk factors. Animal studies have been carried out to determine the role of these chemical factors but, except for nitrosamines and their derivatives (components of tobacco), chemicals have not been proved carcinogenic for the pancreas. Many studies have also been conducted among occupational groups. Several of them showed an excess risk of cancer of the pancreas, especially in the chemical and petroleum industries. The lack of accuracy about the nature of products used, however, does not permit a definitive conclusion as to their carcinogenic role. This paper is a review of publications about occupational exposures and cancer of the pancreas.


Progress toward global eradication of dracunculiasis--January 2012-June 2013.
Dracunculiasis (Guinea worm disease) is caused by Dracunculus medinensis, a parasitic worm. Approximately 1 year after infection from contaminated drinking water, the worm emerges through the skin of the infected person, usually on the lower limb. Pain and secondary bacterial infection can cause temporary or permanent disability that disrupts work and schooling. In 1986, the World Health Assembly (WHA) called for dracunculiasis elimination, and the global Guinea Worm Eradication Program, supported by The Carter Center, World Health Organization (WHO), United Nations Children's Fund (UNICEF), CDC, and other partners, began assisting ministries of health of dracunculiasis-endemic countries in meeting this goal. At that time, an estimated 3.5 million cases occurred each year in 20 countries in Africa and Asia. This report updates published and unpublished surveillance data reported by ministries of health and describes progress toward dracunculiasis eradication. A total of 542 cases were reported in 2012, compared with 1,058 in 2011. The disease remains endemic in four countries in 2013, but the overall rate of reduction in cases has accelerated compared with the first 6 months of 2012. In the month of January 2013, no cases were reported worldwide for the first time since the eradication program began in 1986. Failures in surveillance and containment, lack of clean drinking water, insecurity in Mali and parts of South Sudan, and an unusual epidemiologic pattern in Chad are the main remaining challenges to dracunculiasis eradication.


Tricuspid endocarditis following a Papanicolaou smear: case report.
Infective endocarditis is an uncommon complication of obstetrical and gynecological practice and has not been reported in the literature to be associated with Papanicolaou smears. The authors report a nonintravenous drug user who developed group B streptococcal endocarditis of the tricuspid valve following a routine Papanicolaou smear. She required surgical excision of the valve and replacement after failed antibiotic therapy.


Associations between social and general health factors and symptoms related to temporomandibular disorders and bruxism in a population of 50-year-old subjects.
The aim of this epidemiological study was to examine associations between temporomandibular (TMD)-related problems and variables from three domains: (1) socio-economic attributes, (2) general health and health-related lifestyle, and (3) dental attitudes and behaviors. The overall response rate to a questionnaire mailed to the total population of 50-year-old subjects in two Swedish counties (8,888 individuals) was 71%. Among the 53 questions in the questionnaire, those related to social, general health, and health-related factors were used as independent variables in logistic regression models. Three TMD-related symptoms and reported bruxism were used as dependent variables. Impaired general health was the strongest risk factor for reported TMD symptoms. Along with female gender and dissatisfaction with dental care, impaired general health was significantly associated with all three TMD symptoms. A few more factors were associated with pain from the TMJ only. In comparison, reported bruxism showed more significant associations with the independent variables. In addition to the variables associated with TMD symptoms, being single, college/university education, and daily tobacco use were also significantly correlated with bruxism. Besides female gender, impaired general health, dissatisfaction with dental care, and a few social and health-related factors demonstrated significant associations with TMD symptoms and reported bruxism.


Clinical profile and outcome of patients presenting with mushroom poisoning in a tertiary care center of eastern Nepal.
Accidental mushroom poisoning is constantly seen and regularly reported from all over world. Exact magnitude of problem and its clinical profile in Nepal is not well known. This study was done to evaluate clinical profile and treatment outcome of patients presenting with mushroom poisoning in the department of internal medicine, BPKIHS, Dharan. It is a prospective observational study conducted in department of internal medicine, BPKIHS, Dharan from 1st January 2008 to 31st December 2009. Informed consent was taken. All the patients were subjected to necessary laboratory investigation. They were followed up at 1 week and 1 month after discharge. All together 60 patients were analyzed. Majority of subjects 56 (93.3%) were from rural areas. Vomiting and diarrhea were the two most common presentations seen in 56 (93.3%) subjects. The latent period for the symptoms were >6 hours in 4 (6.7%) and <6 hours in 56 (93.3%) subjects. Fulminant hepatic failure was seen in 6 (10%) subjects and among them 4 (66.7%) expired. After admission 3 (5%) subjects developed GI bleeding. Average duration of hospital stay was 4.6 days. In follow up recovery was complete in all subjects who survived the acute phase of poisoning. Especially in patients coming during rainy season mushroom poisoning should be considered in the differential diagnosis of acute gastroenteritis. Mortality is high in subjects with FHF whereas recovery is complete in subjects who survived the acute phase.


Sensory Attributes of Buckwheat Jelly (Memilmuk) with Mung Bean Starch Added to Improve Texture and Taste.
Buckwheat contains more essential proteins, dietary fiber, vitamins, minerals, and diverse phytochemicals than wheat and rice. The aims of this study are to develop the descriptive sensory attributes and evaluate the consumer acceptability of six buckwheat jellies (memilmuk) with added mung bean starch and to analyze the relationship between their descriptive sensory attributes and consumer acceptability. Statistical analyses were performed by one-way analysis of variance (ANOVA), principal component analysis (PCA), and partial least squares regression (PLSR). A total of 18 sensory attributes of buckwheat jelly, including appearance (brown, brightness, and roughness), odor/aroma (soymilk smell, grain smell, red bean porridge smell, and buckwheat tea smell), flavor or taste (savory flavor, plain taste, buckwheat taste, sweet taste, salty taste, and umami), and texture (squashed, dry, smooth, elasticity and stickiness) were developed. Consumer acceptability tests of six buckwheat jellies were conducted by 93 consumers evaluating for color, smell, savory taste, aftertaste, harmony with the sauce, overall liking, and would recommend or try again. Buckwheat jelly with 25% of mung bean starch (BJ_916) was the most favorable jelly sample among the six samples. All attributes except color, smell, and the savory taste of samples showed a significant difference (p < 0.001). BJ_916 showed a close relationship with a grain smell, elasticity, red bean porridge smell, and sweet taste of descriptive attributes and also all attributes of consumer acceptability. The determination of sensory attributes and consumer acceptability of buckwheat jelly will help to improve sensory characteristics to fulfill consumer needs and desires. Furthermore, this current study will help facilitate the expansion of the buckwheat consumption market.


Antioxidants and Male Fertility: from Molecular Studies to Clinical Evidence.
Spermatozoa are physiologically exposed to reactive oxygen species (ROS) that play a pivotal role on several sperm functions through activation of different intracellular mechanisms involved in physiological functions such as sperm capacitation associated-events. However, ROS overproduction depletes sperm antioxidant system, which leads to a condition of oxidative stress (OS). Subfertile and infertile men are known to present higher amount of ROS in the reproductive tract which causes sperm DNA damage and results in lower fertility and pregnancy rates. Thus, there is a growing number of couples seeking fertility treatment and assisted reproductive technologies (ART) due to OS-related problems in the male partner. Interestingly, although ART can be successfully used, it is also related with an increase in ROS production. This has led to a debate if antioxidants should be proposed as part of a fertility treatment in an attempt to decrease non-physiological elevated levels of ROS. However, the rationale behind oral antioxidants intake and positive effects on male reproduction outcome is only supported by few studies. In addition, it is unclear whether negative effects may arise from oral antioxidants intake. Although there are some contrasting reports, oral consumption of compounds with antioxidant activity appears to improve sperm parameters, such as motility and concentration, and decrease DNA damage, but there is not sufficient evidence that fertility rates and live birth really improve after antioxidants intake. Moreover, it depends on the type of antioxidants, treatment duration, and even the diagnostics of the man's fertility, among other factors. Literature also suggests that the main advantage of antioxidant therapy is to extend sperm preservation to be used during ART. Herein, we discuss ROS production and its relevance in male fertility and antioxidant therapy with focus on molecular mechanisms and clinical evidence.


Intracystic papillary breast carcinoma in a male patient: a case report and review of literature.
Intracystic papillary carcinoma of the breast is a rare subtype of breast cancer accounting for approximately 0.5-1% of all breast carcinomas. To the best of our knowledge, the occurrence of this rare subtype of breast cancer in the male is even lower with less than 20 cases reported in the English literature over the past 30 years. We report a case of an elderly Asian male with intracystic papillary breast carcinoma who initially presented with a right sided breast lump for 4 months duration and his subsequent management. In addition, a review of similar cases in the English literature is included.


Prognostic Value of the Site of Distant Metastasis and Surgical Interventions in Metastatic Gastric Cancer: A Population-Based Study.
Studies on the prognostic significance of site-specific distant metastasis, multiple-site metastases, and the impact of surgery of the primary tumor and metastatic lesion on survival outcomes of patients with metastatic gastric cancer (GC) remain elusive. Therefore, this study aimed to investigate the prognostic significance of the site of distant metastasis among patients with metastatic GC. Furthermore, the effect of surgery of the primary tumor and metastatic lesion on the prognosis of metastatic GC was also analyzed. The data of 4,221 eligible patients, who were diagnosed with metastatic GC between 2010 and 2015, were identified from the Surveillance Epidemiology and End Results (SEER) database. Multivariate logistic regression analysis was performed to assess the association between potential prognostic factors, including the site of metastasis and surgery, and survival of patients with metastatic GC. Overall survival (OS) and cause-specific survival (CSS) were determined using the Kaplan-Meier survival curves and differences were assessed using the Log-rank test. Out of the total 4,221 GC patients with definite organ metastases, 3312 patients had single-site metastasis while 909 patients had multiple-site metastases. GC patients with single-site metastasis of liver or lung exhibited better CSS and OS compared to those with bone metastasis. Furthermore, GC patients with liver metastasis benefited from surgery of both the primary and metastatic lesions, while those with lung metastasis benefited from surgery of metastasis resection only. Multivariate Cox regression analysis revealed that GC patients with single-site metastasis, well-differentiated tumors, GC patients who underwent surgery of the primary tumor and those who received chemotherapy exhibited favorable prognosis. The site of metastasis was an independent prognostic factor for metastatic GC. Surgery had survival benefits in certain cases of metastatic GC; however, further studies are warranted to clarify these benefits in carefully selected patients.


Attitudinal factors associated with community pharmacists' involvement in services for drug misusers.
To assess the relationship between pharmacists' attitudes towards drug misusers and the availability and provision of services for drug misusers. A cross-sectional postal questionnaire survey. All community pharmacies in Scotland (n = 1142). A total of 864 pharmacists managing community pharmacies on a day-to-day basis (response rate 79%). Descriptive data were collected on demography, drug misuse services provided and training in drug misuse. Attitude statements were used to measure attitudes to drug misusers, the role of the pharmacist in dispensing controlled drugs and providing injecting equipment, providing advice on drug misuse and financial aspects of service provision. Statements were incorporated into a scale which was correlated with behavioural data on whether and how services were provided. The attitude scale had good internal reliability and was unidimensional. Pharmacists that provided needle/syringe exchanges, sold needles/syringes, dispensed methadone, supervised the consumption of methadone and provided health promotion services to drug misusers had significantly more positive attitudes towards drug misusers. Attitudes were associated with health board area, sex and number of years registered as a pharmacist. After controlling for these characteristics, attitude was an independent predictor of whether needles/syringes were sold, methadone was dispensed and methadone consumption supervised. Addressing negative attitudes could encourage more pharmacists to provide services and enhance the process of service delivery.


Short and long-term outcome of treatment with high-dose melphalan and stem cell transplantation for multiple myeloma-associated AL amyloidosis.
High-dose melphalan chemotherapy and autologous peripheral blood stem cell transplantation (HDM/SCT) has been shown to result in a durable hematologic response and prolonged overall survival in systemic amyloid light-chain (AL) amyloidosis as well as multiple myeloma. However, little is known about the myeloma associated with AL amyloidosis (MM/AL). In this retrospective study, we evaluated 87 patients with MM/AL from 1994 to 2007. Sixteen of these patients underwent HDM/SCT at Boston University Medical Center. Three patients (19%) died from treatment-related mortality. The overall median survival for all 87 patients was 22 months by Kaplan-Meier estimates. However, this was improved to 54.5 months for those who received HDM/SCT compared to 21 months for those who did not receive HDM/SCT. A hematologic complete response was achieved by 25% (4/16) of patients at 6 months after HDM/SCT. Hematologic relapses occurred in 60% of patients at a median of 1 year after HDM/SCT. In conclusion, HDM/SCT can prolong overall survival in patients with MM/AL who are eligible to receive it.


Characterization of N-acyl homoserine lactones (AHLs) producing bacteria isolated from vacuum-packaged refrigerated turbot (Scophthalmus maximus) and possible influence of exogenous AHLs on bacterial phenotype.
Quorum sensing (QS) is a cell-to-cell communication mechanism through which microbial cells communicate and regulate their wide variety of biological activities. N-acyl homoserine lactones (AHLs) are considered to be the most important QS signaling molecules produced by several Gram-negative bacteria. The present study aimed to screen the AHLs-producing bacteria from spoiled vacuum-packaged refrigerated turbot (Scophthalmus maximus) by biosensor assays, and the profiles of AHLs produced by these bacteria were determined using reversed-phase thin-layer chromatography (RP-TLC) and gas chromatography-mass spectrometry (GC-MS). Effects of exogenous AHLs and QS inhibitor (QSI) on the phenotypes (i.e., extracellular proteolytic activity and biofilm formation) of the AHLs-producing bacteria were also evaluated. Our results demonstrated that eight out of twenty-two isolates were found to produce AHLs. Three of the AHLs-producing isolates were identified as Serratia sp., and the other five were found to belong to the family of Aeromonas. Two isolates (i.e., S. liquefaciens A2 and A. sobria B1) with higher AHLs-producing activities were selected for further studies. Mainly, RP-TLC and GC-MS analysis revealed three AHLs, i.e., 3-oxo-C6-HSL, C8-HSL and C10-HSL were produced by S. liquefaciens A2, while five AHLs, i.e., C4-HSL, C6-HSL, C8-HSL, C10-HSL, and C12-HSL, were produced by A. sobria B1. Moreover, production of AHLs in both bacterial strains were found to be density-dependent, and the AHLs activity reached a maximum level in their middle logarithmic phase and decreased in the stationary phase. The addition of exogenous AHLs and QSI decreased the specific protease activity both of the Serratia A2 and Aeromonas B1. Exogenous AHLs inhibited the biofilm formation of Serratia A2 while it enhanced the biofilm formation in Aeromonas B1. QSI inhibited the specific protease activity and biofilm formation in both bacterial strains.


Characterization of an Enzyme-Catalyzed Crosslinkable Hydrogel as a Wound Dressing in Skin Tissue Engineering.
Introduction: Wound healing can have a very important impact on the patients' quality of life. For its treatment, wound dressings have vital and effective uses. Indeed, the use of a proper wound dressing can improve the healing process and duration. Recently, wound dressings with unique properties have been prepared using natural hydrogels. In addition to the general wound characteristics, new generations of wound dressings, such as those lasting longer on the wound, can have specific properties such as transferring allogeneic cells to enhance the healing effect and speed up the healing process. The present study aimed to prepare a gelatin-based hydrogel and to characterize it for therapeutic purposes. Methods: In this experimental-laboratory study, a gelatin hydrogel was made using a microbial transglutaminase (mTG) enzyme. The prepared hydrogel was evaluated in terms of appearance, physical, and chemical properties. To investigate the biological properties of the hydrogel, cells were cultured on it and the toxicity of the hydrogel for the cells was investigated. The location of the cells on the hydrogel was imaged via an electron microscope. The absorption and reflectance characteristics of the hydrogel were recorded by optical spectroscopy. Data were collected and statistical analysis was performed. Results: The results showed that the mTG gelatin hydrogel had a uniform pore size and good physical, chemical, and mechanical properties for use in wound healing. Cell experiments showed evident cell proliferation and high viability. The results also revealed that the cells grew vigorously and adhered tightly to the hydrogel. Conclusion: The preparation of a gelatin hydrogel under GMP conditions can be considered in the healing of diabetic wounds and burns.


Leptin responsiveness and gene dosage for leptin receptor mutation (fa) in newborn rats.
To determine the degree to which the leptin receptor mutation (fa) influences the responsiveness to leptin during the first postnatal week, we injected recombinant leptin (600 pmol. g-1. day-1 sc from day 1 to day 7) into wild-type (+/+), heterozygous (+/fa), and fatty (fa/fa) rat pups. Growth and final body fat content of these leptin-treated pups were compared with those of saline-treated littermates of the same genotype. The body mass of the leptin-treated +/+ pups, but not that of the +/fa and fa/fa pups, increased more slowly than that of their respective controls, and fat content at day 7 was reduced by 37% in +/+ pups, by 22% in +/fa pups, but not at all in fa/fa pups. Plasma leptin remained excessively high throughout the day under this treatment, but a 30-fold lower leptin dose, causing only moderate changes of plasma leptin, still reduced the body fat of +/+ pups significantly. We conclude that leptin participates in the control of even the earliest stages of fat deposition and that the response to supraphysiological doses of leptin is markedly reduced in 1-wk-old pups with one fa allele and absent in pups with two fa alleles.


Transition Pathways Toward the Prudent Use of Antimicrobials: The Case of Free-Range Broiler Farmers in France.
Reducing antimicrobial use (AMU) on farms is key for controlling the rise of resistant bacteria that have the potential capacity to infect humans via direct animal contact or via the food chain or the environment. To reduce AMU, antimicrobials must be used in a prudent and rational manner. Extensive efforts have been made recently to identify the cognitive and behavioral barriers to the appropriate use of antimicrobials by various livestock sector stakeholders. However, most studies carried out thus far have only partly captured the dynamic and systemic dimension of the processes involved in changes of practices related to AMU on farms. To shed light on the transition pathways implemented to reduce AMU, a qualitative study was conducted in France based on 28 semi-structured interviews with farmers, technicians and veterinarians from the free-range broiler production sector. Based on the thematic analysis of verbatims, we identified technical improvements which are key contributors to reduced AMU. We also highlighted some gaps in knowledge regarding AMU and antimicrobial resistance. We found that, rather than individual motivations alone, the extent to which farmers are embedded in collective organizations is decisive for changes in practices, and downstream operators (distributors and slaughterers) play a key role in the beginning of AMU transition pathways. As a result, we show that change in AMU requires a global rethinking of the overall socio-technical system rather than modifications of a single element in a farming system. Our results also highlight that transition pathways toward reduced AMU cannot just rely on trigger events, but also involves medium or long-term processes, with actors' experiences and practices being modified on an incremental basis over time. Our study sheds light on the need for multi and trans-disciplinary research involving the social sciences to analyze interactions between stakeholders and the collective actions implemented to tackle the challenge of AMU reduction.


Desmoplastic small round cell tumor: postoperative retroperitoneal mass.
We describe the case of a 14-year-old boy who presented with a large, 17.6-cm retroperitoneal mass, along with multiple metastases, and was diagnosed with desmoplastic small round cell tumor. After initial chemotherapy, he underwent gross total resection with a positive margin. On postoperative radiation planning computed tomography, a 6.8-cm heterogeneous mass was noted in the surgical bed. Given the tumor's aggressive nature and positive surgical margins, there was real concern for recurrent disease. Further evaluation with magnetic resonance imaging elucidated that the mass consisted of simple fluid and fat, without contrast enhancement, suggesting a postoperative fluid collection. He was able to continue with adjuvant treatment as planned. This case example illustrates that even large postoperative heterogeneous masses may still be related to postoperative fluid collection in patients with aggressive tumor. However, it is important to rule out recurrent disease before starting adjuvant therapy given improved outcomes with gross total resection in desmoplastic small round cell tumor.


Comparison of nonlinear filtering techniques for photonic systems with blackbody radiation.
This work explores a theoretical solution for noise reduction in photonic systems using blackbody radiators. Traditionally, signal noise can be reduced by increasing the integration time during signal acquisition. However, increasing the integration time during signal acquisition will reduce the acquisition speed of the signal. By developing and applying a filter using a model based on the theoretical equations for blackbody radiation, the noise of the signal can be reduced without increasing integration time. In this work, three filters, extended Kalman filter, unscented Kalman filter (UKF), and extended sliding innovation filter (ESIF), are compared for blackbody photonic systems. The filters are tested on a simulated signal from five scenarios, each simulating different experimental conditions. In particular, the nonlinear filters, UKF and ESIF, showed a significant reduction of noise from the simulated signal in each scenario. The results show great promise for photonic systems using blackbody radiators that require post-process for noise reduction.


DC modeling and the source of flicker noise in passivated carbon nanotube transistors.
DC and intrinsic low-frequency noise properties of p-channel depletion-mode carbon nanotube field effect transistors (CNT-FETs) are investigated. To characterize the intrinsic noise properties, a thin atomic layer deposited (ALD) HfO(2) gate dielectric is used as a passivation layer to isolate CNT-FETs from environmental factors. The ALD HfO(2) gate dielectric in these high-performance top-gated devices is instrumental in attaining hysteresis-free current-voltage characteristics and minimizes low-frequency noise. Under small drain-source voltage, the carriers in the CNT channel are modulated by the gate electrode and the intrinsic 1/f noise is found to be correlated with charge trapping/detrapping from the oxide substrate as expected. When thermionic emission is the dominant carrier transport mechanism in CNT-FETs under large drain-source voltages, the excess 1/f noise is attributed to the noise stemming from metal-CNT Schottky barrier contacts as revealed by the measurements.


[Cestode infections in Poland in 2008].
In the year 2008, 109 intestinal cestode infections were registered in Poland. Among them 69 were caused by Taenia saginata, 2 by T. solium, 30 by Taenia sp., 1 by Diphyllobothrium latum. Moreover, 28 cases of cystic echinococcosis were reported. The obtained results confirmed decreasing frequency of intestinal cestodoses in Poland.


T-bet and eomesodermin are required for T cell-mediated antitumor immune responses.
Cell-mediated adaptive immunity is very important in tumor immune surveillance and tumor vaccination. However, the genetic program underlying an effective adaptive antitumor immunity is elusive. T-bet and Eomesodermin (Eomes) have been suggested to be master regulators of Th1 cells and CD8(+) T cells. However, whether they are important for T cell-mediated antitumor immunity is controversial. In this paper, we show that the combined germline deletion of T-bet and T cell-specific deletion of Eomes resulted in profound defects in adaptive antitumor immune responses. T-bet and Eomes drive Tc1 differentiation by preventing alternative CD8(+) T cell differentiation to Tc17 or Tc2 cells. Surprisingly, T-bet and Eomes are not critical for the generation of systemic CTL activities against cancer cells. Instead, T-bet and Eomes are crucial for tumor infiltration by CD8(+) T cells. This study defines T-bet and Eomes as critical regulators of T cell-mediated immune responses against tumor.


Giant magnetoresistance in oxypnictides (La,Nd)OMnAs.
A sizeable negative magnetoresistance (MR) has been observed for oxypnictides LnOMnAs (Ln = La,Nd). MR up to -24% is observed at 200 K for LaOMnAs which is unprecedented for divalent Mn(2+). Both materials are weak ferromagnets with transition temperatures above room temperature.


[Ankylosing spondylitis (Bechterew's disease)--a current review (author's transl)].
Ankylosing spondylitis is a disease with clinically and radiologically very variable features. It is the intention to direct the attention from the old by orthopedists' influenced association of the stiff back to the polymorphism of the disease especially to the early stages which still frequently are recognized too late. The paper deals with the nosology, the various states of the clinical course with the numerous radiological criteria including therapeutical approaches.


Dynamic and specific interaction between synaptic NR2-NMDA receptor and PDZ proteins.
The relative content of NR2 subunits in the NMDA receptor confers specific signaling properties and plasticity to synapses. However, the mechanisms that dynamically govern the retention of synaptic NMDARs, in particular 2A-NMDARs, remain poorly understood. Here, we investigate the dynamic interaction between NR2 C termini and proteins containing PSD-95/Discs-large/ZO-1 homology (PDZ) scaffold proteins at the single molecule level by using high-resolution imaging. We report that a biomimetic divalent competing ligand, mimicking the last 15 amino acids of NR2A C terminus, specifically and efficiently disrupts the interaction between 2A-NMDARs, but not 2B-NMDARs, and PDZ proteins on the time scale of minutes. Furthermore, displacing 2A-NMDARs out of synapses lead to a compensatory increase in synaptic NR2B-NMDARs, providing functional evidence that the anchoring mechanism of 2A- or 2B-NMDARs is different. These data reveal an unexpected role of the NR2 subunit divalent arrangement in providing specific anchoring within synapses, highlighting the need to study such dynamic interactions in native conditions.


Involvement of GABAergic systems and benzodiazepine receptors in the jumping behavior induced by harmine and apomorphine in rats.
Harmine (HA) induces a jumping behavior in rats when the central dopaminergic function has been activated. Possible involvement of the GABAergic systems and the benzodiazepine receptors (BZA-R) in the jumping behavior induced by HA and apomorphine (APO) was investigated. Pretreatment with GABAergic agonists, muscimol (0.05-0.2 mg/kg) and diazepam (0.2-1.0 mg/kg), and antagonists, picrotoxin (0.1-0.5 mg/kg) and bicuculline (0.1-0.5 mg/kg), suppressed the jumping behavior in a dose-dependent manner in rats treated with HA (10 mg/kg) and APO (2 mg/kg). After treatment with 2, 5 or 10 mg/kg of HA in combination with 2 mg/kg of APO, a decrease in 3H-diazepam binding to the brain regional membranes was observed in the corpus striatum (CS) in a dose-dependent manner, but not in the other brain regions. The decrease in the 3H-diazepam binding to the CS membranes was proportional to the increase in the HA levels in the CS, and the HA levels were correlated with the intensity of jumping behavior. Pretreatment with Ro 15-1788, an antagonist of BZA-R, suppressed the jumping behavior induced by HA and APO. These results indicated the involvement of the GABAergic systems in the jumping behavior and suggested that HA induced the jumping behavior partly as a result of interacting with the BZA-R.


Andrographolide Liquisolid using Porous-Starch as the Adsorbent with Enhanced Oral Bioavailability in Rats.
Andrographolide (AGL) is the major component of Andrographispaniculata. The poor water solubility and low dissolution strongly affect its oral absorption. Liquisolid technology has been used to improve its dissolution and oral bioavailability. Liquisolid powders of AGL (AGL-LS-PSG) were obtained by firstly dissolving AGL in the mixture of NMP, PEG 6000 and Soluplus®, and solidified by absorption of the blend in porous starch. Angle of repose, Carr index and Hauser ratio presented good powder fluidity and compressibility characteristics of AGL-LS-PSG. The results of optical microscopic observation, PXRD and DSC analysis indicated that AGL has been completely adsorbed in porous starch granules and existed in an amorphous or molecularly dispersing state. AGL-LS-PSG can obviously increase the drug dissolution rate compared to commercial guttate pills and raw drug. In vivo pharmacokinetic behavior of AGL-LS-PSG was investigated following a single oral administration to rats. The Cmax (0.37 ± 0.06 μg mL-1) and AUC0-2h (13.55 ± 2.67 μg h mL-1) of AGL-LS-PSG were evidently increased compared to commercial guttate pills (Cmax = 0.30 ± 0.21 μg mL-1, AUC0-2h = 9.88 ± 3.57 μg h mL-1). This study indicated great potential of liquisolid technology in effectively improving the dissolution and bioavailability of AGL.


Computational Modeling of Drug Dissolution in the Human Stomach.
A computational model of drug dissolution in the human stomach is developed to investigate the interaction between gastric flow and orally administrated drug in the form of a solid tablet. The stomach model is derived from the anatomical imaging data and the motion and dissolution of the drug in the stomach are modeled via fluid-structure interaction combined with mass transport simulations. The effects of gastric motility and the associated fluid dynamics on the dissolution characteristics are investigated. Two different pill densities are considered to study the effects of the gastric flow as well as the gravitational force on the motion of the pill. The average mass transfer coefficient and the spatial distributions of the dissolved drug concentration are analyzed in detail. The results show that the retropulsive jet and recirculating flow in the antrum generated by the antral contraction wave play an important role in the motion of the pill as well as the transport and mixing of the dissolved drug concentration. It is also found that the gastric flow can increase the dissolution mass flux, especially when there is substantial relative motion between the gastric flow and the pill.


Assessment of proliferation markers in metastatic melanoma in sentinel lymph nodes.
Some views on sentinel nodes for melanoma seem to cast doubt on the relevance of micrometastases in the sentinel nodes of patients with melanoma, suggesting that small metastases or isolated tumour cells can be ignored. Tumour dormancy has been proposed for their postulated lack of progression. The implication of the argument seems to be that minute metastases are inactive and therefore non-threatening, whereas larger ones are proliferative and therefore have aggressive potential. 54 sentinel lymph nodes were studied with histologically identified micrometastatic melanoma using the protocol accepted by the European Organisation for Research and Treatment of Cancer melanoma group. These were studied with respect to metastasis size and by use of immunohistochemical markers of proliferation (MIB-1) and dormancy (p16). The authors have demonstrated no correlation between the size of metastases and their proliferative activity. Very small metastases may not show proliferative activity, but this may be a reflection of the small number of assessable cells rather than a genuine reflection of the tumoural characteristics. Furthermore, the minute size of some of these metastases resulted in no residual tumour being present in adjacent sections. Where further sections did show more tumour, these small metastases were invariably p16 negative, suggesting dormancy was not the explanation for the lack of measurable proliferation. Occasionally, larger metastases, clearly not clinically insignificant, showed no proliferative activity presumably, considering their size, a transient phenomenon. These findings suggest that variable phases in proliferation occur in metastases, and no conclusion of clinical insignificance can be made on the basis of small size.


Bird terrestrial locomotion as revealed by 3D kinematics.
Most birds use at least two modes of locomotion: flying and walking (terrestrial locomotion). Whereas the wings and tail are used for flying, the legs are mainly used for walking. The role of other body segments remains, however, poorly understood. In this study, we examine the kinematics of the head, the trunk, and the legs during terrestrial locomotion in the quail (Coturnix coturnix). Despite the trunk representing about 70% of the total body mass, its function in locomotion has received little scientific interest to date. This prompted us to focus on its role in terrestrial locomotion. We used high-speed video fluoroscopic recordings of quails walking at voluntary speeds on a trackway. Dorso-ventral and lateral views of the motion of the skeletal elements were recorded successively and reconstructed in three dimensions using a novel method based on the temporal synchronisation of both views. An analysis of the trajectories of the body parts and their coordination showed that the trunk plays an important role during walking. Moreover, two sub-systems participate in the gait kinematics: (i) the integrated 3D motion of the trunk and thighs allows for the adjustment of the path of the centre of mass; (ii) the motion of distal limbs transforms the alternating forward motion of the feet into a continuous forward motion at the knee and thus assures propulsion. Finally, head bobbing appears qualitatively synchronised to the movements of the trunk. An important role for the thigh muscles in generating the 3D motion of the trunk is suggested by an analysis of the pelvic anatomy.


Integral dose conservation in radiotherapy.
Treatment planners frequently modify beam arrangements and use IMRT to improve target dose coverage while satisfying dose constraints on normal tissues. The authors herein analyze the limitations of these strategies and quantitatively assess the extent to which dose can be redistributed within the patient volume. Specifically, the authors hypothesize that (1) the normalized integral dose is constant across concentric shells of normal tissue surrounding the target (normalized to the average integral shell dose), (2) the normalized integral shell dose is constant across plans with different numbers and orientations of beams, and (3) the normalized integral shell dose is constant across plans when reducing the dose to a critical structure. Using the images of seven patients previously irradiated for cancer of brain or prostate cancer and one idealized scenario, competing three-dimensional conformal and IMRT plans were generated using different beam configurations. Within a given plan and for competing plans with a constant mean target dose, the normalized integral doses within concentric "shells" of surrounding normal tissue were quantitatively compared. Within each patient, the normalized integral dose to shells of normal tissue surrounding the target was relatively constant (1). Similarly, for each clinical scenario, the normalized integral dose for a given shell was also relatively constant regardless of the number and orientation of beams (2) or degree of sparing of a critical structure (3). 3D and IMRT planning tools can redistribute, rather than eliminate dose to the surrounding normal tissues (intuitively known by planners). More specifically, dose cannot be moved between shells surrounding the target but only within a shell. This implies that there are limitations in the extent to which a critical structure can be spared based on the location and geometry of the critical structure relative to the target.


Measurement of interaction force between nanoarrayed integrin alphavbeta3 and immobilized vitronectin on the cantilever tip.
Protein nanoarrays containing integrin alphavbeta3 or BSA were fabricated on ProLinker-coated Au surface by dip-pen nanolithography (DPN). An atomic force microscope (AFM) tip coated with ProLinker was modified by vitronectin. We measured the interaction force between nanoarrayed integrin alphavbeta3 or BSA and immobilized vitronectin on the cantilever tip by employing tethering-unbinding method. The unbinding force between integrin alphavbeta3 and vitronectin (1087+/-62 pN) was much higher than that of between BSA and vitronectin (643+/-74 pN). These results demonstrate that one can distinguish a specific protein interaction from non-specific interactions by means of force measurement on the molecular interactions between the nanoarrayed protein and its interacting protein on the AFM tip.


Defining structural requirements for neuropeptide Y receptors using truncated and conformationally restricted analogues.
To further elucidate the minimum bioactive conformation of neuropeptide Y (NPY), a series of truncated and conformationally constrained analogues has been prepared. The synthesis and purification of these peptides was achieved using routine laboratory strategies and techniques. Parent molecules consisted of the native NPY N-terminal 1-4 and C-terminal 25-36 segments, having the residue 5-24 core replaced by either a single flexible omega-aminoalkanoic acid, or a more rigid Pro-Gly or Pro-DAla sequence which was expected to constrain a putative turn, and allow the N- and C-termini to align. Cross-linking between residues 2 and 27 through lactamization using side-chain length and chirality suggested by computer simulations, resulted in cyclo-(2/27)-des-AA7-24[Glu2,Gly6,DDpr27]NPY that exhibited very high affinity (Ki = 0.3 versus 0.3 nM for NPY) for the Y2 receptor using SK-N-BE2 human neuroblastoma cells, yet very low affinity for the Y1 receptor using SK-N-MC human neuroblastoma cells (Ki = 130 versus 2.0 nM for NPY). The added constraint resulting from bridging in this analogue as well as in others suggested that the combination of the deletion of residues 5-24 and the introduction of an internal ring produced exclusive selectivity for the Y2 receptor with little or no loss of affinity. The tolerance of structural recognition was further demonstrated as a second ring was introduced which was expected to constrain the amphiphilic alpha-helix, resulting in the full Y2 agonist dicyclo (2/27,28/32)-des-AA7-24 [Glu2,32,DAla6,DDpr27,Lys28]NPY. Improvement of Y1 binding activity was achieved only by including more residues (des-AA10-17) in the central PP-fold region, while allowing limited flexibility of the termini. Although the length of the bridge seemed to have little effect on binding potency, changes in the location of and chirality at the bridgehead resulted in analogues with different binding affinities. Combination of optimum structural modifications resulted in cyclo-(7/21)-des-AA10-18[Cys7,21]NPY, an analogue shortened by 25% but retaining comparable binding properties to that of native NPY at Y1 and Y2 receptor types (Ki = 5.1 and 1.3 nM, respectively).


Experience of Simultaneous Bilateral Open Surgery and VATS for Pulmonary Metastasectomy.
Resection is the current treatment of choice for resectable bilateral pulmonary metastases. This study aimed to compare the differences in outcomes between simultaneous bilateral open and video-assisted thoracic surgery (VATS) for pulmonary metastasectomy. Forty-three patients underwent pulmonary metastasectomy through one-stage bilateral open thoracotomy (n = 16) and VATS (n = 27) between 2011 and 2020. Perioperative and oncological data were analyzed. The predominant primary tumor histology in both groups was colorectal cancer. The operative time, blood loss, and pain score on postoperative day 1 (POD1) were higher in the open group (p < 0.001, 0.009, and 0.03, respectively). No significant differences in pain score on POD2 and POD3, postoperative length of stay, or complications were found. Notably, numbers of the resected metastatic lung nodules were significantly greater in the open group (median number: 9.5 vs. 3, p < 0.001). Recurrence-free survival (RFS) and overall survival (OS) were comparable. The median RFS was 15 months (interquartile range [IQR], 6-22) in the open group and 18 months (IQR, 8-47) in the VATS group. The median OS was 28 months (IQR, 14-44) and 29 months (IQR, 15-54) in the open group and VATS group, respectively. One-stage bilateral pulmonary metastasectomy is safe and reduces medical expenditures in selected patients regardless of surgical approach. Although the open group harbored a greater number of metastatic foci, perioperative and oncological outcomes were similar to that of the VATS group.


The use of ozone in dentistry and maxillofacial surgery: a review.
Ozone has been successfully used in medicine because of its microbiologic properties for more than 100 years. Its bactericide, virucide, and fungicide effects are based on its strong oxidation effect with the formation of free radicals as well as its direct destruction of almost all microorganisms. In addition, ozone has a therapeutic effect that facilitates wound healing and improves the supply of blood. For medical purposes, ozone may be applied as a gas or dissolved in water. Despite the advantages that the therapeutic use of ozone offers, reservations remain in terms of its application in the oral and maxillofacial area. Particularly, the gaseous application of ozone is critically evaluated because of its possible side effects on the respiratory system. The objective of this article is to provide an overview of the current applications of ozone in dentistry and oral surgery. Research was based on peer-reviewed sources found through a Medline/PubMed search and other textbooks, reviews, and journals.


Fibrin hydrogels promote scar formation and prevent therapeutic angiogenesis in the heart.
Therapeutic angiogenesis is the delivery of factors to promote vascular growth and holds promise for the treatment of ischemic heart conditions. Recombinant protein delivery to the myocardium by factor-decorated fibrin matrices is an attractive approach, thanks to the ability to precisely control both dose and duration of the treatment, the use of a clinically approved material like fibrin, and the avoidance of genetic modification. Here, we investigated the feasibility of inducing therapeutic angiogenesis in the rat myocardium by a state-of-the-art fibrin-based delivery platform that we previously optimized. Engineered versions of murine vascular endothelial growth factor A (VEGF164 ) and platelet-derived growth factor BB (PDGF-BB) were fused with an octapeptide substrate of the transglutaminase coagulation factor fXIIIa (TG) to allow their covalent cross-linking into fibrin hydrogels and release by enzymatic cleavage. Hydrogels containing either 100 μg/mL TG-VEGF alone or in combination with 10 μg/mL TG-PDGF-BB or no factor were injected into rat myocardium. Surprisingly, vascular density was severely reduced in all conditions, both in and around the injection site, where large fibrotic scars were formed. Scar formation was not due to the presence of growth factors, adaptive immunity to human proteins, damage from injection, nor to mechanical trauma from the hydrogel stiffness or volume. Rather scar was induced directly by fibrin and persisted despite hydrogel degradation within 1 week. These results caution against the suitability of fibrin-based platforms for myocardial growth factor delivery, despite their efficacy in other tissues, like skeletal muscle. The underlying molecular mechanisms must be further investigated in order to identify rational targets to prevent this serious side effect.


HSP27 and 70 expression in thymic epithelial tumors and benign thymic alterations: diagnostic, prognostic and physiologic implications.
Thymic Epithelial Tumors (TETs), the most common tumors in the anterior mediastinum in adults, show a unique association with autoimmune Myasthenia Gravis (MG) and represent a multidisciplinary diagnostic and therapeutic challenge. Neither risk factors nor established biomarkers for TETs exist. Predictive and diagnostic markers are urgently needed. Heat shock proteins (HSPs) are upregulated in several malignancies promoting tumor cell survival and metastases. We performed immunohistochemical staining of HSP27 and 70 in patients with TETs (n = 101) and patients with benign thymic alterations (n = 24). Further, serum HSP27 and 70 concentrations were determined in patients with TETs (n = 46), patients with benign thymic alterations (n = 33) and volunteers (n = 49) by using ELISA. HSPs were differentially expressed in histologic types and pathological tumor stages of TETs. Weak HSP tumor expression correlated with worse freedom from recurrence. Serum HSP concentrations were elevated in TETs and MG, correlated with clinical tumor stage and histologic subtype and decreased significantly after complete tumor resection. To conclude, we found HSP expression in the vast majority of TETs, in physiologic thymus and staining intensities in patients with TETs have been associated with prognosis. However, although interesting and promising the role of HSPs in TETs as diagnostic and prognostic or even therapeutic markers need to be further evaluated.


[Impact of demographic changes on drug utilization related to diabetes in Aquitaine].
Diabetes is a chronic disease highly correlated to age. In 1998, the Sickness Find of the Aquitaine region has reimbursed 273 million French Francs for expenditures related to diabetes pharmaceuticals. The amount would increase to 300 million French Francs in 2005, a growth of nearly 10%, whereas the Aquitaine population would increase only 4%, from 2,909,000 in 1998 to 3,024,000 seven years later. The difference comes from population aging, as the calculations are undertaken "other things being equal": the insurance coverage rate, the disease prevalence rate, the consumption of pharmaceuticals per patient are supposed unchanged during the period.


Assessment of hemolysis related quantities in a microaxial blood pump by computational fluid dynamics.
A computational assessment or even quantification of shear induced hemolysis in the predesign phase of artificial organs (e.g., cardiac assist devices) would largely decrease efforts and costs of design and development. In this article, a general approach of hemolysis analysis by means of computational fluid dynamics (CFD) is discussed. A validated computational model of a microaxial blood pump is used for detailed analysis of shear stress distribution. Several methods are presented that allow for a qualitative assessment of shear stress distribution and related exposure times using a Lagrangian approach and mass distribution in combination with shear stress analysis. The results show that CFD offers a convenient tool for the general assessment of shear-induced hemolysis. The determination of critical regions and an estimation of the amount of blood subject to potential damage in relation to the total mass flow are shown to be feasible. However, awareness of limitations and potential flaws in CFD based hemolysis assessments is crucial.


Total Synthesis of (±)-Leonuketal.
Leonuketal is an 8,9-seco-labdane terpenoid with a unique tetracyclic structure, owing to a diversity-generating biosynthetic C-C bond cleavage event. The first total synthesis of leonuketal is reported, featuring a Ti(III)-mediated reductive cyclization of an epoxy nitrile ether, an unusual ring-opening alkyne formation as part of an auxiliary ring strategy, and the previously undescribed Au(I)-catalyzed cyclization of a β-keto(enol)lactone to assemble the core spiroketal motif.