A Cross-Sectional Study on the Knowledge, Attitudes, and Oral Hygiene Practices of Secondary School Students in Al-Qunfudah District, Saudi Arabia.
Background Oral health is closely related to general health awareness and good oral hygiene practices, which makes it an important aspect of general health and well-being. The current study assessed the knowledge, attitudes, and practices of oral hygiene among secondary school students in Al-Qunfudah district, Saudi Arabia. Methods A convenient sample of 383 male and female secondary school students in the Al-Qunfudah district, Saudi Arabia, was included in this descriptive cross-sectional study. The research data were collected from the study sample through a self-administered online survey via WhatsApp and Telegram electronic applications. Finally, the collected data were coded and analyzed through the Statistical Package for the Social Sciences (SPSS) version 25.0 (SPSS Inc., Chicago, IL) and expressed in frequencies, percentages, mean, and standard deviation. The chi-squared and Fisher's exact tests were applied to assess the relationship between the participants' knowledge and practice scores of oral hygiene and their demographic characteristics. A P-value of less than 0.05 was regarded as significant. Results In this study, female students represented 70% of the sample, and most of them were Saudi (97.0%). Many of them identified the great impact of oral hygiene on overall health (89.2%), and more than two-thirds indicated that brushing their teeth regularly would prevent oral problems (89.2%). Nearly two-thirds of them perceived that dental problems would affect their school attendance; however, 59.1% ignored the important role of schools in maintaining students' oral hygiene. The poor practice of dental care was observed among students, as 47.5% brush their teeth twice daily and a third replace their brushes every three months. Despite the fact that the majority of the study population had adequate knowledge (44.4%) and a positive attitude (78.6%) toward oral hygiene, only 39.9% could effectively apply it. The knowledge of oral hygiene was significantly better among females (P = 0.005), older students (P = 0.001), those at a higher academic level (P = 0.016), and students from Al-Qunfudah city (P = 0.007). Furthermore, older pupils, those with a higher academic level, and those from Al-Qunfudah city performed better in terms of dental hygiene than their peers (P-value was 0.001 for each). Conclusion Secondary school students generally have adequate awareness levels and positive attitudes toward oral hygiene, but they practice it with remarkably little consistency. Schools should emphasize their crucial roles in enhancing oral health among their students of different education levels through their curriculum and frequent monitoring of students. Persuasive and realistic oral health education initiatives are recommended for schoolchildren and their family members or caregivers, with a particular emphasis on males, younger children, and those living in rural areas.


Chlotrichenes A and B, Two Lindenane Sesquiterpene Dimers with Highly Fused Carbon Skeletons from Chloranthus holostegius.
Two unprecedented lindenane sesquiterpene dimers, chlotrichenes A (1) and B (2), were obtained from Chloranthus holostegius var. trichoneurus. Their structures were characterized by NMR, ECD, and X-ray diffraction analysis. They possess a new type of spirocarboncyclic dimeric framework formed by endo-Diels-Alder reaction, and the structure of 1 features a unique 3/5/6/6/6/6/5/3-fused octacyclic skeleton by subsequently plausible epoxidation-cyclization reactions of 2. Compound 2 showed synergetic cytotoxicity with DOX on U2 OS cells (CI: 0.94 ± 0.03).


Pyrazolylthiazole as DeltaF508-cystic fibrosis transmembrane conductance regulator correctors with improved hydrophilicity compared to bithiazoles.
Deletion of phenylalanine residue 508 (DeltaF508) in the cystic fibrosis (CF) transmembrane conductance regulator protein (CFTR) is a major cause of CF. Small molecule "correctors" of defective DeltaF508-CFTR cellular processing hold promise for CF therapy. We previously identified and characterized bithiazole CF corrector 1 and s-cis-locked bithiazole 2. Herein, we report the regiodivergent synthesis of Ngamma and Nbeta isomers of thiazole-tethered pyrazoles with improved hydrophilicity compared to bithiazoles. We synthesized a focused library of 54 pyrazolylthiazoles 3, which included examples of both regioisomers 4 and 5. The thiazole-tethered pyrazoles allowed incorporation of property-modulating functionality on the pyrazole ring (ester, acid, and amide) while retaining DeltaF508-CFTR corrector activity (EC(50)) of under 1 microM. The most active pyrazolylthiazole (14h) has an experimentally determined log P of 4.1, which is 1.2 log units lower than bithiazole CF corrector 1.


[Magnetic resonance imaging in prenatal diagnosis].
Author discusses methods of magnetic resonance imaging and in status in the prenatal diagnosis as well as the impact of examination on the management plan for treatment of fetus and newborn.


Distribution of microtubules in cultured RPE cells from normal and dystrophic RCS rats.
Indirect immunofluorescence and antibodies to tubulin were used to visualize the distribution of microtubules (MT) in short-term primary cultures of retinal pigment epithelial (RPE) cells isolated from the eyes of control RCS rats and those with inherited retinal degeneration. At all stages of cell spreading in vitro, the pigment granules (PG) in these cells remained tightly clustered in the perinuclear region, surrounded by numerous MT. Initially, in relatively round cells, the perinuclear region was encompassed by a closely woven ring of circularly arranged MT. At later stages of spreading, the ring had disappeared and MT running in various directions could be observed. Cells that were plated singly assumed at first a discoid, then stellate, shape during spreading, whereas, those plated in small groups formed colonies of wedge-shaped cells. In well-spread single cells or colonies, a brightly fluorescent zone that appeared to contain the highest density of MT within the cells was located between the PG-containing perinuclear region and the spreading edges of the cells. A single prominent star-shaped structure from which a number of MT radiated was situated among the PG in the perinuclear region of each cell; we believe this structure corresponds to the centrioles. It was generally well-separated from the regions of highest MT density. No differences in cell shape or in the distribution of MT, centriole-containing regions or PG in spreading or fully spread cells were detected when RPE cells from normal and dystrophic RCS rats were compared. Thus, the distribution of MT and their assembly during cell spreading appear normal in RPE cells of the dystrophic rat.


Differential expression of tissue factor and tissue factor pathway inhibitor in metastatic melanoma lesions.
Tissue factor (TF) is involved in tumor progression and metastatic potency in some malignant tumors and its function is regulated by tissue factor pathway inhibitor (TFPI) therefore the interaction of both molecules is crucial for their functional role. We evaluated the clinical relevance of TF and TFPI expression in benign and malignant melanocytic lesions. Expression of both was examined by immunoperoxidase staining using serial tissue sections in 16 nevi, 34 primary and 15 metastatic melanoma lesions. TF and TFPI were ubiquitously expressed in benign and malignant melanocytic lesions. This finding was confirmed by Western blot analysis using cultured human melanocytes, nevi cells (NCN) and melanoma cell lines. Although TF expression was not associated with malignant transformation and disease progression, TFPI expression in primary and metastatic melanoma lesions was significantly lower and weaker than that in nevi lesions in terms of intensity and percentage of stained cells. In addition, TFPI expression in metastatic lesions was significantly lower and weaker than that of TF. These results suggest that the relative expression of TF to TFPI may play a crucial role in the malignant transformation and metastatic potency in melanocytic cells.


Pathogenesis and clinical management of Helicobacter pylori gastric infection.
Helicobacter pylori (H. pylori) is a gram-negative bacterium that infects approximately 4.4 billion individuals worldwide. However, its prevalence varies among different geographic areas, and is influenced by several factors. The infection can be acquired by means of oral-oral or fecal-oral transmission, and the pathogen possesses various mechanisms that improve its capacity of mobility, adherence and manipulation of the gastric microenvironment, making possible the colonization of an organ with a highly acidic lumen. In addition, H. pylori presents a large variety of virulence factors that improve its pathogenicity, of which we highlight cytotoxin associated antigen A, vacuolating cytotoxin, duodenal ulcer promoting gene A protein, outer inflammatory protein and gamma-glutamyl transpeptidase. The host immune system, mainly by means of a Th1-polarized response, also plays a crucial role in the infection course. Although most H. pylori-positive individuals remain asymptomatic, the infection predisposes the development of various clinical conditions as peptic ulcers, gastric adenocarcinomas and mucosa-associated lymphoid tissue lymphomas. Invasive and non-invasive diagnostic methods, each of them with their related advantages and limitations, have been applied in H. pylori detection. Moreover, bacterial resistance to antimicrobial therapy is a major challenge in the treatment of this infection, and new therapy alternatives are being tested to improve H. pylori eradication. Last but not least, the development of effective vaccines against H. pylori infection have been the aim of several research studies.


Molecular Sieving of Ethane from Ethylene through the Molecular Cross-Section Size Differentiation in Gallate-based Metal-Organic Frameworks.
Purification of C2 H4 from an C2 H4 /C2 H6 mixture, one of the most important while challenging industrial separation processes, is mainly through energy-intensive cryogenic distillation. Now a family of gallate-based metal-organic framework (MOF) materials is presented, M-gallate (M=Ni, Mg, Co), featuring 3D interconnected zigzag channels, the aperture sizes of which (3.47-3.69 Å) are ideally suitable for molecular sieving of ethylene (3.28×4.18×4.84 Å3 ) and ethane (3.81×4.08×4.82 Å3 ) through molecular cross-section size differentiation. Co-gallate shows an unprecedented IAST selectivity of 52 for C2 H4 over C2 H6 with a C2 H4 uptake of 3.37 mmol g-1 at 298 K and 1 bar, outperforming the state-of-the-art MOF material NOTT-300. Direct breakthrough experiments with equimolar C2 H4 /C2 H6 mixtures confirmed that M-gallate is highly selective for ethylene. The adsorption structure and mechanism of ethylene in the M-gallate was further studied through neutron diffraction experiments.


Pluripotent stem cell-based models of spinal muscular atrophy.
Motor neuron diseases, as the vast majority of neurodegenerative disorders in humans, are incurable conditions that are challenging to study in vitro, owing to the obstacles in obtaining the cell types majorly involved in the pathogenesis. Recent advances in stem cell research, especially in the development of induced pluripotent stem cell (iPSC) technology, have opened up the possibility of generating a substantial amount of disease-specific neuronal cells, including motor neurons and glial cells. The present review analyzes the practical implications of iPSCs, generated from fibroblasts of patients affected by spinal muscular atrophy (SMA), and discusses the challenges in the development and optimization of in vitro disease models. Research on patient-derived disease-specific cells may shed light on the pathological processes behind neuronal dysfunction and death in SMA, thus providing new insights for the development of novel effective therapies.


Homoleptic Alkynylphosphonium Au(I) Complexes as Push-Pull Phosphorescent Emitters.
A series of compounds P1-P4 bearing terminal alkynyl sites connected with a phosphonium group via different π-conjugated linkers have been synthesized. The compounds themselves are efficient push-pull emitters and exhibit bright fluorescence in blue and near-UV regions. P1-P4 were used as alkynyl ligands to obtain a series of homoleptic bis-alkynyl Au(I) complexes 1-4. The complexes demonstrate bright phosphorescence and dual emission with dominating phosphorescence (2-4). Terphenyl derivative complex 3 exhibits warm white emission in DMSO solution and pure white emission in PMMA films. Time-dependent density functional theory calculations have shown that the T1 excited state has a hybrid MLCT/ILCT nature with a dominant contribution of charge transfer across a ligand-centered "D-π-A" system. The variation of linker allows tuning the effect of intermolecular charge transfer and thus changing the electronic and photophysical properties of the organogold "D-π-A" system. The results presented unambiguously display the advances of the conception of organometallic "D-π-A" construction.


Artery of Percheron Infarct - a diagnostic and prognostic conundrum!
A 39 year old male was found unconscious at home. On arrival to the hospital the patient was profoundly somnolent but easily rousable, with no focal neurological deficits. Imaging confirmed bilateral thalamic infarcts from the occlusion of Artery of Percheron, a rare anatomic variant which is a single arterial trunk supplying the thalamus and midbrain bilaterally. Anti-platelet therapy was initiated as soon as the diagnosis was established and the patient showed a rapid remarkable recovery over the next 48 hours. He continued to improve subsequently and was at baseline functional status at 6 months. Extensive investigations for etiologies were mostly unrevealing. In such patients presenting with drowsiness/somnolence, a posterior circulation stroke should be considered if no evidence of other more common causes are found. A CT head must be followed by an MRI to confirm the diagnosis and subsequent focus should be on eliciting risk factors and careful evaluation for etiologies.


Emergent epileptiform activity drives spinal sensory circuits to generate ectopic bursting in intraspinal afferent axons after cord injury.
Spinal cord injury ( SCI ) leads to hyperexcitability and dysfunction in spinal sensory processing. As hyperexcitable circuits can become epileptiform elsewhere, we explored whether such activity emerges in spinal sensory circuits in a thoracic SCI contusion model of neuropathic pain. Recordings from spinal sensory axons in multiple below-lesion segmental dorsal roots ( DRs ) demonstrated that SCI facilitated the emergence of spontaneous ectopic burst spiking in afferent axons, which synchronized across multiple adjacent DRs. Burst frequency correlated with behavioral mechanosensitivity. The same bursting events were recruited by afferent stimulation, and timing interactions with ongoing spontaneous bursts revealed that recruitment was limited by a prolonged post-burst refractory period. Ectopic bursting in afferent axons was driven by GABA A receptor activation, presumably via shifting subthreshold GABAergic interneuronal presynaptic axoaxonic inhibitory actions to suprathreshold spiking. Collectively, the emergence of stereotyped bursting circuitry with hypersynchrony, sensory input activation, post-burst refractory period, and reorganization of connectivity represent defining features of epileptiform networks. Indeed, these same features were reproduced in naïve animals with the convulsant 4-aminopyridine ( 4-AP ). We conclude that SCI promotes the emergence of epileptiform activity in spinal sensory networks that promotes profound corruption of sensory signaling. This corruption includes downstream actions driven by ectopic afferent bursts that propagate via reentrant central and peripheral projections and GABAergic presynaptic circuit hypoexcitability during the refractory period.


Detection of a dynamic topography signal in last interglacial sea-level records.
Estimating minimum ice volume during the last interglacial based on local sea-level indicators requires that these indicators are corrected for processes that alter local sea level relative to the global average. Although glacial isostatic adjustment is generally accounted for, global scale dynamic changes in topography driven by convective mantle flow are generally not considered. We use numerical models of mantle flow to quantify vertical deflections caused by dynamic topography and compare predictions at passive margins to a globally distributed set of last interglacial sea-level markers. The deflections predicted as a result of dynamic topography are significantly correlated with marker elevations (>95% probability) and are consistent with construction and preservation attributes across marker types. We conclude that a dynamic topography signal is present in the elevation of last interglacial sea-level records and that the signal must be accounted for in any effort to determine peak global mean sea level during the last interglacial to within an accuracy of several meters.


Detection and prevalence of Haemoproteus archilochus (Haemosporida, Haemoproteidae) in two species of California hummingbirds.
Haemosporidian blood parasites are transmitted to a wide range of avian hosts via blood-sucking dipteran vectors. Microscopy has revealed an impressive diversity of avian haemosporidia with more than 250 species described. Moreover, PCR and subsequent sequence analyses have suggested a much greater diversity of haemosporidia than morphological analyses alone. Given the importance of these parasites, very few studies have focused on the charismatic hummingbirds. To date, three Haemoproteus species (Haemoproteus archilochus, Haemoproteus trochili, and Haemoproteus witti) and one Leucocytozoon species (Leucocytozoon quynzae) have been described in blood samples taken from hummingbirds (Trochilidae). Unconfirmed Plasmodium lineages have also been detected in hummingbirds. Here, we report the detection of H. archilochus in two hummingbird species (Calypte anna and Archilochus alexandri) sampled in Northern California and perform a phylogenetic analysis of mitochondrial cytochrome b (cyt b) gene lineages. A total of 261 hummingbirds (157 C. anna, 104 A. alexandri) were sampled and screened for blood parasites using PCR and microscopy techniques. Combining both methods, 4 (2.55%) haemosporidian infections were detected in C. anna and 18 (17.31%) haemosporidian infections were detected in A. alexandri. Molecular analyses revealed four distinct H. archilocus cyt b lineages, which clustered as a monophyletic clade. No species of Plasmodium or Leucocytozoon were detected in this study, raising the possibility of specific vector associations with hummingbirds. These results provide resources for future studies of haemosporidian prevalence, diversity, and pathogenicity in California hummingbird populations.


Memory beyond memory in heart beating, a sign of a healthy physiological condition.
We describe two types of memory and illustrate each using artificial and actual heartbeat data sets. The first type of memory, yielding anomalous diffusion, implies the inverse power-law nature of the waiting time distribution and the second the correlation among distinct times, and consequently also the occurrence of many pseudoevents, namely, not genuinely random events. Using the method of diffusion entropy analysis, we establish the scaling that would be determined by the real events alone. We prove that the heart beating of healthy patients reveals the existence of many more pseudoevents than in the patients with congestive heart failure.


[Obstetrical analgesia in a woman allergic to ethylene oxide].
A case is reported of a 28 year old woman, with untreated mitral valve disease and a professional allergy to ethylene oxide and phthalic anhydride, who presented with acute hydramnios during the 35th week of pregnancy. Emergency caesarean section having been decided on, a urinary catheter--sterilized by gamma rays and not ethylene oxide--was inserted; the gloves used had however been sterilized in ethylene oxide gas, and the patient rapidly presented with anaphylactic shock. The needles and intravenous infusion equipment used were all either sterilized in gamma rays or rinsed in large quantities of liquid. It was decided to abandon the caesarean section and attempt a vaginal delivery using morphine spinal analgesia; epidural analgesia was absolutely contraindicated because the catheters were sterilized in ethylene oxide and the patient's haemodynamic state was too precarious. Caudal anaesthesia with 0.25% bupivacaine was used to complete the spinal analgesia and speed up cervical dilation. The child was delivered with forceps and the diagnosis of oesophageal atresia was confirmed.


International comparisons of the home mathematics environment and relations with children's mathematical achievement.
Home mathematics environment (HME) research has focused on parent-child interactions surrounding numerical activities as measured by the frequency of engaging in such activities. However, HME survey questions have been developed from limited perspectives (e.g., Early Childhood Research Quarterly, 27, 2012, 231; Journal of Social Issues, 64, 2008, 95; Early childhood mathematics education research: Learning trajectories for young children, Routledge, New York, 2009), by researchers from a small subset of countries (15; Psychological Bulletin, 147, 2020, 565), which may skew our interpretations. This study broadened international representation by leveraging secondary data from the 2019 TIMSS to examine the variation of the frequency and reliability of the HME scale and its relation to children's mathematical achievement. Across 54 countries, 231,138 parents and children (Mage = 10.22 years; 51% male) participated in the larger study. Parents completed a retrospective home environment survey and children were assessed on mathematics skills. Basic frequency descriptive statistics, Cronbach's alpha reliability coefficients, and Pearson's r correlation coefficients were used to assess variability across countries. Findings suggested that families in certain countries engaged in home mathematics activities more frequently than families in other countries; however, the HME scale demonstrated acceptable internal consistency across families in all countries (M α = .79; range = [.73, .89]). Further, the average relation between HME and mathematical achievement was r = .15 with a range between r = .02 to r = .41. Our results indicate substantial variation across countries in the HME-mathematical achievement association. These findings underscore the importance of international representation in advancing research on the diversity of a child's home environment.


Highly effective synthesis of NiO/CNT nanohybrids by atomic layer deposition for high-rate and long-life supercapacitors.
In this work, we report an atomic layer deposition (ALD) method for the fabrication of NiO/CNT hybrid structures in order to improve electronic conductivity, enhance cycling stability and increase rate capability of NiO used as supercapacitor electrodes. A uniform NiO coating can be well deposited on carbon nanotubes (CNTs) through simultaneously employing O3 and H2O as oxidizing agents in a single ALD cycle of NiO for the first time, with a high growth rate of nearly 0.3 Å per cycle. The electrochemical properties of the as-prepared NiO/CNT were then investigated. The results show that the electrochemical capacitive properties are strongly associated with the thickness of the NiO coating. The NiO/CNT composite materials with 200 cycles of NiO deposition exhibit the best electrochemical properties, involving high specific capacitance (622 F g(-1) at 2 A g(-1), 2013 F g(-1) for NiO), excellent rate capability (74% retained at 50 A g(-1)) and outstanding cycling stability. The impressive results presented here suggest a great potential for the fabrication of composite electrode materials by atomic layer deposition applied in high energy density storage systems.


Results of a culturally directed asthma intervention program in an inner-city Latino community.
To determine the effect of an asthma intervention program targeted to a predominantly Latino population of inner-city, adult asthma patients with a recent emergency department (ED) visit for asthma care. A prospective study measuring changes in asthma quality of life (QOL), asthma knowledge, and ED and hospital utilization in a group of patients enrolled in an outpatient asthma intervention program. Academic medical center located in New York City (NYC) and a local community-based organization. One hundred ninety-eight patients with asthma > 18 years of age and residing in Washington Heights/Inwood, a predominantly Latino community in NYC. Changes were assessed by hospital and ED utilization and mini-Juniper QOL score before and after the intervention. From July 2000 through December 2002, 198 patients agreed to be enrolled into an asthma intervention program. The mini-Juniper QOL score improved by 0.67 points. There was a 40% reduction in ED visits and a 36% reduction in hospitalizations over 1 year, compared with a 10% reduction in ED visits and no reduction in hospitalization rate for a control group who declined the intervention. A culturally targeted asthma intervention program in adult individuals living in a predominantly Latino area of NYC is effective in reducing ED and hospital utilization for asthma, and improving overall asthma-related QOL.


Lanolin for the treatment of nipple pain in breastfeeding women: a randomized controlled trial.
Nipple pain and damage are commonly experienced by breastfeeding women and are associated with negative breastfeeding outcomes. Health care providers often recommend the application of lanolin to treat painful/damaged nipples, yet no randomized controlled trial has evaluated the effectiveness of lanolin on nipple pain and breastfeeding outcomes. The purpose of this study was to evaluate the effect of lanolin on nipple pain among breastfeeding women with damaged nipples. A randomized, single-blind, controlled trial was conducted at a tertiary care hospital in Hamilton, Ontario, Canada. Breastfeeding women (N = 186) identified as having nipple pain/damage were randomized to apply lanolin (intervention group; n = 93) or to receive usual postpartum care (control group; n = 93). The primary outcome was nipple pain at 4 days post-randomization measured by the Numeric Rating Scale. Additional outcomes included nipple pain measured by the Short Form McGill Pain Questionnaire, breastfeeding duration/exclusivity, breastfeeding self-efficacy, and maternal satisfaction with lanolin treatment versus usual care. The results revealed no significant group differences in mean pain scores at 4 days post-randomization. Women in both groups experienced clinically relevant decreases in nipple pain by 7 days post-randomization. Significantly, more women in the lanolin group reported that they were satisfied with treatment compared with those receiving usual care. No significant group differences were found for other secondary outcomes. While more women were satisfied using lanolin, its application to sore/damaged nipples was ineffective for reducing nipple pain or improving breastfeeding outcomes.


[Effects of lipid rafts on signal transmembrane transduction mediated by c-Met].
To study the effects of lipid rafts on cell signal transmembrane transduction mediated by c-Met. After HepG2Cells were treated with MbCD to disrupt the lipid rafts and were treated with artificial recombination hepatocyte growth factor to activate c-Met, the activities of PLCr1/PKC, PI3K/Akt and MAPK signaling pathways in HepG2 cells were analyzed using Western blot. (1) After disruption of lipid rafts with MbCD, phosphorylation of PLCr1 decreased by 35% (P = 0.022); the content of PLCr in the cytoplasm increased by 1.75 fold (P = 0.017); PLCr1 conjugated with membrane decreased by 30% (P = 0.037). (2) The content of PKB in the cytosol decreased by 38% (P = 0.028), and the phosphorylation level of PKB conjugated with membrane decreased by 14% (P = 0.041). At the same time, PDK translocation from cytosol to the plasma membrane and its activation were inhibited by treatment with MbCD. (3) Treatment with MbCD had no significant effect on ErK/MAPK, p38/MAPK and JNK/MAPK signaling pathways. Disruption of lipid rafts with MbCD inhibits the activation of PLCr1/PKC and PI3K/PKB signaling pathways by HGF/cMet, but has no effect on MAPK signaling pathway.


Ultrastructural changes of erythrocytes in whole blood after exposure to prospective in silico-designed anticancer agents: a qualitative case study.
Novel, in silico-designed anticancer compounds were synthesized in our laboratory namely, 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol) and 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16). These compounds were designed to have improved bioavailability when compared to their source compound, 2-methoxyestradiol. This theoretically would be due to their increased binding affinity to carbonic anhydrase II, present in erythrocytes. Since the novel compounds under investigation are proposed to be transported within erythrocytes bound to carbonic anhydrase II, the morphological effect which they may exert on whole blood and erythrocytes is of great significance. A secondary outcome included revision of previously reported procedures for the handling of the whole blood sample. The purpose of this study was twofold. Firstly, the ultrastructural morphology of a healthy female's erythrocytes was examined via scanning electron microscopy (SEM) after exposure to the newly in silico-designed compounds. Morphology of erythrocytes following exposure to ESE-15-ol and ESE-16 for 3 minutes and 24 hours at 22°C were described with the use of SEM. The haemolytic activity of the compounds after 24 hours exposure were also determined with the ex vivo haemolysis assay. Secondly, storage conditions of the whole blood sample were investigated by determining morphological changes after a 24 hour storage period at 22°C and 37°C. No significant morphological changes were observed in the erythrocyte morphology after exposure to the novel anticancer compounds. Storage of the whole blood samples at 37°C for 24 hours resulted in visible morphological stress in the erythrocytes. Erythrocytes incubated at 22°C for 24 hours showed no structural deformity or distress. From this research the optimal temperature for ex vivo exposure of whole blood samples to ESE-15-ol and ESE-16 for 24 hours was determined to be 22°C. Data from this study revealed the potential of these compounds to be applied to ex vivo study techniques, since no damage occurred to erythrocytes ultrastructure under these conditions. As no structural changes were observed in erythrocytes exposed to ESE-15-ol and ESE-16, further ex vivo experiments will be conducted into the potential effects of these compounds on whole blood. Optimal incubation conditions up to 24 hours for whole blood were established as a secondary outcome.


[Surgery in acute pulmonary embolism can be a life-saving therapeutic alternative. A follow up of surgically treated patients].
Acute pulmonary embolism occurs in about 10,000 people annually in Sweden, in more than 1000 of whom it has a fatal outcome. The clinical presentation may vary considerably, and a large number of patients with pulmonary embolism are still misdiagnosed. Most patients are treated with anticoagulants and some also with thrombolysis. During a 40-year period, 1957-1996, 12 patients underwent emergency pulmonary embolectomy at the Karolinska Hospital in Stockholm, Sweden. Of these, two (17%) died from anoxic brain damage within the first postoperative month. Four patients died 15-21 years after surgery. Six patients who were still alive at follow-up in 2003 were contacted 7-36 years after the embolectomy and were all in good health. In none of them had pulmonary embolism recurred, but two had suffered deep venous thrombosis. We conclude that emergency pulmonary embolectomy can be a lifesaving procedure, with a good long-term prognosis in patients who survive the early perioperative period.


A thermodynamic model to predict Phanerochaete chrysosporium INA-12 adhesion to various solid carriers in relation to lignin peroxidase production.
A thermodynamic model was used in this study to predict the adhesion of Phanerochaete chrysosporium INA-12 as conidiospores or mycelium to various solid carriers. Theoretical predictions were closely reflected by experimental results. Amount of immobilized mycelium was higher for hydrophobic (polypropylene and polyurethane) than for hydrophilic carrier (stainless steel and grey). Lignin peroxidase production was stimulated in the same way. However, better results were obtained with polyurethane than with polypropylene and with grey than with stainless steel. These results were attributed to roughness effects of solid surfaces. Surface morphology characterization showed that the surface roughness parameter R(A) was higher for polyurethane and grey as compared to polypropylene and stainless steel, respectively. On the other hand, polyurethane is not simply rugous; it has an intraparticle porosity as well as a higher total surface area as compared to polypropylene.


Co-Learning Non-Negative Correlated and Uncorrelated Features for Multi-View Data.
Multi-view data can represent objects from different perspectives and thus provide complementary information for data analysis. A topic of great importance in multi-view learning is to locate a low-dimensional latent subspace, where common semantic features are shared by multiple data sets. However, most existing methods ignore uncorrelated items (i.e., view-specific features) and may cause semantic bias during the process of common feature learning. In this article, we propose a non-negative correlated and uncorrelated feature co-learning (CoUFC) method to address this concern. More specifically, view-specific (uncorrelated) features are identified for each view when learning the common (correlated) feature across views in the latent semantic subspace. By eliminating the effects of uncorrelated information, useful inter-view feature correlations can be captured. We design a new objective function in CoUFC and derive an optimization approach to solve the objective with the analysis on its convergence. Experiments on real-world sensor, image, and text data sets demonstrate that the proposed method outperforms the state-of-the-art multiview learning methods.


Cytogenetic analysis of human oocytes after subzonal insemination.
Subzonal insemination has been proposed to achieve fertilization in cases where standard in vitro fertilization has failed. We present the results of chromosome analysis of oocytes after subzonal insemination. Our data suggest that the main cause (76 per cent) of the absence of cleavage after subzonal insemination is the total absence of sperm nucleus evolution of the injected spermatozoa. Our results also suggest that spermatozoa chromatin development is normal after subzonal insemination. Aneuploidy does not seem to be increased in zygotes after subzonal insemination. However, polyploidy was often more important than predicted by the observation of pronuclei (PN). Pronucleus development might be asynchronous and can appear earlier or later than after standard IVF. The cytogenetic risk after subzonal insemination might therefore be triploidy (if a triploid egg is transferred, because only 2 PN were seen) rather than aneuploidy or structural abnormalities.


Uterine DCs are essential for pregnancy.
Successful embryo implantation requires complex interactions between the uterus and embryo, including the establishment of maternal immunologic tolerance of fetal material. The maternal-fetal interface is dynamically populated by a wide variety of innate immune cells; however, the relevance of uterine DCs (uDCs) within the decidua to the success of implantation has remained unclear. In this issue of the JCI, Plaks et al. show, in a transgenic mouse model, that uDCs are essential for pregnancy, as their ablation results in a failure of decidualization, impaired implantation, and embryonic resorption (see the related article beginning on page 3954). Depletion of uDCs altered decidual angiogenesis, suggesting that uDCs contribute to successful implantation via their effects on decidual tissue remodeling, including angiogenesis, and independent of their anticipated role in the establishment of maternal-fetal tolerance.


Potential mechanisms in chemical intolerance and related conditions.
The symptom of chemical intolerance may occur in isolation, but often occurs in conjunction with other chronic symptoms such as pain, fatigue, memory disturbances, etc. This frequent clustering of symptoms in individuals has led to the definition of several chronic multisymptom syndromes, such as multiple chemical sensitivity, fibromyalgia, chronic fatigue syndrome, and Gulf War illnesses. The aggregate research into these syndromes has suggested some unifying mechanisms that contribute to symptomatology. Multiple lines of evidence suggest that there is aberrant function of numerous efferent neural pathways, such as the autonomic nervous system and hypothalamic-pituitary axes, in subsets of individuals with these conditions. There is perhaps the greatest evidence for abnormal sensory processing in these syndromes, with a low "unpleasantness threshold" for multiple types of sensory stimuli. Psychological and behavioral factors are known to play a significant role in initiating or perpetuating symptoms in some persons with these illnesses. In the field of pain research, the interrelationship between physiologic and psychologic factors in symptom expression has been well studied. Using both established and novel methodologies, studies have suggested that psychologic factors such as hypervigilance and expectancy are playing a relatively minor role in most individuals with fibromyalgia and that clear evidence exists of physiologic amplification of sensory stimuli. These studies need to be extended to more sensory tasks and to larger numbers of subjects with related conditions. It is of note, though, that existing data on this spectrum of illnesses would suggest that there may be greater psychologic contributions to symptomatology if an illness is defined in part by behavior (e.g., avoidance of chemical exposures) rather than on the basis of symptoms alone.


The Temporal Tuning of the Drosophila Motion Detectors Is Determined by the Dynamics of Their Input Elements.
Detecting the direction of motion contained in the visual scene is crucial for many behaviors. However, because single photoreceptors only signal local luminance changes, motion detection requires a comparison of signals from neighboring photoreceptors across time in downstream neuronal circuits. For signals to coincide on readout neurons that thus become motion and direction selective, different input lines need to be delayed with respect to each other. Classical models of motion detection rely on non-linear interactions between two inputs after different temporal filtering. However, recent studies have suggested the requirement for at least three, not only two, input signals. Here, we comprehensively characterize the spatiotemporal response properties of all columnar input elements to the elementary motion detectors in the fruit fly, T4 and T5 cells, via two-photon calcium imaging. Between these input neurons, we find large differences in temporal dynamics. Based on this, computer simulations show that only a small subset of possible arrangements of these input elements maps onto a recently proposed algorithmic three-input model in a way that generates a highly direction-selective motion detector, suggesting plausible network architectures. Moreover, modulating the motion detection system by octopamine-receptor activation, we find the temporal tuning of T4 and T5 cells to be shifted toward higher frequencies, and this shift can be fully explained by the concomitant speeding of the input elements.


Melkersson-Rosenthal syndrome.
The Melkersson-Rosenthal syndrome (MRS) is a rare condition characterized by the triad of familial relapsing peripheral facial palsy, facial edema, and lingua plicata. Within a well-documented family aggregate of MRS, an index case simultaneously demonstrated all the elements of the triad, as well as gingival changes similar to those of cheilitis granulomatosa. When the incomplete or oligosymptomatic forms are considered, the MRS may be more common than previously thought.


Massive gene swamping among cheese-making Penicillium fungi.
Horizontal gene transfers (HGT), i.e., the transmission of genetic material between species not directly attributable to meiotic gene exchange, have long been acknowledged as a major driver of prokaryotic evolution and is increasingly recognized as an important source of adaptation in eukaryotes. In fungi in particular, many convincing examples of HGT have been reported to confer selective advantages on the recipient fungal host, either promoting fungal pathogenicity on plants or increasing their toxicity by the acquisition of secondary metabolic clusters, resulting in adaptation to new niches and in some cases eventually even in speciation. These horizontal gene transfers involve single genes, complete metabolic pathways or even entire chromosomes. A recent study has uncovered multiple recent horizontal transfers of a 575 kb genomic island in cheese Penicillium fungi, representing ca. 2% of the Penicillium roqueforti's genome, that may confer selective advantage in the competing cheese environment where bacteria and fungi occur. Novel phylogenomic methods are being developed, revealing massive HGT among fungi. Altogether, these recent studies indicate that HGT is a crucial mechanism of rapid adaptation, even among eukaryotes.


Excitation energies from time-dependent density-functional theory beyond the adiabatic approximation.
Time-dependent density-functional theory in the adiabatic approximation has been very successful for calculating excitation energies in molecular systems. This paper studies nonadiabatic effects for excitation energies, using the current-density functional of Vignale and Kohn [Phys. Rev. Lett. 77, 2037 (1996)]. We derive a general analytic expression for nonadiabatic corrections to excitation energies of finite systems and calculate singlet s-->s and s-->p excitations of closed-shell atoms. The approach works well for s-->s excitations, giving a small improvement over the adiabatic local-density approximation, but tends to overcorrect s-->p excitations. We find that the observed problems with the nonadiabatic correction have two main sources: (1) the currents associated with the s-->p excitations are highly nonuniform and, in particular, change direction between atomic shells, (2) the so-called exchange-correlation kernels of the homogeneous electron gas, f(xc) (L) and f(xc) (T), are incompletely known, in particular in the high-density atomic core regions.


Lovesick: How Couples' Relationships Influence Health.
This review highlights recent advances in research addressing intimate partner relationships and health. Consideration of the strong mutual influences that the members of a couple have on each other's mental and physical health trajectories provides a new way to view the health implications of couples' convergence or interdependence; marital closeness can have a clear downside when one partner has mental or physical health problems. Couples' interconnectedness can also be leveraged to promote better treatment outcomes. Major themes include the pivotal role of depression and the importance of gender differences in the pathways from the marital relationship to physiological functioning and health. The health risks and benefits of support are weighed. Additionally, two prominent emerging paths from marital distress to poor health are emphasized: sleep problems and metabolic alterations that promote obesity and its comorbidities.


[Hip screening of newborn infants. Type classification, therapy and follow-up].
Between December 1982 and the end of January 1987, a total of 21,082 hip sonographies were performed at the authors' clinic to establish whether or not screening of newborns, including sonographic follow-up, was desirable. The incidence of sonographically detected neonatal dysplasia up to the eight week of life was 2.23%; the incidence of dislocation was 0.01%. Hip types IB and IIA have a tendency to deteriorate in the eighth and twelfth weeks. During the first few weeks of life more than one-half of all HD cases manifest no symptoms, either clinical or historical. A complete cure was achieved after an average of five months when suitable therapy was instituted post partum, and after eight months when it was instituted later.


Skeletal muscle antagonizes antiviral CD8+ T cell exhaustion.
CD8+ T cells become functionally impaired or "exhausted" in chronic infections, accompanied by unwanted body weight reduction and muscle mass loss. Whether muscle regulates T cell exhaustion remains incompletely understood. We report that mouse skeletal muscle increased interleukin (IL)-15 production during LCMV clone 13 chronic infection. Muscle-specific ablation of Il15 enhanced the CD8+ T cell exhaustion phenotype. Muscle-derived IL-15 was required to maintain a population of CD8+CD103+ muscle-infiltrating lymphocytes (MILs). MILs resided in a less inflamed microenvironment, expressed more T cell factor 1 (Tcf1), and had higher proliferative potential than splenic T cells. MILs differentiated into functional effector T cells after reentering lymphoid tissues. Increasing muscle mass via muscle-specific inhibition of TGFβ signaling enhanced IL-15 production and antiviral CD8+ T cell responses. We conclude that skeletal muscle antagonizes T cell exhaustion by protecting T cell proliferative potential from inflammation and replenishing the effector T cell progeny pool in lymphoid organs.


Long-Acting Reversible Contraception: A Primer for the Primary Care Pediatrician.
Long-acting reversible contraception (LARC) is the most effective method of preventing pregnancy in young women and adolescents. The two types of LARC methods are the intrauterine device and the implantable rod device. The success of these methods is demonstrable due to the "perfect use" and "typical use" failure rates being near identical. Pediatricians must be comfortable counseling patients, including adolescents, about LARC methods and how to access them. This primer provides some background about the types of LARC methods, details about their efficacy and side effects, and the role of the primary pediatrician. [Pediatr Ann. 2017;46(3):e79-e82.].


Methamphetamine-Related Disorders.
Methamphetamine is considered more dangerous than other stimulants because of its acute complications, long-term neurotoxicity, and potential for drug dependence. Until now, there have been no evidence-based guidelines for the treatment of methamphetamine-related disorders, either in Germany or abroad. A systematic literature search was performed on the treatment of methamphetamine-related disorders. Based on this literature review, a multidisciplinary expert panel developed recommendations using the nominal group technique. The evidence base for the treatment of methamphetamine-related disorders is sparse. The efficacy of psychotherapeutic techniques such as cognitive behavioral therapy and contingency management and the efficacy of complex, disorder-specific treatment programs have been proven in ran - domized controlled trials, but it remains unclear which method is best. Persons carrying a diagnosis of substance abuse should be offered psychotherapy. Structured exercise programs, whether self-directed or professionally led, can improve addiction-specific endpoints as well as comorbid disorders and should, therefore, be offered as well. Pharmacotherapy has shown little to no effect in relatively low-quality clinical trials with low case numbers and high dropout rates, and therefore only a few weak recommendations were made. These include tranquilizers for the short-term treatment of agitation and atypical antipsychotics if necessary. Attempts to substitute other substances, such as methylphenidate or dexamphetamine, for methamphetamine have not yielded any robust evidence to date. Sertraline should not be administered due to serious adverse events. Many of the recommendations in the guideline are made with a weak grade of recommendation because of the poor evidence base and the modest size of the reported therapeutic effects. In acute situations, symptomoriented treatment is recommended. Psychotherapy and exercise should be offered as well.


Predicted Impact of the Model for End-Stage Liver Disease 3.0 in a Region Suffering Severe Organ Shortage.
The model for end-stage liver disease 3.0 (MELD3.0) is expected to address the flaws of the current allocation system for deceased donor liver transplantation (DDLT). We aimed to validate MELD3.0 in the Korean population where living donor liver transplantation is predominant due to organ shortages. Korean large-volume single-centric waitlist data were merged with the Korean Network for Organ Sharing (KONOS) data. The 90-day mortality was compared between MELD and MELD3.0 using the C-index in 2,353 eligible patients registered for liver transplantation. Patient numbers and outcomes were compared based on changes in KONOS-MELD categorization using MELD3.0. Possible gains in MELD points and reduced waitlist mortality were analyzed. MELD3.0 performed better than MELD (C-index 0.893 for MELD3.0 vs. 0.889 for MELD). When stratified according to the KONOS-MELD categories, 15.9% of the total patients and 35.2% of the deceased patients were up-categorized using MELD3.0 versus MELD categories. The mean gain of MELD points was higher in women (2.6 ± 2.1) than men (2.1 ± 1.9, P < 0.001), and higher in patients with severe ascites (3.3 ± 1.8) than in controls (1.9 ± 1.8, P < 0.001); however, this trend was not significant when the MELD score was higher than 30. When the possible increase in DDLT chance was calculated via up-categorizing using MELD3.0, reducible waitlist mortality was 2.7%. MELD3.0 could predict better waitlist mortality than MELD; however, the merit for women and patients with severe ascites is uncertain, and reduced waitlist mortality from implementing MELD3.0 is limited in regions suffering from organ shortage, as in Korea.


Language and Speech Characteristics in Autism.
The aim of this paper is to provide information regarding diversity in speech and language profiles of individuals with Autism Spectrum Disorders (ASD) and try to classify these profiles according to the combination of the communication difficulties. Research findings confirm the existence of heterogeneity of communication challenges in ASD across the lifespan. A lot of children with ASD experience communication challenges and strengths across all language sub-systems including pragmatics, grammar, semantics, syntax, phonology, and morphology in both oral and written language, while some children with autism demonstrate exceptional language abilities incl. linguistic creativity. Communication issues vary on a continuum of severity so that some children may be verbal, whereas others remain non-verbal or minimally-verbal. The diversity of profiles in speech and language development stem from either the presence of comorbid factors, as a core symptom of autistic behavior without comorbidity or both, with the development of complex clinical symptoms. Difficulties with the semantic aspect of language affect the individual's skills in abstract thinking, multiple meanings of words, concept categorization, and so on. Finally, the coexistence of ASD with other communication difficulties such as a Language Disorder, Apraxia of Speech, Speech Sound Disorders or/and other neurodevelopmental disorders raises the need for examining more carefully the emergence of new clinical profiles and clinical markers useful in performing differential diagnosis and different intervention.


Hyperresponsiveness to stress: differential effects of prenatal ethanol on males and females.
In this study we investigated the hypothesis that pituitary-adrenal response inhibition is compromised in animals prenatally exposed to ethanol. In the first experiment, we examined whether opportunity to perform a consummatory response reduces the adrenocortical response to a novel test cage. Animals were water deprived for 24 hr and tested in one of three conditions: (a) removed from home cage, blood sample obtained immediately; (b) placed into empty novel cage, blood sample obtained 30 min later; (c) placed into novel cage with water available, blood sample obtained 30 min later. All animals showed an increase in corticoids over basal levels following 24-hr water deprivation, and placement into a novel cage produced a further significant increase in corticosterone. Opportunity to drink reduced the corticosterone response to novelty for all males. However, fetal ethanol-exposed females showed significantly less attenuation of their corticosterone response to novelty than both pair-fed and control females. In the second experiment, we examined adrenocortical habituation to a stressful stimulus. Animals were restrained in plastic tubes which restricted movement, and blood samples were obtained following 30 or 60 min of restraint. All animals showed significant corticoid elevations at 30 min. Males showed no change in corticoids from 30 to 60 min while both pair-fed and control females showed a corticoid decrease at 60 min. Fetal ethanol-exposed females, however, showed no significant corticoid decrease at 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)


Gas chromatographic determination of quazepam and two major metabolites in human plasma.
Two rapid, sensitive, and specific gas chromatographic (GC) methods for the quantitative determination of quazepam (I), 7-chloro-5-(2-fluorophenyl-1,3-dihydro-1-(2,2,2-trifluoroethyl) -2H-1,4-benzodiazepine-2-thione, and its major active plasma metabolites, the 2-oxo compound (II) and the dealkylated oxo compound (III), have been developed; the first measures I and II and the second measures III. The compounds are extracted from plasma with toluene and quantitated by electron-capture detection using the internal standard method. The methods are capable of quantitating plasma levels of I and II as low as 0.75 ng/mL and plasma levels of III as low as 1.5 ng/mL. Correlation coefficients of standard curves were greater than 0.9995 for all compounds. Precision of the methods was measured at two different concentrations for each compound; the CV values were 3-6% for all three compounds. The recovery of all compounds was greater than 80%, and the ratio of recovery of each compound to that of its internal standard did not vary at different concentrations, indicating appropriate internal standards have been selected for the methods. Quazepam metabolites, other benzodiazepines, and drugs which are potential comedication do not interfere with either method. The methods were shown to be suitable for investigating the bioavailability and pharmacokinetics of quazepam at therapeutic doses.


Changes in Typical Portion Sizes of Commonly Consumed Discretionary Foods among Australian Adults from 1995 to 2011-2012.
This study aimed to examine the changes in typical portion sizes of commonly consumed discretionary foods among Australian adults from 1995 to 2011-2012. Data of adults (age ≥19 years) from the 1995 Australian National Nutrition Survey and 2011-2012 National Nutrition and Physical Activity Survey were used. Typical portion sizes (median portion) of fourteen discretionary foods that contributed the most to energy intake were determined. Ten out of fourteen food categories demonstrated a significant change in kJ per typical portion from 1995 to 2011-2012 (p ≤ 0.001). kJ per typical portion increased for pizza, cake, sausage, cereal bar, processed meat, ice cream and wine, with pizza and cake demonstrating the largest increases (+570 kJ and +950 kJ in 2011-2012, respectively; both +66% above 1995). In contrast, kJ per typical portion of pastry, snack food and potato fries decreased by 10-40% over time, and did not change for biscuit, chocolate, sugar-sweetened beverage and beer. Similar changes were observed for grams per typical portion consumed. Temporal trends in typical portion sizes were similar according to age group, gender and socioeconomic status. The findings suggest that population-wide strategies that enable consumers to choose smaller portions of discretionary foods are needed to reduce the excess consumption of these products.


Mobility behaviour and driving status of patients with mental disorders - an exploratory study.
Driving is an important activity of daily life and an integral part of mobility. However, impact of mental illness on road mobility is widely unexplored. Driving status in 1497 psychiatric inpatients (PPs) and a clinical control group of 313 neurological inpatients (NPs) was investigated using a brief questionnaire. 67% of PPs (89% NPs) reported to have a valid driver's licence and 77% of them (92% NPs) reported to regularly use their cars. Within driver's license holders, patients with organic mental disorder (32%), substance dependence (37%) and psychotic disorder (40%) had the lowest proportion of current drivers. Higher educational qualification (odds ratio [OR] from 2.978 to 17.036) and being married/partnered (OR 3.049) or divorced (OR 4.840) significantly advanced the probability of possession of a driving license. Predictive factors for driving cessation were being female, an older age, drawing a pension and having an organic mental disease or schizophrenic disorder. Mental disease has a negative impact on driving status and this is especially true for illnesses frequently being accompanied by distinct cognitive impairments. Factors predicting road mobility elucidate the strong relationship with psychosocial status indicating that recovery of driving competence should be an integral goal of treatment strategies.


[Sporadic colonic juvenile polyps in adults].
Sporadic colonic juvenile polyps are uncommon in adults. We report three cases for which clinical manifestations were presence of occult blood in the stool, rectal bleeding or chronic diarrhea. Two of these polyps occurred in the caecum which is an uncommon localisation. Endoscopic characteristics of these polyps were indistinguishable from adenomas. Endoscopic resection was complicated in one case by bleeding.


Daunorubicin efflux against a concentration gradient in non-P-glycoprotein multidrug-resistant lung-cancer cells.
Multidrug-resistant, human non-small-cell lung carcinoma SW-1573/2R120 (2R120) cells, not containing the drug efflux pump P-glycoprotein (Pgp), have reduced initial daunorubicin (DN) accumulation rates and decreased cellular steady-state drug concentrations. Previously we found indications of the presence of a plasma membrane "vacuum cleaner", pumping DN directly from the membrane, and reported evidence of active DN pumping using digitonin. Further evidence of active DN pumping is now provided via a different methodology and the active drug pump flux is estimated. Cells were exposed to a flowing medium containing the cytotoxic agent DN. After reaching a steady state, in which net DN uptake equals net DN efflux, high concentration pulses of vincristine (VCR) were injected into the flowing medium. A rapid increase in cellular DN content was observed, while only a minimal effect was seen in SW-1573 wild-type cells. After passage of the VCR pulse, the extra accumulated DN was effluxed against a concentration gradient. Upon increasing the VCR concentration, a maximum pump inhibition was reached which was similar to the effect of cellular energy depletion. Similar effects were observed for Pgp-containing SW-1573/2R160 (2R160) cells as well as non-Pgp MDR human small-cell lung carcinoma GLC4/ADR cells. With increasing extracellular DN concentrations, saturation of the VCR-induced DN influx was observed (DN medium concentration 2.5 microM at 1/2 Vmax). At an extracellular DN concentration of 5 microM, higher concentrations of VCR were needed to reach the maximum effect in 2R120 cells than at 0.5 microM DN. This is an indication of competitive interaction between DN and VCR for the putative DN efflux system. In summary, we found indications of inhibition of active DN efflux by VCR and DN efflux against a concentration gradient in non-Pgp MDR 2R120 and GLC4/ADR cells. These features are consistent with the presence of a multidrug transporter, different from Pgp, in the plasma membrane of these cells.


Use of Arabidopsis thaliana to study mechanisms of control of Verticillium wilt by Pseudomonas fluorescens PICF7.
Verticillium wilt (VW), caused by Verticillium dahliae Kleb., is an important disease in many crops and its effective management has proven difficult. Among the various disease control measures to be implemented, the use of microbial antagonists (biological control agents, BCAs) constitutes an environmentally-friendly approach fitting criteria of modern sustainable agriculture. Pseudomonas fluorescens PICF7 was isolated from root tissues of nursery--propagated olive plants. Selection of this strain was based on in vitro growth inhibition of V. dahliae, colonizing ability of olive roots, endophytic lifestyle, and control of the highly-virulent defoliating (D) pathotype of V. dahliae in olive planting stocks. The mode of action by which PICF7 controls VW in olive is as yet unknown; moreover, to uncover potential biocontrol mechanisms poses additional difficulties in this pathosystem because the target is a tree. Therefore we used the model plant Arabidopsis thaliana to study: i) if PICF7 colonizes the rhizosphere of A. thaliana; ii) disease symptoms caused by V. dahliae in A. thaliana; iii) control of VW by PICF7 in different accessions and mutants of A. thaliana; and iv) if motility, antibiosis and/or siderophores are involved in control of V. dahliae by PICF7. Diverse bioassays were conducted and in all of them both the BCA and the pathogen were introduced in the rhizosphere of A. thaliana. Both D and non-defoliating isolates of V. dahliae caused disease symptoms in A. thaliana. PICF7 colonized and persisted in the rhizosphere of different Arabidopsis accessions and could control the D pathotype in some of them. PICF7 mutants affected in antibiosis significantly lost their ability to control VW in A. thaliana. We conclude that the model plant A. thaliana is useful to unravel interactions between this BCA and V. dahliae.


Regulation of Adult CNS Axonal Regeneration by the Post-transcriptional Regulator Cpeb1.
Adult mammalian central nervous system (CNS) neurons are unable to regenerate following axonal injury, leading to permanent functional impairments. Yet, the reasons underlying this regeneration failure are not fully understood. Here, we studied the transcriptome and translatome shortly after spinal cord injury. Profiling of the total and ribosome-bound RNA in injured and naïve spinal cords identified a substantial post-transcriptional regulation of gene expression. In particular, transcripts associated with nervous system development were down-regulated in the total RNA fraction while remaining stably loaded onto ribosomes. Interestingly, motif association analysis of post-transcriptionally regulated transcripts identified the cytoplasmic polyadenylation element (CPE) as enriched in a subset of these transcripts that was more resistant to injury-induced reduction at the transcriptome level. Modulation of these transcripts by overexpression of the CPE binding protein, Cpeb1, in mouse and Drosophila CNS neurons promoted axonal regeneration following injury. Our study uncovered a global evolutionarily conserved post-transcriptional mechanism enhancing regeneration of injured CNS axons.


[Huangjiao granules ameliorate brain injury in rats with cerebral ischemia/reperfusion injury by stimulating PI3K/AKT/mTOR signaling pathway].
Objective To investigate the protective effect of Huangjiao granules on rats with cerebral ischemia/reperfusion injury and the effect on phosphoinositide-3 kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway. Methods The rat models of cerebral ischemia/reperfusion injury were established by suture method and treated with Huangjiao granules. ZeaLonga scoring was used to evaluate the neurological function of rats. The percentage of cerebral infarction was detected by triphenyl tetrazolium chloride (TTC) staining. The pathological changes of brain tissues were observed by HE staining. The levels of interleukin 10 (IL-10), IL-1β and tumor necrosis factor-α (TNF-α) in the brain tissues were detected by ELISA. The expression levels of PI3K, AKT, phosphorylated AKT (p-AKT), mTOR and phosphorylated mTOR (p-mTOR) proteins were detected by Western blot analysis. Results Huangjiao granules could reduce the degree of neurological deficits, decrease the percentage of cerebral infarction, and lessen brain tissue pathological damage in the model rats. The expressions of IL-10, PI3K, p-AKT and p-mTOR in the brain tissues of the model rats were significantly up-regulated by Huangjiao granules, but the expressions of IL-1β and TNF-α in the brain tissues of the model rats were significantly down-regulated by Huangjiao granules. Conclusion The protective effect of Huangjiao granules on rat models of cerebral ischemia/reperfusion injury may be related to the activation of PI3K/AKT/mTOR signaling pathway.


[Repair of collateral ligament rupture in the interphalangeal joint using superficial flexor tendon of finger].
To introduce the surgical procedure and clinical result of microsurgical repair on collateral ligament rupture in the interphalangeal joint using superficial flexor tendon of finger. From 1987, 23 cases with collateral ligament rupture in the interphalangeal joint were repaired by part of superficial flexor tendon of finger. The initial point of collateral ligament was drilled two holes, 2 to 3 mm in distance, and crossed by steel wire. Then the superficial flexor tendon of finger was crossed under the steel wire and sutured to the terminal point of superficial flexor tendon of finger by 5/0 to 7/0 nontraumatic suture thread to maintain suitable tension, and sutured to collateral ligament by 8/0 nontraumatic suture thread. Extension splint fixation was performed 4 to 6 weeks postoperatively. Followed up 3 to 6 months, 15 cases were excellent, 6 cases were better, 2 cases were moderate, and the excellent rate was 91.34% according to Saetta standard. Microsurgical repair on collateral ligament rupture in the interphalangeal joint using superficial flexor tendon of finger is a convenient and effective surgical method.


In-vitro activity of FCE 22101 and synergy studies with other antimicrobial agents.
FCE 22101 is a penem antibiotic with broad in-vitro activity similar to that of imipenem, although less active against Pseudomonas aeruginosa. Combinations of FCE 22101 with ciprofloxacin or gentamicin against methicillin-resistant Staphylococcus aureus and methicillin-resistant Staph. epidermidis resulted in addition or indifference by the chequerboard method. The combination of FCE 22101 and gentamicin against Streptococcus faecalis was usually additive. Against Enterobacter cloacae FCE 22101 had MICs of 16 mg/l whilst in combination with gentamicin (0.25-0.12 mg/l) the MICs were reduced to less than 2 mg/l. Ciprofloxacin and FCE 22101 showed only addition against Enterobacter spp. similar results were obtained with the combinations of FCE 22101 and gentamicin or ciprofloxacin tested against Citrobacter freundii. With Serratia spp. FCE 22101 and gentamicin showed synergy, but FCE 22101 and ciprofloxacin showed indifference. Similar results were obtained with strains of Escherichia coli and Klebsiella, Proteus, and Providencia spp. FCE 22101 plus gentamicin, or aztreonam, against Ps. aeruginosa usually showed indifference, but with ciprofloxacin addition was the rule. In general the combination of FCE 22101 with other agents resulted in an additive rather than a synergistic effect.


Women's experiences with unplanned pregnancy and abortion in Kenya: A qualitative study.
Safe and legal abortions are rarely practiced in the public health sector in Kenya, and rates of maternal mortality and morbidity from unsafe abortion is high. Little is known about women's experiences seeking and accessing abortion in informal settlements in Nairobi, Kenya. Seven focus group discussions were conducted with a total of 71 women and girls recruited from an informal settlement in Nairobi. The interview guide explored participants' perceptions of unplanned pregnancy, abortion, and access to sexual and reproductive health information in their community. Thematic analysis of the focus group transcripts was conducted using MAX QDA Release 12. Participants described a variety of factors that influence women's experiences with abortion in their communities. According to participants, limited knowledge of sexual and reproductive health information and lack of access to contraception led to unplanned pregnancy among women in their community. Participants cited stigma and loss of opportunities that women with unplanned pregnancies face as the primary reasons why women seek abortions. Participants articulated stigma as the predominant barrier women in their communities face to safe abortion. Other barriers, which were often interrelated to stigma, included lack of education about safe methods of abortion, perceived illegality of abortion, as well as limited access to services, fear of mistreatment, and mistrust of health providers and facilities. Women in informal settlements in Nairobi, Kenya face substantial barriers to regulating their fertility and lack access to safe abortion. Policy makers and reproductive health advocates should support programs that employ harm reduction strategies and increase women's knowledge of and access to medication abortion outside the formal healthcare system.


Carbon-Free Cathodes: A Step Forward in the Development of Stable Lithium-Oxygen Batteries.
Lithium-oxygen (Li-O2 ) batteries are receiving considerable interest owing to their potential for higher energy densities than current Li-ion systems. However, the lack stability of carbon-based oxygen electrodes is believed to promote carbonate formation leading to capacity fade and limiting the cycling performance of the battery. To improve the stability and cyclability of these systems, alternative electrode materials are required. Metal oxides are mainly utilized at low current densities, whereas noble metals show outstanding performance at high current densities. Carbides appear to provide a good compromise between electrochemical performance and cost, which makes them interesting materials for further investigations. Here, a critical review of current carbon-free electrode research is provided with the goal of identifying routes to its successful optimization.


Embryonic development and effect of temperature on larval growth of the Peruvian anchovy Engraulis ringens.
Understanding aspects of the biology of early life stages of marine fish is critical if one hopes to reveal the factors and processes that impact the survival and recruitment (year class) strength. The Peruvian anchovy (Engraulis ringens) is a key species in the Humboldt current system, and the present study provides the first description of the embryonic and larval development of this species reared in captivity. Embryonic and early exogenous feeding stages of larvae were illustrated in detail at 18.5°C. Hatching was completed within 42 and 48 h post-fertilization at 18.5 and 14.5°C, respectively. Mean ± 95% C.I. standard length (LS ) at hatch (3.40 ± 0.10 mm at 18.5°C and 2.76 ± 0.34 mm at 14.5°C) was significantly different between the two temperatures. Larval behaviour was assessed at 18.5°C; at the onset of exogenous feeding [3 days post-hatch (dph)], larvae were fed small, motile dinoflagellates, Akashiwo sanguinea. At 7 dph, larvae started to feed almost exclusively on zooplankton (rotifers and Artemia nauplii). Larval activity increased with age, and the first sign of schooling was noted at 31 dph (18.56 mm LS ) at 18.5°C. Temperature had a significant effect on size-at-age, but not on body shape (depth to LS ratio). The size-at-age data for larvae (this study) was used to parameterize a temperature-corrected von Bertalanffy growth function for Peruvian anchovy, the accuracy of which was assessed for juveniles and adults (literature values).


Reversible guest-induced magnetic and structural single-crystal-to-single-crystal transformation in microporous coordination network {[Ni(cyclam)]3[W(CN)8]2}n.
Planar honeycomb-like coordination network {[Ni(cyclam)]3[W(CN)8]2}n (cyclam = 1,4,8,11-tetraazacyclotetradecane) was obtained in the self-assembly reaction of [Ni(cyclam)]2+ and [W(CN)]83-. Its structure is characterized by void channels along the a axis. The compound shows reversible water adsorption in the temperature range of 25-40 degrees C with the formation of {[Ni(cyclam)]3[W(CN)8]2}n.16nH2O, accompanied by single-crystal-to-single-crystal transformation. The structural transformation significantly changes the character of intraplane magnetic exchange interactions.


Lack of the PGA exopolysaccharide in Salmonella as an adaptive trait for survival in the host.
Many bacteria build biofilm matrices using a conserved exopolysaccharide named PGA or PNAG (poly-β-1,6-N-acetyl-D-glucosamine). Interestingly, while E. coli and other members of the family Enterobacteriaceae encode the pgaABCD operon responsible for PGA synthesis, Salmonella lacks it. The evolutionary force driving this difference remains to be determined. Here, we report that Salmonella lost the pgaABCD operon after the divergence of Salmonella and Citrobacter clades, and previous to the diversification of the currently sequenced Salmonella strains. Reconstitution of the PGA machinery endows Salmonella with the capacity to produce PGA in a cyclic dimeric GMP (c-di-GMP) dependent manner. Outside the host, the PGA polysaccharide does not seem to provide any significant benefit to Salmonella: resistance against chlorine treatment, ultraviolet light irradiation, heavy metal stress and phage infection remained the same as in a strain producing cellulose, the main biofilm exopolysaccharide naturally produced by Salmonella. In contrast, PGA production proved to be deleterious to Salmonella survival inside the host, since it increased susceptibility to bile salts and oxidative stress, and hindered the capacity of S. Enteritidis to survive inside macrophages and to colonize extraintestinal organs, including the gallbladder. Altogether, our observations indicate that PGA is an antivirulence factor whose loss may have been a necessary event during Salmonella speciation to permit survival inside the host.


Empirical analysis of farmers' drought risk perception: objective factors, personal circumstances, and social influence.
Drought-induced water shortage and salinization are a global threat to agricultural production. With climate change, drought risk is expected to increase as drought events are assumed to occur more frequently and to become more severe. The agricultural sector's adaptive capacity largely depends on farmers' drought risk perceptions. Understanding the formation of farmers' drought risk perceptions is a prerequisite to designing effective and efficient public drought risk management strategies. Various strands of literature point at different factors shaping individual risk perceptions. Economic theory points at objective risk variables, whereas psychology and sociology identify subjective risk variables. This study investigates and compares the contribution of objective and subjective factors in explaining farmers' drought risk perception by means of survey data analysis. Data on risk perceptions, farm characteristics, and various other personality traits were collected from farmers located in the southwest Netherlands. From comparing the explanatory power of objective and subjective risk factors in separate models and a full model of risk perception, it can be concluded that farmers' risk perceptions are shaped by both rational and emotional factors. In a full risk perception model, being located in an area with external water supply, owning fields with salinization issues, cultivating drought-/salt-sensitive crops, farm revenue, drought risk experience, and perceived control are significant explanatory variables of farmers' drought risk perceptions.


Maxillary fibrous dysplasia associated with McCune-Albright syndrome. A case study.
McCune Albright syndrome (MCA) is a rare complication of genetic origin. The authors present a case study of a patient with MCA diagnosed with multifocal fibrous dysplasia in his limb and craniofacial bones. The symptoms of the disease in the patient's facial and oral tissue and the treatment administered have been described.


Identification of di-substituted ureas that prevent growth of trypanosomes through inhibition of translation initiation.
Some 1,3-diarylureas and 1-((1,4-trans)-4-aryloxycyclohexyl)-3-arylureas (cHAUs) activate heme-regulated kinase causing protein synthesis inhibition via phosphorylation of the eukaryotic translation initiation factor 2 (eIF2) in mammalian cancer cells. To evaluate if these agents have potential to inhibit trypanosome multiplication by also affecting the phosphorylation of eIF2 alpha subunit (eIF2α), we tested 25 analogs of 1,3-diarylureas and cHAUs against Trypanosoma cruzi, the agent of Chagas disease. One of them (I-17) presented selectivity close to 10-fold against the insect replicative forms and also inhibited the multiplication of T. cruzi inside mammalian cells with an EC50 of 1-3 µM and a selectivity of 17-fold. I-17 also prevented replication of African trypanosomes (Trypanosoma brucei bloodstream and procyclic forms) at similar doses. It caused changes in the T. cruzi morphology, arrested parasite cell cycle in G1 phase, and promoted phosphorylation of eIF2α with a robust decrease in ribosome association with mRNA. The activity against T. brucei also implicates eIF2α phosphorylation, as replacement of WT-eIF2α with a non-phosphorylatable eIF2α, or knocking down eIF2 protein kinase-3 by RNAi increased resistance to I-17. Therefore, we demonstrate that eIF2α phosphorylation can be engaged to develop trypanosome-static agents in general, and particularly by interfering with activity of eIF2 kinases.


Overexpression of Derlin 3 is associated with malignant phenotype of breast cancer cells.
Breast cancer (BC) is the most common malignant tumor among women worldwide. Development of novel molecular targets is important to improve prognosis of BC patients. Derlin 3 (DERL3) gene is a member of derlin family, and its coding protein is critical to the endoplasmic reticulum-associated degradation mechanism. However, its oncological role in breast cancer remains unclear. This study evaluated DERL3 expression and function in BC. We analyzed DERL3 mRNA in 13 BC and two non-cancerous cell lines, and explored effects of DERL3 knockdown on BC proliferation, invasion and migration. We also evaluated correlation of DERL3 mRNA expression levels with clinicopathological factors and prognosis in 167 BC patients. DERL3 mRNA expression was detected in five (38%) BC cell lines. Inhibiting DERL3 expression significantly decreased proliferation and invasion in BC cells. Specimens from patients with lymph node metastasis had higher DERL3 mRNA expression than those without (P=0.030). Patients in the highest quartile for DERL3 mRNA expression (n=42) were more likely to experience shorter overall survival than other patients (P=0.032). These findings indicate that DERL3 promotes malignant phenotype in BC cells. DERL3 may serve as a potential prognostic marker and therapeutic target for BC.


Hemodynamics through the congenitally bicuspid aortic valve: a computational fluid dynamics comparison of opening orifice area and leaflet orientation.
A computational fluid dynamics model of a bicuspid aortic valve has been developed using idealised three-dimensional geometry. The aim was to compare how the orifice area and leaflet orientation affect the hemodynamics of a pure bicuspid valve. By applying physiologic material properties and boundary conditions, blood flow shear stresses were predicted during peak systole. A reduced orifice area altered blood velocity, the pressure drop across the valve and the wall shear stress through the valve. Bicuspid models predicted impaired blood flow similar to a stenotic valve, but the flow patterns were specific to leaflet orientation. Flow patterns developed in bicuspid aortic valves, such as helical flow, were sensitive to cusp orientation. In conclusion, the reduced opening area of a bicuspid aortic valve amplifies any impaired hemodynamics, but cusp orientation determines subsequent flow patterns which may determine the specific regions downstream from the valve most at risk of clinical complications.


Cross-protectiveness and immunogenicity of influenza A/Duck/Singapore/3/97(H5) vaccines against infection with A/Vietnam/1203/04(H5N1) virus in ferrets.
Ferrets were immunized with two 7- mu g doses of hemagglutinin from inactivated whole-virus vaccines containing the hemagglutinin gene of A/Duck/Singapore/3/97(H5N3) then inoculated with a lethal dose of A/Vietnam/1203/04(H5N1) (Viet/1203/04). Serum samples did not react with Viet/1203/04 in hemagglutination-inhibition (HI) or virus-neutralization (VN) tests. All vaccinated ferrets survived the challenge, whereas all mock-immunized ferrets died. Immunized ferrets had significantly lower virus titers in the upper respiratory tract and less-severe disease. Vaccine generated from antigenically different H5 virus protects against infection by a highly pathogenic H5 strain. Neither HI nor VN testing provides correlates of cross-protection in ferrets.


Phosphoproteomics Reveals HMGA1, a CK2 Substrate, as a Drug-Resistant Target in Non-Small Cell Lung Cancer.
Although EGFR tyrosine kinase inhibitors (TKIs) have demonstrated good efficacy in non-small-cell lung cancer (NSCLC) patients harboring EGFR mutations, most patients develop intrinsic and acquired resistance. We quantitatively profiled the phosphoproteome and proteome of drug-sensitive and drug-resistant NSCLC cells under gefitinib treatment. The construction of a dose-dependent responsive kinase-substrate network of 1548 phosphoproteins and 3834 proteins revealed CK2-centric modules as the dominant core network for the potential gefitinib resistance-associated proteins. CK2 knockdown decreased cell survival in gefitinib-resistant NSCLCs. Using motif analysis to identify the CK2 core sub-network, we verified that elevated phosphorylation level of a CK2 substrate, HMGA1 was a critical node contributing to EGFR-TKI resistance in NSCLC cell. Both HMGA1 knockdown or mutation of the CK2 phosphorylation site, S102, of HMGA1 reinforced the efficacy of gefitinib in resistant NSCLC cells through reactivation of the downstream signaling of EGFR. Our results delineate the TKI resistance-associated kinase-substrate network, suggesting a potential therapeutic strategy for overcoming TKI-induced resistance in NSCLC.


11β-HSD1 inhibition does not affect murine tumour angiogenesis but may exert a selective effect on tumour growth by modulating inflammation and fibrosis.
Glucocorticoids inhibit angiogenesis by activating the glucocorticoid receptor. Inhibition of the glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) reduces tissue-specific glucocorticoid action and promotes angiogenesis in murine models of myocardial infarction. Angiogenesis is important in the growth of some solid tumours. This study used murine models of squamous cell carcinoma (SCC) and pancreatic ductal adenocarcinoma (PDAC) to test the hypothesis that 11β-HSD1 inhibition promotes angiogenesis and subsequent tumour growth. SCC or PDAC cells were injected into female FVB/N or C57BL6/J mice fed either standard diet, or diet containing the 11β-HSD1 inhibitor UE2316. SCC tumours grew more rapidly in UE2316-treated mice, reaching a larger (P<0.01) final volume (0.158 ± 0.037 cm3) than in control mice (0.051 ± 0.007 cm3). However, PDAC tumour growth was unaffected. Immunofluorescent analysis of SCC tumours did not show differences in vessel density (CD31/alpha-smooth muscle actin) or cell proliferation (Ki67) after 11β-HSD1 inhibition, and immunohistochemistry of SCC tumours did not show changes in inflammatory cell (CD3- or F4/80-positive) infiltration. In culture, the growth/viability (assessed by live cell imaging) of SCC cells was not affected by UE2316 or corticosterone. Second Harmonic Generation microscopy showed that UE2316 reduced Type I collagen (P<0.001), whilst RNA-sequencing revealed that multiple factors involved in the innate immune/inflammatory response were reduced in UE2316-treated SCC tumours. 11β-HSD1 inhibition increases SCC tumour growth, likely via suppression of inflammatory/immune cell signalling and extracellular matrix deposition, but does not promote tumour angiogenesis or growth of all solid tumours.


Stem cell transplantation as a dynamical system: are clinical outcomes deterministic?
Outcomes in stem cell transplantation (SCT) are modeled using probability theory. However, the clinical course following SCT appears to demonstrate many characteristics of dynamical systems, especially when outcomes are considered in the context of immune reconstitution. Dynamical systems tend to evolve over time according to mathematically determined rules. Characteristically, the future states of the system are predicated on the states preceding them, and there is sensitivity to initial conditions. In SCT, the interaction between donor T cells and the recipient may be considered as such a system in which, graft source, conditioning, and early immunosuppression profoundly influence immune reconstitution over time. This eventually determines clinical outcomes, either the emergence of tolerance or the development of graft versus host disease. In this paper, parallels between SCT and dynamical systems are explored and a conceptual framework for developing mathematical models to understand disparate transplant outcomes is proposed.


A combined atomic force microscopy and nanoindentation technique to investigate the elastic properties of bone structural units.
To our knowledge, this study applied for the first time a recently developed combination of atomic force microscopy (AFM) and nanoindentation on trabecular and compact bone tissue. The major aim was to check the advantage of the available AFM-mode over the conventionally used optical microscope. First, we investigated if removal of the water content helped to prevent enzymatic degradation of the bone tissue and preserve its mechanical properties during a week. After the positive issue of this test, we quantified the intrinsic mechanical properties of single bone structural units (BSU). Bone specimens were obtained from the femoral neck of an 86 year old female. Four BSU were randomly selected and tested each with 24 indents of 5 mN maximum force. The available AFM mode proved to be a very useful tool for surface characterization and precise selection of the indentation area. The elastic modulus ranged from 18 -/+ 1.7 GPa for a BSU of compact bone to 22.5 -/+ 3.1 GPa for a BSU of trabecular bone. Hardness showed values between 0.6 -/+ 0.11 GPa for compact bone and 1.1 -/+ 0.17 GPa for trabecular bone. The results suggest that the micromechanics of bone tissue may also be described as an assembly of distinct structural units with rather homogeneous material properties.


Translation of Cellular Protein Localization Using Convolutional Networks.
Protein localization in cells has been analyzed by fluorescent labeling using indirect immunofluorescence and fluorescent protein tagging. However, the relationships between the localization of different proteins had not been analyzed using artificial intelligence. Here, we applied convolutional networks for the prediction of localization of the cytoskeletal proteins from the localization of the other proteins. Lamellipodia are one of the actin-dependent subcellular structures involved in cell migration and are mainly generated by the Wiskott-Aldrich syndrome protein (WASP)-family verprolin homologous protein 2 (WAVE2) and the membrane remodeling I-BAR domain protein IRSp53. Focal adhesion is another actin-based structure that contains vinculin protein and promotes lamellipodia formation and cell migration. In contrast, microtubules are not directly related to actin filaments. The convolutional network was trained using images of actin filaments paired with WAVE2, IRSp53, vinculin, and microtubules. The generated images of WAVE2, IRSp53, and vinculin were highly similar to their real images. In contrast, the microtubule images generated from actin filament images were inferior without the generation of filamentous structures, suggesting that microscopic images of actin filaments provide more information about actin-related protein localization. Collectively, this study suggests that image translation by the convolutional network can predict the localization of functionally related proteins, and the convolutional network might be used to describe the relationships between the proteins by their localization.


Properties of alpha 1-antitrypsin secreted by human adenocarcinoma cell lines.
alpha 1-Antitrypsin; (alpha 1-AT) produced by various human carcinoma (non-hepatoma) cell lines were analyzed. Five out of eight cell lines secreted detectable amounts of alpha 1-AT into the conditioned media. All were adenocarcinoma cell lines. The tumor cell-derived alpha 1-ATs had higher molecular weights (MW) than the normal plasma form. Most of this difference was an overall reflection of altered N-glycosylation. As judged by binding of lectins, the glycosylation had shifted towards higher levels of triantennary oligosaccharides and higher levels of fucosylation. The conditioned media also contained lower MW alpha 1-AT species, possibly, proteolytically cleaved forms.


Effects of farmland abandonment on anthropogenic-alluvial soil microbiota and contaminant residues in Lycium barbarum fields.
There has been an increasing tendency to abandon crop cultivation and farming in old Lycium barbarum (wolfberry) stands to allow for natural restoration. However, little research has been dedicated to deciphering how soil quality changes in L. barbarum fields following abandonment from a physicochemical and microbiological perspective. Here we assessed the effects of farmland abandonment on anthropogenic-alluvial soil microbiota and contaminant residues in L. barbarum fields in Ningxia, China. Soil microbiota, heavy metal, and neonicotinoid pesticide profiles in L. barbarum fields abandoned for one to four years were characterized. Microbial community analysis was performed by high-throughput sequencing of the bacterial 16S ribosomal RNA genes and the fungal nuclear ribosomal internal transcribed spacer region. Soil bacterial diversity increased from before abandonment to year three after abandonment, and fungal diversity peaked in year one after abandonment. Enrichment of potentially beneficial taxa (e.g. Limnobacter, Cavicella) as well as pathogenic taxa (e.g. Ilyonectria) was observed in the abandoned field soils, along with depletion of other taxa (e.g. Planococcus, Bipolaris). Soil copper, zinc, cadmium, imidacloprid, and acetamiprid concentrations all decreased with increasing time since abandonment and had varied correlations with soil quality, microbial diversity, and the relative abundances of major phyla. Soil available phosphorus, nitrate-nitrogen, and pH were the key factors shaping bacterial communities. The structuring of fungal communities was strongly influenced by soil pH, available phosphorus, and available nitrogen contents. There were positive consequences of farmland abandonment in L. barbarum fields, such as optimized microbial community structure, reduced heavy metal accumulation, and enhanced pesticide degradation.


Resolution of oligomeric species during the aggregation of Aβ1-40 using (19)F NMR.
In the commonly used nucleation-dependent model of protein aggregation, aggregation proceeds only after a lag phase in which the concentration of energetically unfavorable nuclei reaches a critical value. The formation of oligomeric species prior to aggregation can be difficult to detect by current spectroscopic techniques. By using real-time (19)F NMR along with other techniques, we are able to show that multiple oligomeric species can be detected during the lag phase of Aβ1-40 fiber formation, consistent with a complex mechanism of aggregation. At least six types of oligomers can be detected by (19)F NMR. These include the reversible formation of large β-sheet oligomer immediately after solubilization at high peptide concentration, a small oligomer that forms transiently during the early stages of the lag phase, and four spectroscopically distinct forms of oligomers with molecular weights between ∼30 and 100 kDa that appear during the later stages of aggregation. The ability to resolve individual oligomers and track their formation in real-time should prove fruitful in understanding the aggregation of amyloidogenic proteins and in isolating potentially toxic nonamyloid oligomers.


Health professionals' views and experiences around the dietary and lifestyle management of gestational diabetes in New Zealand.
This study aimed to investigate New Zealand health professionals' views and experiences around the dietary and lifestyle management of gestational diabetes. Semi-structured interviews were conducted remotely with health professionals; sessions were recorded and transcribed. Core themes were extracted using inductive thematic analysis using a framework method. Twenty-seven health professionals were interviewed (13 diabetes dietitians, 8 specialist diabetes midwives, 2 community midwives, 1 antenatal clinic midwife, 1 obstetrician and 2 endocrinologists). Themes were organised into three central domains: (a) Social and cultural barriers, (b) Service provision and (c) Nutrition advice. Enabling themes included professional collaboration, innovation and creating trusting and supportive environments. Key barriers identified included accessibility, cultural barriers, overwhelmed service, fragmentation and conflicting information and nutrition resource gaps. Findings highlight foremost a deficit in primary antenatal nutrition advice that may play a significant role in the fragmentation identified. Investment in community-inclusive services providing antenatal nutrition and diabetes education appears critical to overcome barriers associated with misinformation and poor outcomes. Pathways to include nutrition education from various primary care health providers should be investigated to ease the burden from specialist gestational diabetes clinicians and allow effective delegation of dietetic resources. Revision of current nutrition guidelines for the management of gestational diabetes in New Zealand is needed to facilitate consistent messaging and standards of care.


[Heart reHeart remodeling in patients with severe systolic dysfunction due tocancer chemotherapymodeling in patients with severe systolic dysfunction due tocancer chemotherapy.]
Objective Comparative analysis of structural and functional specific features of the heart in patients with toxic cardiomyopathy (TCMP) with a low left ventricular ejection fraction (LVEF) and severe, chronic heart failure (CHF) and in patients with idiopathic dilated cardiomyopathy (DCMP) and similar LVEF and CHF severity.Materials and Methods This observational, single-site study included 15 patients with TCMP (12 of them received treatment including anthracycline antibiotics and 3 patients received targeted therapies) and 26 patients with idiopathic DCMP. Data of echocardiography were compared for patients with TCMP and DCMP with comparably low LVEF of <40 %.Results In patients with severe heart damage associated with antitumor therapy with low LVEF, volumetric and linear indexes of left and right ventricles and the left atrium (left atrial volume index (LAVI), 33.7 (21.5-36.9) ml / m2; right ventricular end-diastolic dimension (RVDd), 2.49 (1.77-3.53) cm; and end-diastolic volume index (EDVI), 78.0 (58.7-90.0) ml / m2) were considerably less than in the DCMP group (LAVI, 67.1 (51.1-85.0) ml / m2; RVDd, 4.05 (3.6-4.4) cm; and EDVI, 117.85 (100.6-138.5) ml / m2, p<0.0001). Furthermore, LV wall thickness and pulmonary artery systolic pressure did not differ in these groups. Both in men and women with TCMP, LAVI and EDVI were significantly less than in men and women with DCMP.Conclusion The study showed significant differences in parameters of cardiac remodeling. In TCMP patients as distinct from DCMP patients, despite a pronounced decrease in LVEF, LV dilatation was absent or LV volumetric parameters were moderately increased with a more severe somatic status.


Expanding our conceptualization of program implementation: lessons from the genealogy of a school-based nutrition program.
This work presents a theoretical framework in which health promotion and health education program implementation can be conceived as an open dynamic system. By tracing the evolution of an elementary school-based nutrition program from its conception to its recent form, we construct a program genealogy. Data were derived from two interviews and three historical documents from which historical events were identified and reconstructed in the form of a tree analogy. Data analysis ensued using concepts from the actor-network theory about social innovation. These concepts identified social and technical program attributes and situated them within a process which evolved over time, thus permitting the program's genealogy to appear. The genealogy was found to be influenced by the ways in which the involved actors interpreted the issue of food security, namely, as a professional issue, with a nutrition education response and as a social issue, with a community-building response. The interaction between the interests of the actors and the technical components of the program resulted in three temporal program iterations. The results highlight the important role played by the involved actors during program implementation and suggest the need to take these interests into consideration during all phases of program planning.