What is the mechanism of psychological change? A qualitative analysis of six individuals who experienced personal change and recovery.
The mechanism of psychological change, whether this occurs as a result of psychotherapeutic intervention or during natural recovery, remains unknown. The aim of this study was to explore and understand how and why psychological change occurs. This study presents the accounts of six individuals who experienced psychological change and recovery following a significant problem in their lives using the qualitative method of interpretative phenomenological analysis (IPA). A semi-structured interview covered several aspects of their experience which included details of the problem they faced, how the problem affected their lives, how they were able to overcome the problem, and how they felt about their problem looking back. Four superordinate themes emerged from the analysis: hopelessness and issues of control; the change process; new self versus old self; and putting the problem into perspective. Findings are discussed in relation to existing literature on hopelessness and locus of control, experiential avoidance, acceptance and mindfulness, insight, and adversarial growth. The findings are also discussed in relation to a theory of self-regulation known as perceptual control theory (PCT). It is proposed that this theory may provide a valid account of the mechanism of psychological change.


Observation of 4f electron transfer from Ce to B6 in the Kondo crystal CeB6 and its mechanism by multi-temperature X-ray diffraction.
Electron density distributions (EDD) in CeB(6) were measured by X-ray diffraction at 100, 165, 230 and 298 K. Analysis with a weak-field model, in which the spin-orbit interaction dominates the energy splitting of the 4f levels, revealed that more 4f electrons were donated from Ce to B(6) at the lower temperature. Donated electrons localize around the B-B bonds connecting B(6) octahedra. The localized electrons and an expansion of the outermost 5p orbitals change the effective atomic potentials and enhance the anharmonic vibration (AHV) of constituent atoms at lower temperature. Enhanced AHV increases the entropy and makes the electron donation inevitable. Changes in crystal structure, EDD, electron configuration and AHV are found to be closely correlated with one another and the mechanism of the electron transfer in the Kondo crystal CeB(6) in the studied temperature range was elucidated. This is, to the authors' knowledge, the first multi-temperature measurement of EDD that elucidates a mechanism of change from the temperature dependence of the EDD. Parameters change consistently at all the temperatures except 298 K, at which the excited states Gamma(7) of the Ce 4f states have significant electron population. The thermal excitation to Gamma(7) levels expands the B(6) octahedra, since Gamma(7) has main lobes along <111> or from Ce to the centre of B(6) octahedra. The energy gap between the ground state Gamma(8) and Gamma(7) was calculated to be 470 K from the ratio of electron populations of both states. The present experiment opens the door to accurate X-ray EDD analyses of rare earth complexes.


Positive selection as a developmental progression initiated by alpha beta TCR signals that fix TCR specificity prior to lineage commitment.
During positive selection, immature thymocytes commit to either the CD4+ or CD8+ T cell lineage ("commitment") and convert from short-lived thymocytes into long-lived T cells ("rescue"). By formal precursor-progeny analysis, we now identify what is likely to be the initial positive selection step signaled by alpha beta TCR, which we have termed "induction". During induction, RAG mRNA expression is downregulated, but lineage commitment does not occur. Rather, lineage commitment (which depends upon the MHC class specificity of the alpha beta TCR) only occurs after downregulation of RAG expression and the consequent fixation of alpha beta TCR specificity. We propose that positive selection can be viewed as a sequence of increasingly selective developmental steps (induction-->commitment-->rescue) that are signaled by alpha beta TCR engagements of intrathymic ligands.


Endocrine therapy initiation, discontinuation and adherence and breast imaging among 21-gene recurrence score assay-eligible women under age 65.
Aside from chemotherapy utilization, limited data are available on the relationship between gene expression profiling (GEP) testing and breast cancer care. We assessed the relationship between GEP testing and additional variables and the outcomes of endocrine therapy initiation, discontinuation and adherence, and breast imaging exams in women under age 65 years. Data from five state cancer registries were linked with claims data and GEP results. We assessed variables associated with survivorship care outcomes in an incident cohort of 5014 commercially insured women under age 65 years, newly diagnosed with stage I or II hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2) non-positive breast cancer from 2006 to 2010. Among tested women, those with high Oncotype DX® Breast Recurrence Score® (RS) were significantly less likely to initiate endocrine therapy than women with low RS tumors (OR 0.40 (95% CI 0.20 to 0.81); P = 0.01). Among all test-eligible women, receipt of Oncotype DX testing was associated with a greater likelihood of endocrine therapy initiation (OR 2.48 (95% CI 2.03 to 3.04); P <0.0001). The odds of initiation were also significantly higher for tested vs. untested women among women who did not initiate chemotherapy within six months of diagnosis (OR 3.25 (95% CI 2.53 to 4.16)), with no effect in women who received chemotherapy. Discontinuation and adherence and breast imaging exams were unrelated to tested status or RS. Lower endocrine therapy initiation rates among women with high RS tumors and among untested women not receiving chemotherapy are concerning, given its established efficacy. Additional research is needed to suggest mechanisms to close this gap.


Mutations in the Sindbis virus capsid gene can partially suppress mutations in the cytoplasmic domain of the virus E2 glycoprotein spike.
Assembly and budding of alphaviruses are postulated to occur by protein-protein interactions between sites on the cytoplasmic domain of the transmembranal envelope E2 glycoprotein and on the surface of the nucleocapsid protein subunits. Genetic data to support this model have been obtained by isolating revertants of two slow-growth mutants of Sindbis virus and analyzing the sequences of the genes encoding their structural proteins. The slow-growth phenotypes of the mutants were previously shown to result from site-directed mutations of 2 amino acids in the sequence corresponding to the 33 amino acids at the carboxyl terminus of E2, which are localized to the cytoplasmic face of the plasma membrane. Putative revertants of these two mutants with faster growth rates were isolated by sequential passaging of virus grown on insect cells or chicken embryo fibroblasts. Sequence analysis of plaque-purified viruses that grew significantly better than the original mutant revealed that the original E2 mutation was present and that there were additional amino acid changes in the virus capsid. Two of the latter were introduced separately into the wild-type virus cDNA and into the genomes of the original mutants. The new strains of virus that contained both capsid and E2 mutations produced many more extracellular particles than those with the E2 mutations alone, indicating substantial suppression of the original E2 mutation. Both capsid mutations appear to be localized near a hydrophobic pocket of the capsid, which is postulated to be the site for docking of hydrophobic amino acids of the E2 cytoplasmic domain. This genetic study provides strong support for the current models of alphavirus assembly.


Bilateral subdural hygromas after endovascular coiling for ruptured aneurysmal subarachnoid hemorrhage: an unusual and rare complication.
Subarachnoid hemorrhage (SAH) with subdural hygroma (SH) was rarely reported after endovascular coiling. A 60-year-old male presented with impaired consciousness and convulsions due to SAH from a ruptured aneurysm. It was managed by endovascular coiling 20 h after the onset of symptoms. Serial brain imaging for 2 weeks revealed progressive bilateral SHs, more on contralateral side of leaking aneurysm. Management of SH was discussed in a multidisciplinary setting to be conservative as there was neither significant mass effect nor hydrocephalus. The patient recovered neurologically except for mild dysarthria. The SH persisted for 2 months and then cleared gradually. We concluded that SH may arise and become symptomatic as an unusual sequela of post-coiling of a ruptured intracranial aneurysm, in which the SH can complicate the clinical course of SAH. However, the symptomatic SH may resolve spontaneously and completely without any intervention, but needs meticulous neurological assessment and follow-up.


Fractional erbium-doped yttrium aluminum garnet laser-assisted drug delivery of hydroquinone in the treatment of melasma.
Melasma is a difficult-to-treat hyperpigmentary disorder. Ablative fractional laser (AFL)-assisted delivery of topically applied drugs to varied targets in the skin has been an area of ongoing study and research. The objective of this study was to evaluate the efficacy and safety of fractional erbium-doped yttrium aluminum garnet (Er:YAG) laser as an assisted drug delivery for enhancing topical hydroquinone (HQ) permeation into the skin of melasma patients. Thirty female patients with bilateral melasma were randomly treated in a split-face controlled manner with a fractional Er:YAG laser followed by 4% HQ cream on one side and 4% HQ cream alone on the other side. All patients received six laser sessions with a 2-week interval. The efficacy of treatments was determined through photographs, dermoscopic photomicrographs and Melasma Area Severity Index (MASI) score, all performed at baseline and at 12 weeks of starting therapy. The patient's level of satisfaction was also recorded. Er:YAG laser + HQ showed significantly better results (p<0.005) with regard to decrease in the degree of pigmentation as assessed on the 4-point scale than HQ alone. There was a significant decrease in MASI scores on Er:YAG laser + HQ side vs HQ side. Minor reversible side effects were observed on both sides. AFL-assisted delivery of HQ is a safe and effective method for the treatment of melasma.


Low-level deficits in beat perception: neither necessary nor sufficient for explaining developmental dyslexia in a consistent orthography.
This article reports two different studies examining the theoretical account of low-level deficits in beat perception as an alternative explanation of developmental dyslexia in Greek, an orthographically consistent language. Study I examined the relationship of amplitude rise time and frequency discrimination with measures of phonological processing, working memory, and reading fluency in a large unselected sample of Grade 4 children. Study II examined the presence of beat perception deficits in groups of Grade 2, 4, and 6 children with dyslexia and their chronological age controls. The results provided no evidence to support meaningful associations between beat perception tasks and reading or the theoretical account of beat perception deficits as a sufficient explanation or contributing factor to dyslexia. Implications on the importance of auditory processing in reading in orthographically consistent languages are discussed.


Long-term survival and risk factors for failure of the native hip joint after operatively treated displaced acetabular fractures.
Our aim in this study was to describe the long-term survival of the native hip joint after open reduction and internal fixation of a displaced fracture of the acetabulum. We also present long-term clinical outcomes and risk factors associated with a poor outcome. A total of 285 patients underwent surgery for a displaced acetabular fracture between 1993 and 2005. For the survival analysis 253 were included, there were 197 men and 56 women with a mean age of 42 years (12 to 78). The mean follow-up of 11 years (1 to 20) was identified from our pelvic fracture registry. There were 99 elementary and 154 associated fracture types. For the long-term clinical follow-up, 192 patients with complete data were included. Their mean age was 40 years (13 to 78) with a mean follow-up of 12 years (5 to 20). Injury to the femoral head and acetabular impaction were assessed with CT scans and patients with an ipsilateral fracture of the femoral head were excluded. A total of 36 patients underwent total hip arthroplasty (THA). The overall ten-year survival of the hip joint was 86% (95% confidence interval (CI) 81% to 90%) and the 20-year survival was 82% (95% CI 76% to 87%). Injury to the femoral head and acetabular impaction were the strongest predictors of failure, with the long-term survival rate falling towards 50% in these patients. The survival fell to 0% at three years when both these risk factors were present in patients aged > 60 years. The long-term survival of the native hip joint after acetabular fractures was good, but the presence of injury to the femoral head and acetabular impaction proved to be strong predictors of failure, especially in patients aged > 60 years. These patients may be better treated with a combination of open reduction and internal fixation and primary arthroplasty. Cite this article: Bone Joint J 2017;99-B:834-40.


Synthesis of alpha-amino acids via asymmetric phase transfer-catalyzed alkylation of achiral nickel(II) complexes of glycine-derived Schiff bases.
Achiral, diamagnetic Ni(II) complexes 1 and 3 have been synthesized from Ni(II) salts and the Schiff bases, generated from glycine and PBP (7) and PBA (11), respectively, in MeONa/MeOH solutions. The requisite carbonyl-derivatizing agents pyridine-2-carboxylic acid(2-benzoyl-phenyl)-amide 7 (PBP) and pyridine-2-carboxylic acid(2-formyl-phenyl)-amide 11 (PBA) were readily prepared from picolinic acid and o-aminobenzophenone or picolinic acid and methyl o-anthranilate, respectively. The structure of 1 was established by X-ray crystallography. Complexes 1 and 3 were found to undergo C-alkylation with alkyl halides under PTC conditions in the presence of beta-naphthol or benzyltriethylammonium bromide as catalysts to give mono- and bis-alkylated products, respectively. Decomposition of the complexes with aqueous HCl under mild conditions gave the required amino acids, and PBP and PBA were recovered. Alkylation of 1 with highly reactive alkyl halides, carried out under the PTC conditions in the presence of 10% mol of (S)- or (R)-2-hydroxy-2'-amino-1,1'-binaphthyl 31a (NOBIN) and/or its N-acyl derivatives and by (S)- or (R)-2-hydroxy-8'-amino-1,1'-binaphthyl 32a (iso-NOBIN) and its N-acyl derivatives, respectively, gave rise to alpha-amino acids with high enantioselectivities (90-98.5% ee) in good-to-excellent chemical yields at room temperature within several minutes. An unusually large positive nonlinear effect was observed in these reactions. The Michael addition of acrylic derivatives 37 to 1 was conducted under similar conditions with up to 96% ee. The (1)H NMR and IR spectra of a mixture of the sodium salt of NOBIN and 1 indicated formation of a complex between the two components. Implications of the association and self-association of NOBIN for the observed sense of asymmetric induction and nonlinear effects are discussed.


Activation and inhibition of the calcium-release channel of isolated skeletal muscle heavy sarcoplasmic reticulum. Models of the calcium-release channel.
Calcium-independent calcium efflux from heavy sarcoplasmic reticulum (HSR) of skeletal muscle was found to be biphasic, with half-times of 2-6 s and 200-400 s for the first and second phase, respectively. Calcium-, AMP- and caffeine-induced calcium efflux was triphasic, with half-times of 0.05-0.2 s, 1-5 s and 100-400 s for the first, second and third phases, respectively. This very fast first phase is certainly due to calcium efflux via the calcium-release channel of HSR vesicles. Both ruthenium red and neomycin inhibited the first phase of the calcium-independent calcium efflux and the first phase of the calcium-, AMP- or caffeine-induced calcium efflux completely, whilst the second phase was fully inhibited by ruthenium red only and partially inhibited by neomycin at high concentrations, indicating that the second phase of calcium release also occurs via the calcium-release channel. Various models for calcium efflux through the release channel have been tested by simulation. Activation and inhibition of the channel-mediated calcium efflux from HSR cannot be explained by two states of the calcium-release channel (open or closed), but requires the existence of at least three states. A channel with one open state and two closed states, resulting in a rapid inactivation, is the most simple model compatible with the experimental data. According to this model, activation is assumed to reduce inactivation of the channel, whilst inhibition assumes an acceleration of channel inactivation. This mechanism most likely applies to neomycin. An additional open-blocked state has to be assumed for inhibition by ruthenium red.


Microsatellite characterization of Plasmodium falciparum from cerebral and uncomplicated malaria patients in southern Vietnam.
If parasite genotype influences the clinical course of malaria, we expect that isolates from patients with similar pathology would be more closely related than would be expected by chance. To explore this prediction, we typed nine microsatellite markers in sympatric Plasmodium falciparum isolates from cerebral and uncomplicated malaria patients from Vietnam. Temporal structure and linkage disequilibrium were also examined in this data set.


Targeting non-Hodgkin lymphoma with blinatumomab.
Management of patients with relapsed or refractory non-Hodgkin lymphoma (NHL) remains challenging, and novel effective agents are eagerly awaited. Blinatumomab is a bispecific T-cell engager, targeting CD19. While blinatumomab's primary clinical use has been in B-cell acute lymphoblastic leukemia (B-ALL), there are increasing data for its use in B-lineage lymphomas. Areas covered: The aim of this review is to highlight the clinical data for blinatumomab use in NHL. Herein, the authors provide an overview of blinatumomab, its mechanism of action, its proven efficacy against B-ALL, and its phase I-II data assessing its use in NHL Expert opinion: Blinatumomab has modest activity in phase I-II trials in NHL, and may represent a means of bridging patients with relapsed disease to hematopoietic stem cell transplant. More widespread use is currently hampered by lack of phase III data, multiple competing agents, an onerous administration schedule and significant side effect profile. Further studies are eagerly awaited assessing its use in combination with other immunotherapy strategies.


A prospective longitudinal study on visuo-cognitive development in Dravet syndrome: Is there a "dorsal stream vulnerability"?
A group of five DS patients whose first development was already reported were longitudinally followed up till the scholar age. Beside the general and epileptic clinical evolution, visual and cognitive functions were investigated in order to define their trajectory and possibly provide information about mechanisms of cognitive decline as well as to improve prognosis and tertiary prevention. Neuropsychological assessment was performed with a test battery investigating the development of visual function that progressively integrates into extrastriate components and higher cognitive skills (global form and motion coherence, stereopsis, crowding cards, ABCDEFV battery, general intelligence and specific cognitive tests). Main results showed a fall in visuo-motor items including global motion coherence and specific cognitive skills, presenting a continuity of the visual function deterioration extended from basic abilities to visuo-motor dorsal pathway skills. Moreover, a case whose previous visual and cognitive functions had been in the normal range began showing a visual deterioration with increasing age, followed by the cognitive decline; that prevents from excluding in early ages a poor development in presence of a normal visual function. A dorsal stream vulnerability seems thus shown in this sample of DS patients, like in other genetic syndromes (Williams, Prader Willi. fragile-X), providing new information about mechanisms underlying cognitive decline and suggesting a possible strategy to improve their neuropsychological outcome. Larger cohorts may confirm whether these findings are part of a specific pattern of DS neuropsychological phenotype.


No end to caring?
In a recent issue of Politics and the Life Sciences Mark Walker presented a compelling proposition for reducing evil in the world via an interdisciplinary program he calls the "Genetic Virtue Project" (GVP). As Walker explains, the purpose of the GVP is "to discover and enhance human ethics using biotechnology genetic correlates of virtuous behavior." PLS subsequently published several critiques of this proposal. While most of these critiques focused on conventional doubts about the technical feasibility or the ethics of such interventions, the more fundamental concern revealed by both Walker's proposal and its critiques is in the largely unquestioned assumption that more morality is necessarily better. Human history is marked by a gradual if uneven extension of moral concern to increasingly distant others, which many take as evidence of the rationality of morality. There is substantial evidence, though, that this expansion is fundamentally biological in origin and therefore not ultimately limited by rationality. Because these expanding moral feelings feel so good to us, we are incapable of perceiving the danger from their ever-expanding focus, in particular from the sincere but increasingly maladaptive collective policies they will engender. Utilizing the philosophy of Friedrich Nietzsche as a platform, the feasibility of different natural and cultural responses to this impending crisis of caring are examined, none of which are found capable of counteracting this expanding morality. Instead, the best hope for a successful response to this dangerous expansion of caring is actually a sort of reverse GVP, in which the biological mechanisms for this unchecked moral expansion are manipulated via genetic engineering to dial back this expansion. However, the likelihood of actually implementing such an admittedly counterintuitive and controversial program within an increasingly democratized world is doubtful. Ultimately, if we are unable to overcome this betrayal by our best intentions, where does that leave us as a species?


TransVG++: End-to-End Visual Grounding With Language Conditioned Vision Transformer.
In this work, we explore neat yet effective Transformer-based frameworks for visual grounding. The previous methods generally address the core problem of visual grounding, i.e., multi-modal fusion and reasoning, with manually-designed mechanisms. Such heuristic designs are not only complicated but also make models easily overfit specific data distributions. To avoid this, we first propose TransVG, which establishes multi-modal correspondences by Transformers and localizes referred regions by directly regressing box coordinates. We empirically show that complicated fusion modules can be replaced by a simple stack of Transformer encoder layers with higher performance. However, the core fusion Transformer in TransVG is stand-alone against uni-modal encoders, and thus should be trained from scratch on limited visual grounding data, which makes it hard to be optimized and leads to sub-optimal performance. To this end, we further introduce TransVG++ to make two-fold improvements. For one thing, we upgrade our framework to a purely Transformer-based one by leveraging Vision Transformer (ViT) for vision feature encoding. For another, we devise Language Conditioned Vision Transformer that removes external fusion modules and reuses the uni-modal ViT for vision-language fusion at the intermediate layers. We conduct extensive experiments on five prevalent datasets, and report a series of state-of-the-art records.


The Chinese Catquest-9SF: validation and application in community screenings.
The purpose of this study was to validate the Chinese Catquest-9SF questionnaire in community screenings and explore the correlation between Catquest-9SF scores and Lens Opacities Classification System (LOCS) III cataract grading. This was a prospective questionnaire validation study. The Catquest-9SF questionnaire was translated into Chinese and was completed by 104 Chinese cataract patients who were diagnosed in community screening. Rasch analysis was used to assess its psychometric properties, and Spearman correlation coefficient was employed to determine the correlation between Catquest-9SF scores and LOCS III cataract grading. The Catquest-9SF questionnaire demonstrated ordered response categories and unidimensionality (item fit statistics range: 0.70-1.35); the PSI and PR of the category probability curves were 2.00 and 0.80, respectively. There was a fair but statistically significant correlation between Catquest-9SF (Q6, Q7, and Q8) and LOCS III scores and a moderate correlation between Q4 in Catquest-9SF and subcapsular components for the better eye (r = - 0.546, p < 0.001). The Chinese version of Catquest-9SF is a valid and reliable questionnaire in community screenings. Thus, this questionnaire may be expected to be an auxiliary tool for preliminary cataract screening use.


Bioinformatics analysis of the gene expression profile in Bladder carcinoma.
Bladder carcinoma, which has the ninth highest incidence among malignant tumors in the world, is a complex, multifactorial disease. The malignant transformation of bladder cells results from DNA mutations and alterations in gene expression levels. In this work, we used a bioinformatics approach to investigate the molecular mechanisms of bladder carcinoma. Biochips downloaded from the Gene Expression Omnibus (GEO) were used to analyze the gene expression profile in urinary bladder cells from individuals with carcinoma. The gene expression profile of normal genomes was used as a control. The analysis of gene expression revealed important alterations in genes involved in biological processes and metabolic pathways. We also identified some small molecules capable of reversing the altered gene expression in bladder carcinoma; these molecules could provide a basis for future therapies for the treatment of this disease.


Positive Predictive Value of a Single Assessment of Estimated GFR in the Diagnosis of Chronic Kidney Disease.
The positive predictive value (PPV) of a single assessment of estimated glomerular filtration rate (eGFR) in the diagnosis of chronic kidney disease (CKD) is not known. Our objective was to determine the PPV of a single assessment of eGFR among adults with at least one eGFR <60 mL/min in their lifetime, using the Distributed Area Research and Therapeutics Network CKD natural history dataset. In all, 47,104 adults who were cared for by 113 practices in the United States were included. Proportions of patients in eGFR categories at baseline were calculated using the following categories: <15 mL/min, 15 to 29.99 mL/min, 30 to 44.99 mL/min, and 45 to 59.99 mL/min. Comparisons were then made between the baseline and the endpoint to identify patients who had a follow-up eGFR that remained at <60 mL/min. The proportions of patients in each eGFR category were compared baseline to endpoint using cross-tabulations. To test the proposed cutpoint, the proportions of patients who had an eGFR that remained at <60 mL/min were measured, using the cutpoints that included the highest cumulative proportion of patients. The sensitivity and specificity of that cutpoint were calculated. A cutpoint of <45 mL/min was identified, yielding a PPV of 93% with a sensitivity of 28% and a specificity of 94%. A valid cutpoint to screen for CKD was identified. This cutpoint may prove important to early screening for CKD while reducing the burden on the healthcare system and patients suspected of having CKD.


Crohn's disease complicated by intestinal infection with methicillin-resistant Staphylococcus aureus.
We report on a 24-year-old male patient with history of bloody diarrhea, abdominal pain and vomiting. Endoscopy revealed massive ulcerative discontinuous proctosigmoiditis with deep, sharply demarcated epithelial denudations and enterotoxigenic methicillin-resistant Staphylococcus aureus (MRSA) was detected in mucosal biopsies. After treatment with linezolide and steroids, a significant amelioration of colitis was detected and testing for MRSA became negative. In face of the case presented here, we suggest that in patients with refractory inflammatory bowel disease (IBD), microbiological assessment should be performed to detect a possible Staphylococcus aureus infection in order to initiate an antimicrobial treatment in addition to IBD-specific treatment.


Management and outcomes of axial isolated distal deep vein thrombosis at North Shore Hospital, New Zealand: a retrospective audit.
It is standard of care to treat proximal vein deep vein thrombosis (DVT) for a minimum of 3 months. Conversely, management of isolated distal DVT (IDDVT) is controversial, with options including observation and repeat ultrasound scan within 1 week to detect and anticoagulate those with proximal propagation, or anticoagulation for periods of up to 3 months. The aim was to assess the rates of proximal propagation and venous thromboembolism (VTE) recurrence within 3 months of diagnosis of IDDVT, and to examine how the duration of treatment might influence this. Study patients were identified by retrospective audit of data from the North Shore Hospital VTE database. All patients presenting with established axial vein distal DVT from July 2007 to June 2012 were included. A 6-week treatment duration cut-off was used to separate the treatment arms (<6 weeks vs 6 weeks vs >6 weeks), and Fisher's exact or Pearson's Chi-squared tests were used to assess between-group comparisons. Five hundred and seven patients were included in the study, mean age 59.7 years; 53% female. There were three cases of proximal propagation, all occurring in those receiving <6 weeks treatment. There were six VTE recurrences, three in the <6 week and three in the ≥6 week treatment groups respectively. Malignancy was the only significant predictor of VTE recurrence (P = 0.001). A 6-week duration of anticoagulation appears to be an effective and safe treatment for isolated axial distal DVT, with low rates of VTE recurrence and proximal propagation.


Nakazawaea todaengensis f.a., sp. nov., a yeast isolated from a peat swamp forest in Thailand.
Strain DMKU-PS11(1)T was isolated from peat in a swamp forest in Thailand. DNA sequence analysis showed that it belonged to a novel species that was most closely related to Nakazawaea laoshanensis. However, it differed from the type strain of N. laoshanensis (NRRL Y-63634T) by 2.3 % nucleotide substitutions in the D1/D2 region of the large subunit (LSU) rRNA gene, 1.0 % nucleotide substitutions in the small subunit (SSU) rRNA gene and 8.0 % nucleotide substitutions in the internal transcribed spacer (ITS) region. The phylogenetic analyses based on the combined sequences of the SSU and the D1/D2 region and that of the SSU sequences alone confirmed the placement of the novel species in the Nakazawaea clade and its close affinity with N. laoshanensis. Hence, the species Nakazawaea todaengensis f.a., sp. nov. is proposed. The type strain is DMKU-PS11(1)T (=CBS 14555T=TBRC 6559T). The MycoBank number for Nakazawaea todaengensis f.a., sp. nov. is MB 819513.


Individual and Store Characteristics Associated with Brand Choices in Select Food Category Redemptions among WIC Participants in Virginia.
The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) often allows participants to redeem food benefits for various brands at different costs. To aid the program's food cost containment efforts, it is important to understand the individual and store characteristics associated with brand choices. This study used the WIC Electronic Benefit Transfer (EBT) data for 239,062 Virginia WIC participants' brand choices in infant fruits and vegetables (F&Vs) and whole grain bread in May 2014-February 2015, one of the first such data sets available in the U.S. for research purposes. Mixed effects logistic regression models were used to analyze the choice of higher-priced brands over lower-priced brands. Minority participants were significantly more likely to redeem higher-priced brands of infant F&Vs, but more likely to choose lower-priced brands of bread. Participants shopping in urban stores or midsized stores (with 5-9 registers) were less likely to choose higher-priced brands compared to rural stores or large stores (with 9+ registers). Race/ethnicity and store characteristics may be significant factors in participants' brand choices. The results can help develop interventions that encourage targeted participants to redeem lower-priced but equivalently healthy brands. This may not only help contain WIC program costs, but help participants manage their own non-WIC food expenses as well.


Assisted living, elderly women and sense of self: communicating the impact of reduction of long-standing activities.
Through the use of in-depth interviews this study examines elderly women's communication about transitioning to assisted living and personal sense of self. A combination of communication and aging theory and socio historical factors aid in understanding the communication elderly women use to describe themselves within the context of life events prior to and after becoming an assisted living resident. Findings reveal that decrease in long-standing feminine sphere (traditionally female household) tasks due to the transition to assisted living is the major factor leading to the inability to communicate the sense of self. Inability to adjust and accept the downsizing of feminine sphere activities leads to several mental, physical and social implications.


Ene-adducts from 1,4-dihydropyridines and α,β-unsaturated nitriles: asynchronous transition states displaying aromatic features.
Hydride transfer reactions involving 1,4-dihydropyridines play a central role in bioorganic chemistry as they represent an important share of redox metabolism. For this class of reactions, direct hydride transfer is the commonly accepted mechanism; however, an Alder-Ene-like pathway has been proposed as a plausible alternative. The reaction between 1,4-ditrimethylsilyl-1,4-dihydropyridine and α,β-unsaturated nitriles is a solid candidate for this latter pathway. In this work, we perform high level ab initio and density functional theory computations to characterize the mechanism of this reaction, taking into account diverse reaction paths, and evaluating the effect of solvent polarity and variations in the chemical structure. Our analysis explains the stereochemical aspects of the reaction, characterizing the up to now unresolved spatial configurations of the predominant products, and may contribute to the understanding of enzymatic reactions involving NADP(H). The reactions are found to proceed in an asynchronous fashion, with transition states that display significant aromatic features. With this observation in mind, Alder-Ene and direct hydride transfer pathways can be understood as two extremes of a continuous mechanistic spectrum for this kind of reaction, with the analyzed systems located approximately equidistant from both ends.


Pharmacokinetics, pharmacodynamics and adherence to oral topotecan in myelodysplastic syndromes: a Cancer and Leukemia Group B study.
To evaluate medication adherence, pharmacokinetics and exposure versus response relationships in patients with myelodysplastic syndromes (MDS). Ninety adult patients with MDS received oral topotecan (1.2 mg/m2) either once a day for 10 days or twice a day for 5 days every 21 days for up to six cycles. Dosing histories were collected using electronic monitoring devices fitted to medication vials. Topotecan plasma concentrations were measured, and exposure was determined by a sparse sampling approach and Bayesian estimation methods. Relationships between exposure and clinical response and toxicity were evaluated using logistic regression. Overall adherence was excellent with 90% of patients taking the prescribed number of doses in cycle 1. Adherence did not differ between the two regimens. Topotecan pharmacokinetics were described using a one compartment open model with first order absorption and elimination. Pharmacokinetic parameter estimates did not differ between the once a day and twice a day dosing groups. While topotecan exposure was greater in the twice a day arm compared to the once a day arm due to drug accumulation, exposure did not correlate with clinical response. However, the probability of needing a platelet transfusion in the twice a day arm was significantly increased (by 35%) as a result of greater steady-state plasma topotecan concentrations. Adherence is high in patients with MDS receiving oral topotecan, whether the drug is prescribed once or twice daily. The optimal schedule cannot be determined from this study, as there was no evident relationship between any pharmacokinetic parameter and clinical response.


Retinotopic distribution of chromatic responses in human primary visual cortex.
In non-human primates at least three anatomically and functionally distinct channels convey signals from the retina to the primary visual cortex (V1). Two of these channels, the parvocellular and the koniocellular, are sensitive to chromatic contrasts and form the basis of color vision. In humans, common phylogenetic history with other primates and psychophysical experiments suggest identical retinocortical mechanisms but separate evaluation of the distinct anatomical channels has been difficult because signals are already combined in V1. We studied the spatial distribution of activation to chromatic stimuli along the two opponent chromatic axes in human V1 with multifocal functional magnetic resonance imaging. The signal strength was quantified from three experiments with stimuli up to 20 degrees eccentricity. The hypothesis was that, although the parvo- and koniocellular signals are mixed in V1, distinct distributions of signal strength would be evident. We found that whereas different conditions activated the same areas of cortex, indicating that they have identical magnification factors, the responses to red/green stimulation were stronger close to the fovea whereas the blue/yellow responses were much less diminished with increasing eccentricity. Both chromatic axes showed saturating contrast response functions. Our measure directly from human V1 is in line with earlier psychophysical studies suggesting relatively stronger parvocellular channel representation close to the fovea, and more uniform distribution of the koniocellular and achromatic channels. In addition, our study presents a way to rapidly quantify retinotopic signal transmission in distinct retinocortical pathways of individual subjects.


Liposomal paclitaxel induces apoptosis, cell death, inhibition of migration capacity and antitumoral activity in ovarian cancer.
The main goal of this study is to evaluate the efficacy of the paclitaxel (PTX) drug formulated with a liposomal nanosystem (L-PTX) in a peritoneal carcinomatosis derived from ovarian cancer. In vitro cell viability studies with the human ovarian cancer line A2780 showed a 50% decrease in the inhibitory concentration for L-PTX compared to free PTX. A2780 cells treated with the L-PTX formulation demonstrated a reduced capacity to form colonies in comparison to those treated with PTX. Cell death following L-PTX administration hinted at apoptosis, with most cells undergoing initial apoptosis. A2780 cells exhibited an inhibitory migration profile when analyzed by Wound Healing and real-time cell analysis (xCELLigence) methods after L-PTX administration. This inhibition was related to decreased expression of the zinc finger E-box-binding homeobox 1 (ZEB1) and transforming growth factor 2 (TGF-β2) genes. In vivoL-PTX administration strongly inhibited tumor cell proliferation in ovarian peritoneal carcinomatosis derived from ovarian cancer, indicating higher antitumor activity than PTX. L-PTX formulation did not show toxicity in the mice model. This study demonstrated that liposomal paclitaxel formulations are less toxic to normal tissues than free paclitaxel and are more effective in inhibiting tumor cell proliferation/migration and inducing ZEB1/TGF-β2 gene expression.


Extracellular matrix deposited by Wharton's jelly mesenchymal stem cells enhances cell expansion and tissue specific lineage potential.
This article aims to explore whether Wharton's jelly (WJ) derived mesenchymal stem cells (MSCs) (WJ-MSCs) decellularized extracellular matrix (dECM) can rejuvenate MSCs during in vitro expansion. Passage 10 synovium-derived mesenchymal stem cells (SDSCs) and WJ-MSCs were expanded on plastic flasks (PL) or dECMs derived from SDSCs and WJ-MSCs. Flow cytometry was applied to evaluate surface phenotypes and proliferation capacity. Early (7 days) and late (21 days) chondrogenic potentials were assessed using histology, immunohistochemistry, and real-time polymerase chain reaction (PCR). Western blot analysis was applied to evaluate the potential involvement of MAPK and Wnts signals during the proliferation and chondrogenic processes. Cells were further evaluated for their osteogenic potential using alkaline phosphatase staining and RT-PCR and adipogenic potential using oil red O staining and RT-PCR. Compared to PL expanded cells, dECMs yielded expanded cells with better proliferation capacity as well as decreased percentage of HLA-DR positive SDSCs. Meanwhile, a decrease in CD105 median fluorescence intensity of WJ-MSCs groups were observed compared to the corresponding SDSCs groups. Moreover, both SDSCs and WJ-MSCs acquired better chondrogenic potential after dECM treatment, as evidenced by increased pellet sizes and increased expression of chondrogenic marker genes. WJ-MSCs dECM was inferior to SDSCs dECM in enhancing early stage chondrogenic differentiation, which was compensated during late stage chondrogenesis, despite causing an increased type X collagen accumulation. p-JNK and p-38 were implicated in the expansion and late chondrogenic differentiation stages, respectively. However, dECM preconditioning did not enhance either osteogenic or adipogenic potential of SDSCs and WJ-MSCs. WJ-MSCs dECM is superior to SDSCs dECM on enhancing proliferation, lowering immunogenicity and promoting late stage chondrogenesis.


Genetic variability and population structure of Plasmodium falciparum parasite populations from different malaria ecological regions of Kenya.
Transmission intensity, movement of human and vector hosts, biogeographical features, and malaria control measures are some of the important factors that determine Plasmodium falciparum parasite genetic variability and population structure. Kenya has different malaria ecologies which might require different disease intervention methods. Refined parasite population genetic studies are critical for informing malaria control and elimination strategies. This study describes the genetic diversity and population structure of P. falciparum parasites from the different malaria ecological zones in Kenya. Twelve multi-locus microsatellite (MS) loci previously described were genotyped in 225 P. falciparum isolates collected between 2012 and 2013 from five sites; three in lowland endemic regions (Kisumu, Kombewa, and Malindi) and two in highland, epidemic regions (Kisii and Kericho). Parasites from the lowland endemic and highland epidemic regions of western Kenya had high genetic diversity compared to coastal lowland endemic region of Kenya [Malindi]. The Kenyan parasites had a mean genetic differentiation index (FST) of 0.072 (p=0.011). The multi-locus genetic analysis of the 12 MS revealed all the parasites had unique haplotypes. Significant linkage disequilibrium (LD) was observed in all the five parasite populations. Kisumu had the most significant index of association values (0.16; p<0.0001) whereas Kisii had the least significant index of association values (0.03; p<0.0001). Our data suggest high genetic diversity in Kenyan parasite population with the exception of parasite from Malindi where malaria has been on the decline. The presence of significant LD suggests that there is occurrence of inbreeding in the parasite population. Parasite populations from Kisii showed the strongest evidence for epidemic population structure whereas the rest of the regions showed panmixia. Defining the genetic diversity of the parasites in different ecological regions of Kenya after introduction of the artemether-lumefantrine is important in refining the spread of drug resistant strains and malaria transmission for more effective control and eventual elimination of malaria in Kenya.


Antigenic characteristics of polypeptides of Coxiella burnetii isolates.
Eighteen Coxiella burnetii strains from a variety of clinical and geographical sources were screened for antigenic variation of polypeptides by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) coupled with Coomassie brilliant blue (CBB) staining or immunoblotting. These polypeptide profiles showed the greatest variability in the region from 33 to 8.1 kDa. Such differences in the antigenicity of the polypeptides were also recognized by immunoblotting with 15 various mouse anti-C. burnetii antisera. In addition, we detected a polypeptide at about 28 kDa which was immunodominant in strains from human cases of acute Q fever, milk and ticks but not immunogenic in strains from human cases of chronic Q fever. These findings suggest that this polypeptide is a marker to distinguish between acute and chronic strains.


Proteomics for the development of vaccines and therapeutics.
Proteomics permits the large-scale and high-throughput analysis of proteins and has become a powerful tool with which to study the pathogenic mechanisms of bacteria. It not only provides a metabolic snapshot at a particular moment in the life of a pathogen, but can also determine where a protein resides, its function, whether it is secreted, and its interactions with other proteins, including those of the host. Comparative proteomics can yield important information on the differences between attenuated and pathogenic organisms and whether a protein is conserved among various strains. Our laboratory has utilized traditional and novel techniques to investigate the global and subproteomes of Bacillus anthracis as they relate to vaccine and therapeutic development. Recently, our efforts have focused on the use of mass spectrometry for B-cell epitope discovery and identification of components of a pathogen that interact with host proteins. Development of vaccines and therapeutics based on proteomic data in combination with novel adjuvants and delivery systems will be presented.


New Insights into the Remarkable Difference between CH5- and SiH5.
It has long been known that there is a fundamental difference in the electronic structures of CH5- and SiH5-, two isoelectronic molecules. The former is a saddle point for the SN2 exchange reaction H- + CH4 → [CH5-]‡ → CH4 + H-, while the latter is a stable molecule that is bound relative to SiH4 + H-. SCGVB calculations indicate that this difference is the result of a dramatic difference in the nature of the axial electron pairs in these anions. In SiH5-, the axial pairs represent two stable bonds-a weak recoupled pair bond dyad. In CH5-, the axial electron pairs represent an intermediate transition between the electron pairs in the reactants and those in the products. Furthermore, the axial orbitals at the saddle point in CH5- are highly overlapping, giving rise to strong Pauli repulsion and a high barrier for the SN2 exchange reaction.


Aminoglycoside treatment and mortality after bacteraemia in patients given appropriate empirical therapy: a Danish hospital-based cohort study.
The effectiveness and safety of aminoglycoside (AG)/beta-lactam combination therapy has been questioned in several meta-analyses. We examined the association between AG combination therapy and mortality and increase in serum creatinine in adult patients with bacteraemia given appropriate empirical antibiotic therapy. Historical cohort study based on prospective registration of bacteraemias in a Danish hospital 1996-2002. AG + beta-lactam was the recommended empirical therapy for severe sepsis. We identified 1,257 patients, of whom 969 received gentamicin or tobramycin (AG cohort); 288 patients not given AGs formed the non-AG cohort. We used Cox regression analysis to compare adjusted mortality rates; the association between AG therapy and increase in serum creatinine was analysed by logistic regression. The cumulative 30 day mortality in the AG cohort was 17.3% versus 18.1% in the non-AG cohort [adjusted mortality rate ratio (MRR) 1.02; 95% CI 0.74-1.39]. The adjusted 31-180 day MRR in the AG cohort was 1.72 (95% CI 1.15-2.55). AG therapy was associated with lower 30 day mortality in patients with an abdominal focus (adjusted 30 day MRR 0.52; 95% CI 0.24-1.10) or a urinary tract focus (adjusted 30 day MRR 0.48; 95% CI 0.22-1.08), but with a worse prognosis in patients with a respiratory tract focus (adjusted 30 day MRR 2.06; 95% CI 0.93-4.53). An increase in serum creatinine of >or=45 micromol/L was observed similarly often in AG- and non-AG-treated patients [14.1% versus 12.4%, adjusted odds ratio 1.06; 95% CI 0.63-1.79]. Among patients with bacteraemia receiving appropriate empirical coverage, AG combination therapy was not associated with increased 30 day mortality and only a modest risk of raised serum creatinine. The longer-term prognosis should, however, be explored further.


Bumblebees can be used in combination with juvenile hormone analogues and ecdysone agonists.
This study examined the lethal and sublethal effects on the beneficial insect Bombus terrestris by two classes of insect growth regulators (IGRs) that are commercially used in agriculture to control pest insects. Three juvenile hormones analogues (JHAs) (pyriproxyfen, fenoxycarb and kinoprene) and two ecdysone agonists or moulting accelerating compounds (MACs) (tebufenozide and methoxyfenozide) were tested. The bumblebee workers were exposed to the insecticides via three different routes of exposure: dermally by topical contact, and orally via the drinking sugar water or the pollen. In the first series of experiments the IGRs were applied at their respective maximum field recommended concentration (MFRC). These risk hazard tests showed that the tested IGRs caused no acute toxicity on the workers, and any compound had an adverse effect on reproduction (production of males). In addition, larval development was followed in the treated nests compared with the controls. After application of the two MACs and the JHA fenoxycarb no adverse effects were observed on larval development. However, in the nests where the workers were exposed to the JHAs pyriproxyfen and kinoprene higher numbers of dead larvae were scored. These larvae were third and fourth instars, implying a lethal blockage of development before metamorphosis. In a second test, a series of dilutions was made for kinoprene, and these results revealed that only the MFRC caused a toxic effect on the larval development. On the other hand, kinoprene at lower concentrations (0.0650 mg ai/l) had a stimulatory effect on brood production. It was remarkable that ovaries of such treated dominant workers were longer and contained more eggs than in the controls. In a last experiment, the cuticular uptake was determined for a JHA and MAC to evaluate to what extent worker bees accumulate these classes of IGRs. Cuticular uptake ranged from 34 to 83% at 24 h after topical application. Overall, the obtained results indicate that the tested IGRs at their recommended concentration are safe to be used in combination with B. terrestris.


Neurohormones in mitral stenosis before and after percutaneous balloon mitral valvotomy.
The hormonal response to percutaneous balloon mitral valvotomy (PBMV) has been described in patients in sinus rhythm (SR) and with atrial fibrillation (AF). The study aim was to evaluate the effect of hemodynamic parameters and PBMV on atrial natriuretic factor (ANF) secretion and plasma renin activity (PRA) in mitral stenosis in SR and AF. Thirty-one patients (26 females, five males; mean age 50.5+/-14 years) with pure rheumatic mitral stenosis underwent PBMV. Fourteen patients had AF, and 17 were in SR. PRA and ANF were measured 24 h before, and at 30 and 60 min, 24 h and one month after PBMV, after resting in a supine position for > or =2 h. Digitalis and diuretics were withdrawn 48 h before sampling; neither had patients received ACE inhibitors or beta-blockers during the previous month. PBMV was successful in all cases, without complication. Mitral valve area was increased and wedge pressure decreased in both groups after PBMV. In AF patients, neither PRA nor ANF were significantly affected before and after PBMV; in SR patients, ANF was decreased and PRA increased significantly, notably 24 h after PBMV. The cardiac index was increased in both groups, but was distinctly lower in AF patients both before and after PBMV. Despite similar hemodynamic results, reversal of the hormonal pattern after PBMV occurred only in SR patients, most likely because in AF patients a low cardiac index elicits a hormonal response similar to heart failure. This abnormal hormonal pattern may limit functional recovery after PBMV; hence, PBMV is best attempted while patients are still in SR.


Effects of grain processing and dietary lipid source on performance, carcass characteristics, plasma fatty acids, and sensory properties of steaks from finishing cattle.
An experiment was conducted to evaluate the effects of grain processing and lipid addition to finishing diets on cattle performance, carcass characteristics, and meat quality. Eighty Hereford x Angus steers (384 kg +/- 17 kg of BW) were fed diets containing steam-flaked corn (SFC) or dry-rolled corn (DRC) with and without the addition of tallow (SFC/Fat and DRC/Fat) or steam-flaked corn with ground flaxseed (SFC/Flax). Ribeye steaks from steers fed SFC, SFC/Fat, or SFC/ Flax were used to evaluate the effects of fat source on meat quality. Cattle fed SFC and SFC/Fat tended to have greater ADG, G:F, HCW, and USDA yield grade, compared with those fed DRC and DRC/Fat (P < 0.10). Steaks from steers fed SFC/Flax developed a detectable off-flavor (P < 0.05) compared with steaks from steers fed SFC and SFC/Fat, and steaks from steers fed SFC retained desirable color longer than those from steers fed SFC/Flax (P < 0.05). Feeding SFC/Flax increased deposition of alpha-linolenic acid in muscle tissue compared with feeding SFC or SFC/Fat (P < 0.01). Dietary treatment did not cause differences in tenderness, juiciness, or flavor intensity. Ground flaxseed can replace tallow in finishing diets without loss in performance, but flax may affect flavor and color stability of beef. Feeding flaxseed can effectively alter composition of carcass tissues to yield beef that is high in n-3 fatty acids.


High throughput inclusion body sizing: Nano particle tracking analysis.
The expression of pharmaceutical relevant proteins in Escherichia coli frequently triggers inclusion body (IB) formation caused by protein aggregation. In the scientific literature, substantial effort has been devoted to the quantification of IB size. However, particle-based methods used up to this point to analyze the physical properties of representative numbers of IBs lack sensitivity and/or orthogonal verification. Using high pressure freezing and automated freeze substitution for transmission electron microscopy (TEM) the cytosolic inclusion body structure was preserved within the cells. TEM imaging in combination with manual grey scale image segmentation allowed the quantification of relative areas covered by the inclusion body within the cytosol. As a high throughput method nano particle tracking analysis (NTA) enables one to derive the diameter of inclusion bodies in cell homogenate based on a measurement of the Brownian motion. The NTA analysis of fixated (glutaraldehyde) and non-fixated IBs suggests that high pressure homogenization annihilates the native physiological shape of IBs. Nevertheless, the ratio of particle counts of non-fixated and fixated samples could potentially serve as factor for particle stickiness. In this contribution, we establish image segmentation of TEM pictures as an orthogonal method to size biologic particles in the cytosol of cells. More importantly, NTA has been established as a particle-based, fast and high throughput method (1000-3000 particles), thus constituting a much more accurate and representative analysis than currently available methods.


Synthesis of fluorine-18-labeled biotin derivatives: biodistribution and infection localization.
Recently there has been much interest in the exploitation of the high binding affinity of avidin/biotin as a means of targeting drugs and radionuclides for in vivo applications. We are interested in broadening the application of the avidin/biotin complex to PET. To this end we set out to prepare 18F-labeled biotin analogs. Two 18F biotin derivatives, [3aS-(3a alpha,4 beta,6a alpha)]-hexahydro-2-oxo-1H-thieno[3,4- d]imidazole-4-(N-3-(1-[18F]fluoropropyl))pentanamide (1) and [3aS-(3a alpha,4 beta,6a alpha)]-tetrahydro-4-(5-(1-[18F]fluoropentyl)- 1H-thieno[3,4-d]imidazol-2(3H)-(2) were prepared with high specific activity (NCA) and evaluated for their potential in infection localization. Compound 1 binds to avidin and the biodistribution of these derivatives were studied in Escherichia coli infected rats. Half of the infected rats were treated with avidin 24 hr prior to intravenous injection of the 18F-labeled biotin analogs. Biotin 1, without avidin pretreatment, showed a selectivity of 6.08 +/- 1.12 for infection compared to normal muscle. With avidin pretreatment, selectivity increased slightly, giving an infection to normal muscle ratio of 6.39 +/- 0.96. In contrast, the biodistribution of biotin 2 indicated more binding to normal muscle with an infection to normal muscle ratio of 0.58 +/- 0.07. This lack of selectivity illustrates the importance of the side-chain amide group in infection localization. There was some defluorination of 1 and 2, as evidenced by increased 18F bone uptake after 60 min: 2.94 +/- 0.37 and 1.17 +/- 0.21 %IG/g +/- s.d., respectively. Biotin derivatives could be radiofluorinated with high specific activity. Biotin 1, is a potential positron tomography tracer for infection imaging.


Immunolocalization of the lactotransferrin receptor on the human T lymphoblastic cell line Jurkat.
Monoclonal antibodies have been raised against the soluble lactotransferrin binding protein purified from the cell culture supernatant of Jurkat cell line, a human T-lymphoblastic cell. All monoclonal antibodies were able to specifically bind to the membrane of Jurkat cells. One of the monoclonal antibodies, DP5B3G10, recognized both the soluble lactotransferrin-binding protein and the membrane lymphocyte lactotransferrin receptor after SDS-PAGE in presence of 2-mercaptoethanol and electrotransfer on nitrocellulose. The monoclonal antibody DP5B3G10 inhibited the binding of lactotransferrin to Jurkat cells and human peripheral activated lymphocytes. In addition, lactotransferrin inhibited the binding of the monoclonal antibody to the cell surface. These results suggest that the 95 kDa lactotransferrin-binding protein isolated from the cell culture medium corresponds to the soluble form of the 105 kDa lymphocyte lactotransferrin receptor. Corresponding proteins of 105 kDa molecular mass were identified in Jurkat and CEM T-cells and Raji B-cells. Finally, the monoclonal antibody DP5B3G10 was used to immunolocalize the lactotransferrin receptor on the Jurkat cells. Using fluorescence and electron microscopy, the receptor was localized both inside and at the cell surface. The cell membrane receptor was associated into clusters. After permeabilization of the plasma membrane, the staining was positive in the peri-membrane area. The region near the nucleus was devoid of receptor.


The influence of semantic context on the perception of Spanish-accented American English.
In this article, the authors examine (a) the effect of semantic context on accentedness, comprehensibility, and intelligibility of Spanish-accented American English (AE) as judged by monolingual AE listeners and (b) the interaction of semantic context and accentedness on comprehensibility and intelligibility. Twenty adult native (L1) Spanish speakers proficient in AE and 4 L1 AE speakers (controls) read 48 statements consisting of true-false, semantically meaningful, and semantically anomalous sentences. Eighty monolingual AE listeners assessed accentedness, comprehensibility, and intelligibility of the statements. A significant main effect was found for semantic category on all 3 dependent variables. Accents were perceived to be stronger, and both comprehensibility and intelligibility were worse, in semantically anomalous contexts. Speaker data were grouped into strong, mid-level, and mild accents. The interaction between semantic category and accent was significant for both comprehensibility and intelligibility. The effect of semantic context was strongest for strong accents. Intelligibility was excellent for speakers with mid-level accents in true-false and semantically meaningful contexts, and it was excellent for mild accents in all contexts. Listeners access semantic information, in addition to phonetic and phonotactic features, in the perception of nonnative speech. Both accent level and semantic context are important in research on foreign-accented speech.


[Mycoplasma heat shock proteins and their genes].
Mycoplasmas (class Mollicutes) are the most simply organized prokaryotic organisms capable to self-reproduction. They are considered as a model of "minimal" cell. Systems preserved by mycoplasmas in their reductive evolution may play a fundamental role in viability of any cell. Information on the genes encoding heat shock proteins (HSP) in completely sequenced mycoplasma genomes was summarized and systematized. An attempt was made to explain the presence or absence in mycoplasmas of important bacterial chaperones and proteases. These HSP are necessary not only for cell stress resistance, but for protein homeostasis under normal conditions. The mechanisms of regulation of transcription of corresponding genes are considered. Properties and functions of the most completely characterized mycoplasmal HSP are discussed: DnaK, DnaJ-like, GroEL/GroES, ClpB, and small heat shock proteins (sHSP).


Binary small molecule organic nanoparticles exhibit both direct and diffusion-limited ultrafast charge transfer with NIR excitation.
Here we describe a facile, one-step synthesis of a binary organic nanoparticle composed completely of NIR-absorbing small molecules, a quatterylene diimide and a vanadyl napthalocyanine, using Flash Nanoprecipitation. We show that the molecules are co-encapsulated within an amphiphilic block copolymer shell by observing distinct ultrafast dynamics in the binary nanoparticles compared to nanoparticles of their individual components, which we rationalize as a photoinduced charge transfer. We then draw similarities between the charge transfer dynamics studied in our system and the charge dissociation process in macroscale organic bulk heterojunction blends for OPV applications by assigning the ultrafast time component (∼10 ps) to direct interfacial charge transfer and the slow component (70-200 ps) to diffusion limited charge transfer. This discovery can inspire the development of mixed-composition nanoparticles with new functionality for optoelectronic and theranostic applications.


Time trends in medication use and expenditures in older patients with rheumatoid arthritis.
We sought to examine how expansions in insurance coverage of nonbiologic and biologic disease-modifying antirheumatic drugs affected the access, costs, and health status of older patients with rheumatoid arthritis. We identified a nationally representative sample of older adults with rheumatoid arthritis in the 2000-2006 Medicare Current Beneficiary Survey (unweighted n=1051). We examined changes in disease-modifying antirheumatic drug use, self-reported health status, functional status (activities of daily living), and total costs and out-of-pocket costs for medical care and prescription drugs. Tests for time trends were conducted using weighted regressions. Between 2000 and 2006, the proportion of older adults with rheumatoid arthritis who received biologics tripled (4.6% vs 13.2%, P=.01), whereas the proportion of people who used a nonbiologic did not change. During the same period, the proportion of older patients with rheumatoid arthritis rating their health as excellent/good significantly increased (43.0% in 2000 to 55.6% in 2006; P=.015). Significant improvements occurred in activities of daily living measures of functional status. Total prescription drug costs (in 2006 US dollars) increased from $2645 in 2000 to $4685 in 2006, P=.0001, whereas out-of-pocket prescription costs remained constant ($842 in 2000 vs $832 in 2006; P=.68). Total medical costs did not significantly increase ($16,563 in 2000 vs $19,510 in 2006; P=.07). Receipt of biologics in older adults with rheumatoid arthritis increased over a period of time when insurance coverage was expanded without increasing patients' out-of-pocket costs. During this time period, concurrent improvements in self-reported health status and functional status suggest improved arthritis care.


Microarray analysis of lung long non-coding RNAs in cigarette smoke-exposed mouse model.
Several studies have demonstrated the function of long nonâ€'coding RNAs (lncRNAs) in various biological processes, yet their role underlying the susceptibility to cigarette smoke (CS)-induced airway inflammation remains limited. In the present study, we aimed to profile the expression of lncRNAs and mRNAs in CS-exposed mice. C57BL/6 mice were assigned into a single cigarette-smoking machine with or without CS exposure for 4 weeks, followed by lung tissue harvest and RNA isolation. Microarray analysis identified 108 lncRNAs and 119 mRNAs with differential expression levels in CS-exposed mouse lung tissue compared with those in control mice. The expression patterns of several lncRNAs were further confirmed by qRT-PCR. GO and pathway analyses showed that the altered mRNAs were mainly related to the processes of immune response, defense response and cell chemotaxis, cytokine-cytokine receptor interaction and chemokine signaling pathway. Moreover, a single lncRNA may co-expressed with several mRNAs, and so was the mRNA. Our findings uncovered the expression profile of lncRNAs and mRNAs in the lungs of CS-exposed mice, which may offer new insights into pathogenesis of CS-associated airway inflammatory disorders.


Enrichment of phosphoproteins for proteomic analysis using immobilized Fe(III)-affinity adsorption chromatography.
We described an efficient protocol to strongly enrich phosphoproteins from mixtures of total cellular proteins using homemade, recyclable Fe(III)-affinity columns. An integral feature of the method is the use of a detergent cocktail that allows use of different pHs for total protein extraction (pH 6.8) and for subsequent affinity capture of phosphoproteins (pH 3.4). Affinity captured proteins from rat fibroblasts were fractionated on 2D gels and random selection was identified by mass spectrometry. More than 85% of identified proteins were previously known to be phosphorylated. The specificity of the method was further validated by isolating proteins from (32)P labeled cells. Our comparison of the clusters of acidic residues in the captured proteins with acidic clusters in proteins of the rat genome indicates that affinity for phosphate groups dominates over adsorption of proteins with acidic clusters.


Discontinuity of the annuity curves. III. Two types of vital variability in Drosophila melanogaster.
We confirm five-phased construction of Drosophila annuity curves established earlier. Annuity curves were composed of stable five-phase component and variable one. Variable component was due to differences in phase durations. As stable, so variable components were apparent for 60 generations. Stochastic component was described as well. Viability variance which characterize «reaction norm» was apparent for all generation as well. Thus, both types of variability seem to be inherited.


A Unified Strategy to Improve Lipid Nanoparticle Mediated mRNA Delivery Using Adenosine Triphosphate.
A central goal of chemical and drug delivery sciences is to maximize the therapeutic efficacy of a given drug at the lowest possible dose. Here, we report a generalizable strategy that can be utilized to improve the delivery of mRNA drugs using lipid nanoparticles (LNPs), the clinically approved chemistry platforms utilized in the Moderna and Pfizer/BioNTech COVID-19 vaccines. In brief, our strategy updates the chemistry of LNPs to incorporate adenosine triphosphate (ATP) alongside mRNA, a modification that results in upward of a 79-fold increase in LNP-delivered mRNA-encoded protein expression in vitro and a 24-fold increase in vivo when compared to parent mRNA LNP formulations that do not contain ATP. Notably, we find that our ATP co-delivery strategy increases LNP-delivered mRNA-encoded protein expression across eight different LNP chemistries and three different cell lines, under normoxia and hypoxia, and in a well-tolerated fashion. Notably, our strategy also improves the expression of mRNA encoding for intracellular and secreted proteins both in vitro and in vivo, highlighting the utility of leveraging ATP co-delivery within mRNA LNPs as a means to increase protein expression. In developing this strategy, we hope that we have provided a simple yet powerful approach to improving mRNA LNPs that may one day be useful in developing therapies for human disease.


The effect of high altitude and caloric restriction on reactive carbonyl derivatives and activity of glutamine synthetase in rat brain.
Both exposure to high altitude (HA) and caloric restriction (CR) may influence free radical generation. The aim of the present study was to evaluate the effects of 4 wk chronic exposure to 4,000m of HA and CR (60% of CR of control (C) rats) on protein oxidation in brain. Eighteen rats with similar body mass were assigned to CR, HA and C rats. Reactive carbonyl derivatives (RCD), marker of protein oxidation, were measured by Western blot. In addition, the activity and protein content of glutamine synthetase (GS) were determined. The body mass of C rats was significantly higher (P< 0.001) than that of HA and CR groups. The quantified signal intensity of RCD was significantly stronger in C rats than in HA and CR rats. The activity of GS was significantly increased in CR rats, while the protein content of GS was decreased in HA rats compared to C group. The data suggest that both HA and CR decreases the accumulation of RCD in the brain, however the mechanism of the decrease seems to be different during HA and CR.


The phase property of membrane phospholipids is affected by the functionality of signal peptides from the Escherichia coli ribose-binding protein.
We examined the effects of synthetic signal peptides from the wild-type, export-defective mutant and its revertant species of ribose-binding protein on the phase properties of lipid bilayers. The lateral segregation of phosphatidylglycerol (PG) in the lipid bilayer was detected through quenching between NBD-PGs upon the reconstitution of signal peptide into the liposome made with the Escherichia coli inner membrane composition. The tendency of lipid segregation was highly dependent on the export competency of signal peptides in vivo, with a decreasing order of wild-type, revertant, and mutant species. The colocalizations of pyrene-PG with BODIPY-PG were also induced by the signal peptides, confirming the phase separation of the acidic phospholipid. The wild-type and revertant signal peptides predominantly formed alpha-helical conformations with the presence of acidic phospholipid as determined by circular dichroism spectroscopy. In addition, they restricted the motion of lipid acyl chains as monitored by fluorescence anisotropy of DPH, suggesting a deep penetration of signal peptide into the lipid bilayer. However, the alpha-helical content of mutant signal peptide was only about half that of the wild-type or revertant peptide with a significantly smaller degree of penetration into the bilayer. An association of the defective signal peptides into the membrane was affected by salt extraction, whereas the functional ones were not. The aforementioned results indicate that the functionality of signal peptide is accomplished through its topologies in the membrane and also by its ability to induce lateral segregation of acidic phospholipid. We propose that the clustering of acidic phospholipid by the functional signal peptide is responsible for the formation of non-bilayer membrane structure, thereby promoting an efficient translocation of secretory proteins.


Photoinduced Schottky barrier in photorefractive materials.
We report on the first experimental evidence of a Schottky barrier effect produced by the action of light in an otherwise purely Ohmic contact between a nominally undoped photorefractive titanosillenite Bi12TiO20 crystal and a transparent conductive SnO2 electrode. The photorefractive crystal is sandwiched between two transparent electrodes and a Schottky barrier is built up in the illuminated crystal-electrode interface under the action of light with photonic energy large enough to excite charge carriers from the Fermi level into the conduction band. The contact remains purely Ohmic under illumination with photonic energy below that of the Fermi gap and the photoinduced barrier almost disappears if the photonic energy is large enough to produce electron-hole pairs.


[Association between alcohol consumption and cardiovascular risk factors: a narrative review].
Moderate alcohol consumption has been associated with lower coronary heart disease (CHD) risk. However, the impact of higher alcohol consumption on cardiovascular risk factors (CVRFs) is conflicting. We examined the association between alcohol consumption, CVRFs and the estimated 10-year CHD risk in the population-based CoLaus study in Lausanne, Switzerland. Among 5,769 participants without cardiovascular disease, 73% of the participants were alcohol drinkers; 16% consumed 14-34 drinks/week and 2% consumed > or = 35 drinks/week. This article shows the impact of high alcohol consumption on CVRFs and reviews the literature on the associations between alcohol consumption and CVRFs.


Structural and evolutionary characteristics of pyruvate phosphate dikinase in Giardia lamblia and other amitochondriate protozoa.
Pyruvate phosphate dikinase (PPDK) reversibly catalyzes the interconversion of phosphoenolpyruvate (PEP) and pyruvic acid, leading to catabolism and adenosine triphosphate (ATP) synthesis or gluconeogenesis and ATP consumption. Molecular modeling of PPDKs from divergent organisms demonstrates that the orientation of the phosphorylatable histidine residue within the central domain of PPDK determines whether this enzyme promotes catabolism or gluconeogenesis. The goal of this study was to determine whether PDDK from Giardia underwent adaptive evolution in order to produce more energy under anaerobic conditions. A total of 123 PPDK sequences from protozoans, proteobacteria, plants, and algae were selected, based upon sequence similarities to Giardia lamblia PPDK and Zea mays PPDK. Three-dimensional (3-D) models were generated for PPDKs from divergent organisms and were used to compare the orientation of the phosphorylatable histidine residue within the central domain of PPDKs. These PPDKs were compared using a maximum-likelihood tree. For PPDK from Giardia, as well as from other anaerobic protozoans, the central domain tilted toward the N-terminal nucleotide-binding domain, indicating that this enzyme catalyzed ATP synthesis. Furthermore, the orientation of this central domain was determined by interactions between the N- and C-terminal domains. Phylogenetic analysis of the N- and C-terminal sequences of PPDKs from different species suggested that PPDK has likely undergone adaptive evolution in response to differences in environmental and metabolic conditions. These results suggested that PPDK in anaerobic organisms is functionally adapted to generate energy more efficiently in an anaerobic environment.


Total Synthesis of Bruceolline I.
The first total synthesis of the natural product bruceolline I, isolated in small quantities from the ethanol extract of Brucea mollis stems, was achieved in 29% yield over nine steps and with high enantiomeric purity (>98%). The key step of the process is the tandem gold-catalyzed rearrangement/Nazarov reaction of a propargylic acetate derivative. This synthesis provides a sufficient amount of synthesized bruceolline I for further bioassays.


A link between neutrophils and chronic disease manifestations of Chlamydia muridarum urogenital infection of mice.
Vigorous acute inflammatory responses accompany Chlamydia muridarum infections in mice and are positively correlated with adverse urogenital and respiratory tract infection outcomes in the mouse model. Thus, we tested the hypothesis that neutrophils induce an acute inflammatory insult that, in the repair phase, leads to the chronic sequelae of hydrosalpinx - a surrogate marker of infertility in the mouse model. To this end, we induced neutropenia in mice using a neutrophil-depleting monoclonal antibody during acute phases of C. muridarum urogenital infection only (days 2-21 postinfection). To prove induced neutropenia, peripheral blood was monitored for neutrophils during the treatment regimen. Neutropenic mice had a similar infection course as control mice, but had significantly reduced levels of certain histopathological parameters, reduced production of matrix metalloproteinase-9 (MMP-9) and reduced rates of hydrosalpinx following resolution of the infection. We conclude that neutrophils are a major source of MMP-9, a previously proved pathological factor in this model. Further, we conclude that acute inflammation in the form of neutrophils and neutrophil activation products are at least partially responsible for inducing the histological changes that ultimately result in fibrosis and infertility in the mouse model of chlamydial upper genital tract disease.


Changes in the spontaneous action potentials from the whole, isolated, intact bovine pituitary gland following an injection of various bovine pituitary intraglandular colloid fractions.
Bovine pituitary intraglandular colloid (IGC) of intermediate lobe (IL) origin with accessions from the anterior lobe (AL), can modify the spontaneous action potentials (SAP) from AL, IL and posterior lobe (PL) cells. It was discovered that intraglandular colloid contains peptides ACTH, alpha-MSH, and beta-LPH when subjected to a series of radioimmunoassays. These peptides are thought, in part, to be responsible for altering the SAP.


[MTBE litholysis and extracorporeal shock wave lithotripsy of gallstones].
Two new therapies for cholesterol gallstones, MTBE litholysis and extracorporeal shock-wave lithotripsy, have been developed and clinically tested in the last five years. In principle MTBE litholysis is applicable in 50-80% of gallstone patients and shock-wave lithotripsy in 25-30%. In MTBE litholysis a pigtail catheter is placed in the gallbladder by the percutaneous-transhepatic route using ultrasound-guidance. The gallstones can than be dissolved with the cholesterol contact solvent MTBE (methyl tert-butyl ether). With appropriate selection criteria the successful dissolution rate is 80-90%. Over 99% of radiolucent gallstones (1-3 stones per gallbladder) can be fragmented by extracorporeal shockwaves. Bile acids must be administered as adjuvant litholytic therapy, and thus the remaining fragments can be dissolved in 91% of cases within 2-18 months. In view of the limited experience with these procedures at the present time they are mainly indicated for symptomatic surgical high-risk patients and for those who strongly wish to avoid surgery. With careful evaluation of study data a broader indication policy may be possible in the future. The new methods and the essential study data are presented.


Impact of Educational Intervention to Promote Jordanian Community Pharmacists' Knowledge and Perception Towards Antimicrobial Stewardship: Pre-Post Interventional Study.
The aim of this study was to assess the impact of an online educational workshop on improving the knowledge, and perception of community pharmacists in Jordan towards the antimicrobial stewardship (AMS) and enhancing their ability to appropriately select correct antibiotic therapy. This is a pre-post study that was conducted in Jordan in December 2020. An electronic questionnaire was used to assess the awareness, perception of community pharmacists towards AMS, and their ability to appropriately select correct antibiotic before and after the educational workshop. The two-days' workshop was conducted on Zoom application. Analysis was conducted using Wilcoxon signed-rank test, McNemar's test using SPSS version 22. During the study period, 100 community pharmacists attended the educational workshop. Pharmacists' knowledge was assessed prior to their participation which revealed a relatively good knowledge score with a median score of 6/10 (IQR = 4); their scores have improved significantly following the educational workshop with a median score of 7/10 (IOR = 2), p-value<0.001. Although one-third of the participants knew the definition of AMS prior to the workshop, almost half of the respondents (n = 56, 56%) knew the definition after the educational workshop. Regarding community pharmacist's ability to appropriately select correct antibiotic therapy, they showed a significant improvement in selecting the optimal antimicrobial for the virtual cases following the workshop (p-value < 0.05). Perceptions towards AMS were consistently positive before and after the workshop. This study revealed the benefit of AMS-focused workshops for improving community pharmacists' knowledge and appropriate antibiotic prescribing. Thus, efforts are required to implement more AMS educational workshops for community pharmacists.


Computer-aided diagnostic system based on deep learning for classifying colposcopy images.
Colposcopy is widely used to detect cervical cancer, but developing countries lack the experienced colposcopists necessary for accurate diagnosis. Artificial intelligence (AI) is being widely used in computer-aided diagnosis (CAD) systems. In this study, we developed and validated a CAD model based on deep learning to classify cervical lesions on colposcopy images. Patient data, including clinical information, colposcopy images, and pathological results, were collected from Qilu Hospital. The study included 15,276 images from 7,530 patients. We performed two tasks in this study: normal cervix (NC) vs. low grade squamous intraepithelial lesion or worse (LSIL+) and high-grade squamous intraepithelial lesion (HSIL)- vs. HSIL+. The residual neural network (ResNet) probability was calculated for each patient to reflect the probability of lesions through a ResNet model. Next, a combination model was constructed by incorporating the ResNet probability and clinical features. We divided the dataset into a training set, validation set, and testing set at a ratio of 7:1:2. Finally, we randomly selected 300 patients from the testing set and compared the results with the diagnosis of a senior colposcopist and a junior colposcopist. The model that combines ResNet and clinical features performs better than ResNet alone. In the classification of NC and LSIL+, the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 0.953, 0.886, 0.932, 0.846, 0.838, and 0.936, respectively. In the classification of HSIL- and HSIL+, the AUC, accuracy, sensitivity, specificity, PPV, and NPV were 0.900, 0.807, 0.823, 0.800, 0.618, and 0.920, respectively. In the two classification tasks, the diagnostic performance of the model was determined to be comparable to that of the senior colposcopist and exhibited a stronger diagnostic performance than the junior colposcopist. The CAD system for cervical lesion diagnosis based on deep learning performs well in the classification of cervical lesions and can provide an objective diagnostic basis for colposcopists.


[Detection of Ethoprophos Using SERS Coupled with Magnetic Fe3O4/Ag Composite Materials].
The magnetic Fe3O4/Ag composite materials were synthesized by reducing AgNO3 with sodium citrate in the presence of Fe3O4 which were prepared by co-precipitation firstly. The enrichment and extraction of ethoprophos assembled on Fe3O4/Ag were achieved with the applied magnetic field. The different concentrations of ethoprophos adsorbed on Fe3O4/Ag were analyzed by SERS and it was showed that the trace analysis of ethoprophos had been established, while the enhancement factor of probe molecules on Fe3O4/Ag was 1. 48 X 10(5). The structure and morphology of Fe3O4/Ag were characterized by UV-Vis, EDX and TEM. Compared with Ag, the UV-Vis absorption peak of Fe3O4/Ag shifted from 417 to 369 nm, and the UV-Vis of Fe3O4 almost had no characteristic absorption peak in this region. At the same time, it was showed that the surface properties of Fe3O4/Ag changed with Raman enhancement effect during the aggregation process of Ag around the surface of Fe3O4. Further EDX images of micro area element analysis suggested that the chemical composition of products were Ag, Fe and O while the Cu peak was from the copper mesh. In addition, TEM images indicated that the average particle size of Fe3O4 was between 30 and 60 nm with shape tended to be spherical. And the silver nanoparticles were attached to the Fe3O4 particles and agglomeration occured. Density functional theory calculations which can be applied to qualitative judgment of molecule was carried out to obtain the molecular optimization structure and theoretical Raman spectra. It was found that the stabilized SERS signals were detected under the saturated adsorption equilibrium after 15 min. Finally, Raman response of ethoprophos was achieved with lower than 2 X 10(-8) mol . L-1 , indicatint that the established method had reached the requirements of ethoprophos residues detection and could be used for analysis of sulfur-containing organophosphorus pesticide.


Transvaginal sonography for diagnosing ectopic pregnancy: positivity criteria and performance characteristics.
Despite the widespread use of TVS for diagnosing EP and extensive literature on the subject, there is no consensus regarding the best positivity criterion for adnexal findings or the performance characteristics of TVS. We conducted a literature search to identify original studies presenting suitable data on the use of TVS for the diagnosis of EP. The data were combined to determine the sensitivity and specificity of four sonographic criteria for EP, listed in order from most to least stringent: Criterion A, living extrauterine pregnancy; criterion B, extrauterine gestational sac containing yolk sac or embryo; criterion C, empty "tubal ring" or extrauterine gestational sac containing yolk sac or embryo; and criterion D, any adnexal mass other than a simple cyst. Positive and negative predictive values were computed using Bayes' theorem. Ten studies involving a total of 2216 patients, 565 with EP and 1651 without EP, were included in our analysis. Based on the combined data from these studies, criteria A, B, and C all have high specificities (99.5-100%) and positive predictive values (97.8-100%) but low sensitivities (20.1-64.6%) and mediocre negative predictive values (78.5-89.1%). Criterion D, the most lax criterion, has the most uniformly excellent characteristics, with only slightly lower specificity (98.9%) and positive predictive value (96.3%) but considerably higher sensitivity (84.4%) and negative predictive value (94.8%). The performance characteristics of TVS criteria for EP, computed by pooling data from published studies, indicate that the appropriate TVS criterion to diagnose EP is any noncystic adnexal mass. These performance characteristics can be used as a basis for comparing TVS with other proposed diagnostic modalities for EP.


Extension and Limits of Cryoscopy for Nanoconfined Solutions.
This work investigates the phase behavior of aqueous solutions of glycerol confined in MCM-41 and SBA-15 nanoporous matrixes by calorimetry. Limitations due to overfilling and eutectic freezing are prevented by the absence of an external liquid reservoir and by the glass-forming property of glycerol. Consequently, the stability of nanoconfined ice in equilibrium with aqueous solutions is studied over a wide range of compositions. In confinement, a large temperature depression of the liquidus line is observed. A thermodynamic model accounting simultaneously for the cryoscopic and the Gibbs-Thomson effects gives a consistent view of the phase diagram for large pores (Rp = 4.15 nm). For smaller pores (Rp = 1.8 nm), it reveals that the water activity strongly deviates from the bulk solution with the same composition, indicating the possible role of concentration heterogeneities in determining the onset of ice freezing in strongly nanoconfined solutions.


Probing the structural and binding mechanism heterogeneity of molecularly imprinted polymers.
We devised a strategy, using a de novo building approach, to construct model molecularly imprinted polymers (MIPs) and assess their ability at binding various target molecules. While our models successfully reproduce the gross experimental selectivities for two xanthines, our atomistic models reveal in detail the considerable heterogeneity of the structure and binding mechanisms of different imprints within such a material. We also demonstrate how nonimprinted regions of a MIP are also responsible for much of binding of target molecules. High levels of cross-linking are shown to produce less specific imprints.


Collisional energy transfer in the intermediate states used for optical-optical double resonance excitation of ion-pair states in I2.
The optical-optical double resonance spectra of I(2) and I(2)-Xe mixtures at room temperature reported in the literature using a fixed-wavelength, broad band pump laser have now been recorded using a tuneable, narrow band source. We show that during the time of the overlapped laser pulses ( approximately 10 ns) and with 10-20 Torr of Xe there is widespread collisional energy transfer in the intermediate state and that this phenomenon offers an alternative explanation for the broad bands in the excitation spectrum, assigned to XeI(2) complexes by the authors of the earlier study (M. E. Akopyan, I. Y. Novikova, S. A. Poretsky and A. M. Pravilov, Chem. Phys., 2005, 310, 287). Dispersed emission bands, previously attributed to direct fluorescence from the ion-pair state(s) of the complexes, are re-assigned to emission from ion-pair states of the parent I(2) that are populated by collisional energy transfer out of the initially excited state.


[The role of lncRNA in regulation of neural stem cell fate.]
Recent advances in analysis technology have revealed that non-coding RNAs(ncRNA)that are not translated and function as RNA itself. It has been revealed that long ncRNA(lncRNA), which has more than and 200 nucleotides, is involved in the regulation of fate decision in neural stem cells. In this article, we introduce some functional lncRNAs regulating neural stem cells and discuss the future perspective about this field.


Some observations on magnesium in cerebrospinal fluid.
Investigation of 67 patients with neurological disorders (excluding meningitis) showed a mean level of Mg in cerebrospinal fluid of 1.93 +/- 0.03 mEq./l. These figures are significantly lower than earlier figures published in the literature. Patients with polyradiculo-neuritis do not show the fall in cerebrospinal fluid Mg levels reported in cases of infective meningitis. The level of Mg in cerebrospinal fluid is maintained in the presence of low levels of plasma Mg.


Space-confined creation of nanoframes in situ on reduced graphene oxide.
Nanoframes (NFs) are created in situ on reduced graphene oxide (rGO) through confining the evolutions of precursor nanosheets, such as ZnS(EN)0.5 (EN = ethylenediamine), and nanoparticles within quasi-two-dimensional spaces generated from graphene oxide. The resultant composites of ZnS-NF@rGO exhibit excellent photocurrent responses. This work provides a new strategy to synthesize and modulate nanostructures and nanomaterials for rGO composites.


Complement system in lung transplantation.
The complement system is a cascade of multiple proteins that have been known to mediate inflammatory response. This tightly regulated system has been recognized to play a role in adaptive immunity via humoral and cell-mediated processes. There is evidence from animal and human studies that the complement system is involved in various outcomes of solid organ transplantation. Most of the studies have been done in the field of kidney transplantation. In this paper, we review the studies looking at lung transplantation. The complement cascade appears to have a prominent role in mediating lung allograft damage in the setting of ischemia-reperfusion injury, humoral rejection, as well as chronic allograft dysfunction. In this review, we look at the available data regarding the role of complement in these outcomes and propose some ideas about future direction of research in this field.


The extraocular muscle stem cell niche is resistant to ageing and disease.
Specific muscles are spared in many degenerative myopathies. Most notably, the extraocular muscles (EOMs) do not show clinical signs of late stage myopathies including the accumulation of fibrosis and fat. It has been proposed that an altered stem cell niche underlies the resistance of EOMs in these pathologies, however, to date, no reports have provided a detailed characterization of the EOM stem cell niche. PW1/Peg3 is expressed in progenitor cells in all adult tissues including satellite cells and a subset of interstitial non-satellite cell progenitors in muscle. These PW1-positive interstitial cells (PICs) include a fibroadipogenic progenitor population (FAP) that give rise to fat and fibrosis in late stage myopathies. PICs/FAPs are mobilized following injury and FAPs exert a promyogenic role upon myoblasts in vitro but require the presence of a minimal population of satellite cells in vivo. We and others recently described that FAPs express promyogenic factors while satellite cells express antimyogenic factors suggesting that PICs/FAPs act as support niche cells in skeletal muscle through paracrine interactions. We analyzed the EOM stem cell niche in young adult and aged wild-type mice and found that the balance between PICs and satellite cells within the EOM stem cell niche is maintained throughout life. Moreover, in the adult mdx mouse model for Duchenne muscular dystrophy (DMD), the EOM stem cell niche is unperturbed compared to normal mice, in contrast to Tibialis Anterior (TA) muscle, which displays signs of ongoing degeneration/regeneration. Regenerating mdx TA shows increased levels of both PICs and satellite cells, comparable to normal unaffected EOMs. We propose that the increase in PICs that we observe in normal EOMs contributes to preserving the integrity of the myofibers and satellite cells. Our data suggest that molecular cues regulating muscle regeneration are intrinsic properties of EOMs.


Understanding long-term fruit fly (Diptera: Tephritidae) population dynamics: implications for areawide management.
Fruit flies (Diptera: Tephritidae) are devastating agricultural pests worldwide but studies on their long-term population dynamics are sparse. Our aim was to determine the mechanisms driving long-term population dynamics as a prerequisite for ecologically based areawide pest management. The population density of three pestiferous Anastrepha species [Anastrepha ludens (Loew), Anastrepha obliqua (Macquart), and Anastrepha serpentina (Wiedemann)] was determined in grapefruit (Citrus x paradisi Macfad.), mango (Mangifera indica L.), and sapodilla [Manilkara zapota (L.) P. Royen] orchards in central Veracruz, México, on a weekly basis over an 11-yr period. Fly populations exhibited relatively stable dynamics over time. Population dynamics were mainly driven by a direct density-dependent effect and a seasonal feedback process. We discovered direct and delayed influences that were correlated with both local (rainfall and air temperature) and global climatic variation (El Niño Southern Oscillation [ENSO] and North Atlantic Oscillation [NAO]), and detected differences among species and location of orchards with respect to the magnitude and nature (linear or nonlinear) of the observed effects, suggesting that highly mobile pest outbreaks become uncertain in response to significant climatic events at both global and local levels. That both NAO and ENSO affected Anastrepha population dynamics, coupled with the high mobility of Anastrepha adults and the discovery that when measured as rate of population change, local population fluctuations exhibited stable dynamics over time, suggests potential management scenarios for the species studied lie beyond the local scale and should be approached from an areawide perspective. Localized efforts, from individual growers will probably prove ineffective, and nonsustainable.