The impact of Ki-67 in the context of multidisciplinary care in primary inflammatory breast cancer.
Background: Research on the prognostic or predictive value of Ki-67 among patients with inflammatory breast cancer (IBC) is limited. Methods: Using the comprehensive database of the Morgan Welch Inflammatory Breast Cancer Research Program at MD Anderson Cancer Center, we identified a cohort of breast cancer patients who were diagnosed with IBC between 1992 and 2012. Distributions of survival outcomes were estimated by the Kaplan-Meier method and compared by log-rank tests and Cox models. Results: Among a total of 257 patients with stage III IBC, the mean percentage of tumor cells that stained positive for Ki-67 was 48%, (range, 4% to 100%). Using a cutoff of 20% as being Ki-67 positive, this characteristic tended to be associated with worse overall survival (p=0.07) in the univariate analysis. After controlling for hormone receptor (HR) status, human epidermal growth factor receptor 2 (HER2) status and having received trimodality treatment, the association between Ki-67 status and overall survival remained marginally significant (p=0.07). The effects of trimodality treatment on overall survival were statistically significantly different between patients with Ki-67-positive tumors (hazard ratio=0.26, 95% confidence interval [CI]=0.15-0.44, p<0.01) and those with Ki-67-negative tumors (hazard ratio =2.04, 95% CI=0.45-9.29, p=0.36) after adjusting for other tumor characteristics (p=0.01). Conclusion: IBC patients with Ki-67-positive tumors tended to have worse overall survival, but were more likely to benefit from trimodality treatment, with better overall survival and distant metastasis-free survival. Patients with Ki-67-negative tumors had similar survival distributions, regardless of whether they received trimodality treatment.


Genome Analysis of Endobacterium cerealis, a Novel Genus and Species Isolated from Zea mays Roots in North Spain.
In the present work, we analyse the genomic and phenotypic characteristics of a strain named RZME27T isolated from roots of a Zea mays plant grown in Spain. The phylogenetic analyses of 16S rRNA gene and whole genome sequences showed that the strain RZME27T clustered with the type strains of Neorhizobium galegae and Pseudorhizobium pelagicum from the family Rhizobiaceae. This family encompasses several genera establishing symbiosis with legumes, but the genes involved in nodulation and nitrogen fixation are absent in its genome. Nevertheless, genes related to plant colonization, such as those involved in motility, chemotaxis, quorum sensing, exopolysaccharide biosynthesis and hydrolytic enzymes production were found. The comparative pangenomic analyses showed that 78 protein clusters present in the strain RZME27T were not found in the type strains of its closest relatives N. galegae and P. pelagicum. The calculated average nucleotide identity (ANI) values between the strain RZME27T and the type strains of N. galegae and P. pelagicum were 75.61% and 75.1%, respectively, similar or lower than those found for other genera from family Rhizobiaceae. Several phenotypic differences were also found, highlighting the absence of the fatty acid C19:0 cyclo ω8c and propionate assimilation. These results support the definition of a novel genus and species named Endobacterium cerealis gen. nov. sp. nov. whose type strain is RZME27T.


Glutathione depletion as a mechanism of 3,4-dideoxyglucosone-3-ene-induced cytotoxicity in human peritoneal mesothelial cells: role in biocompatibility of peritoneal dialysis fluids.
The potential detrimental effects of glucose degradation products (GDPs) contained in peritoneal dialysis fluids (PDFs) on peritoneal mesothelial cells (PMCs) may impair intraperitoneal homeostasis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). A recent study showed that 3,4-dideoxyglucosone-3-ene (3,4-DGE) was the most strongly cytotoxic among all identified GDPs in PDFs. The present study examined the effects of clinically relevant concentrations of 3,4-DGE on the proliferative capacity of PMCs and oxidative injury to them. The concentrations of eight GDPs in commercially available PDFs were determined by HPLC. The effect of cell growth media spiked with GDPs on the proliferation capacity of PMCs was evaluated. As a marker of the cellular redox status, total cellular glutathione (tGSH) was determined in PMCs incubated with GDPs. The reaction of 3,4-DGE with GSH under nonenzymatic conditions was analysed by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). The concentrations of 3,4-DGE in a heat-sterilized single-compartment standard-type PDF (S-PDF) and in a heat-sterilized dual-chamber-type PDF (N-PDF) were 16 microM and 1.7 microM, respectively. The most cytotoxic GDP was 3,4-DGE, and the concentration at which it causes 50% inhibition of cell growth was 35 microM. A significant decrease in the cellular tGSH levels was observed in the cells treated with 10 microM 3,4-DGE. 3,4-DGE disappeared on incubation with GSH under nonenzymatic conditions for 1 h, and the 3,4-DGE-GSH conjugate was confirmed by accurate mass measurement using LC-ESI-MS. These data demonstrated that the change in the cellular redox status by GSH depletion might be a contributory factor in 3,4-DGE-induced cytotoxicity. 3,4-DGE is a highly reactive GDP and is responsible for the depletion of the total intracellular glutathione. 3,4-DGE has an intense impact on PMC growth at concentrations found in standard PDFs. It is desired that the amount of 3,4-DGE in PDFs should be minimized.


[Dentofacial orthopedics and orthopedic surgery].
The authors describe five cases of surgical correction of dysmorphisms of the maxillaries requiring orthodontic treatment before surgery. Pre-operative orthodontic treatment of the adult has the advantage of enabling the arches to be aligned, facilitating the operation when the osteotomized fragments are positioned and resulting in immobilisation in a good position.


From the shopping basket to the landfill: Drivers of consumer food waste behaviour.
The EU, where nearly 57 million tonnes of food waste are generated annually, has set a target to halve this amount by 2030. However, the amount of food waste produced varies greatly between EU countries. While several EU countries are far from reaching this target, the Czech Republic already meets it. Despite this, little to no attention is paid to Czech consumers' food waste behaviour. This study responds to the unfulfilled need by drawing attention to food waste and its reduction, and possibly even serving as a model example for the EU target. We identify key factors influencing food waste by conducting a survey with 1,551 respondents on stated preferences. The results using the PLS-SEM approach show that the price of food does not have as great an impact on the level of food waste as its characteristics or planning, which is part of consumers' purchasing behaviour. Furthermore, consumers' attitudes and awareness of food waste reduce food losses. The causes of food waste remain decidedly similar before and during the pandemic COVID-19, except that people paid more attention to food attributes during the pandemic. Product attributes are an essential part of decision-making, especially for women and people with higher levels of education. We conclude that it is desirable to sufficiently educate and teach consumers to properly plan their consumption and better estimate the amount of food needed when shopping, which should be a conscious decision rather than an impulsive one.


How motifs condition critical thresholds for tipping cascades in complex networks: Linking micro- to macro-scales.
In this study, we investigate how specific micro-interaction structures (motifs) affect the occurrence of tipping cascades on networks of stylized tipping elements. We compare the properties of cascades in Erdős-Rényi networks and an exemplary moisture recycling network of the Amazon rainforest. Within these networks, decisive small-scale motifs are the feed forward loop, the secondary feed forward loop, the zero loop, and the neighboring loop. Of all motifs, the feed forward loop motif stands out in tipping cascades since it decreases the critical coupling strength necessary to initiate a cascade more than the other motifs. We find that for this motif, the reduction of critical coupling strength is 11% less than the critical coupling of a pair of tipping elements. For highly connected networks, our analysis reveals that coupled feed forward loops coincide with a strong 90% decrease in the critical coupling strength. For the highly clustered moisture recycling network in the Amazon, we observe regions of a very high motif occurrence for each of the four investigated motifs, suggesting that these regions are more vulnerable. The occurrence of motifs is found to be one order of magnitude higher than in a random Erdős-Rényi network. This emphasizes the importance of local interaction structures for the emergence of global cascades and the stability of the network as a whole.


Dentition status and treatment needs among children with impaired hearing attending a special school for the deaf and mute in Udaipur, India.
The present cross-sectional study was conducted to assess the prevalence of caries and treatment needs among 127 institutionalized subjects aged 5-22 years attending a special school for students with hearing impairment in Udaipur City, Rajasthan, India. The data were collected using the methods and standards recommended by the WHO for oral health surveys, 1997. Dentition status and treatment needs along with DMFT, DMFS, dmft, dmfs were recorded using a Type III examination procedure. ANOVA, chi-squared test and multiple regression analysis were conducted using the SPSS software package (version 11.0). The mean DMFT was 2.61. Of the 127 subjects, 111 (87.4 %) needed treatment. Filling of one tooth surface was necessary for 79.5% of the subjects. Pulp treatment was needed in less than 7%. There was a high prevalence (83.92%) of decayed teeth, whereas only 7.14% of subjects had filled teeth. Multiple regression analysis showed that DMFT had a close association with age. Linear regression analysis revealed that age explained a variance of 32% and 25.4% for DMFT and dmft respectively The findings of this study demonstrate that young people with impaired hearing in this region have a high prevalence of dental caries, poor oral hygiene, and extensive unmet needs for dental treatment. This highly alarming situation requires immediate attention.


Antibody-mediated immuno-regulation in chick embryos and baby chicks.
Two- and three-week old chicks that received at hatching serum from either unimmunized birds or from chickens immunized with bovine serum albumin responded with normal hemagglutinin titers to immunization with mouse erythrocytes (MRBC). Other chicks administered at hatching or as embryos with homologous serum high in anti-MRBC activity responded poorly to MRBC immunization. When donor serum samples collected on different days after immunization were tested, the immunosuppressive capacity was negligible the first two days, increased in potency thereafter to a maximum level by the end of the week. The increase with time in the inhibiting property of the donor serum paralleled the serum anti-MRBC hemagglutinin response profile. The immune capacity of the antibody-treated recipients was severely depressed for over two weeks. By the fourth week, however, the immune responsiveness to MRBC, as measured by serum hemagglutinin titers and production of antigen sensitive units, had recovered to near normal levels.


Facial Growth of Patients With Complete Unilateral Cleft Lip and Palate Treated With Alveolar Bone Grafting at 6 Years.
To investigate the effect that alveolar bone grafting (ABG) around 6 years of age has on facial growth by assessing craniofacial growth outcomes. Retrospective cohort study. North American cleft centers. A total of 33 children with complete unilateral cleft lip and palate who were consecutively treated with secondary ABG around 6 years of age were compared to 148 participants from 4 centers with late secondary ABG. Preorthodontic standardized lateral cephalometric radiographs were analyzed and traced according to the Americleft Study protocol. Sixteen angular and 2 proportional measurements were performed. The outcomes of all ABG were assessed using the Standardized Way to Assess Graft scale. Measurement means from the study center (SC) were compared to 4 North American centers using analysis of variance and Welch modified t tests, and P < .05 was considered statistically significant. For the SC, the mean age (SD) at the time of bone graft was 5.85 (0.71) years and the mean age at the time of the lateral cephalogram was 13.4 (1.8) years. The sagittal maxillary prominence of the SC was comparable to the 4 other centers. The mean SNA (78.1 [4.3]) for the SC was significantly higher compared to one center that used primary bone grafting ( P = .03). The soft tissue mean ANB (3.52 [4.09]) for the SC was significantly lower compared to 3 of the centers. Early secondary ABG around 6 years of age did not result in reduced midface projection as assessed by SNA and thus did not compromise anterior maxillary growth.


Development-Dependent Changes in the NR2 Subtype of the N-Methyl-D-Aspartate Receptor in the Suprachiasmatic Nucleus of the Rat.
The suprachiasmatic nucleus (SCN) is the main brain clock that regulates circadian rhythms in mammals. The SCN synchronizes to the LD cycle through the retinohypothalamic tract (RHT), which projects to ventral SCN neurons via glutamatergic synapses. Released glutamate activates N-methyl-D-aspartate (NMDA) receptors, which play a critical role in the activation of signaling cascades to enable phase shifts. Previous evidence indicates that presynaptic changes during postnatal development consist of an increase in RHT fibers impinging on SCN neurons between postnatal day (P) 1 to 4 and P15. The aim of this study was to evaluate postsynaptic developmental changes in the NR2 subunits that determine the pharmacological and biophysical properties of the neuronal NMDA receptors in the ventral SCN. To identify the expression of NR2 subtypes, we utilized RT-PCR, immunohistochemical fluorescence, and electrophysiological recordings of synaptic activity. We identified development-dependent changes in NR2A, C, and D subtypes in mRNA and protein expression, whereas NR2B protein was equally present at all analyzed postnatal ages. The NR2A antagonist PEAQX (100 nM) reduced the frequency of NMDA excitatory postsynaptic currents (EPSCs) at P8 significantly more than at P34, but the antagonists for NR2B (3 μM Ro 25-6981) and NR2C/D (150 nM PPDA) did not influence NMDA EPSCs differently at the 2 analyzed postnatal ages. Our results point to P8 as the earliest analyzed postnatal age that shows mRNA and protein expression similar to those found at the juvenile stage P34. Taken together, our findings indicate that postsynaptic development-dependent modifications in the NR2 subtypes of the NMDA receptor could be important for the synchronization of ventral SCN neurons to the LD cycle at adult stages.


A Bio-Inspired Methylation Approach to Salt-Concentrated Hydrogel Electrolytes for Long-Life Rechargeable Batteries.
Hydrogel electrolytes hold great promise in developing flexible and safe batteries, but the presence of free solvent water makes battery chemistries constrained by H2 evolution and electrode dissolution. Although maximizing salt concentration is recognized as an effective strategy to reduce water activity, the protic polymer matrices in classical hydrogels are occupied with hydrogen-bonding and barely involved in the salt dissolution, which sets limitations on realizing stable salt-concentrated environments before polymer-salt phase separation occurs. Inspired by the role of protein methylation in regulating intracellular phase separation, here we transform the "inert" protic polymer skeletons into aprotic ones through methylation modification to weaken the hydrogen-bonding, which releases free hydrogen bond acceptors as Lewis base sites to participate in cation solvation and thus assist salt dissolution. An unconventionally salt-concentrated hydrogel electrolyte reaching a salt fraction up to 44 mol % while retaining a high Na+ /H2 O molar ratio of 1.0 is achieved without phase separation. Almost all water molecules are confined in the solvation shell of Na+ with depressed activity and mobility, which addresses water-induced parasitic reactions that limit the practical rechargeability of aqueous sodium-ion batteries. The assembled Na3 V2 (PO4 )3 //NaTi2 (PO4 )3 cell maintains 82.8 % capacity after 580 cycles, which is the longest cycle life reported to date.


Monoclonal antibody directed to MHC class I antigen (Bra23/9): characterization and utilization for study of antigen expression in differentiation of U 937 cell line.
The monoclonal antibody Bra23/9 (IgG2a) elicited by a non-T, non-B ALL cell line (REH), reacted in microscopic immunofluorescence, enzyme-linked immunoassay (ELISA), complement-dependent cytotoxicity tests and immunocytofluorometric measurements with hemopoietic cell lines and peripheral blood lymphocytes, monocytes and granulocytes from healthy donors in a pattern characteristic for MHC class I antigens. Immunoprecipitation of lactoperoxidase radioiodinated cell surface proteins and surface sialoglycoproteins radiolabeled by sodium metaperiodate/tritiated sodium borohydride technique confirmed the structure gp44,p12 (consisting of a 44 kDa glycopeptide linked with a nonglycosylated 12 kDa peptide) typical for MHC class I antigen(s) as a structure recognized by the Bra23/9 monoclonal antibody. The increase of MHC class I antigen density (immunofluorescence intensity) induced by a phorbol ester (TPA) in monoblast U 937 lymphoma cell line was observed by immunocytofluorometry as a predominant tendency in several TPA-induction experiments, where a certain variability among individual experiments in TPA-induced MHC class I antigen alterations was observed.


Omega-3 fatty acids and endothelial function: A GRADE-assessed systematic review and meta-analysis.
N-3 polyunsaturated fatty acids (PUFAs) supplementation has been reported to have an impact on flow-mediated dilatation (FMD), a conventionally used clinical technique for estimating endothelial dysfunction. However, its proven effects on endothelial function are unclear. This systematic review and meta-analysis were conducted to evaluate the effects of n-3 PUFAs supplementation on FMD of the brachial artery. This study was performed following the PRISMA guidelines. To identify eligible RCTs, a systematic search was completed in PubMed/Medline, Scopus and Web of Science using relevant keywords. A fixed- or random-effects model was utilized to estimate the weighted mean difference (WMD) and 95% confidence interval (95% CI). Thirty-two studies (with 35 arms) were included in this meta-analysis, involving 2385 subjects with intervention duration ranging from 4 to 48 weeks. The pooled meta-analysis demonstrated a significant effect of omega-3 on FMD (WMD = 0.8%, 95% CI = 0.3-1.3, p = .001) and heterogeneity was significant (I2 = 82.5%, p < .001). We found that n-3 PUFA supplementation improves endothelial function as estimated by flow-mediated dilatation of the brachial artery.


Predictors and consequences of "Phubbing" among adolescents and youth in India: An impact evaluation study.
"Phubbing" phenomenon, in the frequent use of a smartphone, describes the habit of snubbing someone in favor of a mobile phone. Its predictors and consequences are few in developed countries, but the literature lacks information on its actual occurrence and impact on adolescents and youth in a developing country such as India. This impact evaluation study was carried out as part of the Phubbing Project of the University of Poland for 6 months (November 15, 2016-May 15, 2017) on a sample of 400 adolescents and youth selected randomly from the five colleges in the district of Muzaffarnagar of Uttar Pradesh state in India. Data were collected through the Internet using e-questionnaires sent to all students. The phubbing predictors' and consequences' scales available in literature were used and data were analyzed by a mixed method to get the study findings. The prevalence of phubbing was 49.3%. The most important predictors associated with phubbers were Internet addiction (p < 0.0001, Odds Ratio 2.26), smartphone addiction (OR 25.9), fear of missing out (OR 18.8), and the lack of self-control (p < 0.0001, OR = 0.73-1.72). Phubbing also had significant consequences on their social health, relationship health, and self-flourishing, and was significantly related to depression and distress. Logistic regression analysis showed significant impact of phubbing predictors on phubbing consequences in phubbers, especially in depressed and distress status. Adolescents and youth of India need special guidance from government adolescent clinics or colleges or even families to control this habit in order to promote better physical, mental, and social health.


Cannabinoid control of neuroinflammation related to multiple sclerosis.
The cannabis plant (Cannabis sativa) has been known by many names but the question remains 'Can we call it medicine?' There has been renewed interest in the value of cannabis for the control of neuroinflammatory conditions such as multiple sclerosis, where it has been shown to have some effect on spasticity and pain both experimentally and in clinical trials in humans. However, in addition to symptom control potential, the question remains whether cannabinoids can modify the neuroinflammatory element which drives relapsing neurological attacks and the accumulation of progressive disability. In experimental studies it has been recently shown that synthetic cannabinoids can affect the immune response both indirectly via CB1 receptor-mediated signalling nerve centres controlling the systemic release of immunosuppressive molecules and directly by CB2 receptor-mediated inhibition of lymphocyte and macrophage/microglial cell function. However, these immunosuppressive possibilities that would limit the frequency of relapsing attacks will probably not be realized clinically, following use of medical cannabis, due to dose constraints. However, cannabinoids may still affect the glial response within the damaged central nervous system, which facilitate the slow, neurodegenerative processes that account for progressive neurodegeneration, and therefore may have utility in addition to value of cannabis-related drugs for symptom control.


Microwave synthesis of zirconia nanoparticles.
Zirconia nanoparticles were prepared by microwave synthesis from zirconium acetate hydroxide. The samples were characterized by various techniques like X-ray diffraction (XRD), Scanning Electron microscopy (SEM), Transmission Electron microscopy (TEM), Raman Spectroscopy (RS). By XRD the average crystallite size is obtained around 10 nm and which is comparable to observation by SEM and TEM.


Competitive adsorption of copper(II), cadmium(II), lead(II) and zinc(II) onto basic oxygen furnace slag.
Polluted and contaminated water can often contain more than one heavy metal species. It is possible that the behavior of a particular metal species in a solution system will be affected by the presence of other metals. In this study, we have investigated the adsorption of Cd(II), Cu(II), Pb(II), and Zn(II) onto basic oxygen furnace slag (BOF slag) in single- and multi-element solution systems as a function of pH and concentration, in a background solution of 0.01M NaNO(3). In adsorption edge experiments, the pH was varied from 2.0 to 13.0 with total metal concentration 0.84mM in the single element system and 0.21mM each of Cd(II), Cu(II), Pb(II), and Zn(II) in the multi-element system. The value of pH(50) (the pH at which 50% adsorption occurs) was found to follow the sequence Zn>Cu>Pb>Cd in single-element systems, but Pb>Cu>Zn>Cd in the multi-element system. Adsorption isotherms at pH 6.0 in the multi-element systems showed that there is competition among various metals for adsorption sites on BOF slag. The adsorption and potentiometric titrations data for various slag-metal systems were modeled using an extended constant-capacitance surface complexation model that assumed an ion-exchange process below pH 6.5 and the formation of inner-sphere surface complexes at higher pH. Inner-sphere complexation was more dominant for the Cu(II), Pb(II) and Zn(II) systems.


Hepatitis B immune globulin as a prophylactic measure for spouses exposed to acute type B hepatitis.
Because the value of usual immune globulin preparations in preventing Type B hepatitis is doubtful, we carried out a double-blind comparison of a control human immune globulin preparation with one--identified as HBIG--that had a high concentration (442 mug per milliliter) of antibodies to surface components of hepatitis B virus. Effectiveness was tested in spouses of patients with acute Type B hepatitis. Within 150 days after injection, nine of 33 spouses in the control group had symptomatic Type B hepatitis, compared with one of 25 spouses receiving HBIG. One non-B case also occurred in the HBIG group. Five control globulin recipients had evidence of subclinical hepatitis B infection, compared with one HBIG recipient. Thus, HBIG appeared effective in suppressing not only disease, but also infection itself. Prophylactic value has been demonstrated in persons who should now be recognized as being at exceptionally high risk.


Associations between maternal eating behaviors and feeding practices in toddlerhood.
Few studies have examined the associations between parents' own eating behaviors and their feeding practices. We aimed to study the associations between maternal eating behaviors and feeding practices in toddlerhood. In this cross-sectional analysis, maternal eating behaviors and feeding practices were assessed at 2-year follow-up by using the Three-Factor Eating Questionnaire (TFEQ-R21) and the Comprehensive Feeding Practices Questionnaire (CFPQ), respectively, among mothers of 1322 children from the EDEN mother-child cohort. Depending on their distributions, scores from the two questionnaires were considered continuous or binary variables, according to the median. Linear or logistic regression models were used as appropriate to assess the associations between maternal eating behaviors, considered simultaneously in a combined model, and their feeding practices. Maternal cognitive restraint was positively associated with maternal restriction for health and restriction for weight. Maternal uncontrolled eating was positively associated with pressure to eat and use of food to regulate the child's emotions. Maternal uncontrolled eating was also negatively associated with restriction for weight, but only among boys. This study supports that mothers' own eating behaviors are associated with their feeding practices in toddlerhood. Further studies are needed to understand the role of parental feeding practices in the familial transmission of eating behavior.


Topical antimicrobial prophylaxis in minor wounds.
To evaluate the ability of a novel topical antimicrobial gel containing cetrimide, bacitracin, and polymyxin B sulfate to prevent infections of minor wounds. A clinical trial compared the test preparation with placebo and a povidone iodine antiseptic cream. Five primary schools in Sydney, Australia, participated in the study over a 6-week spring/summer school term. Children aged 5-12 years with parental consent were eligible for study participation. Accidental injuries occurring at school were treated in a standardized manner by nurses at each site. Wounds were evaluated by the medical practitioner after 3 days of topical treatment. The clinical outcome was classified as resolution or suspected infection. If a clinical infection was suspected, the injury was swabbed for microbiologic evaluation. Growth of a dominant microorganism was classified as a microbiologic infection. Of the 177 injuries treated, there were nine clinical infections. A comparison of these showed a significant difference among treatment groups (p < 0.05). This difference was associated with the test preparation and placebo; the test preparation reduced the incidence of clinical infection from 12.5% to 1.6% (p < 0.05; 95% CI, 0.011 to 0.207). A comparison of microbiologic infections showed no significant differences among treatment groups (p > 0.05). The novel gel preparation containing cetrimide, bacitracin, and polymyxin B sulfate showed therapeutic action and reduced the incidence of clinical infections in minor accidental wounds. It may be a suitable product for first aid prophylaxis.


Dose-response study of sajabalssuk ethanol extract from Artemisia princeps Pampanini on blood glucose in subjects with impaired fasting glucose or mild type 2 diabetes.
Previously we reported that an ethanol extract from Artemisia princeps Pampanini lowered blood glucose in db/db mice. Here we report a preliminary study in which the blood glucose-lowering effects of two different doses of sajabalssuk ethanol extract (SBE), containing eupatilin and jaseocidin, were examined in hyperglycemic subjects with fasting blood glucose (FBG) levels of 100-150 mg/dL. Subjects were randomized into four groups: negative control (2,000 mg of lactose /day), positive control (1,140 mg of pinitol/day), low-dose SBE (2,000 mg of SBE/day), and high-dose SBE (4,000 mg of SBE/day). After 8 weeks of supplementation, FBG and glycosylated hemoglobin levels were significantly lowered in low-and high-dose SBE groups compared to the baseline values; high-dose SBE also resulted in significantly lower plasma free fatty acid levels and systolic blood pressure. This study demonstrated that supplementation of 2 g or 4 g of SBE daily can significantly reduce blood glucose in hyperglycemic subjects, although high-dose SBE seemed to be more effective than low-dose SBE for lowering plasma free fatty acid level and systolic blood pressure.


CMA's proposal for a voluntary, universally available Health Benefits Program. A socio-economic report of the Bureau of Research and Planning, California Medical Association.
The May 4, 1970 issue of the American Medical News contains an article on a report released in April by the British Medical Association following a two-year study of the British National Health Service. Although the BMA study is oriented to the specific program as it has evolved in Great Britain since 1946, its main thrust is in the development of a system of voluntary health insurance which would provide for greater consumer choice, based upon nationally determined guidelines and regulations. BMA's recommendations would have the NHS utilize a combination of tax-supported and voluntary-supported mechanisms in providing medical services to various segments of the population, based upon categories of illness and income levels. Since the BMA proposal as reported in the AMA News parallels in some respects the one approved by the CMA House of Delegates and submitted to the AMA House of Delegates for its consideration, the reader will be interested in seeing the concept for a Voluntary Universally Available Health Benefits Program, independently developed by the California Medical Association. It is interesting to note that the CMA proposal attempts to avoid many of the problems with which the NHS has been identified, and at the same time would establish a single, coherent, integrated approach for development over the next decade, incorporating public programs into a unified system of medical care which utilizes the multiplicity of voluntary health insurance approaches and mechanisms.


[Specified pathogen-free poultry flocks: the current situation].
Before the implementation of strategies to establish specified pathogen-free commercial poultry flocks, the ultimate goals need to be identified: 1) consumer protection by minimizing the risk for zoonotic diseases and food-borne pathogens, and/or 2) animal health protection against primary and secondary pathogens. The success for the establishment of specific pathogen-free poultry flocks depends on the biological characteristics, the epidemiological distribution and the transmission route of each pathogen. For zoonotic pathogens such as Salmonella Typhimurium, Salmonella Enteritidis, Campylobacter jejuni or the high pathogenic avian influenza virus, eradication has to be ultimate goal. Despite tremendous control efforts in field, only partial control of these pathogens has been achieved so far. In the future it will be necessary to continue these eradication efforts by combining optimized hygiene programs at all production levels with intensive monitoring and immunoprophylaxis. For primary pathogens affecting the health condition of poultry without known zoonotic potential, such as Salmonella Gallinarum, avian Mycoplasma or leucosis virus, specified pathogen free flocks have been established on the parent and grandparent level. In order to achieve a status free of these pathogens, rigid hygiene control, especially on the hatchery level and monitoring programs combined with elimination of pathogen- and antibody-positive birds were implemented. Nevertheless, the economically most important diseases of modern poultry production are of multifactorial origin. Ubiquitous secondary pathogens in combination with insufficient management or immunosuppressive agents induce great economic losses for the poultry producers. These secondary pathogens can not be eliminated due to their ubiquitous distribution. In the future only a reduction of these factorial diseases will be possible combining hygiene management and optimization of poultry husbandry. For the establishment of specified pathogen free poultry flocks in the field, risk analysis is necessary and the structure of poultry production has to be considered before and eradication program can be carried out successfully.


Morphine diesters. I. Synthesis and action on guinea pig ileum.
3,6-Dipropanoylmorphine (DPM), 3,6-dibutanoylmorphine (DBM), and 3,6-dihexanoylmorphine (DHM) were prepared as prospective long-acting narcotic analgesics. The purity and structure of these compounds were authenticated by high pressure liquid chromatography and direct probe mass spectrometry. In aqueous solution the stability of the HCI salts of these compounds decreased with increasing alkyl chain length such that DHM underwent rapid hydrolysis to 6-monohexanoylmorphine (MHM). A comparison of DPM, DBM, and MHM with morphine (MO) and 3,6-diacetylmorphine (DAM, heroin) in the electrically stimulated guinea pig ileum myenteric plexus longitudinal muscle strip preparation (GUPIL) revealed similar potencies and efficacies for all compounds, but marked differences in the onset of drug action (MO greater than DAM greater than MHM greater than DPM greater than DBM, faster to slower). In a periodically washed GUPIL preparation DBM and MHM were five times longer acting than MO, DAM or DPM.


Google matrix, dynamical attractors, and Ulam networks.
We study the properties of the Google matrix generated by a coarse-grained Perron-Frobenius operator of the Chirikov typical map with dissipation. The finite-size matrix approximant of this operator is constructed by the Ulam method. This method applied to the simple dynamical model generates directed Ulam networks with approximate scale-free scaling and characteristics being in certain features similar to those of the world wide web with approximate scale-free degree distributions as well as two characteristics similar to the web: a power-law decay in PageRank that mirrors the decay of PageRank on the world wide web and a sensitivity to the value alpha in PageRank. The simple dynamical attractors play here the role of popular websites with a strong concentration of PageRank. A variation in the Google parameter alpha or other parameters of the dynamical map can drive the PageRank of the Google matrix to a delocalized phase with a strange attractor where the Google search becomes inefficient.


Flexible P-Doped Carbon Cloth: Vacuum-Sealed Preparation and Enhanced Na-Storage Properties as Binder-Free Anode for Sodium Ion Batteries.
In this work, a flexible and self-supporting P-doped carbon cloth (FPCC), which is composed of interwoven mesh of hollow microtubules with porous carbon walls, is prepared via a vacuum-sealed doping technology by employing the commercially available cotton cloth as sustainable and scalable raw material. When directly used as binder-free anode for sodium-ion batteries, the as-prepared FPCC delivers superior Na-storage properties in terms of specific capacity up to 242.4 mA h g-1, high initial Coulombic efficiency of ∼72%, excellent rate capabilities (e.g., 123.1 mA h g-1 at a high current of 1 A g-1), and long-term cycle life (e.g., ∼88% capacity retention after even 600 cycles). All these electrochemical data are better than the undoped carbon cloth control, demonstrating the significance of P-doping to enhance the Na-storage properties of cotton-derived carbon anode. Furthermore, the technologies of electrochemical impedance spectroscopy and galvanostatic intermittent titration technique are implemented to disclose the decrease of charge transfer resistance and improvement of Na-migration kinetics, respectively.


McCune-Albright syndrome progressing with severe fibrous dysplasia.
We present the case of an 11-year-old girl with McCune-Albright syndrome associated with severe fibrous dysplasia. In addition to bone lesions, she has apparent manifestations of precocious puberty. In examination, a mass at the mentum spreading to mandibular corpus bilaterally was seen. This mass has affected the mandibular teeth. It was nearly 20 x 20 x 15 cm in size and had local necrotic regions on it. The lower lip was expanded too much by the mass. Another mass filled the left maxillary sinus, expanding the left zygomatic region outwardly and closing the left nasal fossa completely. A rectangular skull shape was related to the involvement of cranial bones. After stainless steel, custom-made mandibular prosthesis was prepared, the patient underwent surgery. A partial mandibulectomy was performed, and resulting mandibular bone defect was reconstructed by steel prosthesis. Craniofacial involvement occurs in 100% of disseminated cases. In the dental literature, mandibular involvement was found in 20% of cases. However, in studied literature, we did not find a dramatic mandibular lesion as severe as that presented here.


Determination of As, Se, and Hg in fuel samples by in-chamber chemical vapor generation ICP OES using a Flow Blurring® multinebulizer.
In this work, a new and simple analytical methodology based on in-chamber chemical vapor generation has been developed for the spectrochemical analysis of commercial fuel samples. A multiple nebulizer with three nebulization units has been employed for this purpose: One unit was used for sample introduction, while the other two were used for the necessary reagent introduction. In this way, the aerosols were mixed inside the spray chamber. Through this method, analyte transport and, therefore, sensitivity are improved in inductively coupled plasma-optical emission spectrometry. The factors (i.e., variables), influencing chemical vapor generation, have been optimized using a multivariate approach. Under optimum chemical vapor generation conditions ([NaBH4] = 1.39%, [HCl] = 2.97 M, total liquid flow = 936 μL min-1), the proposed sample introduction system allowed the determination of arsenic, selenium, and mercury up to 5 μg g-1 with a limit of detection of 25, 140, and 13 μg kg-1, respectively. Analyzing spiked commercial fuel samples, recovery values obtained were between 96 and 113%, and expanded uncertainty values ranged from 4 to 16%. The most striking practical conclusion of this investigation is that no carbon deposit appears on the plasma torch after extended periods of working. Graphical abstract A new and simple analytical methodology based on in-chamber chemical vapor generation has been developed for the spectrochemical analysis of commercial fuel samples in ICP OES.


A Triboelectric-Based Artificial Basilar Membrane to Mimic Cochlear Tonotopy.
A triboelectric-based artificial basilar membrane (TEABM) can mimic cochlear tonotopy by triboelectrification between Kapton film and aluminum foil. The two films are stacked and clamped to form a beam structure. The TEABM tonotopy is tested using an animal model to verify the feasibility of a self-powered acoustic sensor for a prototype cochlear implant.


Ethnicity in Dutch health research: situating scientific practice.
A growing body of work is examining the role health research itself plays in the construction of 'ethnicity.' We discuss the results of our investigation as to how the political, social, and institutional dynamics of the context in which health research takes place affect the manner in which knowledge about ethnicity and health is produced. Qualitative content analysis of academic publications, interviews with biomedical and health researchers, and participant observation at various conferences and scientific events. We identified four aspects related to the context in which Dutch research takes place that we have found relevant to biomedical and health-research practices. Firstly, the 'diversity' and 'inclusion' policies of the major funding institution; secondly, the official Dutch national ethnic registration system; a third factor was the size of the Netherlands and the problem of small sample sizes; and lastly, the need for researchers to use meaningful ethnic categories when publishing in English-language journals. Our analysis facilitates the understanding of how specific ethnicities are constructed in this field and provides fruitful insight into the socio-scientific co-production of ethnicity, and specifically into the manner in which common-sense ethnic categories and hierarchies are granted scientific validity through academic publication and, are subsequently, used in clinical guidelines and policy.


Sex and relationships for HIV-positive women since HAART: a qualitative study.
There is little available on HIV-positive women's sexual relationships other than within-risk behavior paradigms. Increased life expectancy with the advent of highly active antiretroviral therapies (HAART) may increase the opportunity for women to develop sexual relationships. This study investigates sexual functioning in HIV-positive women and presents the analysis of interviews with 21 seropositive heterosexual women (age range, 22-54). Fourteen (67%) were black African, 6 (29%) white European, and 1 (5%) "other." Thirteen (62%) were currently or had been sexually active since becoming aware of their diagnosis. Dominant themes identified included: (1) difficulties with sexual functioning, in particular lowered libido and enjoyment and reduced intimacy; (2) barriers to forming new relationships: fears of HIV disclosure, fears of infecting partners; (3) coping strategies: included relationship avoidance and having casual partners to avoid disclosure; (4) safer sex: personal dislike of condoms, lack of control, lack of suitable alternatives. Women are experiencing a range of sexual and relationship difficulties that appear to be relatively unchanged despite the advent of HAART. Culturally appropriate, focused psychosexual and couples work should be more readily available for women living with HIV and their partners.


Phase II trial of veliparib and temozolomide in metastatic breast cancer patients with and without BRCA1/2 mutations.
We evaluated the efficacy and safety of poly-(adenosine diphosphate-ribose) polymerase (PARP) 1 and 2 inhibitor veliparib and temozolomide in metastatic breast cancer patients with and without germline BRCA1/2 mutations. In this single-arm phase II trial, patients with metastatic breast cancer received veliparib 30 to 40 mg twice daily on days 1 to 7 with concurrent temozolomide 150 mg/m2 on days 1 to 5 of a 28-day cycle. The primary cohort was unselected for BRCA mutation status, and an expansion cohort enrolled only BRCA1/2 carriers. The primary endpoint was objective response rate (ORR) in each cohort. Secondary endpoints included progression-free survival (PFS), clinical benefit rate (CBR), and evaluation of safety and tolerability. In the primary cohort of 41 unselected patients, which included 9 BRCA mutation carriers, the ORR was 10% and clinical benefit rate at 4 months (CBR) was 27%. In the expansion cohort of 21 BRCA1/2 carriers, the ORR was 14% and CBR was 43%. Among all 30 BRCA1/2 carriers, the ORR was 23% versus 0% among non-carriers. In the subset of BRCA1/2 carriers, the ORR was 32% among platinum-naïve patients versus 9% among platinum-exposed patients. The median PFS was 3.3 months among BRCA1/2 carriers compared to 1.8 months among non-carriers (HR: 0.48, p = 0.006). A longer median PFS of 6.2 months was observed among BRCA1/2 carriers who had no prior platinum therapy. The most common grade 3 and 4 toxicities were thrombocytopenia (32%) and neutropenia (21%) that generally improved with dose modifications. Veliparib and temozolomide demonstrated clinical activity in platinum-naïve BRCA-associated metastatic breast cancer with manageable toxicity at doses of veliparib well below the single-agent active dose. Although the study did not meet its primary endpoint in unselected nor BRCA-associated breast cancer, this regimen was further evaluated in the BROCADE 2 study. NCT01009788 (ClinicalTrials.gov), November 9, 2009.


[Gastrointestinal polyposis and hereditary large bowel cancer].
Hereditary large bowel cancer is roughly divided into the hereditary gastrointestinal polyposis (HGIP) that is including adenomatosis coli (AC), Peutz-Jeghers syndrome and juvenile polyposis, and non-polyposis familial large bowel cancer (NPF) which is including cancer family syndrome and its related conditions. In the HGIP, AC is most frequent and of highest risk of large bowel cancer, and epidemiological method of approach to patients has been well studied. NPF, however, has been insufficiently studied because of lacking of distinctive marker as seen in the polyposis in spite of that it may be actually present much more frequently than AC. In order to extract NPF from the general large bowel cancer group, the marker or criteria for it has been studied. The factors besides family history presently considered to be useful for detecting NPF are multiple cancers, proximal cancer, association of multiple adenoma and young (50 years or younger) onset of the disease.


Power and efficiency of the TDT and case-control design for association scans.
Sample size required for the TDT and the case-control designs was studied for marker-based genome-wide scans for disease association. The influence of various parameters on sample size required to attain a given level of power was analyzed in detail. Small genotypic relative risks, low levels of linkage disequilibrium, and departure from equal frequencies for the disease allele and associated marker allele, significantly and similarly increase sample size required by either the TDT or case-control design. Under the case-control paradigm, we show that the optimal strategy will often be to collect many more control individuals than disease cases with the optimal ratio depending on the relative cost of acquiring cases as compared to controls. For the TDT, the number of required simplex families is virtually equal to the number of cases required for similar power in case-control studies with an equal number of cases and controls. The case-control approach may therefore prove to be more economical and expeditious than the TDT design for diseases in which the cost and time required to collect simplex families is much greater than that needed to acquire isolated disease cases. Nevertheless, possible population stratification needs to be addressed when the case-control design is applied.


The large groove found in the gH/gL structure is an important functional domain for Epstein-Barr virus fusion.
Epstein-Barr virus (EBV) mediates viral entry into cells using four glycoproteins-gB, the gH/gL complex, and gp42-and fusion is cell type specific. gB and gH/gL are required for epithelial cell fusion; B cell fusion also requires gp42. To investigate functional domains within the gH/gL structure, we constructed site-directed EBV gH/gL mutants with alterations of residues located in a large groove that separates domain I (D-I) from domain II (D-II) within the gH/gL structure. We found that substitution of alanine for leucine 207 reduces both epithelial and B cell fusion and is accompanied by reduced gp42 binding. We also observed that substitution of alanine for arginine 152, histidine 154, or threonine 174 reduces fusion with epithelial cells but not with B cells. To test whether flexibility of the region between D-I and D-II of gH/gL could be important for membrane fusion activity and to allow potential interactions across the D-I/D-II groove, we mutated D-I amino acids V47, P48, and G49 to cysteine, allowing novel intersubunit disulfide bonds to form with the free C153 located in D-II. We found that the G49C mutant, predicted to bridge D-I and D-II with C153 of gH/gL, had normal B cell fusion activity but reduced epithelial cell fusion activity, which was partially restored by treatment with dithiothreitol. We conclude that structural rearrangements and/or interactions across the D-I/D-II groove of gH/gL are required for fusion with epithelial cells but not for fusion with B cells.


Hormonal regulation of appetite and food intake.
Several clinical disorders are strongly influenced by hormones involved in appetite and weight regulation. Obesity and eating disorders are of major importance, because they are associated with severe morbidity and considered to be among the greatest health problems in the Western world today. This review describes recent findings in hormonal regulation of food intake by substances acting both centrally, such as corticotropin-releasing factor, neuropeptide Y and leptin, and peripherally, such as cholecystokinin and somatostatin. Sex hormones and glucocorticoids play an important role in long-term regulation of metabolism. The role of these hormones in appetite and weight changes during life as well as during pregnancy and lactation is discussed. Furthermore, the development of obesity and eating disorders is influenced, in particular, by steroid hormones. Treatment with sex hormones, as in hormone replacement therapy, affects appetite and weight and may have beneficial effects in preventing android obesity. Currently, there is great effort in developing endogenous neurohumoral substances into effective drugs for the treatment of obesity and eating disorders. Leptin and neuropeptide Y analogues are of interest as potential antiobesity agents.


Spoilage bacteria in canned foods. II. Sulfide spoilage bacteria in canned mushrooms and a versatile medium for the enumeration of Clostridium nigrificans.
Clostridium nigrificans was found to be a spoilage organism of canned mushrooms in Taiwan. A modified beef extract tryptone iron medium, both in broth and agar form, was designed for the detection and recovery of the organisms. A procedure of simple plate counting method of C. nigrificans was established.


Assessment of the progression of cardiac allograft vasculopathy by dobutamine stress echocardiography.
After heart transplantation, accelerated coronary vasculopathy is a major factor that limits long-term survival and is usually detected by serial coronary angiography. The aim of this study was to determine whether dobutamine stress echocardiography could accurately identify the progression of cardiac allograft vasculopathy. Two sequential controls by dobutamine stress echocardiography were performed at an 18-month interval in 37 heart transplant recipients at the time of their routine coronary angiography. The first control (control 1) occurred 37+/-20 months after transplantation, and the second control (control 2) occurred after 56+/-21 months. Standard echocardiographic views were acquired at baseline and at incremental dobutamine infusion levels. Regional wall motion score was calculated in a 16-segment model, and each segment was graded from 1 (normal) to 4 (dyskinesia). Visual and quantitative coronary angiographic analysis were used to assess the severity of the coronary vasculopathy. The incidence of coronary vasculopathy increased from 46% (17/37 patients, four of whom had stenoses > 50%) at control 1 fo 70% (26/37 patients, six of whom had stenoses > 50%) at control 2. Progression of coronary vasculopathy was diagnosed by coronary angiography in 25 patients (new abnormalities in 19 and worsening of previous abnormalities in 6). Dobutamine stress echocardiography correctly identified the progression of vasculopathy in 21 of these 25 patients (84%) with new abnormalities in 17 and worsening in four. In the four remaining patients with evidence of progression of vasculopathy on coronary angiography, the result of dobutamine stress echocardiography was abnormal in three patients and normal in only one. Therefore dobutamine stress echocardiography results were abnormal in 12 patients at control 1 (sensitivity: 65%, specificity: 95%) and in 27 at control 2 (92% sensitivity, 73% specificity). Dobutamine stress echocardiography is a sensitive, noninvasive method to diagnose the progression of allograft vasculopathy, and a negative test result is a strong predictor of absence of allograft coronary vasculopathy. Therefore serial routine coronary angiography may be deferred when dobutamine stress echocardiography results are normal.


Exploring the binding mode of donepezil with calf thymus DNA using spectroscopic and molecular docking methods.
Donepezil (DNP) is one of approved drugs to treat Alzheimer's disease (AD). However, the potential effect of DNP on DNA is still unclear. Therefore, the interaction of DNP with calf thymus DNA (DNA) was studied in vitro using spectroscopic and molecular docking methods. Steady-state and transient fluorescence experiments showed that there was a clear binding interaction between DNP and DNA, resulting from DNP fluorescence being quenched using DNA. DNP and DNA have one binding site between them, and the binding constant (Kb ) was 0.78 × 104 L·mol-1 at 298 K. In this binding process, hydrophobic force was the main interaction force, because enthalpy change (ΔH) and entropy change (ΔS) of DNP-DNA were 67.92 kJ·mol-1 and 302.96 J·mol-1 ·K-1 , respectively. DNP bound to DNA in a groove-binding mode, which was verified using a competition displacement study and other typical spectroscopic methods. Fourier transform infrared (FTIR) spectrum results showed that DNP interacted with guanine (G) and cytosine (C) bases of DNA. The molecular docking results further supported the results of spectroscopic experiments, and suggested that both Pi-Sigma force and Pi-Alkyl force were the major hydrophobic force functioning between DNP and DNA.


Outcomes in surgical treatment of "idiopathic-like" scoliosis associated with syringomyelia.
Patients with "idiopathic-like" spinal deformities associated with syringomyelia were retrospectively reviewed. Ten patients had surgical stabilization of their curvatures with at least a 2-year follow-up, and an additional five patients were evaluated for deformity pattern with <2 years of follow-up. Paralytic curve patterns, scoliosis associated with spina bifida, congenital scoliosis, or other associated syndromes were discarded. All 10 patients with surgery who were followed for an average of 46 months lost 10 degrees correction above, through, or below the instrumented segments. A total of 50% lost correction through the instrumented segments. Anterior fusion stabilized the instrumented portion of the spine better than posterior instrumentation alone. Eighty percent of the 15 patients had thoracic kyphosis >40 degrees. Only one patient was lordoscoliotic. Syringomyelia deformities tend to be kyphoscoliotic in 80% of cases and behave more like paralytic curvatures postoperatively. MRI is recommended for apparent idiopathic scoliotic curvatures that are kyphoscoliotic and not lordoscoliotic.


A Case of Constrictive Pericarditis Associated with Melioidosis in an Immunocompetent Patient Treated by Pericardiectomy.
BACKGROUND Melioidosis is a rare tropical bacterial infection caused by the Gram-negative soil saprophyte, Burkholderia pseudomallei. Melioidosis can mimic a variety of diseases due to its varied presentation, and unless it is treated rapidly, it can be fatal. A rare case of melioidosis, with pericarditis and pericardial effusion, is described, which demonstrates the value of early diagnosis with echocardiography and pericardiocentesis. CASE REPORT A 38-year-old native (Iban) East Malaysian man presented with shortness of breath and tachycardia. Transthoracic echocardiography (TTE) showed cardiac tamponade. Urgent pericardiocentesis drained a large amount of purulent pericardial fluid that grew Burkholderia pseudomallei. Despite appropriate dose and duration of intravenous treatment with ceftazidime followed by meropenem, the patient developed recurrent pericardial effusion and right heart failure due to constrictive pericarditis. The diagnosis of constrictive pericarditis was confirmed by computed tomography (CT) and surgical exploration. Following pericardiectomy, his symptoms resolved, but patient follow-up was recommended for possible sequelae of constrictive pericarditis. CONCLUSIONS After the onset of melioidosis pericarditis, the authors recommend follow-up and surveillance for possible complication of constrictive pericarditis.


Interactive virtual endoscopy in coronary arteries based on multimodality fusion.
A novel approach for platform-independent virtual endoscopy in human coronary arteries is presented in this paper. It incorporates previously developed and validated methodology for multimodality fusion of two X-ray angiographic images with pullback data from intravascular ultrasound (IVUS). These modalities pose inherently different challenges than those present in many tomographic modalities that provide parallel slices. The fusion process results in a three- or four-dimensional (3-D/4-D) model of a coronary artery, specifically of its lumen/plaque and media/adventitia surfaces. The model is used for comprehensive quantitative hemodynamic, morphologic, and functional analyses. The resulting quantitative indexes are then used to supplement the model. Platform-independent visualization is achieved through the use of the ISO/IEC-standardized Virtual Reality Modeling Language (VRML). The visualization includes an endoscopic fly-through animation that enables the user to interactively select vessel location and fly-through speed, as well as to display image pixel data or quantification results in 3-D. The presented VRML virtual-endoscopy system is used in research studies of coronary atherosclerosis development, quantitative assessment of coronary morphology and function, and vascular interventions.


Highly enantioselective 1,3-dipolar cycloaddition of azomethine ylides catalyzed by copper(I)/TF-BiphamPhos complexes.
A new and highly efficient Cu(I)/TF-BiphamPhos catalytic system exhibited excellent reactivity, enantio-/diastereoselectivity, and structural scope in asymmetric 1,3-dipolar cycloaddition of azomethine ylides with 0.1-3 mol % of catalyst loading. The present methodology is the best result for asymmetric cycloaddition of azomethine ylides, especially derived from amino esters other than glycinate in terms of reactivity and enantioselectivity.


One wouldn't expect an expert bowler to hit only two pins: Hierarchical predictive processing of agent-caused events.
Evidence is accumulating that our brains process incoming information using top-down predictions. If lower level representations are correctly predicted by higher level representations, this enhances processing. However, if they are incorrectly predicted, additional processing is required at higher levels to "explain away" prediction errors. Here, we explored the potential nature of the models generating such predictions. More specifically, we investigated whether a predictive processing model with a hierarchical structure and causal relations between its levels is able to account for the processing of agent-caused events. In Experiment 1, participants watched animated movies of "experienced" and "novice" bowlers. The results are in line with the idea that prediction errors at a lower level of the hierarchy (i.e., the outcome of how many pins fell down) slow down reporting of information at a higher level (i.e., which agent was throwing the ball). Experiments 2 and 3 suggest that this effect is specific to situations in which the predictor is causally related to the outcome. Overall, the study supports the idea that a hierarchical predictive processing model can account for the processing of observed action outcomes and that the predictions involved are specific to cases where action outcomes can be predicted based on causal knowledge.


Impact of donor-recipient major ABO mismatch on allogeneic transplantation outcome according to stem cell source.
Major ABO incompatibility between donor and recipient is not considered a barrier to successful allogeneic hematopoietic stem cell transplantation (HSCT), even if it can be associated with several immunohematologic complications. Nevertheless, conflicting data still exist as to its influence on graft-versus-host disease (GVHD) incidence, relapse rate, and survival. To further investigate the relevance of ABO major mismatch on transplantation outcome, we retrospectively analyzed results from 414 patients with major or major/minor ABO-mismatched bone marrow (BM), peripheral blood (PB), and cord blood (CB) allogeneic HSCT. Transplantation outcome was assessed by comparison with results from a 395-patient ABO-compatible population with similar characteristics. Median time to red cell transfusion independence was significantly longer in ABO-incompatible BM recipients (median time, 63 days vs 41 days; P =.001), with faster disappearance of antidonor IgM hemagglutinins in unrelated recipients (median time, 36 days vs 44 days; P = .03) and in patients with grade > or =II acute GVHD (aGVHD) (median time, 35 days vs 59 days ; P = .001). In PB stem cell (PBSC) and CB transplantation, erythroid reconstitution was not significantly delayed, regardless of donor type or presence of aGVHD. A slight correlation between ABO incompatibility and GVHD incidence was found in PBSC recipients when considering grade > or =II aGVHD incidence (63% in ABO-matched HSCT vs 83% in ABO-mismatched HSCT; P = .055), but this was not confirmed in multivariate analysis. In patients with acute leukemia, multivariate analysis revealed an association between major ABO mismatch and decreased relapse rate with borderline statistical significance (hazard ratio, 0.65; P = .04). Major ABO incompatibility mainly, if not exclusively, affects red blood cell engraftment after BM transplantation. Somewhat surprisingly, the graft-versus-plasma cell effect seems to be confined to this stem cell source.


Sharing Reliable COVID-19 Information and Countering Misinformation: In-Depth Interviews With Information Advocates.
The rampant spread of misinformation about COVID-19 has been linked to a lower uptake of preventive behaviors such as vaccination. Some individuals, however, have been able to resist believing in COVID-19 misinformation. Further, some have acted as information advocates, spreading accurate information and combating misinformation about the pandemic. This work explores highly knowledgeable information advocates' perspectives, behaviors, and information-related practices. To identify participants for this study, we used outcomes of survey research of a national sample of 1498 adults to find individuals who scored a perfect or near-perfect score on COVID-19 knowledge questions and who also self-reported actively sharing or responding to news information within the past week. Among this subsample, we selected a diverse sample of 25 individuals to participate in a 1-time, phone-based, semistructured interview. Interviews were recorded and transcribed, and the team conducted an inductive thematic analysis. Participants reported trusting in science, data-driven sources, public health, medical experts, and organizations. They had mixed levels of trust in various social media sites to find reliable health information, noting distrust in particular sites such as Facebook (Meta Platforms) and more trust in specific accounts on Twitter (X Corp) and Reddit (Advance Publications). They reported relying on multiple sources of information to find facts instead of depending on their intuition and emotions to inform their perspectives about COVID-19. Participants determined the credibility of information by cross-referencing it, identifying information sources and their potential biases, clarifying information they were unclear about with health care providers, and using fact-checking sites to verify information. Most participants reported ignoring misinformation. Others, however, responded to misinformation by flagging, reporting, and responding to it on social media sites. Some described feeling more comfortable responding to misinformation in person than online. Participants' responses to misinformation posted on the internet depended on various factors, including their relationship to the individual posting the misinformation, their level of outrage in response to it, and how dangerous they perceived it could be if others acted on such information. This research illustrates how well-informed US adults assess the credibility of COVID-19 information, how they share it, and how they respond to misinformation. It illustrates web-based and offline information practices and describes how the role of interpersonal relationships contributes to their preferences for acting on such information. Implications of our findings could help inform future training in health information literacy, interpersonal information advocacy, and organizational information advocacy. It is critical to continue working to share reliable health information and debunk misinformation, particularly since this information informs health behaviors.


[The experience with the application of the selective electro-stimulation impacts in the children presenting with the disturbances of the locomotor function].
The objective of the present study was the improvement of the effectiveness of medical rehabilitation of the children presenting with the disturbances of the locomotor function using a «LymphaVision» apparatus for the selective electrical stimulation. The study included 42 patients with movement disorders divided into two groups depending on the method of non-drug therapy. The main group was comprised of the patients receiving the treatment by electrical stimulation with the use of the «LymphaVision» apparatus while the remaining patients made up the group of comparison (they were treated with by means of Vermel electrophoresis with the use of a 1% sodium bromide solution). The increase of the muscular strength evaluated based on the scoring system and the number of motor skills were used as the criteria of the effectiveness of the treatment. The applied Statistica for Windows package, version 6.0 («StatSoft», USA). Was employed for the statistical analysis of the data obtained. The significance and number of differences between two independent samples of the quantitative features were assessed using the Mann-Whitney U test. The Wilcoxon matched pairs test was used to compare the two matched groups. The children comprising the group treated by means of selective exposure to electrical stimulation with the use of the «LymphaVision» apparatus in the course of the rehabilitation process exhibited a significant increase in the strength of the muscles of the lower extremities and the trunk over the baseline values (p=0.003 and p=0.04 respectively) and acquired a significantly greater number of the new motor skills (p=0.02). The application of the proposed method is characterized by the highly pronounced clinical efficiency. This approach is pathogenetically well-substantiated for the treatment of the children presenting with the locomotor disorders developing as the consequences of perinatal lesions in the central nervous system and promotes the restoration of the capabilities of the child's body, such as normalization of the muscle tone, increase of the motor activity and muscle strength.


Ancient mtDNA diversity reveals specific population development of wild horses in Switzerland after the Last Glacial Maximum.
On large geographical scales, changes in animal population distribution and abundance are driven by environmental change due to climatic and anthropogenic processes. However, so far, little is known about population dynamics on a regional scale. We have investigated 92 archaeological horse remains from nine sites mainly adjacent to the Swiss Jura Mountains dating from c. 41,000-5,000 years BP. The time frame includes major environmental turning points such as the Last Glacial Maximum (LGM), followed by steppe vegetation, afforestation and initial re-opening of the landscape by human agricultural activities. To investigate matrilinear population dynamics, we assembled 240 base pairs of the mitochondrial d-loop. FST values indicate large genetic differentiation of the horse populations that were present during and directly after the LGM. After the retreat of the ice, a highly diverse population expanded as demonstrated by significantly negative results for Tajima's D, Fu's FS and mismatch analyses. At the same time, a different development took place in Asia where populations declined after the LGM. This first comprehensive investigation of wild horse remains on a regional scale reveals a discontinuous colonisation of succeeding populations, a pattern that diverges from the larger Eurasian trend.


Simvastatin Reduces Capsular Fibrosis around Silicone Implants.
Capsular fibrosis and contracture occurs in most breast reconstruction patients who undergo radiotherapy, and there is no definitive solution for its prevention. Simvastatin was effective at reducing fibrosis in various models. Peri-implant capsular formation is the result of tissue fibrosis development in irradiated breasts. The purpose of this study was to examine the effect of simvastatin on peri-implant fibrosis in rats. Eighteen male Sprague-Dawley rats were allocated to an experimental group (9 rats, 18 implants) or a control group (9 rats, 18 implants). Two hemispherical silicone implants, 10 mm in diameter, were inserted in subpanniculus pockets in each rat. The next day, 10-Gy of radiation from a clinical accelerator was targeted at the implants. Simvastatin (15 mg/kg/day) was administered by oral gavage in the experimental group, while animals in the control group received water. At 12 weeks post-implantation, peri-implant capsules were harvested and examined histologically and by real-time polymerase chain reaction. The average capsular thickness was 371.2 μm in the simvastatin group and 491.2 μm in the control group. The fibrosis ratio was significantly different, with 32.33% in the simvastatin group and 58.44% in the control group (P < 0.001). Connective tissue growth factor (CTGF) and transforming growth factor (TGF)-β1 gene expression decreased significantly in the simvastatin group compared to the control group (P < 0.001). This study shows that simvastatin reduces radiation-induced capsular fibrosis around silicone implants in rats. This finding offers an alternative therapeutic strategy for reducing capsular fibrosis and contracture after implant-based breast reconstruction.


[Orthodontic treatment of a crown-fused tooth after separated and partially extracted: a case report].
The fused tooth is a kind of teeth developmental malformation whose incidence is approximately 2.31%. Clinically, there are several treatments according to different situation, such as retaining by root canal therapy or extraction. In this paper, a crown-fused tooth was separated and partially extracted, then orthodontic treatment was implemented.


Tunneling resistance model for piezoresistive carbon nanotube polymer composites.
Carbon nanotube (CNT) polymer composites exhibit outstanding electrical conductivity that enables a myriad of sensing and actuation applications. Highly sensitive strain sensors can be realized through piezoresistivity in which a resistance change is induced by mechanical strains. Tunneling conduction between CNTs in close proximity is a major mechanism contributing to the overall piezoresistivity of the CNT network, and is sensitive to the separation distance, lattice registry and the orbital overlap of the interacting CNTs. In this paper, we propose a tunneling resistance model that relate these effects to the CNT chirality, geometry, and orientation. We construct the model based on the distance-dependent Landauer equation, and introduce two additional geometric variables, namely the lattice alignment angle and the axis alignment angle. The tunneling resistance model is incorporated into a CNT network representative volume element to determine the piezoresistivity of the CNT polymer composite. The model reproduces the periodic variation of tunneling resistance consistent with experimental observations and quantum simulations in the literature, and provides improved predictive accuracy of piezoresistivity in CNT polymer composites.


Occurrence of overweight and obesity among adult rural population in Eastern Poland. Relationship between obesity and selected socio-economic factors.
The objective of the study was evaluation of the prevalence of overweight, obesity and abdominal obesity among adult rural population in the Lublin Region, and the relationship between the occurrence of obesity, and selected socio-economic factors. The study covered a random sample of 2,260 rural inhabitants - 1,390 females and 870 males; mean age 51.6. Overweight and obesity was diagnosed in 60% of the total number of the population examined (63.1% of males and 58% of females). Overweight was more frequently observed in males, while obesity more often occurred in females. The number of people with overweight and obesity increased with age. No statistically significant relationship was noted between the occurrence of obesity and abdominal obesity, and the occupation performed, occupational activity and source of maintenance of the people examined. Obesity and abdominal obesity was more often observed in those who were married.


Human models of breast cancer.
Experimental systems using human mammary tissue, secretions and tumours may be based on in vitro culture or on growth of tissue or tumour fragments in the nude mouse. In the development of in vitro culture systems, a detailed characterization of the cultured cells within the framework of the epithelial cell lineages found in vivo is crucial. Monoclonal antibodies are useful tools for defining the profile of antigens expressed by the basal and luminal cells in the normal gland and in distinguishing subclasses between these two major groups. When these same reagents are used to characterize breast cancers, the majority are found to show the phenotype of luminal cells, with a small subset showing some evidence of basal markers. Luminal epithelial cells cultured from milk or reduction mammoplasty tissue have a short life span in vitro but can be immortalized using SV40TAg. Demonstrably malignant cells are difficult to culture from primary breast cancer, but ER+ and ER- cell lines showing the luminal phenotypes have been readily developed from metastases: some ER- breast cancer cell lines show a more undifferentiated phenotype, and these may have developed from tumours expressing basal markers. As with in vitro culture, it is difficult to obtain tumour growth in the nude mouse from primary breast cancer specimens, and established cell lines are also difficult to grow in this animal. We have focused our studies on cell lines with the luminal phenotype developed from milk. These non-tumorigenic cell lines differ from breast cancer cell lines (a) in being able to form organized three dimensional structures in the presence of an extracellular matrix and (b) in the correct glycosylation of the polymorphic epithelial mucin, which is expressed and aberrantly glycosylated in cancers. These cell lines are therefore being used to study the mechanisms underlying morphogenesis and the processing of PEM, and also as recipients for oncogenes and proto-oncogenes.


Preoperative sonographic features of follicular thyroid carcinoma predict biological behavior: A retrospective study.
Little is known regarding biological behavior of follicular thyroid carcinomas (FTCs) according to ultrasonography features. We investigated whether there was a difference in biological behavior between benign-looking FTCs (B-FTCs) and malignant-looking FTCs (M-FTCs).A total of 55 cases of FTC between January 2000 and December 2015 were included. B-FTCs were defined as showing none of the accepted ultrasonography criteria for malignancy, and M-FTCs were defined as showing at least one of the accepted ultrasonography criteria for malignancy. Clinicopathologic factors and sonographic features were compared between B-FTCs and M-FTCs. Based on the degree of invasiveness, FTCs were divided into minimally invasive FTCs (MI-FTCs) and widely invasive FTCs (WI-FTCs) on pathology. Sonographic features were compared between MI-FTCs and WI-FTCs.Compared with the patients with B-FTCs (31/55, 56.4%), the patients with M-FTCs showed a significantly higher prevalence of WI-FTCs, central lymph node metastases, lateral lymph node metastases as well as extrathyroidal extension (P < .001, P = .012, P = .031, and P = .032, respectively). M-FTCs with more than one malignancy features on ultrasonography showed a significantly higher prevalence of extrathyroidal extension than M-FTCs with only one ultrasonography malignancy feature (P = .022). Compared with MI-FTCs (41/55, 74.5%), an irregular shape, a spiculated/microlobulated boundary, no peripheral halo ring, hypoechogenicity and microcalcification were more frequent in WI-FTCs (P < .001, P = .003, P = .002, P = .015, and P = .016, respectively).Our results demonstrated that B-FTCs had better prognostic indicators than M-FTCs. Therefore, preoperative US features can serve as a useful tool for predicting biological behavior in FTC.


An elastase-specific inhibitor from human bronchial mucus. Isolation and characterization.
It was shown previously that human bronchial mucus contains an acid-stable proteinase inhibitor directed against trypsin and chymotrypsin, polymorphonuclear granulocyte elastase and cathepsin G. In addition to this well-characterized inhibitor, designated here as BSI-ATE (identical with the inhibitor HUSI-I from human seminal plasma or antileucoprotease), another acid-stable inhibitor BSI-E is present in the mucus which exerts inhibitory activity towards porcine pancreatic and human granulocytic elastase, but not against trypsin, chymotrypsin, or granulocytic cathepsin G. This elastase-specific inhibitor was isolated by affinity chromatography. Its molecular mass and its amino acid composition are very similar to those of BSI-TE. An immunological cross-reactivity between both inhibitor species was not observed. In the mucus of patients suffering from obstructive airway disease the elastase-specific inhibitor is not present in the free form but can be liberated by acidification.


Novel Phenylene Lipids That Are Positive Allosteric Modulators of Glycine Receptors and Inhibitors of Glycine Transporter 2.
Chronic pain is a complex condition that remains resistant to current therapeutics. We previously synthesized a series of N-acyl amino acids (NAAAs) that inhibit the glycine transporter, GlyT2, some of which are also positive allosteric modulators of glycine receptors (GlyRs). In this study, we have synthesized a library of NAAAs that contain a phenylene ring within the acyl tail with the objective of improving efficacy at both GlyT2 and GlyRs and also identifying compounds that are efficacious as dual-acting modulators to enhance glycine neurotransmission. The most efficacious positive allosteric modulator of GlyRs was 2-[8-(2-octylphenyl)octanoylamino]acetic acid (8-8 OPGly) which potentiates the EC5 for glycine activation of GlyRα1 by 1500% with an EC50 of 664 nM. Phenylene-containing NAAAs with a lysine headgroup were the most potent inhibitors of GlyT2 with (2S)-6-amino-2-[8-(3-octylphenyl)octanoylamino]hexanoic acid (8-8 MPLys) inhibiting GlyT2 with an IC50 of 32 nM. The optimal modulator across both proteins was (2S)-6-amino-2-[8-(2-octylphenyl)octanoylamino]hexanoic acid (8-8 OPLys), which inhibits GlyT2 with an IC50 of 192 nM and potentiates GlyRs by up to 335% at 1 μM. When tested in a dual GlyT2/GlyRα1 expression system, 8-8 OPLys caused the greatest reductions in the EC50 for glycine. This suggests that the synergistic effects of a dual-acting modulator cause greater enhancements in glycinergic activity compared to single-target modulators and may provide an alternate approach to the development of new non-opioid analgesics for the treatment of chronic pain.


Mild Method for 2-Naphthylmethyl Ether Protecting Group Removal Using a Combination of 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and β-Pinene.
The use of a combination of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and β-pinene permits the removal of 2-naphthylmethyl (Nap) ether protecting groups on highly sensitive substrates. The reaction tolerates both acid and base sensitive protecting groups, and products are afforded in 68-96% yield. The utility of the method is demonstrated by the removal of the Nap protecting groups on highly sensitive 2,6-dideoxy-sugar disaccharides.


[Occurrence of sexual abuse among students in Trondheim].
Few studies of the prevalence and incidence of sexual abuse have been conducted in the Nordic countries. The aim of the present study was to estimate the prevalence of accounts of sexual abuse and to calculate the incidence of rape and attempted rape among students. A questionnaire was handed out to a random sample of 1,322 students in Trondheim. The response rate was 77%. Among the 510 women, a total of 99 (19%) had experienced some kind of sexual abuse before 18 years of age. 23 (5%) had experienced at least one episode of very severe sexual abuse (attempted or completed coitus). The equivalent numbers among the 486 males were 17 (4%) and 3 (1%). Based on information on reported events during the year prior to the study, the yearly incidence of rape/attempted rape among women was 12 per 1,000. Only attempted rape was reported in the same time interval among men, giving a yearly incidence of two per 1,000. Applied to the total population of students in Trondheim, 87 female and 16 male students are exposed to rape/attempted rape every year.


Overcoming hopelessness and social isolation: the ENGAGE model for working with neglecting families toward permanence.
The Adoption and Safe Families Act of 1997 (ASFA) mandates policies designed to increase the frequency and speed with which permanency is achieved for children in the child welfare system. ASFA's focus is on child safety, permanency, and well-being. The expectation that parents correct neglectful conditions within specified time frames places an increased ethical responsibility on child welfare staff. Carrying out this responsibility requires vigorous and innovative approaches to engaging and working with neglectful families. Drawing on a well-established conceptual framework for understanding the determinants of effective parenting, the authors derive the ENGAGE (Engagement, Needs assessment, Goal setting, Assessment of progress, Goal achievement, Ending work) model for achieving permanency within the policy structure. The model incorporates creative client engagement, assessment of family needs, mutual goal setting, the goal achievement process, termination, and aftercare.


[The subacromial impingement syndrome].
The subacromial impingement syndrome describes the pathological contact between the rotatory cuff and the acromion. It is only a symptom and not a generic term for the different pathological diseases of the subacromial region. It is the diagnostical aim to verify the pathogenesis of the impingement syndromes and it is essential to differentiate structural versus functional causes. The diagnosis "impingement syndrome" should not have an acromioplastic procedure as general consequence. Because the expression "impingement syndrome" does not show causal approach it should no longer be used as a diagnosis. The term subacromial syndrome, in conjunction with the underlying pathological cause, acquires more therapeutic and prognostic clarity.


Evidence-based nursing practice, Part 2: Building skills through research roundtables.
Numerous articles describe barriers to nurses conducting research and achieving evidence-based practice as well as strategies for overcoming barriers. The Research Roundtable format is one such strategy. It is an interactive means for providing novice nurse researchers and nursing students with the skill sets required to drive application of existing evidence to nursing practice and conduct outcome studies to derive new evidence. The authors discuss their Research Roundtable series that addressed a number of barriers to research, research utilization, and evidence-based practice and how the series increased nurses knowledge and skills, demystified the research process, provided role models, demonstrated managerial and collegial support, and provided library, fiscal, and other resource support to complete staff projects. The details of the Research Roundtable series will guide others in replicating the process in their own organizations and academic communities.


A Protocol to Characterize the Morphological Changes of Clostridium difficile in Response to Antibiotic Treatment.
Assessment of antibiotic action with new drug development directed towards anaerobic bacteria is difficult and technically demanding. To gain insight into possible MOA, morphologic changes associated with antibiotic exposure can be visualized using scanning electron microscopy (SEM). Integrating SEM imaging with traditional kill curves may improve our insight into drug action and advance the drug development process. To test this premise, kill curves and SEM studies were conducted using drugs with known but different MOA (vancomycin and metronidazole). C. difficile cells (R20291) were grown with or without the presence of antibiotic for up to 48 h. Throughout the 48 h interval, cells were collected at multiple time points to determine antibiotic efficacy and for imaging on the SEM. Consistent with previous reports, vancomycin and metronidazole had significant bactericidal activity following 24 h of treatment as measured by colony-forming unit (CFU) counting. Using SEM imaging we determined that metronidazole had significant effects on cell length (> 50% reduction in cell length for each antibiotic; P< 0.05) compared to controls and vancomycin. While the phenotypic response to drug treatment has not been documented previously in this manner, they are consistent with the drug's MOA demonstrating the versatility and reliability of the imaging and measurements and the application of this technique for other experimental compounds.


[The heart and underwater diving].
Cardiovascular examination of a certain number of candidates for underwater diving raises justifiable questions of aptitude. An indicative list of contraindications has been proposed by the French Federation of Underwater Studies and Sports but a physiopathological basis gives a better understanding of what is involved. During diving, the haemodynamic changes due not only to the exercise but also to cold immersion, hyperoxaemia and decompression impose the absence of any symptomatic cardiac disease. Moreover, the vasoconstriction caused by the cold and hyperoxaemia should incite great caution in both coronary and hypertensive patients. The contraindication related to betablocker therapy is controversial and the debate has not been settled in France. The danger of drowning makes underwater diving hazardous in all pathologies carrying a risk of syncope. Pacemaker patients should be carefully assessed and the depth of diving limited. Finally, the presence of right-to-left intracardiac shunts increases the risk of complications during decompressionand contraindicates underwater diving. Patent foramen ovale is a special case but no special investigation is required for its detection. The cardiologist examining candidates for underwater diving should take all these factors into consideration because, although underwater diving is a sport associated with an increased risk, each year there are more and more people, with differing degrees of aptitude, who wish to practice it.


Creatine biosynthesis during embryonic development. False feedback suppression of liver amidinotransferase by N-acetimidoylsarcosine and 1-carboxymethyl-2-iminoimidazolidine (cyclocreatine).
The level of arginine:glycine amidinotransferase in liver of the developing chick embryo is partially suppressed following injection of arginine into the yolk, and the level can be completely suppressed following injection of guanidinoacetate or creatine (Walker, J.B. (1963), Proc. Soc. Exp. Biol. Med. 112, 245; Walker, J.B., and Wang, S.-H. (1964), Biochim, Biophys. Acta 81, 435). In this investigation structural requirements for the physiological suppressor were examined by testing certain analogues of creatine and its biosynthetic precursors for their ability to suppress liver amidinotransferase levels in developing chick embryos and growing chicks. The creatine analogues, N-acetimidoylsarcosine and 1-carboxymethyl-2-iminoimidazolidine (cyclocreatine), were found to suppress liver amidinotransferase levels of both developing embryos and growing chicks. Compounds ineffective as suppressors included: the arginine analogue, N5-acetimidoylornithine; the guanidinoacetate analogue, N-acetimidoylglycine; and the creatine analogue, 1-carboxymethyl-2-iminohexahydropyrimidine. Our findings suggest that (i) arginine and guanidinoacetate must be converted to creatine before serving as a suppressor, and (ii) creatine, not phosphocreatine, is most closely related to the physiological suppressor of amidinotransferase.


Effect of genomic variation in the challenge virus on the neutralization titres of recipients of inactivated JE vaccines--report of a collaborative study on PRNT50 assays for Japanese encephalitis virus (JE) antibodies.
Japanese encephalitis (JE) viruses are grouped into four genotypes. Although currently available vaccines are derived only from viruses in genotype III, vaccines are known to protect against naturally occurring strains. Studies were undertaken to assess the suitability of a freeze-dried pool of human anti-JE plasma, collected from recipients of Biken (Nakayama-NIH) killed vaccine, to serve as an International Standard for antibodies to JE virus. Five participants in five countries submitted data from 11 assays on the candidate International Standard and seven coded samples including sera from recipients of vaccines containing a range of virus strains. The results of the study indicated that the 50% plaque reduction neutralization test (PRNT(50)titres) obtained for serum from recipients of killed vaccines, including the candidate standard, vary depending on the virus strain used in the neutralization tests, namely higher PRNT(50)titres were obtained when the challenge virus was homologous to the vaccine strain compared to use of a heterologous virus. Potencies expressed relative to the candidate standard are therefore affected by the strain of virus used in assays and the use of a standard would therefore not facilitate direct comparison of data from laboratories that have used different challenge strains.


Metastasis prognostic factors and cancer stem cell-related transcription factors associated with metastasis induction in canine metastatic mammary gland tumors.
Canine mammary gland tumor (MGT) is the most common cancer in aged female dogs. Although it's important to identify reliable metastasis or prognostic factors by evaluating related to cell division, adhesion, and cancer stem cell-related transcription factor (TF) in metastasis-induced canine MGT, but there are limited studies. We aimed to identify metastasis prognostic factors and cancer stem cell-TFs in canine MGTs. Age-matched female dogs diagnosed with MGT only were classified into metastatic and non-metastatic groups by histopathological staining of MGT tissues. The mRNA levels of cancer prognostic metastasis molecular factors (E-cadherin, ICAM-1, PRR14, VEGF, HPRT1, RPL4 and hnRNP H) and cancer stem cell-related TFs (Oct4, Sox2, and Nanog) were compared between metastatic and non-metastatic canine MGT tissues using qRT-PCR analysis. The mRNA levels of ICAM-1, PRR14, VEGF, hnRNP H, Oct4, Sox2, and Nanog in metastatic MGT group were significantly higher than those in non-metastatic MGT group. However, mRNA level of RPL4 was significantly lower in metastatic MGT group. Loss of E-cadherin and HPRT1 was observed in the metastatic MGT group but it was not significant. Consistent expression patterns of all metastasis-related factors showing elevation in ICAM-1, PRR14, VEGF, hnRNP H, Oct4, Sox2, and Nanog, but decreases in RPL4 levels occurred in canine MGT tissues, which was associated with metastasis. Thus, these cancer prognostic metastasis factors and TFs of cancer stem cells, except for E-cadherin and HPRT1, can be used as reliable metastasis factors for canine MGT and therapeutic strategy.


Batch and continuous studies on the removal of heavy metals from aqueous solution using biosynthesised melanin-coated PVDF membranes.
Heavy metals like mercury, chromium, lead and copper present in groundwater at lower concentrations cause severe health issues and can even be fatal when consumed. The biopigment/biopolymer melanin can be reaped from different sources like bacterium, fungus, and human hair. It has excellent heavy metal ion scavenging property and can be exploited for non-biological applications, substantially including water purification. In this work, melanin nanoparticles were derived from the marine bacterium Pseudomonas stutzeri and were coated onto hydrophobic polyvinylidene fluoride (PVDF) membrane as a support, for batch and continuous removal of heavy metal studies. Batch studies on the effect of pH, temperature and adsorbate dose and continuous adsorption studies on the effect of flow rate, adsorbate and adsorbent mass loadings were carried out by using biosynthesised melanin-coated PVDF membranes for the removal of Hg(II), Cr(VI), Pb(II) and Cu(II). Scanning electron microscope (SEM) images revealed the surface morphology, Fourier-transform infrared spectroscopy (FTIR) and energy-dispersive X-ray spectroscopy (EDS) deciphered the chemical characteristics of melanin-coated PVDF membranes before and after adsorption. Contact angle measurement confirmed the improvement in hydrophilicity of PVDF membrane upon coating with melanin. The maximum removal percentages of heavy metals achieved by melanin-coated PVDF membranes under batch mode operation were 87.6%, 88.45%, 91.8% and 95.8% for mercury, chromium, lead and copper, respectively optimised at 318 K and pH of 3 for chromium and 5 for other metals. However, the continuous mode of operation with a flow rate of 0.5 mL/min having 1 mg/L of heavy metal solution concentration exposed to 50 mg of melanin loading with a working volume of 200 mL showed better removal efficiencies compared with batch mode. The dynamic studies using Thomas and Yoon-Nelson models described the transient stage of the breakthrough curve and the model constants were calculated for column design and scale-up.


[Restriction fragment length polymorphism analysis of ventricular myosin light chain 1 gene in families with congenital heart disease].
Genomic DNAs isolated from 9 families and 13 unrelated individual patients with 4 different types of congenital heart disease were examined by Southern blot analysis using a cDNA probe which codes for the full length human ventricular myosin light chain 1. Restriction fragment length polymorphisms were detected in two families and were not associated with any type of congenital heart disease.


Follicles in gut-associated lymphoid tissues create preferential survival niches for follicular Th cells escaping Thy-1-specific depletion in mice.
Although a substantial number of T cells may escape depletion following in vivo mAb treatment in patients undergoing immunosuppression, their specific tissue location and phenotypic characteristics in different peripheral lymphoid tissues have not been analyzed in detail. Here we investigated the survival of CD4(+) T cells immediately following anti-Thy-1 mAb treatment in mice. We found a preferential survival of CD4(+) T cells expressing Thy-1 antigen in the Peyer's patches (PP) and also in mesenteric lymph nodes (MLN), where the relative majority of the surviving CD4(+) T cells displayed CD44(high)/CD62L(-) phenotype corresponding to effector memory T-cell features. These CD4(+) T cells also expressed CXCR5 and PD-1 (programmed cell death-1) markers characteristic for follicular Th cells (TFH). We also demonstrate that the immediate survival of these cells does not involve proliferation and is independent of IL-7. Induction of germinal center formation in spleen enhanced while the dissolution of follicular architecture by lymphotoxin-β receptor antagonist treatment slightly reduced TFH survival. Our results thus raise the possibility that the follicles within PP and MLN may create natural support niches for the preferential survival of TFH cells of the memory phenotype, thus allowing their escape during T-cell depletion.