Degradation of 5-Dialkylamino-Substituted Chlorsulfuron Derivatives in Alkaline Soil.
Sulfonylurea herbicides are widely used as acetolactate synthase (ALS) inhibitors due to their super-efficient activity. However, some sulfonylurea herbicides show toxicity under crop rotation due to their long degradation time, for example, chlorsulfuron. Our research goal is to obtain chlorsulfuron-derived herbicides with controllable degradation time, good crop safety and high herbicidal activities. Based on our previously reported results in acidic soil, we studied the degradation behaviors of 5-dialkylamino-substituted chlorsulfuron derivatives (NL101-NL108) in alkaline soil (pH 8.39). The experimental data indicate that addition of the 5-dialkylamino groups on the benzene ring of chlorsulfuron greatly accelerated degradation in alkaline soil. These chlorsulfuron derivatives degrade 10.8 to 51.8 times faster than chlorsulfuron and exhibit excellent crop safety on wheat and corn (through pre-emergence treatment). With a comprehensive consideration of structures, bioassay activities, soil degradation and crop safety, it could be concluded that 5-dialkylamino-substituted chlorsulfuron derivatives are potential green sulfonylurea herbicides for pre-emergence treatment on both wheat and corn. The study also provides valuable information for the discovery of new sulfonylurea herbicides for crop rotation.


Changes in the Levels of Calmodulin and of a Calmodulin Inhibitor in the Early Phases of Radish (Raphanus sativus L.) Seed Germination: Effects of Aba and Fusicoccin.
An inhibitor of Ca(2+)-calmodulin (Cam)-dependent brain phosphodiesterase was present in the soluble fraction of embryo axes from ungerminated radish (Raphanus sativus L.) seeds. This inhibitor is a Ca(2+)-dependent, Cam-binding protein; in fact: (a) its effect was strongly reduced by treatment with proteases; (b) the inhibition was counteracted by Cam but not by Ca(2+); (c) on gel filtration in the presence of Ca(2+), Cam co-chromatographed with the inhibitor. The inhibitor is heat stable and positively charged at pH 7.5. During early phases of germination, the fresh weight and the levels of DNA and RNA of embryo axes increased, the level of the inhibitor decreased, and the level of Cam increased. Abscisic acid (ABA) inhibited germination, the decrease of inhibitor, and the increase of Cam. Fusicoccin (FC) stimulated the increase in fresh weight but not the increase in the RNA and DNA levels; in this condition, the inhibitor level decreased and the increase in Cam level was higher than in the control. In the presence of both ABA and FC, there was an increase in fresh weight not accompanied by an increase in DNA and RNA levels; Cam increased and, on a fresh weight basis, reached the value of the control. These results indicate that the Ca(2+)-Cam system was activated in early germination of radish seeds by an increase in Cam and a decrease in the inhibitor levels, that FC, probably through the activation of membrane functions, increased Cam level, and that the ABA inhibition on germination was not mediated by the Ca(2+)-Cam system.


Unitary distance of actin-myosin sliding studied using an in vitro force-movement assay system combined with ATP iontophoresis.
To obtain information about the mechanism of ATP-dependent actin-myosin sliding responsible for muscle contraction, we studied the "unitary" distance of sliding between a myosin-coated glass microneedle and actin filament arrays (actin cables) in a giant algal cell induced by iontophoretic application of ATP, attention being focused on the minimum distance of ATP-induced sliding when the amount of applied ATP was gradually decreased in the presence of hexokinase and D-glucose. The number of myosin heads interacting with actin cables was reduced to less than 100, as judged from the maximal force Po (approximately 100 pN) generated by myosin heads on the needle in the presence of 2 mM ATP. When the amount of iontophoretically applied ATP was decreased by reducing the amount of charge passed through the ATP electrode from 80 to 2 nC, the distance of ATP-induced actin-myosin sliding decreased almost linearly from approximately 100 to approximately 10 nm, no detectable actin-myosin sliding being observed with further reduction of the charge passed through the electrode. The amount of external load exerted by the bent microneedle was less than 1% of Po for the sliding distance < 50 nm. The actin-myosin sliding distances with a small amount of ATP slightly above the amount required to induce the minimum sliding distance were distributed around integral multiples of 10 nm, suggesting that the unitary distance of actin-myosin sliding coupled with ATP hydrolysis is of the order of 10 nm.


Intramolecular dimers: a new strategy to fluorescence quenching in dual-labeled oligonucleotide probes.
Many genomics assays use profluorescent oligonucleotide probes that are covalently labeled at the 5' end with a fluorophore and at the 3' end with a quencher. It is generally accepted that quenching in such probes without a stem structure occurs through Förster resonance energy transfer (FRET or FET) and that the fluorophore and quencher should be chosen to maximize their spectral overlap. We have studied two dual-labeled probes with two different fluorophores, the same sequence and quencher, and with no stem structure: 5'Cy3.5-beta-actin-3'BHQ1 and 5'FAM-beta-actin-3'BHQ1. Analysis of their absorption spectra, relative fluorescence quantum yields, and fluorescence lifetimes shows that static quenching occurs in both of these dual-labeled probes and that it is the dominant quenching mechanism in the Cy3.5-BHQ1 probe. Absorption spectra are consistent with the formation of an excitonic dimer, an intramolecular heterodimer between the Cy3.5 fluorophore and the BHQ1 quencher.


Semibiological left heart assist.
Previous investigations have revealed that the semibiological left heart assist gave a reasonably good performance under simulated physiological pressures, flow and rate conditions. The present study gives details of 50 animal experiments where the duration of the left ventricular-aorta bypass pumping varied between 2 and 24 hours. It was demonstrated that the device can be inserted and used without systemic or local anticoagulants and with a negligible degree of blood trauma up to 24 hours.


Nucleosome remodelling: structural insights into ATP-dependent remodelling enzymes.
ATP-dependent chromatin remodelling enzymes play a fundamental role in determining how nucleosomes are organised, and render DNA sequences accessible to interacting proteins, thereby enabling precise regulation of eukaryotic genes. Remodelers conserved from yeast to humans are classified into four families based on the domains and motifs present in their ATPase subunits. Insights into overall assembly and the mode of interaction to the nucleosome by these different families of remodelers remained limited due to the complexity of obtaining structural information on these challenging samples. Electron microscopy and single-particle methods have made advancement and uncovered vital structural information on the number of remodelling complexes. In this article, we highlight some of the recent structural work that advanced our understanding on the mechanisms and biological functions of these ATP-dependent remodelling machines.


Geometry dependence of surface plasmon polariton lifetimes in nanohole arrays.
We study surface plasmon polariton lifetimes in two-dimensional arrays of blind holes on gold surfaces. The lifetimes are determined from the line widths of the resonant dips appearing in the specular reflection spectra. We find a strong dependence of lifetimes on the resonant wavelength and the hole geometry. Through both experiments and numerical simulations, we analyze the validity of the Rayleigh approximation and also explore the range of wavelengths and geometric parameters where it fails. Finally, we show that, within the range of geometries and wavelengths considered in our experiments, the behavior of surface plasmon polariton lifetimes can be understood as resulting from the interplay between the intrinsic metal absorption and the scattering of surface waves by single isolated holes.


Conduits for coronary bypass: strategies.
Strategic planning is integral to any operation but complexity varies immensely and therefore the effort necessary to create the optimal plan. The previous three reports have discussed individual conduits and herein is an attempt to present approaches to common situations which the author favors. Although much has been learned over 45 years about use and subsequent behavior of venous and arterial grafts we continue to learn and, as a result, evolve new strategies or modify those now popular. Thus the reader must recognize that in spite of trying to be balanced and inclusive all surgeons have personal opinions and also prejudices which influence the approach taken and which may not be the optimal one for others or for the patient.


Endothelialized silicone aneurysm models for in vitro evaluation of flow diverters.
The goal of this work was to endothelialize silicone aneurysm tubes for use as in vitro models for evaluating endothelial cell interactions with neurovascular devices. The first objective was to establish consistent and confluent endothelial cell linings and to evaluate the silicone vessels over time. The second objective was to use these silicone vessels for flow diverter implantation and assessment. Silicone aneurysm tubes were coated with fibronectin and placed into individual bioreactor systems. Human umbilical vein endothelial cells were deposited within tubes to create silicone vessels, then cultivated on a peristaltic pump and harvested at 2, 5, 7, or 10 days to evaluate the endothelial cell lining. A subset of silicone aneurysm vessels was used for flow diverter implantation, and evaluated for cell coverage over device struts at 3 or 7 days after deployment. Silicone vessels maintained confluent, PECAM-1 (platelet endothelial cell adhesion molecule 1) positive endothelial cell linings over time. These vessels facilitated and withstood flow diverter implantation, with robust cell linings disclosed after device deployment. Additionally, the endothelial cells responded to implanted devices through coverage of the flow diverter struts with increased cell coverage over the aneurysm seen at 7 days after deployment as compared with 3 days. Silicone aneurysm models can be endothelialized and successfully maintained in vitro over time. Furthermore, these silicone vessels can be used for flow diverter implantation and assessment.


Chitosan Oligosaccharides Show Protective Effects in Coronary Heart Disease by Improving Antioxidant Capacity via the Increase in Intestinal Probiotics.
We explored the effects of chitosan oligosaccharides (COS) on coronary heart disease (CHD) patients. The component of COS was measured by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). CHD patients were evenly assigned into the COS group (COG) and the placebo group (CG). The duration of treatment was 6 months and therapeutic results were explored by measuring left ventricular ejection fraction (LVEF) value, Lee scores, quality of life (QOL), blood urea nitrogen, and serum creatinine. The intestinal flora were determined by 16s rDNA sequencing. The circulating antioxidant levels and lipid profiles were compared between two groups. There were 7 different degrees of polymerization (DP4-10) in COS. Lee scores, QOL scores, and LVEF values in the COG group were higher than those in the CG group (P < 0.05). COS treatment improved blood urea nitrogen and serum creatinine when compared with controls (P < 0.05). Circulating antioxidant levels were higher in the COG group than in the CG group. COS consumption increased the serum levels of SOD and GSH and reduced the levels of ALT and AST (P < 0.05). Meanwhile, lipid profiles were improved in the COG group. COS consumption increased the abundance of Faecalibacterium, Alistipes, and Escherichia and decreased the abundance of Bacteroides, Megasphaera, Roseburia, Prevotella, and Bifidobacterium (P < 0.05). On the other hand, COS consumption increased the probiotic species Lactobacillus, Lactococcus, and Phascolarctobacterium. The increased species have been reported to be associated with antioxidant properties or lipid improvement. COS had similar effects with chitohexaose on the growth rate of these species. Therefore, COS ameliorate the symptoms of CHD patients by improving antioxidant capacities and lipid profiles via the increase of probiotics in the intestinal flora.


Pentalogy of Cantrell in Full Term Neonate.
Pentalogy of Cantrell (PC) is an uncommon congenital disorder characterized by severe defects in the chest and abdomen, including abdominal visceral prolapsed via umbilical cord (omphalocele), defect in the lower part of the sternum, defect in the front of the diaphragm, defects in the anterior part of the pericardium, and the ectopiacordis. Here, we report a 2-hour-old girl, weighing 3,500 g, who was referred to Shahid Madani Hospital in Khorramabad due to the large omphalocele on her chest with pulsating mass above it. The baby was the first child of a 24-year-old mother who was born with an uncomplicated vaginal delivery. Very rare cases of PC are born as a term new-born.


[Application of udenafil for the correction of endothelial disorders in patients with stress-induced erectile dysfunction].
The study was aimed to the evaluation of vascular endothelium status in patients with stress-induced arterial hypertension, coupled with erectile dysfunction (ED). 51 patients underwent examination. Laurent--Segal Male Copulative Function Questionnaire (MCF), and International Index of Erectile Function (IIEF) were used for the detection of ED and assessment of its severity. Microcirculation in penile vessels was evaluated by laser Doppler flowmetry. Markers of endothelial function--endothelin 1 and asymmetric dimethylarginine-were measured. For the correction of violations identified, the drug udenafil (zydena) was used at a dose of 50 mg daily for 1 month. Against the background of therapy with udenafil, restoration of function of endothelial cells was detected. This suggested the functional nature of the violations in the genital sphere, and was regarded as a manifestation of stress-induced ED. Elimination of endothelial dysfunction led to significant reduction in ED symptoms.


Ontogenetic changes in the epiphyseal cartilage of Rana (Pelophylax) caralitana (Anura: Ranidae).
We document histological changes through ontogeny in the epiphyseal cartilage of the third phalanx of Rana caralitana from Turkey and provide an assessment of the maturation of the epiphysis from newly metamorphosed froglets to 10-year-old individuals. The epiphysis of R. caralitana is compared to other Rana taxa previously studied, and we report on novel histological data pertaining to later stages of epiphyseal growth in this taxon. In addition, we document the development of endochondral ossification in late stages of ontogeny in R. caralitana. Our results suggest a correlation between the long lifespan of R. caralitana and the developmental changes and maturation of the epiphyseal cartilage in this taxon. This study also provides a quantitative assessment of the different regions of the epiphyseal cartilage in the epiphysis of Rana through ontogeny, and has therefore permitted quantifiable deductions about the relative maturation and differentiation of the chondrocytes of the epiphysis through time.


[The myasthenic syndrome after chloroquine].
The author presents a case of a 52-year old woman who suffered from dermatitis seborrhoica. She was treated with chloroquine. During the third month of treatment with chloroquine the symptoms of myasthenia appeared and led to hospitalization. The neurological and additional examinations confirmed the diagnosis. Four days after withdrawal of chloroquine treatment the myasthenic symptoms began to disappear and they finally ceased after two weeks. At this all other drugs were also withdrawn. The control examination after two months showed normal neurological status.


Charcot-Marie-Tooth disease: an update.
The purpose of this review is to assist neurologists, neuroscientists and other interested readers in following the expanding volume of information relating to the inherited peripheral neuropathies collectively referred to as Charcot-Marie-Tooth disease. Currently, mutations in multiple different genes expressed in Schwann cells and neurons cause a variety of overlapping clinical phenotypes. Recent articles clarify molecular pathways involved in the pathogenesis of these disorders, and for the first time provide rational treatment strategies for the most common form of Charcot-Marie-Tooth disease. The identification of many new genes associated with neuropathy demonstrate the role of axonal transport and abnormal protein trafficking in causing various forms of Charcot-Marie-Tooth. They also further define the role of axonal signaling and the molecular architecture of both Schwann cells and neurons in maintaining normal peripheral nervous system function. Finally, recent reports have shown that progesterone antagonists and ascorbic acid can successfully treat rodent models of Charcot-Marie-Tooth disease type 1A. Taken together, results from these articles support the concept that genetic causes of Charcot-Marie-Tooth disease serve as a living microarray system to identify molecules necessary for normal peripheral nervous system function. When we can make sense of these microarrays we are likely to understand the pathogenesis and develop rational therapies for many neurodegenerative diseases including Charcot-Marie-Tooth.


Relationship between antibody to cytotoxin and Helicobacter pylori infection.
Broth culture supernatants from 14 (34%) out of the 41 H. pylori strains tested, induced vacuolization in Intestine 407 cells in titers ranging from 1:2 to 1:64. 20% of H. pylori strains isolated from children and 42% of strains isolated from adults expressed vacuolating activity. Serum antibody to cytotoxin produced by H. pylori was detected with a neutralization assay. Anticytotoxic antibodies were present in all sera from patients infected with cytotoxic H. pylori strains. The toxin-neutralizing activity of sera from individuals infected with H. pylori suggests that the cytotoxin is produced in vivo.


New records of fish parasitic isopods of the gill-attaching genus Mothocya Costa, in Hope, 1851 from the Virgin Islands, Caribbean, with description of a new species.
Two species of Mothocya Costa, in Hope, 1851 are reported from the Virgin Islands. Mothocya xenobranchia Bruce, 1986 was collected from St. John Island from the gills of the Atlantic needlefish, Strongylura marina, which is a new locality record and also confirms a previously uncertain host identity. Mothocya bertlucy sp. n. is described from St. Thomas, St John and Guana Islands, from the gills of the redlip blenny, Ophioblennius macclurei, the first record of a blenny as host for any Mothocya. The distinguishing characters of Mothocya bertlucy sp. n. include its small size (< 9 mm) and eyes, the slender pleotelson with a narrowly rounded caudomedial point, extended uropod peduncle and uropods which do not extend past the pleotelson posterior margin, and the narrow pleon which is only slightly overlapped by pereonite 7.


Is alcohol intake associated with breast cancer in Hispanic women? The New Mexico Women's Health Study.
Previous studies have shown an increased breast cancer risk associated with modest or high alcohol intake, however, few of these studies have included Hispanic women. The alcohol/breast cancer association was investigated in a New Mexico (NM) statewide bi-ethnic study. A population-based, case-control study. Incident breast cancer cases (N = 712), aged 30-74 years, were ascertained by the New Mexico Tumor Registry (NMTR). Controls (N = 844) were identified by random digit dialing and were frequency-matched for ethnicity, age-group, and health planning district. Data were collected via in-person interview, which included questions regarding recent and past alcohol intake and breast cancer risk factors. The highest level of recent alcohol intake, compared to no intake, was associated with breast cancer risk for postmenopausal Hispanic women (odds ratio [OR] = 2.0 95%, confidence interval [CI] 0.8-5.1, 42+ grams/ week) and postmenopausal non-Hispanic White women (OR = 2.2, 95% Cl 1.0-5.0, 148+ grams/week), although estimates were unstable and statistically non-significant. Lower recent alcohol intake (< 148 grams/week) was associated with reduced risk for non-Hispanic Whites (OR = 0.49, 95% Cl 0.35-0.69). This pattern was independent of hormone-receptor status and was present for both premenopausal (OR = 0.29, 95% Cl 0.15-0.56) and postmenopausal women (OR = 0.56, 95% Cl 0.35-0.90). Results for past alcohol intake and breast cancer association did not demonstrate any trends and were non-significant. Alcohol intake does not appear to have a consistent or significant association with breast cancer in Hispanic women.


Anatomic-electrophysiological correlations concerning the pathways for atrioventricular conduction.
The remarkable success of radiofrequency ablation in recent decades in curing atrioventricular nodal reentrant tachycardias has intensified efforts to provide a solid theoretical basis for understanding the mechanisms of atrioventricular transmission. These efforts, which were made by both anatomists and electrophysiologists, frequently resulted in seemingly controversial observations. Quantitatively and qualitatively, our understanding of the mysteries of propagation through the inhomogeneous and extremely complex atrioventricular conduction axis is much deeper than it was at the beginning of the past century. We must go back to the initial sources, nonetheless, in an attempt to provide a common ground for evaluating the morphological and electrophysiological principles of junctional arrhythmias. In this review, we provide an account of the initial descriptions, which still provide an appropriate foundation for interpreting recent electrophysiological findings.


Alveolar soft-part sarcoma presenting with eosinophilia and shunt.
Alveolar soft-part sarcoma (ASPS) is a rare soft tissue tumour found in young adults that usually arises in skeletal muscle and occurs most frequently in the lower limbs. Radiological and pathological findings of ASPS in a 34-year-old man who presented with increasing shortness of breath over a period of four to six weeks with peripheral blood eosinophilia, hypoxemia and a significant arteriovenous shunt are reported. The present article is the fourth report of eosinophilia in association with sarcoma, and the first involving ASPS.


Cognitive development, culture, and conversation: comments on Harris and Koenig's "truth in testimony: how children learn about science and religion".
Harris and Koenig make a compelling case for the importance of adult "testimony" and its influence on children's developing conceptions of topics in science and religion. This commentary considers how their analysis relates to constructivist and sociocultural theories and discusses several ways in which Harris and Koenig's arguments help to debunk some prevalent assumptions about research on the social context of cognitive development. Finally, a number of additional issues are raised for debate and discussion, and some critiques and suggestions for future research are discussed. The issues discussed by Harris and Koenig are crucial if we are to take seriously the importance of culture in cognitive development.


Motherhood experiences from the perspective of first-time mothers.
This study explored the early motherhood experiences of 79 first-time mothers. All women reported normal pregnancies and deliveries, delivered healthy infants at term, and were surveyed at 6 weeks postpartum using the Inventory of Functional Status After Childbirth. Mothers' written comments were subjected to a content analysis, and much of their commentary revolved around the "conspiracy of silence" that appeared to exist about the realities of motherhood. Most commented that no one had prepared them for the unrelenting demands of infant care, the level of fatigue they would experience, the loss of personal time and space, and the realities of 24-hour-a-day infant care. The women also cited their partners as their main support person during the early weeks of motherhood. Although maternal child health nurses and midwives are well placed to offer prenatal education and long-term professional support postpartum, perhaps what is needed is active, anticipatory preparation for motherhood that begins long before the first pregnancy becomes a reality.


Changes in membrane biophysical properties induced by sphingomyelinase depend on the sphingolipid N-acyl chain.
Ceramide (Cer) is involved in the regulation of several cellular processes by mechanisms that depend on Cer-induced changes on membrane biophysical properties. Accumulating evidence shows that Cers with different N-acyl chain composition differentially impact cell physiology, which may in part be due to specific alterations in membrane biophysical properties. We now address how the sphingolipid (SL) N-acyl chain affects membrane properties in cultured human embryonic kidney cells by overexpressing different Cer synthases (CerSs). Our results show an increase in the order of cellular membranes in CerS2-transfected cells caused by the enrichment in very long acyl chain SLs. Formation of Cer upon treatment of cells with bacterial sphingomyelinase promoted sequential changes in the properties of the membranes: after an initial increase in the order of the fluid plasma membrane, reorganization into domains with gel-like properties whose characteristics are dependent on the acyl chain structure of the Cer was observed. Moreover, the extent of alterations of membrane properties correlates with the amount of Cer formed. These data reinforce the significance of Cer-induced changes on membrane biophysical properties as a likely molecular mechanism by which different acyl chain Cers exert their specific biological actions.


Characterization of periodontal structures of enamelin-null mice.
Enamelin-null (ENAM(-/-)) mice have no enamel. When characterizing ENAM(-/-) mice, alveolar bone height reduction was observed, and it was hypothesized that enamel defects combined with diet are associated with the periodontal changes of ENAM(-/-)mice. The aim of the present study is to compare the dimension of interradicular bone of ENAM(-/-) (knock-out [KO]) with wild-type (WT) mice, maintained on hard (HC) or soft (SC) chow. A total of 100 animals divided into four groups were studied at 3, 8, and 24 weeks of age: 1) KO/HC; 2) KO/SC; 3) WT/HC; and 4) WT/SC. Microcomputed tomography was performed, and the following measurements were made between mandibular first (M1) and second (M2) molars: relative alveolar bone height (RBH), crestal bone width (CBW), bone volume (BV), bone mineral content (BMC), and bone mineral density (BMD). The position of M1 and M2 in relation to the inferior border of the mandible was also determined at 24 weeks. All variables were analyzed by one-way analysis of variance and Dunnett test for pairwise comparisons. Morphologic analyses were conducted on hematoxylin and eosin-stained sections. Radiographically, the enamel layer was absent in ENAM(-/-) mice. Interproximal open contacts were observed exclusively in ENAM(-/-) mice, and the prevalence decreased over time, suggesting that a shifting of tooth position had occurred. Additionally, in the two ENAM(-/-) groups, RBH was significantly lower at 8 and 24 weeks (P <0.02); CBW, BV, and BMC were significantly less (P <0.05) at 24 weeks. No differences in BMD were found among the four groups. The molars migrated to a more coronal position in ENAM(-/-) mice and mice on HC. Histologic findings were consistent with radiographic observations. After eruption, the junctional epithelium was less organized in ENAM(-/-) mice. The interdental bone density was not affected in the absence of enamelin, but its volume was, which is likely a consequence of alternations in tooth position.


Career intentions of medical students in the setting of Nepal's rapidly expanding private medical education system.
The number of medical students trained in Nepal each year has increased nearly fifty-fold in the last 15 years, primarily through the creation of private medical schools. It is unknown where this expanding cohort of new physicians will ultimately practice. We distributed an anonymous survey to students in their last 2 years of medical school at four medical schools in Nepal to examine two dimensions of career intention: the intention to practice in Nepal and the intention to practice in rural areas. Eighty-five per cent of the eligible study population participated, for a total of 469 medical students. Of these, 88% thought it was likely they would practice in Nepal and 88% thought it likely they would practice in urban areas. Those students who indicated a greater likelihood of practicing abroad came from families with higher incomes, were more likely to think earning a good salary was very important to their decision to become a physician, and were less likely to think they could earn a good salary in Nepal. Students whose tuition was paid by the government were no more likely to indicate an intention to practice in Nepal than students paying their own tuition at private medical schools. Students who indicated a greater likelihood of practicing in rural areas were more likely to be male, to have gone to a government secondary school, to have been born in a village, or to have received a scholarship from the Ministry of Education that requires rural service. Based on our findings, we suggest the following policy changes: (1) medical schools consider selecting for students from rural backgrounds or government secondary schools who are more likely to intend to practice in rural areas, and (2) increase the number of post-graduate positions--weighted toward rural health needs--to retain students in Nepal.


Removal of lead ions using OA-Fe3O4 magnetic nanoparticles-based pickering emulsion liquid membrane: process optimization using box-behnken response surface methodology.
The purpose of this study is to explore the pickering emulsion liquid membrane (PELM) performance for removing divalent lead ions (Pb II) from aqueous solution. In the present work, the membrane phase was prepared by dissolving methyltrioctylammonium chloride (Aliquat 336) with Mahua oil and adding oleic acid coated-ferrosoferric oxide (OA-Fe3O4) as magnetic nanoparticles. Experimental investigation on percentage removal of lead ions was carried out by studying the influencing process parameters such as pH, agitation speed, stripping concentration, initial feed concentration, surfactant concentration, treat ratio, M/S ratio and carrier concentration. The optimum condition to remove 98.52% of lead ions from the feed solutions has achieved at a stripping phase concentration of 0.3 M, treat ratio of 3, agitation speed of 300 rpm, initial feed concentration of 10 ppm and stabilizer concentration of 2 wt%. The experimental results were validated using box-behnken response surface methodology. The extraction ability of OA-Fe3O4 magnetic nanoparticles-based PELM has been evaluated using statistical optimization of all the affecting process factors using the design of the experiments.


Enhancing the efficiency of a PCR using gold nanoparticles.
We found that the PCR could be dramatically enhanced by Au nanoparticles. With the addition of 0.7 nM of 13 nm Au nanoparticles into the PCR reagent, the PCR efficiency was increased. Especially when maintaining the same or higher amplification yields, the reaction time could be shortened, and the heating/cooling rates could be increased. The excellent heat transfer property of the nanoparticles should be the major factor in improving the PCR efficiency. Different PCR systems, DNA polymerases, DNA sizes and complex samples were compared in this study. Our results demonstrated that Au nanoparticles increase the sensitivity of PCR detection 5- to 10-fold in a slower PCR system (i.e. conventional PCR) and at least 10(4)-fold in a quicker PCR system (i.e. real-time PCR). After the PCR time was shortened by half, the 100 copies/microl DNA were detectable in real-time PCR with gold colloid added, however, at least 10(6) copies/microl of DNA were needed to reach a detectable signal level using the PCR reagent without gold colloid. This innovation could improve the PCR efficiency using non-expensive polymerases, and general PCR reagent. It is a new viewpoint in PCR, that nanoparticles can be used to enhance PCR efficiency and shorten reaction times.


Responses of Low-Cost Input Combinations on the Microbial Structure of the Maize Rhizosphere for Greenhouse Gas Mitigation and Plant Biomass Production.
The microbial composition of the rhizosphere and greenhouse gas (GHG) emissions under the most common input combinations in maize (Zea mays L.) cultivated in Brazil have not been characterized yet. In this study, we evaluated the influence of maize stover coverage (S), urea-topdressing fertilization (F), and the microbial inoculant Azospirillum brasilense (I) on soil GHG emissions and rhizosphere microbial communities during maize development. We conducted a greenhouse experiment and measured methane (CH4), carbon dioxide (CO2), and nitrous oxide (N2O) fluxes from soil cultivated with maize plants under factorial combinations of the inputs and a control treatment (F, I, S, FI, FS, IS, FIS, and control). Plant biomass was evaluated, and rhizosphere soil samples were collected at V5 and V15 stages and DNA was extracted. The abundance of functional genes (mcrA, pmoA, nifH, and nosZ) was determined by quantitative PCR (qPCR) and the structure of the microbial community was assessed through 16S rRNA amplicon sequencing. Our results corroborate with previous studies which used fewer input combinations and revealed different responses for the following three inputs: F increased N2O emissions around 1 week after application; I tended to reduce CH4 and CO2 emissions, acting as a plant growth stimulator through phytohormones; S showed an increment for CO2 emissions by increasing carbon-use efficiency. IS and FIS treatments presented significant gains in biomass that could be related to Actinobacteria (19.0%) and Bacilli (10.0%) in IS, and Bacilli (9.7%) in FIS, which are the microbial taxa commonly associated with lignocellulose degradation. Comparing all factors, the IS (inoculant + maize stover) treatment was considered the best option for plant biomass production and GHG mitigation since FIS provides small gains toward the management effort of F application.


Expression of PiT1 and PiT2 retroviral receptors and transduction efficiency of tumor cells.
Recombinant retroviral vectors are still the most common gene delivery vehicles for gene therapy purposes, especially for construction of genetically modified tumor vaccines (GMTV). However, these vehicles are characterized by relatively low titre and in the case of many tumor cell lines, low transduction efficiency. We constructed bicistronic retroviral vector pseudotypes of amphotropic murine leukemia virus (A-MuLV) and gibbon ape leukemia virus (GaLV), encoding enhanced green fluorescent protein (EGFP) as a rapid and easily detectable reporter gene. Transduction of five different human melanoma and four renal carcinoma cell lines by these two virus pseudotypes revealed differences in transduction efficiency, which wase markedly lower for the renal carcinoma cell lines. Stimulation of retroviral receptor expression (PiT1 and PiT2) by phosphate depletion induced a limited increase of receptor mRNA levels, but did not improve the gene transfer efficiency. In contrast, simultaneous transduction with both vector pseudotypes markedly increased the transduction efficiency, compared to GaLV or A-MuLV alone. The same effect could be achieved by several repeated exposures of target cells to fresh vector preparation. Overexpression of GaLV receptor (PiT1) in target cells significantly increased the transduction rate and enabled retrovirus mediated gene transfer into the cells which normally are not transducible by GaLV pseudotypes. We demonstrated that, using different transduction strategies, the relatively inefficient, widely used retroviral vector systems could be significantly improved.


Faecal Microbiota in Infants and Young Children with Functional Gastrointestinal Disorders: A Systematic Review.
Functional gastrointestinal disorders (FGIDs) refer to gastrointestinal tract issues that lack clear structural or biochemical causes. Their pathophysiology is still unclear, but gut microbiota alterations are thought to play an important role. This systematic review aimed to provide a comprehensive overview of the faecal microbiota of infants and young children with FGIDs compared to healthy controls. A systematic search and screening of the literature resulted in the inclusion of thirteen full texts. Most papers reported on infantile colic, only one studied functional constipation. Despite methodological limitations, data show alterations in microbial diversity, stability, and colonisation patterns in colicky infants compared to healthy controls. Several studies (eight) reported increases in species of (pathogenic) Proteobacteria, and some studies (six) reported a decrease in (beneficial) bacteria such as Lactobacilli and Bifidobacteria. In addition, accumulation of related metabolites, as well as low-grade inflammation, might play a role in the pathophysiology of infantile colic. Infants and toddlers with functional constipation had significantly lower levels of Lactobacilli in their stools compared to controls. Microbial dysbiosis and related changes in metabolites may be inherent to FGIDs. There is a need for more standardised methods within research of faecal microbiota in FGIDs to obtain a more comprehensive picture and understanding of infant and childhood FGIDs.


Differential expression of IGF-binding protein-3 in normal and malignant colon and its influence on apoptosis.
IGF-binding protein-3 (IGFBP-3) has been reported to exert a protective influence on the pathogenesis of colorectal cancer. This may reflect its modulation of IGF-I bioactivity as well as IGF-I-independent effects on cell proliferation and apoptosis. Although local expression of IGF-I in the colon is increasingly recognised as having important regulatory consequences, the role of locally expressed IGFBP-3 remains unknown. The aims of the present study were: (i) to quantify and localise the expression of IGFBP-3 in human normal and malignant colon; (ii) to relate this expression to that of other components of the IGF-I axis; and (iii) to investigate the effects of IGFBP-3 on colonic epithelial cell proliferation and apoptosis. RNA was extracted from 46 paired samples of normal and malignant colonic tissue. IGFBP-3, IGF-I, IGF-I receptor and GH receptor mRNA levels were quantified using real-time RT-PCR. Laser-capture microdissection of the same samples was used to isolate mRNA from epithelium and stromal components and localise mRNA expression. Expression was confirmed at a protein level by immunohistochemistry. Human colorectal cancer HT-29 and CaCo-2 cells were cultured with IGFBP-3 (200 ng/ml), +/- IGF-I (20 ng/ml), +/- sodium butyrate (5 mM). Cell number was assessed by an MTS assay (a modification of the MTT assay), and apoptosis assessed by cell morphology and FACS analysis using both annexin and propidium iodide staining. UO146, a MAP kinase inhibitor, and wortmannin, an inhibitor of the phosphatidylinositol 3-kinase (PI-3K) pathway, were used to determine the contribution of these signalling pathways on the effects of IGFBP-3. IGFBP-3 mRNA was detected in all samples (mean copy number/mug total RNA in normal colon, 2.6 x 10(6) compared with 1.3 x 10(7) in the cancers; P < 0.0001). Immunohistochemistry confirmed the expression and showed it to be equally distributed between epithelial and stromal components in normal tissue, but to be mainly restricted to the stromal component of malignant tissue. This differential expression was confirmed by RT-PCR of RNA from laser-capture microdissected samples. IGF-I mRNA was detected in 31 samples of normal colon; mean IGFBP-3 copy number was higher in the IGF-I-positive samples compared with IGF-I-negative samples. IGFBP-3 on its own induced apoptosis in HT-29 cells (P < 0.001). Co-incubation of 200 ng/ml IGFBP-3 with butyrate (5 mM) resulted in the potentiation of its apoptosis (P < 0.0001), which was not rescued by co-incubation with IGF-I (P < 0.0001). The addition of UO126 caused a decrease in cell number and increased the effects of IGFBP-3. IGFBP-3 is differentially expressed between stromal and epithelial components of normal and malignant colon, which may reflect its pro-apoptotic, IGF-I-independent effect on colonic epithelial cells. These effects are mediated in part by the PI-3K pathway in contrast to the MAP kinase pathway used by IGF-I.


[Possibilities of remaxol in prevention of toxic hepatitis during chemotherapy for cancer patients].
The effectiveness of planning polychemotherapy (PCT) for cancer patients depends on the functional state of the liver. The use of remaxol was studied in 100 patients with advanced forms of cancer (including breast cancer) in a preventive mode in comparison with the control group (100 patients, essentiale group of 40 patients) and in the process of PCT. Remaxol, compared with the control group, allowed reducing the frequency of drug hepatotoxicity by 30 +/- 3.7% and by 6.5 +/- 2.9% in comparison with the group of patients who received essentiale.


The use of fluorescent in-situ hybridization (FISH) for the analysis of in-vitro fertilization embryos: a diagnostic tool for the infertile couple.
We use triple colour fluorescent in-situ hybridization (FISH) to sex human embryos for preimplantation diagnosis of X-linked disease, to analyse chromosome numbers in embryos donated for research purposes and as a diagnostic tool for patients undergoing infertility treatment, especially in cases where abnormal embryo development occurs. We have reported on the use of FISH in a case where all embryos showed accelerated cleavage. Here we report on the use of triple colour FISH in a case where five out of seven oocytes were multi-nucleated when examined for pronuclei. The embryos were spread whole using HCl/Tween 20 and triple colour FISH performed with probes for chromosomes X, Y and 1 in a 2 h procedure. Two embryos were normal for the probes used, and three showed abnormalities, including one 4-cell embryo where all nuclei were X,X,X,Y,1,1,1,1. FISH indicated that fertilization had occurred, but that the majority of embryos were abnormal confirming that such embryos should not be considered for transfer. In these cases, or where there is recurrent in-vitro fertilization failure or spontaneous abortions, embryos in future cycles can be examined using FISH to ascertain the level of chromosome abnormality which may aid future infertility treatment.


Indicators of immunosuppression peripartum in dual purpose cows in the tropics affected health, productive and reproductive parameters.
The objective of the study was to identify immunosuppression peripartum indicators in dual purpose cows in the tropics and determine their effects on productive and reproductive parameters. The indicators used were: changes in leukocyte and neutrophils population, concentrations of energy metabolites (β-hydroxybutyrate and glucose) and body condition scores (BCS). Blood sampling and BCS (scale 1 - 5) were taken weekly during the peripartum. Uterine health was assessed (3 weeks postpartum) by ultrasonography and using a vaginal score (0-3) described by Sheldon et al. (2006). Cows (n=30) were classified as healthy or clinical endometritis (CE). CE prevalence was as high as 29.6%. Leukocyte and neutrophils populations diminished while in the peripartum and were lower (P<0.05) in cows suffering CE. Healthy cows had higher (P<0.05) daily milk production than those with CE (18.84±0.63 vs 14.76±0.84 kg). CE cows had lower (P<0.05) reproductive performance compared with healthy cows (open days: 244.40 ± 35.00 vs 178.00 ± 23.33 and services by conception 3.33 ± 0.51 vs 1.83 ± 0.34). BCS similarly (P>0.05) decreased following parturition in both groups. Concentrations of energy metabolites during peripartum fluctuated in a similar (P>0.05) manner in healthy and CE cows. In summary, dual purpose cows in tropical conditions, presented peripartum immunosuppression indicators, characterized by a decline in the leukocyte population, mainly neutrophils, as well as decreased glucose concentrations and BCS postpartum. In addition to it, there was a rise in the β-hydroxybutyrate concentrations and cows presenting CE had a negative effect in the productive and reproductive parameters.


The Journey for the Total Chemical Synthesis of a 53 kDa Protein.
Chemical protein synthesis has been proved as an efficient way to afford medium-sized proteins with high homogeneity in workable quantities for various biochemical, structural, and functional studies. In particular, chemical protein synthesis has enabled access to proteins that are difficult or impossible to prepare by molecular biology approaches, such as those with post-translational modifications and mirror-image proteins. One prominent example is related to ubiquitination, a well-known modification that mediates a variety of cellular processes (e.g., proteasomal degradation). Ubiquitination is considered as a modification that is difficult to introduce into proteins in a test tube to generate ubiquitin (Ub) conjugates with high homogeneity with respect to the chain length and the anchored Lys residue in workable quantities to perform the biochemical and biophysical studies. Chemical protein synthesis has emerged as a powerful approach to prepare Ub conjugates for studies aiming to understand ubiquitination in great detail and decipher its roles in cell processes. Nevertheless, in order to answer more challenging questions in this field, it has been clear that researchers must also prepare Ub conjugates with increased size and complexity. Employing solid-phase peptide synthesis and chemoselective ligation, chemical protein synthesis offers a powerful way to furnish polypeptides composed of 100-200 residues. However, to synthesize larger proteins such as Ub conjugates, longer and more segments are required. This on the other hand leads to difficulties related to solubility, purification, ligation, and late-stage modifications. These challenges have encouraged us to explore more practical synthetic tools to facilitate the synthesis of complex Ub conjugates. In this Account, we summarize the synthetic tools that we have developed to achieve these goals. These include (1) δ-mercaptolysine-mediated isopeptide chemical ligation, (2) chemical synthesis of Ub building blocks, (3) palladium-mediated deprotection of key side chains during protein synthesis, (4) one-pot ligation and desulfurization, and (5) improving the solubility of peptide segments. The developed chemical toolbox has been a key for our successes in the synthesis of diverse and complex Ub conjugates. In this Account, we describe our approaches for generating various Ub conjugates, including (1) the K48 tetra-Ub chain composed of 304 amino acids, (2) the ubiquitinated histones and their analogues made of >200 amino acids, (3) the di-Ub-SUMO-2 hybrid chain composed of 245 amino acids, and (4) the 53 kDa tetra-Ub-α-globin composed of 472 amino acids, which represents the largest protein composed of natural amino acids ever made using chemical protein synthesis. The last target, Flag-Ub-Ub-Ub-Myc-Ub-(HA-α-globin), was prepared in the labeled form where the proximal Ub and distal Ub in the chain were labeled with Myc and Flag tags, respectively, while the α-globin was labeled with the HA tag. Applying the tetra-Ub-α-globin in proteasomal degradation studies assisted us to shed light on the proteolytic signal and the fates of the Ub moieties in the chains. Although these developments have contributed to the synthesis of interesting and challenging targets related to Ub signaling, several other targets may enforce new synthetic challenges. Hence, there is still a need to optimize the current synthetic tools and explore novel synthetic approaches to facilitate this process.


Retargeting NK92 cells using an HLA-A2-restricted, EBNA3C-specific chimeric antigen receptor.
Advances in adoptive cell immunotherapy have led to several promising options for cancer patients. Single-chain variable fragments (scFvs) were isolated from a human phage display library by panning on recombinant human leukocyte antigen (HLA)-A2-peptide complexes. A scFv (EBNA Clone 315) specific for HLA-A2 carrying a 10 amino acid peptide (LLDFVRFMGV) derived from the Epstein-Barr virus latent protein EBNA3C was fully characterized. EBNA Clone 315 displayed exquisite specificity toward its targeted T-cell epitope (TCE) and did not cross-react with the free peptide, HLA-A2 complexes, which carried irrelevant peptides, or HLA-A2(-) cells. Furthermore, after engineering into a scFv-Fc fusion protein, we were able to determine its affinity, detection sensitivity, and ability to induce antibody-dependent cellular cytotoxicity (ADCC). As a proof-of-principle, a chimeric antigen receptor (CAR) version of EBNA Clone 315 was used to reprogram NK92MI cells. CAR-expressing NK92MI cells showed highly specific and potent cytotoxicity toward the targeted TCE, with detection sensitivity of approximately 25 molecules and cytolytic capacity threefold greater than scFv-Fc-mediated ADCC. For the first time, we show the successful reprogramming of non-T cells toward a specific TCE using a CAR.


Advanced glomerulosclerosis is reversible in nephrotic mice.
Advanced glomerulosclerosis, a common hallmark of chronic renal diseases (CRD) is believed to be irreversible, and it is thought that glomerular hyperfiltration and hypertrophy may participate in its pathogenesis. We demonstrate here that glomerulosclerosis is "reversible" in an animal model. We used nephrotic ICGN (nep/nep) mice which showed a rapid progression of glomerulosclerosis, accompanied by histological findings for glomerular hyperfiltration. It is known that ureter ligation reduces glomerular filtration in ligated kidneys. When ureter ligation was applied to our model, glomerulosclerosis (characterized by myofibroblast hyperplasia and over-accumulated matrix protein) weakened in conjunction with suppressed glomerular hypertrophy. During this process, glomerular myofibroblasts showed apoptotic cell death after unilateral ureter ligation (UUO) treatment. Our results suggest that inhibition of glomerular filtration in sclerotic tufts may cause glomerular remodeling through the modulation of molecular and cellular sclerogenesis.


Buccal micronucleus cytome assay: Inter-laboratory scoring exercise and micronucleus and nuclear abnormalities frequencies in different populations from Brazil.
The Buccal Micronucleus Cytome Assay (BMCyt) has become an important biomonitoring tool for assessing cytogenetic damage in many studied populations. Each laboratory applies protocols that vary according to the method of collecting and preparing samples. Besides, Brazil is a country of great territorial extensions that received immigrants from various parts of the world with different genetic backgrounds. Therefore, the present study aimed to evaluate the inter-laboratory variation in scoring the same set of slides using the more comprehensive scoring criteria, to standardize the BMCyt protocol, to observe the basal alterations in populations of different Brazilian regions and to compare it with other places around the world. Our results showed that a valuable number of laboratories participated, ten laboratories from different regions of the country, for the validation of the BMCyt in human biomonitoring studies, resulting in the 804 healthy individuals. This was possible because we observed: a range of measures needs to be considered, such as the baseline frequency of DNA damage and cell death in non-exposed individuals; age when grouped showed an influence on DNA damage, although when evaluated by group we did not see an influence; association between smoking habit and all endpoints of the BMCyt (except karyolytic cells) was evident; the basal MN frequency, in the majority of groups, follows those around the world; and the BMCyt was confirmed as a good health status biomarker. We emphasize the need for constant discussions on the parameters of cell death due to greater difficulty among the analyzers.


Mechanisms of spin-polarized current-driven magnetization switching.
The mechanisms of the magnetization switching of magnetic multilayers driven by a current are studied by including exchange interaction between local moments and spin accumulation of conduction electrons. It is found that this exchange interaction leads to two additional terms in the Landau-Lifshitz-Gilbert equation: an effective field and a spin torque. Both terms are proportional to the transverse spin accumulation and have comparable magnitudes.


Who participates in the gastric cancer screening and on-time rescreening in the National Cancer Screening Program? A population-based study in Korea.
Gastric cancer (GC) screening is a major challenge in countries where the disease is highly prevalent. This study was conducted to identify the factors associated with participation in GC screening and on-time rescreening among the average-risk population in Korea. The study population was derived from the National Cancer Screening Program database. The population for this study was 22 913 618 individuals aged ≥40 years who had been invited to participate in a GC screening program from 2005 to 2006. We determined whether these individuals had attended the GC screening program and which method - an upper gastrointestinal series (UGIS) or endoscopy-they underwent. We followed the participants to determine whether they had a second GC screening after 2 years. The overall participation rate in the GC screening was 20.5%. More people underwent UGIS than endoscopy. Individuals who had been screened by endoscopy rather than UGIS were more likely to be younger, male, or those who were National Health Insurance (NHI) beneficiaries with a higher premium rate. Of those who underwent baseline screening, 59.4% participated in a rescreening program 2 years later. NHI beneficiaries with a higher premium rate were significantly more likely to be rescreened than medical aid recipients. The results from this study showed that the UGIS were more commonly used in organized GC screenings in Korea, and those who underwent UGIS were more likely to return for subsequent screening compared to those who underwent an endoscopy.


Distinct temporal phases of microvascular rarefaction in skeletal muscle of obese Zucker rats.
Evolution of metabolic syndrome is associated with a progressive reduction in skeletal muscle microvessel density, known as rarefaction. Although contributing to impairments to mass transport and exchange, the temporal development of rarefaction and the contributing mechanisms that lead to microvessel loss are both unclear and critical areas for investigation. Although previous work suggests that rarefaction severity in obese Zucker rats (OZR) is predicted by the chronic loss of vascular nitric oxide (NO) bioavailability, we have determined that this hides a biphasic development of rarefaction, with both early and late components. Although the total extent of rarefaction was well predicted by the loss in NO bioavailability, the early pulse of rarefaction developed before a loss of NO bioavailability and was associated with altered venular function (increased leukocyte adhesion/rolling), and early elevation in oxidant stress, TNF-α levels, and the vascular production of thromboxane A2 (TxA2). Chronic inhibition of TNF-α blunted the severity of rarefaction and also reduced vascular oxidant stress and TxA2 production. Chronic blockade of the actions of TxA2 also blunted rarefaction, but did not impact oxidant stress or inflammation, suggesting that TxA2 is a downstream outcome of elevated reactive oxygen species and inflammation. If chronic blockade of TxA2 is terminated, microvascular rarefaction in OZR skeletal muscle resumes, but at a reduced rate despite low NO bioavailability. These results suggest that therapeutic interventions against inflammation and TxA2 under conditions where metabolic syndrome severity is moderate or mild may prevent the development of a condition of accelerated microvessel loss with metabolic syndrome.


Molecular biology of the human foamy virus.
Foamy viruses also known as spumaretroviruses are complex retroviruses infecting cell lines with no apparent specific cellular tropism and induce the formation of multinucleated cells with numerous vacuoles. Far less well characterized than oncoviruses and lentiviruses, this class of viruses is thought to be innocuous in vivo. However, several important discoveries on foamy viruses brought new insights in the field of retrovirology.


Antileishmanial effects, cellular mechanisms, and cytotoxicity of Elettaria cardamomum essential oil against Leishmania major infection.
Leishmaniasis is an infectious disease with various clinical manifestations. We studied the therapeutic effects of Elettaria cardamomum essential oil (ECEO) against Leishmania major infection. In vitro effects of ECEO against L. major were examined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and macrophage assays. Nitric oxide (NO) production, infection inhibition in macrophages, and the apoptotic activity of ECEO in treated parasites were also measured. By calculating the 50% cytotoxic concentrations (CC50), we studied the cytotoxicity effects of ECEO on human macrophage cells (THP-1). The efficacy of ECEO for improving cutaneous leishmaniasis (CL) lesions in mice (BALB/c) was determined by evaluating the size of lesions and the number of amastigotes before and after four weeks of treatment. The effects of ECEO on liver and kidney function in the tested mice were also evaluated. ECEO dose-dependently (p<0.001) inhibited the viability and the mean number of promastigotes and amastigote forms of L. tropica. Four weeks of treatment with ECEO at the doses of 2.5 and 5 mg/kg/ day significantly (p<0.001) improved the CL lesions and reduced the number of parasites in the infected mice. ECEO significantly increased NO production, apoptosis induction, and infection rate in parasites. The CC50 value for ECEO and MA was 303.4 µg/mL and 835.2 µg/mL, respectively. In the mice receiving ECEO at the doses of 2.5 and 5 mg/kg/day for 28 days, no significant change was reported between the serum level of liver enzymes and kidney factors when compared with the control group. ECEO displayed promising efficacy in parasite reduction in vitro and in the animal model. ECEO can thus be used as an alternative medicine to treat CL.


Equity in global health research in the new millennium: trends in first-authorship for randomized controlled trials among low- and middle-income country researchers 1990-2013.
Developing the research capacity of low- and middle-income countries (LMICs) has been shown to be one of the key ways that international health programmes and health research can create sustained benefit in these countries. The aim of this study was to examine trends in first-authorship for researchers from LMIC institutions (LMIC first-authors) over the period 1990-2013. This study systematically reviewed research articles about randomized controlled trials (RCTs) in HIV/AIDS, malaria and tuberculosis (TB) conducted in LMICs from 1990 to 2013, and identified the institutional affiliations of the authors. Key variables extracted from the articles included author affiliation, funding source, disease, intervention type, region and year of publication. Poisson regression was used to explore the impact of these key variables on LMIC first-authorship over time. A total of 1593 articles were identified, of which 49.8% had LMIC first-authors. From 1990 to 2000 a total of 222 trials were published, and from 2001 to 2013 a total of 1371 trials were published, with a steady year-on-year increase over the period particularly evident in trials conducted in Africa. Whereas the absolute total number of LMIC first-authors has increased, as a proportion of all authors it declined. The relative rate increase in first-authorships post 2000 was 11.8-fold for non-LMIC first-authors and 2.8-fold for LMIC authors. LMIC first-authorship increased over time for research funded from LMIC; but LMIC first-authorship declined over time for research funded from high income countries (HIC). The absolute increase in the number of trials in HIV/AIDS, malaria and tuberculosis in Africa has led to a modest increase in LMIC first-authors, and a much larger increase in non-LMIC authors. The findings suggest that more inclusive policies by international funders are important in shifting research control to LMICs and improving research equity in the future.


Analysis of Human Faecal Host Proteins: Responsiveness to 10-Week Dietary Intervention Modifying Dietary Protein Intake in Elderly Males.
Faecal proteomics targeting biomarkers of immunity and inflammation have demonstrated clinical application for the identification of changes in gastrointestinal function. However, there are limited comprehensive analyses of the host faecal proteome and how it may be influenced by dietary factors. To examine this, the Homo sapiens post-diet proteome of older males was analysed at the completion of a 10-week dietary intervention, either meeting the minimum dietary protein recommendations (RDA; n = 9) or twice the recommended dietary allowance (2RDA, n = 10). The host faecal proteome differed markedly between individuals, with only a small subset of proteins present in ≥ 60% of subjects (14 and 44 proteins, RDA and 2RDA, respectively, with only 7 common to both groups). No differences were observed between the diet groups on the profiles of host faecal proteins. Faecal proteins were detected from a wide range of protein classes, with high inter-individual variation and absence of obvious impact in response to diets with markedly different protein intake. This suggests that well-matched whole food diets with two-fold variation in protein intake maintained for 10 weeks have minimal impact on human faecal host proteins.


Nanoscale hybrid systems based on carbon nanotubes for biological sensing and control.
This paper provides a concise review on the recent development of nanoscale hybrid systems based on carbon nanotubes (CNTs) for biological sensing and control. CNT-based hybrid systems have been intensively studied for versatile applications of biological interfaces such as sensing, cell therapy and tissue regeneration. Recent advances in nanobiotechnology not only enable the fabrication of highly sensitive biosensors at nanoscale but also allow the applications in the controls of cell growth and differentiation. This review describes the fabrication methods of such CNT-based hybrid systems and their applications in biosensing and cell controls.


The health promoting sports club in Finland--a challenge for the settings-based approach.
The purpose of this article is, first, to compile a frame of reference for the health promoting sports club and, second, to develop standards for the concept. This concept is based on the settings-based health promotion approach. Sports clubs are a new setting for health promotion, which until now has been little examined from a settings point of view. Nevertheless, this concept has much potential. For example, sports clubs attract a large number of children and adolescents and their educational nature can be considered to be informal. The present standards were developed using the Delphi method. The researcher, in cooperation with a panel of experts (experts in health promotion, n = 11, and experts in sports clubs, n = 16), sought to create a consensus statement on the standards. At the preliminary stage of the study 64 original standards were created on the basis of existing literature and the principles of the Ottawa Charter. During the three rounds of the Delphi process 15 standards were evaluated as the most important. After the Delphi process, the researcher modified the standards by eliminating overlap, interpolating seven standards to involve all strategic areas of the Ottawa Charter and creating a preliminary typology of the standards. At the subsequent stages of the study, indicators for these standards will be drafted and tested in practice. Therefore, this study would provide tools for determining and evaluating how health promoting a particular sports club is.


A prospective study of long-term caregiver and family adaptation following brain injury in children.
We examined long-term differences in family adaptation following traumatic brain injuries (TBI) and orthopedic injuries. Families of children with severe TBI (n = 53), moderate TBI (n = 56), and orthopedic injuries (n = 80) were assessed at baseline, 6 months, and 12 months post injury and at an extended follow-up an average of 4.1 years post injury. Caregiver and family outcomes were examined using mixed model analysis. Patterns of adaptation over time varied across groups but indicated long-standing injury-related stress and burden in the severe TBI group. Severe TBI results in persistent caregiver stress for a substantial proportion of families.


[Differential diagnosis of osteomyelitis of the calcaneus].
The authers avalyse 6 cases of calcaneal osteomyelitis with rather chronic development. They present radiological and clinical differential diagnostic problems. Osteomyelitis was to seperate from Sever's disease, benign and malignant bone tumours. In 3 cases only histology or bacteriology allowed the proper diagnosis.


Stapedectomy training with the carbon dioxide laser.
All primary carbon dioxide (CO2) laser stapedectomies supervised by the senior author since 1986 were retrospectively reviewed and reported according to 1995 American Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing guidelines. Sixty-three cases had more than 6 weeks of follow-up with an average residual gap of 6.49 dB (SD = 5.55 dB) and an 89% success rate. Thirty cases had more than 1 year of follow-up with the average hearing result of 6.58 dB (SD = 5.93 dB) and an 87% success rate. In 11 cases, 14 operative problems or complications occurred. Suctioning the vestibule occurred in five cases. Because suction is required to evacuate laser smoke, these cases are attributed to the laser. One of these patients had delayed sensorineural hearing loss. One patient had profound delayed sensorineural hearing loss as a result of granuloma formation. These were the only major complications. The laser is a tool that gives reproducible technique and good success rates.


Structure of DNA-CMG-Pol epsilon elucidates the roles of the non-catalytic polymerase modules in the eukaryotic replisome.
Eukaryotic origin firing depends on assembly of the Cdc45-MCM-GINS (CMG) helicase. A key step is the recruitment of GINS that requires the leading-strand polymerase Pol epsilon, composed of Pol2, Dpb2, Dpb3, Dpb4. While a truncation of the catalytic N-terminal Pol2 supports cell division, Dpb2 and C-terminal Pol2 (C-Pol2) are essential for viability. Dpb2 and C-Pol2 are non-catalytic modules, shown or predicted to be related to an exonuclease and DNA polymerase, respectively. Here, we present the cryo-EM structure of the isolated C-Pol2/Dpb2 heterodimer, revealing that C-Pol2 contains a DNA polymerase fold. We also present the structure of CMG/C-Pol2/Dpb2 on a DNA fork, and find that polymerase binding changes both the helicase structure and fork-junction engagement. Inter-subunit contacts that keep the helicase-polymerase complex together explain several cellular phenotypes. At least some of these contacts are preserved during Pol epsilon-dependent CMG assembly on path to origin firing, as observed with DNA replication reconstituted in vitro.


In vivo comparison of the follicle-stimulating hormone-suppressing activity of follistatin and inhibin in ovariectomized rats.
The present study was performed to compare and contrast the effects of two gonadal polypeptides, inhibin and follistatin, on ovariectomy-induced hypersecretion of FSH and LH. Ovariectomies were performed 1 week before study. Follistatin was purified from porcine follicular fluid, and human inhibin A was produced by recombinant DNA technology. On the day of study, a blood sample was taken from intraatrial cannulae inserted on the previous day, the materials were injected, and additional blood samples were taken at various times thereafter. Serum FSH and LH levels were determined by RIA. Both follistatin and inhibin exhibited dose-dependent suppression of circulating FSH but not LH levels, with initial decreases in FSH levels by both materials observed between 2-4 h post injection. Maximal suppression of FSH by each polypeptide occurred between 4-6 h depending on dose. Based on the dose-response relationships, it was determined that inhibin was approximately five times as potent as follistatin in suppressing FSH release. However, despite the greater biopotency of inhibin than follistatin, the duration of action of even the highest dose of inhibin (50 micrograms) was between 4-9 h, whereas the duration of FSH-suppressing activity by the two highest doses of follistatin (40 and 80 micrograms) was between 10-21 h. Data obtained from a second experiment conducted to examine the effects of inhibin and follistatin on anterior pituitary gonadotropin responses to LHRH were consistent with in vitro data showing direct pituitary effects of the gonadal polypeptides. Collectively, these results demonstrate that both purified porcine follistatin and recombinant human inhibin A profoundly suppress serum FSH levels in a dose- and time-dependent manner, with inhibin being more potent in this regard. Whereas the onset of action is similar for the two polypeptides, the duration of action of follistatin is longer than that for inhibin, suggesting, among other factors, different metabolic clearance rates or different pretranscriptional mechanisms of action of follistatin and inhibin.


Representations of minimum unit pricing for alcohol in UK newspapers: a case study of a public health policy debate.
Mass media influence public acceptability, and hence feasibility, of public health interventions. This study investigates newsprint constructions of the alcohol problem and minimum unit pricing (MUP). Quantitative content analysis of 901 articles about MUP published in 10 UK and Scottish newspapers between 2005 and 2012. MUP was a high-profile issue, particularly in Scottish publications. Reporting increased steadily between 2008 and 2012, matching the growing status of the debate. The alcohol problem was widely acknowledged, often associated with youths, and portrayed as driven by cheap alcohol, supermarkets and drinking culture. Over-consumption was presented as a threat to health and social order. Appraisals of MUP were neutral, with supportiveness increasing slightly over time. Arguments focused on health impacts more frequently than more emotive perspectives or business interests. Health charities and the NHS were cited slightly more frequently than alcohol industry representatives. Emphases on efficacy, evidence and experts are positive signs for evidence-based policymaking. The high profile of MUP, along with growing support within articles, could reflect growing appetite for action on the alcohol problem. Representations of the problem as structurally driven might engender support for legislative solutions, although cultural explanations remain common.


Lymphadenopathy secondary to lamotrigine (Lamictal).
We report lymphadenopathy in a 5-yo-female most likely secondary to lamotrigine. Lamotrigine is effective in the treatment of partial and generalized seizure disorders and often prescribed by neurologists and pediatricians because of its effectiveness in children with idiopathic, resistant generalized seizure disorders; it lacks cognitive impairment. Lamotrigine's chemical structure contains an aromatic ring and is similar to phenytoin, carbamazepine and phenobarbital. The patient had a documented drug allergy to both phenytoin and carbamazepine, and clinically improved following discontinuation of the lamotrigine. Clinicians should be aware of this potential adverse event for patients treated with lamotrigine.


Use of complementary therapies by patients attending musculoskeletal clinics.
Patients with musculoskeletal disorders commonly seek treatment outside orthodox medicine (complementary therapy). In patients attending hospital clinics we investigated the prevalence of such behaviour and the reasons for it. Patients attending rheumatology and orthopaedic clinics who agreed to participate were interviewed on the same day by means of a structured questionnaire in three sections: the first section about demographic characteristics; the second about the nature and duration of the complaint, the length of any treatment and whether the patient was satisfied with conventional treatment; and the third about the use of complementary medicine, the types of therapy that had been considered and the reasoning behind these decisions. The data were examined by univariate and bivariate analysis as well as logistic regression multivariate analysis. 166 patients were interviewed (99% response rate) and the predominant diagnosis was rheumatoid arthritis (22.3%). 109 patients (63%) were satisfied with conventional medical treatment; 63 (38%) had considered the use of complementary therapies, and 47 (28%) had tried such a therapy. 26 of the 47 who had used complementary therapy said they had gained some benefit. Acupuncture, homoeopathy, osteopathy and herbal medicine were the most popular types of treatment to be considered. Patients of female gender (P = 0.009) and patients who had expressed dissatisfaction with current therapies (P = 0.01) were most likely to have considered complementary medicine. These results indicate substantial use of complementary therapy in patients attending musculoskeletal disease clinics. The reasons for dissatisfaction with orthodox treatment deserve further investigation, as does the effectiveness of complementary treatments, which must be demonstrated before they are integrated with orthodox medical practice.


Efficacy of a mineralized collagen bone-grafting material for peri-implant bone defect reconstruction in mini pigs.
The mechanism of the mineralization process induced by natural mineralized collagen (MC) has been investigated for decades. The purpose of this study was to investigate the efficacy of self-assembled MC for peri-implant bone defect reconstruction in a mini pig. A standardized peri-implant bone defect model was created using 14 mini pig mandibles. Two materials were evaluated, i.e. a mixture of hydroxyapatite and collagen (Type A, TA), and self-assembled MC (Type B, TB). Bio-Oss (BO) and untreated (blank control, BC) groups were used as controls. After 3- and 6-month healing periods, the mini pigs were sacrificed for histomorphometric and microcomputed tomography analysis. After 3 months of healing, the average alveolar ridge height was 3.27 ± 1.57 mm for group TA, 3.28 ± 2.02 mm for group TB and 3.37 ± 1.09 mm for group BO, while group BC showed the lowest height of 2.68 ± 0.47 mm. After 6 months of healing, the average alveolar ridge height was 2.64 ± 1.13 mm for group TA, 4.31 ± 1.80 mm for group TB and 3.87 ± 1.38 mm for group BO, while group BC showed the lowest height of 2.48 ± 1.80 mm. The experimental groups and control group showed similar bone volume density, bone complexity and histological reaction. The self-assembled MC (Type B) stimulated new bone formation in the reconstruction of deficient alveolar ridges around the dental implant; it also displayed excellent clinical operability compared with bone grafts without collagen.


Antihypertensive treatment in concomitant peripheral vascular disease: current experience and the potential of carvedilol.
The relative importance of hypertension as a risk factor for peripheral vascular disease is of the same order as coronary artery disease. The design of drug studies in occlusive vascular disease presents several problems. First, investigations must be placebo-controlled and crossover in design. Second, since these patients are very much at risk from other vascular occlusions, length of treatment phase is critical. Third, drug doses are also critical--probably best chosen by titration to similar antihypertensive effect. Fourth, patients must be trained in treadmill procedure. Fifth, measurements of limb blood flow must be accompanied where possible by "functional" assessment, e.g., claudication distance. With respect to the specific problem of low perfusion pressure distal to the blockage of peripheral vasculature, resting blood flow may remain normal, implying compensatory reduction in tone of arteriolar resistance vessels. Thus, regional circulation distal to blockage is sensitive to changes in perfusion pressure. There is the risk of "steal" with vasodilator agents; however, conflict exists in the literature over effects of beta-blockers in this situation. In view of its peripheral hemodynamic profile, the theoretical possibilities with the beta-blocker/vasodilator carvedilol in patients with hypertension and peripheral vascular disease seem extremely rewarding, but remain to be borne out in practice.


Compression strategies for large-scale electrophysiology data.
Objective.With the rapid adoption of high-density electrode arrays for recording neural activity, electrophysiology data volumes within labs and across the field are growing at unprecedented rates. For example, a one-hour recording with a 384-channel Neuropixels probe generates over 80 GB of raw data. These large data volumes carry a high cost, especially if researchers plan to store and analyze their data in the cloud. Thus, there is a pressing need for strategies that can reduce the data footprint of each experiment.Approach.Here, we establish a set of benchmarks for comparing the performance of various compression algorithms on experimental and simulated recordings from Neuropixels 1.0 (NP1) and 2.0 (NP2) probes.Main results.For lossless compression, audio codecs (FLACandWavPack) achieve compression ratios (CRs) 6% higher for NP1 and 10% higher for NP2 than the best general-purpose codecs, at the expense of decompression speed. For lossy compression, theWavPackalgorithm in 'hybrid mode' increases the CR from 3.59 to 7.08 for NP1 and from 2.27 to 7.04 for NP2 (compressed file size of ∼14% for both types of probes), without adverse effects on spike sorting accuracy or spike waveforms.Significance.Along with the tools we have developed to make compression easier to deploy, these results should encourage all electrophysiologists to apply compression as part of their standard analysis workflows.


A noncanonical NF-κB pathway through the p50 subunit regulates Bcl-2 overexpression during an oxidative-conditioning hormesis response.
Cells can respond to damage and stress by activating various repair and survival pathways. One of these responses can be induced by preconditioning the cells with sublethal stress to provoke a prosurvival response that will prevent damage and death, and which is known as hormesis. Bcl-2, an antiapoptotic protein recognized by its antioxidant and prosurvival functions, has been documented to play an important role during oxidative-conditioning hormesis. Using an oxidative-hormetic model, which was previously established in the L929 cell line by subjecting the cells to a mild oxidative stress of 50 μM H₂O₂ for 9 h, we identified two different transductional mechanisms that participate in the regulation of Bcl-2 expression during the hormetic response. These mechanisms converge in activating the nuclear transcription factor NF-κB. Interestingly, the noncanonical p50 subunit of the NF-κB family is apparently the subunit that participates during the oxidative-hormetic response.


Human papillomavirus 16 in the blood of women treated for cervical cancer.
In the present paper we study the behaviors of HPV 16 DNA in the blood of women during oncological treatment. Disappearance of HPV from the blood depends on the clinical Stage of cancer. It is possible that HPV remaining in the blood for a long time after oncological treatment might be some marker showing that the cancer tissue was not completely removed. There is some suggestion that detecting HPV in the cervix or in the blood of women without morphological lesions but with CIN in the past might indicate higher risk of cervical cancer recurrence.


Metabolic alterations in Parkinson's disease after thalamotomy, as revealed by 1H MR spectroscopy.
To determine, using proton magnetic resonance spectroscopy (1H MRS) whether thalamotomy in patients with Parkinson's disease gives rise to significant changes in regional brain metabolism. Fifteen patients each underwent stereotactic thalamotomy for the control of medically refractory parkinsonian tremor. Single-voxel 1H MRS was performed on a 1.5T unit using a STEAM sequence (TR/TM/TE, 2000/14/20 msec), and spectra were obtained from substantia nigra, thalamus and putamen areas, with volumes of interest of 7-8 ml, before and after thalamotomy. NAA/Cho, NAA/Cr and Cho/Cr metabolite ratios were calculated from relative peak area measurements, and any changes were recorded and assessed. In the substantia nigra and thalamus, NAA/Cho ratios were generally low. In the substantia nigra of 80% of patients (12/15) who showed clinical improvement, decreased NAA/Cho ratios were observed in selected voxels after thalamic surgery (p < 0.05). In the thalamus of 67% of such patients (10/15), significant decreases were also noted (p < 0.05). Our results suggest that the NAA/Cho ratio may be a valuable criterion for the evaluation of Parkinson's disease patients who show clinical improvement following surgery. By highlighting variations in this ratio, 1H MRS may help lead to a better understanding of the pathophysiologic processes occurring in those with Parkinson's disease.


Beta vulgaris Assisted Fabrication of Novel Ag-Cu Bimetallic Nanoparticles for Growth Inhibition and Virulence in Candida albicans.
Beta vulgaris extract contains water-soluble red pigment betanin and is used as a food colorant. In this study, the biogenic Ag-Cu bimetallic nanoparticles were synthesized and characterized by different spectroscopic and microscopic techniques, including UV-Visible, FTIR, TEM. SEM-EDX, XRD, and TGA. Further, Ag-Cu bimetallic nanoparticles capped with Beta vulgaris biomolecules were evaluated for their antifungal activity against Candida albicans via targeting its major virulence factors, including adherence, yeast to hyphae transition, extracellular enzyme secretion, biofilm formation, and the expression of genes related to these pathogenic traits by using standard methods. C. albicans is an opportunistic human fungal pathogen that causes significant morbidity and mortality, mainly in immunocompromised patients. The current antifungal therapy is limited with various shortcomings such as host toxicity and developing multidrug resistance. Therefore, the development of novel antifungal agents is urgently required. Furthermore, NPs were screened for cell viability and cytotoxicity effect. Antifungal susceptibility testing showed potent antifungal activity of the Ag-Cu bimetallic NPs with a significant inhibitory effect on adherence, yeast to hyphae transition, extracellular enzymes secretion, and formation of biofilms in C. albicans at sub-inhibitory and inhibitory concentrations. The RT-qPCR results at an MIC value of the NPs exhibited a varying degree of downregulation in expression levels of virulence genes. Results also revealed the dose-dependent effect of NPs on cellular viability (up to 100%) using MUSE cell analyzer. Moreover, the low cytotoxicity effect of bimetallic NPs has been observed using haemolytic assay. The overall results indicated that the newly synthesized Ag-Cu bimetallic NPs capped with Beta vulgaris are proven to possess a potent anticandidal activity, by affecting the vital pathogenic factors of C. albicans.


Berberine Recovered Oxidative Stress Induced by Sodium Nitrite in Rat Erythrocytes.
Berberine, a plant derived alkaloid, present in Berberis species is well known as one of the most important antioxidants. The current research aimed to study the heamatoprotective characteristics of berberine and clarify its plausible mechanisms against sodium nitrite. Forty numbers of male Sprague Dawley rats were categorized into five equal groups, including group 1: control (normal saline); group 2: berberine (100 mg/kg); group 3: sodium nitrite (80 mg/kg); group 4: sodium nitrite (80 mg/kg) plus berberine (50 mg/kg) and group 5: sodium nitrite (80 mg/kg) plus berberine (100 mg/kg) groups. All animals were orally administrated for two months once daily. At the end of the 60th day, blood samples were withdrawn by cardiac puncture and collected in test vials when the animals had been anesthetized with ketamine (70 mg/kg). Then, hemolysate was prepared and the oxidative stress biomarkers, lipid peroxidation, and antioxidant capacity of erythrocytes were evaluated. Feeding of rats with sodium nitrite remarkably enhanced malondialdehyde (MDA) (p=0.001) levels and considerably reduced the levels of glutathione (GSH) (p=0.001), and also reduced the enzymatic activities of glutathione peroxidase (GPx) (p=0.02), superoxide dismutase (SOD) (p=0.001), glutathione reductase (GR) (p=0.02), and catalase (CAT) (p=0.01). However, the co-administration of these animals with 100 mg/kg of berberine remarkably reverted the values to reach nearly a normal level. While 50 mg/kg berberine failed to restore significantly all of these antioxidant biomarkers at a normal level. Our results clearly demonstrated that berberine in a dose-dependent manner led to protection against sodium nitrite-induced oxidative injury in rat erythrocytes, which possibly reflects the antioxidant ability of this alkaloid.


Optimization of Railway Mixed Goods Loading Layout considering Stability.
It is well known that stability, center-of-gravity balance, and concentrated-weight are key factors of the transportation safety. The reasonable formulation of the loading layout scheme ensures the safety of shipment based on fully utilizing the effective volume and load capacity of freight vehicles. This paper takes the railway mixed goods loading layout as the research object, considering the constraints such as goods loading center-of-gravity balance, the allowable moment of concentrated-weight, supporting and goods placement mode, and taking the maximum comprehensive utilization rates for both effective volume and load capacity of freight vehicle as the optimization objective, an optimization model of railway mixed goods balanced and anticoncentrated-weight loading layout considering stability is built. Additionally, this paper designs mixed goods classified and simple/general goods block composition methods. We improve the representation and selection of layout space, construct goods block selection algorithm based on the greedy d-step lookahead tree search and goods block evaluation function and propose a goods block placement strategy and update rules of layout space after goods block placement. An optimization algorithm of railway mixed goods balanced and anticoncentrated-weight load layout considering stability is designed. The results show that the formulated scheme not only ensures that the goods meet the full support constraints, but also the comprehensive utilization rate of the effective volume and load capacity of the vehicle is not less than 89%, and the probability of meeting the loading center-of-gravity balance and allowable moment of concentrated-weight are as high as 99% and 99.47%, respectively. The proposed method realizes the balanced and anticoncentrated-weight loading of railway mixed goods, ensures the safe, stable, and efficient goods loading, and provides decision support for the safe loading layout of railway goods.


Pregnancy wastage and reproductive aging: the oocyte donation model.
Women are most successful in achieving pregnancy and delivering a healthy child when in their twenties. Natural selection against conception contributes to pregnancy wastage as women age. This phenomenon is principally a result of detrimental changes occurring within the pool of available oocytes. Oocyte donation provides a unique opportunity to study the effect of individual components of the reproductive tract by isolating the uterus from the gamete. When oocytes from young women are used to create embryos for transfer to older recipients, implantation and pregnancy rates mimic those seen in younger individuals. Furthermore, following oocyte donation, the number of miscarriages and chromosomal anomalies dramatically decreases, implying that the uterus is not responsible for the poor outcomes normally experienced by women of advanced reproductive age.


Nonlinear Band Gap Dependence of Mixed Pb-Sn 2D Ruddlesden-Popper PEA2Pb1-xSnxI4 Perovskites.
Two-dimensional (2D) Ruddlesden-Popper perovskites (RPPs) of the form PEA2Pb1-xSnxI4 can be used as the tunable active layer in photovoltaics, as the passivating layer for 3D perovskite photovoltaics or in light emitting diodes. Here, we show a nonlinear band gap behavior with Sn content in mixed phase 2D RPPs. Density functional theory calculations (with and without spin-orbit coupling) are employed to study the effects of the short-range ordering of Pb and Sn in PEA2Pb1-xSnxI4 compositions with x = 0, 0.25, 0.5, 0.75, and 1. Analysis of the partial density of states shows that the energy mismatch of the Pb 6s and Sn 5s states in the valence band maximum determines the nonlinearity of the band gap, leading to a bowing parameter of 0.35-0.38 eV. This research provides a critical insight for the design of future metal alloy 2D perovskite materials. The positions of the tunable energy band discontinuity may point to intraband transitions of interest to device engineers.


Decreasing the costs of constant observation.
A performance improvement project employed a bachelor's-prepared psychiatric liaison nurse (PLN) to reduce one-to-one (1:1) constant observation (CO) on all medical patient-care areas of a large, metropolitan hospital. The project succeeded in cutting the costs of CO in half. It showed that PLNs can safely facilitate large reductions in CO without associated increases in falls or restraint prevalence, yielding significant cost savings for hospitals.


Lucky Rhythms in Orbitofrontal Cortex Bias Gambling Decisions in Humans.
It is well established that emotions influence our decisions, yet the neural basis of this biasing effect is not well understood. Here we directly recorded local field potentials from the OrbitoFrontal Cortex (OFC) in five human subjects performing a financial decision-making task. We observed a striking increase in gamma-band (36-50 Hz) oscillatory activity that reflected subjects' decisions to make riskier choices. Additionally, these gamma rhythms were linked back to mismatched expectations or "luck" occurring in past trials. Specifically, when a subject expected to win but lost, the trial was defined as "unlucky" and when the subject expected to lose but won, the trial was defined as "lucky". Finally, a fading memory model of luck correlated to an objective measure of emotion, heart rate variability. Our findings suggest OFC may play a pivotal role in processing a subject's internal (emotional) state during financial decision-making, a particularly interesting result in light of the more recent "cognitive map" theory of OFC function.


Long-term pulmonary sequelae in children who were treated with extracorporeal membrane oxygenation for neonatal respiratory failure.
Extracorporeal membrane oxygenation (ECMO) is a life-saving therapy for neonates with intractable respiratory failure, but the long-term pulmonary outcome is unknown. Our aim was to investigate the long-term pulmonary sequelae of these children. We studied 50 children at 11.1 +/- 1.1 years (mean +/- SD) who had been treated with neonatal ECMO for meconium aspiration syndrome (38%), sepsis (18%), sepsis with pneumonia (12%), congenital diaphragmatic hernia (12%), congenital heart disease (8%), persistent pulmonary hypertension of the newborn (6%), and respiratory distress syndrome (4%) and 27 healthy controls (10.8 +/- 1.6 years). All subjects completed a respiratory questionnaire and performed pulmonary function and graded cardiopulmonary exercise testing. Neonatal ECMO survivors had hyperinflation (median residual volume: 131%), airway obstruction (median forced expired volume in 1 second: 79%), lower oxygen saturation with exercise, and lower peak oxygen consumption than controls. The ECMO group achieved similar exercise minute ventilation to controls, with more rapid and shallow breathing. ECMO survivors had an increased frequency of exercise-induced bronchospasm. Those who required higher inspired oxygen tension and ventilator pressures after weaning from ECMO had lower forced expired volume in 1 second and oxygen saturation values. Neonatal ECMO survivors experience lung injury lasting into later childhood. Lung dysfunction correlates with the extent and duration of barotrauma and oxygen exposure as neonates.


[Elimination of hepatitis C, our progress, challenges and hopes].
Hepatitis C infection is a serious public health threat, and the World Health Organization has recommended the elimination of public health threats from viral hepatitis, including hepatitis C, by 2030. Many countries and regions are actively exploring strategies and models to eliminate the public health threat of hepatitis C. It is estimated that there are at least 7.6 million cases of chronic hepatitis C in China, with both diagnosis and treatment rates far away to 2030 target. China's government, social organizations and doctors at different levels are also actively exploring the mode of eliminating the public health threat of hepatitis C in China, including the main mode supported by national standards, government-led mode, social institution undertaking and government-supported mode, medical alliance mode, screening in high-prevalence areas and services contracted with family doctors. China can have a lessons learning from international and ourselves experience, particularly as "Test and treat all based on needs and demand" strategy in Covid-19 control, finally achieve eliminate the public health threat of hepatitis C as soon as possible.


T-independent activation of single B cells: an orderly analysis of overlapping stages in the activation pathway.
This review has three chief purposes. It describes a microculture system in which single, hapten-specific B lymphocytes can be microscopically observed, cultured and assayed for antibody production in isolation and thus are the unequivocal target of ligands present in the culture fluid. It defines the respective roles of antigens and cytokines acting singly or in combination in the four discernible phases of the immunoproliferative cascade, namely activation, clonal expansion, IgM antibody secretion and isotype switching. It then argues that this precise stepwise analysis can yield useful information concerning important immunological situations, such as experimentally induced immunological tolerance or the effects of constitutive expression of the c-myc oncogene. Evidence is presented that initial activation of the resting B cell in "T-independent" triggering can be achieved either by attachment of a molecule that has B-cell stimulatory properties, such as FLU-LPS or FLU-polymerized flagellin (FLU-POL) or by the lymphokine interleukin 4 (IL-4). IL-4 + FLU-POL is somewhat more effective than either agent alone. IL-4 alone or, better, FLU-POL + IL-4 can stimulate clonal proliferation of the B cell, but FLU-POL alone does not achieve this. Moreover, IL-4 or FLU-POL + IL-4 lead to very little antibody formation. None of IL-1, IL-2 or IL-5 acting alone causes either activation or proliferation. IgM antibody formation is stimulated most strongly by FLU-POL + IL-5, somewhat less strongly by FLU-POL + IL-1 + IL-2 and rather weakly with antigen plus only one of the latter cytokines. The cloning efficiency in the single cell system, and the median clone size can be markedly enhanced by the addition of small numbers of fibroblast or other filler cells to the cultures. While filler cell-free clones do not progress to the stage of isotype switching, filler cell-supported ones can do so in up to 30% of cases. The only cloned lymphokine which has so far been found to promote such switching is IL-4, and the fact that it is at least as powerful as a T-cell supernatant may mean that it is the only agent active in this particular system. However, the detailed pattern of secreted isotypes is different from that seen when MHC-restricted, carrier-specific T cells act on hapten-specific B cells. Hapten-specific B cells from animals rendered neonatally tolerant to FLU-HGG exhibit anergy in the single cell system.(ABSTRACT TRUNCATED AT 400 WORDS)