Bridging the generation gap in plants: pollination, parental fecundity, and offspring demography.
Despite extensive study of pollination and plant reproduction on the one hand, and of plant demography on the other, we know remarkably little about links between seed production in successive generations, and hence about long-term population consequences of variation in pollination success. We bridged this "generation gap" in Ipomopsis aggregata, a long-lived semelparous wildflower that is pollinator limited, by adding varying densities of seeds to natural populations and following resulting plants through their entire life histories. To determine whether pollen limitation of seed production constrains rate of population growth in this species, we sowed seeds into replicated plots at a density that mimics typical pollination success and spacing of flowering plants in nature, and at twice that density to mimic full pollination. Per capita offspring survival, flower production, and contribution to population increase (lambda) did not decline with sowing density in this experiment, suggesting that typical I. aggregata populations freed from pollen limitation will grow over the short term. In a second experiment we addressed whether density dependence would eventually erase the growth benefits of full pollination, by sowing a 10-fold range of seed densities that falls within extremes estimated for the natural "seed rain" that reaches the soil surface. Per capita survival to flowering and age at flowering were again unaffected by sowing density, but offspring size, per capita flower production, and lambda declined with density. Such density dependence complicates efforts to predict population dynamics over the longer term, because it changes components of the life history (in this case fecundity) as a population grows. A complete understanding of how constraints on seed production affect long-term population growth will hinge on following offspring fates at least through flowering of the first offspring generation, and doing so for a realistic range of population densities.


Selenium and COVID-19: A spotlight on the clinical trials, inventive compositions, and patent literature.
Selenium is an indispensable trace element for all living organisms. It is an essential structural component of several selenium-dependent enzymes, which support the human body's defense mechanism. Recently, the significance of selenium in preventing/treating COVID-19 has been documented in the literature. This review highlights the clinical studies, compositions, and patent literature on selenium to prevent/treat COVID-19. Selenium exerts its anti-COVID-19 action by reducing oxidative stress, declining the expression of the ACE-2 receptor, lowering the discharge of pro-inflammatory substances, and inhibiting the 3CLPro (main protease) and PLpro enzyme of SARS-CoV-2. The data of clinical studies, inventive compositions, and patent literature revealed that selenium monotherapy and its compositions with other nutritional supplements/drugs (vitamin, iron, zinc, copper, ferulic acid, resveratrol, spirulina, N-acetylcysteine, fish oil, many herbs, doxycycline, azithromycin, curcumin, quercetin, etc.,) might be practical to prevent/treat COVID-19. The studies have also suggested a correlation between COVID-19 and selenium deficiency. This indicates that adequate selenium supplementation may provide promising treatment outcomes in COVID-19 patients. The authors foresee the development and commercialization of Selenium-based compositions and dosage forms (spray, inhalers, control release dosage forms, etc.) to battle COVID-19. We also trust that numerous selenium-based compositions are yet to be explored. Accordingly, there is good scope for scientists to work on developing novel and inventive selenium-based compositions to fight against COVID-19. However, there is also a need to consider the narrow therapeutic window and chemical interaction of selenium before developing selenium-based compositions.


Harnessing Syk family tyrosine kinases as signaling domains for chimeric single chain of the variable domain receptors: optimal design for T cell activation.
T cells of tumor bearers often show defective TCR-mediated signaling events and, therefore, exhibit impaired immune responses. As such, patients with heavy tumor burden are often not amenable to adoptive T cell therapy. To overcome this limitation, we have developed a chimeric receptor that joins an extracellular single chain Fv (scFv) of a specific Ab for Ag recognition to an intracellular protein tyrosine kinase (PTK) for signal propagation. Stimulation through the scFv-PTK receptor should bypass defective TCR-proximal events and directly access the T cell's effector mechanisms. In this study we describe the optimization of a scFv-PTK configuration, leading to complete T cell activation. The cytosolic PTK Syk is superior to its family member, Zap-70, for intracellular signaling. As a transmembrane (TM) domain, CD4 performs better than CD8 when plastic-immobilized Ag serves as a stimulator. However, when APC are used to trigger chimeric receptors, the need for a flexible spacer between the scFv and TM domains becomes apparent. The CD8alpha-derived hinge successfully performs this task in chimeric scFv-Syk receptors regardless of its cysteine content. A cytotoxic T cell hybridoma expressing chimeric receptor genes composed of scFv-CD8(hinge)-CD8(TM)-Syk or scFv-CD8(hinge)-CD4(TM)-Syk is efficiently stimulated to produce IL-2 upon interaction with APC and specifically lyses appropriate target cells in a non-MHC-restricted manner.


Mechanical properties and fracture behavior of flowable fiber reinforced composite restorations.
The aim was to evaluate the effect of short glass-fiber/filler particles proportion on fracture toughness (FT) and flexural strength (FS) of an experimental flowable fiber-reinforced composite (Exp-SFRC) with two methacrylate resin formulations. In addition, we wanted to investigate how the fracture-behavior of composite restorations affected by FT values of SFRC-substructure. Exp-SFRC was prepared by mixing 50wt% of dimethacrylate based resin matrix (bisGMA or UDMA based) to 50wt% of various weight fractions of glass-fiber/particulate filler (0:50, 10:40, 20:30, 30:20, 40:10, 50:0wt%, respectively). FT and FS were determined for each experimental material following standards. Specimens (n=8) were dry stored (37°C for 2 days) before they were tested. Four groups of posterior composite crowns (n=6) composed of different Exp-SFRCs as substructure and surface layer of commercial particulate filler composite were fabricated. Crowns were statically loaded until fracture. Failure modes were visually examined. The results were statistically analysed using ANOVA followed by post hoc Tukey's test. ANOVA revealed that ratio of glass-fiber/particulate filler had significant effect (p<0.05) on tested mechanical properties of the Exp-SFRC with both monomer systems. Exp-SFRC (50wt%) had significantly higher FT (2.6MPam1/2) and FS (175.5MPa) (p<0.05) compared to non-reinforced material (1.3MPam1/2, 123MPa). Failure mode analysis of crown restorations revealed that FT value of the substructure directly influenced the failure mode. This study shows that short glass-fibers can significantly reinforce flowable composite resin and the FT value of SFRC-substructure has prior importance, as it influences the crack arresting mechanism.


ECMPride: prediction of human extracellular matrix proteins based on the ideal dataset using hybrid features with domain evidence.
Extracellular matrix (ECM) proteins play an essential role in various biological processes in multicellular organisms, and their abnormal regulation can lead to many diseases. For large-scale ECM protein identification, especially through proteomic-based techniques, a theoretical reference database of ECM proteins is required. In this study, based on the experimentally verified ECM datasets and by the integration of protein domain features and a machine learning model, we developed ECMPride, a flexible and scalable tool for predicting ECM proteins. ECMPride achieved excellent performance in predicting ECM proteins, with appropriate balanced accuracy and sensitivity, and the performance of ECMPride was shown to be superior to the previously developed tool. A new theoretical dataset of human ECM components was also established by applying ECMPride to all human entries in the SwissProt database, containing a significant number of putative ECM proteins as well as the abundant biological annotations. This dataset might serve as a valuable reference resource for ECM protein identification.


Selective synergy of immunoglobulin enhancer elements in B-cell development: a characteristic of kappa light chain enhancers, but not heavy chain enhancers.
We have examined the interactions of the enhancers of the kappa immunoglobulin light chain gene as well as the interactions of the intron, mu, and 3' alpha enhancers of the heavy chain locus in mouse. We have observed that each of the kappa enhancers is very weak in comparison with the heavy chain intron enhancer. The mouse heavy chain 3' alpha enhancer is relatively weak as well. However, two kappa enhancers together synergistically activate transcription of a luciferase reporter gene to a level that is roughly equivalent to the heavy chain mu enhancer. Additionally, dimerization of either kappa enhancer results in synergistic increases in transcription. This property of synergism appears to be confined to the enhancers of the kappa locus, as addition of the 3' alpha E to mu E containing constructs increases transcription only modestly, and neither heavy chain enhancer synergizes when dimerized. We have gone on to characterize some of the minimal requirements for synergism between the kappa enhancers and find that the KB and E2 sites are required, but not the E3 site. The implications of these results for the coordinate regulation of the heavy and light chain transcription are discussed.


The role of semantic diversity in lexical organization.
Recent research has challenged the notion that word frequency is the organizing principle underlying lexical access, pointing instead to the number of contexts that a word occurs in (Adelman, Brown, & Quesada, 2006). Counting contexts gives a better quantitative fit to human lexical decision and naming data than counting raw occurrences of words. However, this approach ignores the information redundancy of the contexts in which the word occurs, a factor we refer to as semantic diversity. Using both a corpus-based study and a controlled artificial language experiment, we demonstrate the importance of contextual redundancy in lexical access, suggesting that contextual repetitions in language only increase a word's memory strength if the repetitions are accompanied by a modulation in semantic context. We introduce a cognitive process mechanism to explain the pattern of behaviour by encoding the word's context relative to the information redundancy between the current context and the word's current memory representation. The model gives a better account of identification latency data than models based on either raw frequency or document count, and also produces a better-organized space to simulate semantic similarity.


Bcl2-independent chromatin cleavage is a very early event during induction of apoptosis in mouse thymocytes after treatment with either dexamethasone or ionizing radiation.
We have quantified the emergence of early chromatin breaks during the signal transduction phase of apoptosis in mouse thymocytes after treatment with either ionizing radiation or dexamethasone. Dexamethasone at 1 microM can induce significant levels of DNA breaks (equivalent to the amount induced directly by 7.5 Gy ionizing radiation) within 0.5 h of treatment. The execution phase of apoptosis was not observed until 4-6 h after the same treatment. The presence of the Bcl2 transgene under the control of the p56lck promoter almost completely inhibited apoptosis up to 24 h after treatment, but it had virtually no effect on the early chromatin cleavage occurring in the first 6 h. Ionizing radiation induced chromatin cleavage both directly by damaging DNA and indirectly with kinetics similar to the induction of chromatin cleavage by dexamethasone. The presence of the Bcl2 transgene had no effect on the direct or indirect radiation-induced cleavage in the first 6 h, but after the first 6 h, the Bcl2 gene inhibited further radiation-induced chromatin cleavage. These results suggest that endonucleases are activated within minutes of treatment with either dexamethasone or ionizing radiation as part of the very early signal transduction phase of apoptosis, and prior to the irreversible commitment to cell death.


Dopamine antagonism does not impair learning of Pavlovian conditioned approach to manipulable or non-manipulable cues but biases responding towards goal tracking.
Dopamine's (DA) role in reward-processing is currently discussed as either providing a teaching signal to guide learning or mediating the transfer of incentive salience (i.e. motivational aspects) from unconditioned stimuli (US) to conditioned stimuli (CS). We used a Pavlovian conditioned approach (PCA) procedure to further investigate DAs contribution to these processes. Experiment 1 assessed the acquisition of PCA to a manipulable lever cue for 7days under DA-blockade with Flupenthixol (FLU; 225μg/kg) or Saline (SAL) treatment, followed by 6-days off-drug testing. FLU decreased the number of conditioned responses (CR) during the treatment phase, but cessation of treatment resulted in an immediate increase in CR to levels comparable to SAL controls; notably, CR in FLU-treated rats were restricted to goal tracking behaviour. During continued off-drug testing, rats from the FLU group developed sign tracking with a similar temporal pattern as controls. In experiment 2, acquisition of PCA to a non-manipulable auditory cue was investigated. FLU reduced the number of CR during treatment, and removing DA antagonism resulted in a similar rapid increase of CR as seen in experiment 1. These data complement other reports by demonstrating that, independently from the physical properties of the CS, DA is not required for learning predictive aspects of a CS-US relationship but for the development of behaviour (namely sign tracking) which is based on the motivational aspects of a CS-US relationship.


A Semi-Supervised Autoencoder-Based Approach for Protein Function Prediction.
After the development of next-generation sequencing techniques, protein sequences are abundantly available. Determining the functional characteristics of these proteins is costly and time-consuming. The gap between the number of protein sequences and their corresponding functions is continuously increasing. Advanced machine-learning methods have stepped up to fill this gap. In this work, an advanced deep-learning-based approach is proposed for protein function prediction using protein sequences. A set of autoencoders is trained in a semi-supervised manner with protein sequences. Each autoencoder corresponds to a single protein function only. In particular, 932 autoencoders corresponding to 932 biological processes and 585 autoencoders corresponding to 585 molecular functions are trained separately. Reconstruction losses of each protein sample for every autoencoder are used as a feature to classify these sequences into their corresponding functions. The proposed model is tested on test protein samples and achieves promising results. This method can be easily extended to predict any number of functions having an ample amount of supporting protein sequences. All relevant codes, data and trained models are available at https://github.com/richadhanuka/PFP-Autoencoders.


N-formylation of lysine in histone proteins as a secondary modification arising from oxidative DNA damage.
The posttranslational modification of histone and other chromatin proteins has a well recognized but poorly defined role in the physiology of gene expression. With implications for interfering with these epigenetic mechanisms, we now report the existence of a relatively abundant secondary modification of chromatin proteins, the N(6)-formylation of lysine that appears to be uniquely associated with histone and other nuclear proteins. Using both radiolabeling and sensitive bioanalytical methods, we demonstrate that the formyl moiety of 3'-formylphosphate residues arising from 5'-oxidation of deoxyribose in DNA, caused by the enediyne neocarzinostatin, for example, acylate the N(6)-amino groups of lysine side chains. A liquid chromatography (LC)-tandem mass spectrometry (MS) method was developed to quantify the resulting N(6)-formyl-lysine residues, which were observed to be present in unperturbed cells and all sources of histone proteins to the extent of 0.04-0.1% of all lysines in acid-soluble chromatin proteins including histones. Cells treated with neocarzinostatin showed a clear dose-response relationship for the formation of N(6)-formyl-lysine, with this nucleosome linker-selective DNA-cleaving agent causing selective N(6)-formylation of the linker histone H1. The N(6)-formyl-lysine residue appears to represent an endogenous histone secondary modification, one that bears chemical similarity to lysine N(6)-acetylation recognized as an important determinant of gene expression in mammalian cells. The N(6)-formyl modification of lysine may interfere with the signaling functions of lysine acetylation and methylation and thus contribute to the pathophysiology of oxidative and nitrosative stress.


Attachment styles, memories of parental rearing and therapeutic bond: a study with eating disordered patients, their parents and therapists.
Patients diagnosed with anorexia nervosa (n = 30) and bulimia nervosa (n = 27), their parents and therapists were recruited for this study aimed at examining differences between clinical groups and a control group (n = 35) in terms of attachment styles and perceptions of memories of parental rearing. Within the clinical groups, relations among these variables and therapeutic bond were explored. In addition, parents' and their daughters' attachment styles were compared. The results showed differences between clinical and control groups: the daughters in the control group reported lower levels of attachment anxiety compared to those of the clinical groups; their mothers exhibited higher security than mothers of anorectic patients and lower avoidance than mothers of bulimic patients. For the anorectic group, therapeutic bond was associated to higher father's emotional support and lower rejection; in the bulimic group, therapeutic bond was related to higher maternal emotional support and lower rejection as well as to lower paternal overprotection.


Neuroprotective effects of several korean medicinal plants traditionally used for stroke remedy.
The neuroprotective effect of six aqueous extracts and one alcoholic extract prepared from seven medicinal plants that have been recorded as having therapeutic effects for stroke in Korean traditional medicine were studied using both in vitro and in vivo cerebral ischemia models. Among the extracts tested, the aqueous extracts of Acorus gramineus, Chrysanthemum indicum, and Pinus densiflora and the alcoholic extract of Vitis vinifera significantly increased the cell viability of SK-N-SH human neuroblastoma cells exposed to oxygen-glucose deprivation (P < .05). Following two-vessel occlusion in gerbils, extracts of P. densiflora and V. vinifera significantly increased the number of surviving cells/mm(2) of the CA1 region by 2.1-2.2-fold (P < .01). Oral or intraperitoneal administration of S-allyl cysteine, as a positive control, also markedly increased cell survival up to about 3.3-fold at the dosage of 300 mg/kg of body weight (P < .01). These results indicate that P. densiflora and V. vinifera exert neuroprotective effects against ischemic insults in both the in vitro and in vivo cerebral ischemia models and prompted us to further characterize the detailed mechanism of action and elucidate the active principles.


The enigmatic cytochrome b-559 of oxygenic photosynthesis.
The ubiquitous and obligatory association of cytochrome b-559 with the photosystem II reaction center of oxygenic photosynthesis is a conundrum since it seems not to have a function in the primary electron transport pathway of oxygen evolution. A model for the cytochrome structure that satisfies the cis-positive rule for membrane protein assembly consists of two short, non-identical hydrophobic membrane-spanning polypeptides (α and β), each containing a single histidine residue, as ligands for the bridging heme prosthetic group that is on the side of the membrane opposite to the water splitting apparatus. The ability of the heterodimer, but not the single α-subunit, to satisfy the cis-positive rule implies that the cytochrome inserts into the membrane as a heterodimer, with some evidence implicating it as the first membrane inserted unit of the assembling reaction center. The very positive redox potential of the cytochrome can be explained by a position for the heme in a hydrophobic niche near the stromal aqueous interface where it is also influenced by the large positive dipole potential of the parallel α-helices of the cytochrome. The requirement for the cytochrome in oxygenic photosynthesis may be a consequence of the presence of the strongly oxidizing reaction center needed for H2 O-splitting. This may lead to the need, under conditions of stress or plastid development, for an alternate source of electrons when the H2 O-splitting system is not operative as a source of reductant for the reaction center.


Agreement between gastrointestinal panel testing and standard microbiology methods for detecting pathogens in suspected infectious gastroenteritis: Test evaluation and meta-analysis in the absence of a reference standard.
Multiplex gastrointestinal pathogen panel (GPP) tests simultaneously identify bacterial, viral and parasitic pathogens from the stool samples of patients with suspected infectious gastroenteritis presenting in hospital or the community. We undertook a systematic review to compare the accuracy of GPP tests with standard microbiology techniques. Searches in Medline, Embase, Web of Science and the Cochrane library were undertaken from inception to January 2016. Eligible studies compared GPP tests with standard microbiology techniques in patients with suspected gastroenteritis. Quality assessment of included studies used tailored QUADAS-2. In the absence of a reference standard we analysed test performance taking GPP tests and standard microbiology techniques in turn as the benchmark test, using random effects meta-analysis of proportions. No study provided an adequate reference standard with which to compare the test accuracy of GPP and conventional tests. Ten studies informed a meta-analysis of positive and negative agreement. Positive agreement across all pathogens was 0.93 (95% CI 0.90 to 0.96) when conventional methods were the benchmark and 0.68 (95% CI: 0.58 to 0.77) when GPP provided the benchmark. Negative agreement was high in both instances due to the high proportion of negative cases. GPP testing produced a greater number of pathogen-positive findings than conventional testing. It is unclear whether these additional 'positives' are clinically important. GPP testing has the potential to simplify testing and accelerate reporting when compared to conventional microbiology methods. However the impact of GPP testing upon the management, treatment and outcome of patients is poorly understood and further studies are needed to evaluate the health economic impact of GPP testing compared with standard methods. The review protocol is registered with PROSPERO as CRD42016033320.


Iodine Concentration and Optimization in Computed Tomography Angiography: Current Issues.
Computed tomography (CT) technology has seen a dramatic evolution in the recent past that has deeply changed the face of this diagnostic modality. Since the early days of helical single-slice and then multislice CT, CT angiography (CTA) has been one of the most technically demanding applications, both in terms of scanning technique and contrast medium (CM) injection protocol, due to the need to acquire a large amount of high-resolution data over a limited period corresponding to the peak contrast enhancement of the arterial system. Iodine concentration is one of the main determinants of arterial enhancement in CTA, and current low-osmolar and iso-osmolar nonionic CM for intravascular administration still come in a handful of molecules, but a relatively wide range of different iodine concentrations. This gives the opportunity to optimize CTA protocols as a function of several factors such as patient characteristics, CT technology, and CM features in an attempt to maximize the diagnostic yield of CTA examinations while considering patient safety and avoiding unnecessary extra costs. Our aim is to provide an up-to-date overview of the existing evidence on how changing iodine concentration can have an impact on CTA performance, especially with the use of state-of-the-art CT and power injector technology, in the perspective of improving patient care while minimizing overall exposure to iodinated CM and ionizing radiation.


Visual Size Processing in Early Visual Cortex Follows Lateral Occipital Cortex Involvement.
Neural activation in the early visual cortex (EVC) reflects the perceived rather than retinal size of stimuli, suggesting that feedback possibly from extrastriate regions modulates retinal size information in EVC. Meanwhile, the lateral occipital cortex (LOC) has been suggested to be critically involved in object size processing. To test for the potential contributions of feedback modulations on size representations in EVC, we investigated the dynamics of relevant processes using transcranial magnetic stimulation (TMS). Specifically, we briefly disrupted the neural activity of EVC and LOC at early, intermediate, and late time windows while participants performed size judgment tasks in either an illusory or neutral context. TMS over EVC and LOC allowed determining whether these two brain regions are relevant for generating phenomenological size impressions. Furthermore, the temporal order of TMS effects allowed inferences on the dynamics of information exchange between the two areas. Particularly, if feedback signals from LOC to EVC are crucial for generating altered size representations in EVC, then TMS effects over EVC should be observed simultaneously or later than the effects following LOC stimulation. The data from 20 humans (13 females) revealed that TMS over both EVC and LOC impaired illusory size perception. However, the strongest effects of TMS applied over EVC occurred later than those of LOC, supporting a functionally relevant feedback modulation from LOC to EVC for scaling size information. Our results suggest that context integration and the concomitant change of perceived size require LOC and result in modulating representations in EVC via recurrent processing.SIGNIFICANCE STATEMENT How we perceive an object's size is not entirely determined by its physical size or the size of its retinal representation but also the spatial context. Using transcranial magnetic stimulation, we investigated the role of the early visual cortex (EVC) and the higher-level visual area, lateral occipital cortex (LOC), known to be critically involved in object processing, in transforming an initial retinal representation into one that reflects perceived size. Transcranial magnetic stimulation altered size perception earlier over LOC compared with EVC, suggesting that context integration and the concomitant change in perceived size representations in EVC rely on feedback from LOC.


The Outcomes of Small-Molecule Kinase Inhibitors and the Role of ROCK2 as a Molecular Target for the Treatment of Alzheimer's Disease.
Alzheimer's disease is rapidly becoming a major threat to public health, with an increasing number of individuals affected as the world's population ages. In this sense, studies have been carried out aiming at the identification of new small-molecule kinase inhibitors useful for the treatment of Alzheimer's disease. In the present study, we investigated the compounds developed as inhibitors of different protein kinases associated with the pathogenesis of Alzheimer's disease. The applied methodology was the use of the Clarivate Analytics Integrity and ClinicalTrials. com databases. Moreover, we highlight ROCK2 as a promising target despite being little studied for this purpose. A careful structure-activity relationship analysis of the ROCK2 inhibitors was performed to identify important structural features and fragments for the interaction with the kinase active site, aiming to rationally design novel potent and selective inhibitors. We were able to notice some structural characteristics that could serve as the basis to better guide the rational design of new ROCK2 inhibitors as well as some more in-depth characteristics regarding the topology of the active site of both isoforms of these enzymes, thereby identifying differences that could lead to planning more selective compounds. We hope that this work can be useful to update researchers working in this area, enabling the emergence of new ideas and a greater direction of efforts for designing new ROCK2 inhibitors to identify new therapeutic alternatives for Alzheimer's disease.


Predictive validity of a computerized emergency triage tool.
Emergency department (ED) triage prioritizes patients on the basis of the urgency of need for care. eTRIAGE is a Web-based triage decision support tool that is based on the Canadian Triage and Acuity Scale (CTAS), a five level triage system (CTAS 1 = resuscitation, CTAS 5 = nonurgent). To examine the validity of eTRIAGE on the basis of resource utilization and cost as measures of acuity. Scores on the CTAS, specialist consultations, computed-tomography use, ED length of stay, ED disposition, and estimated ED and hospital costs (if the patient was subsequently admitted to hospital) were collected for each patient over a six month period. These data were queried from a database that captures all regional ED visits. Correlations between CTAS score and each outcome were measured by using logistic regression models (categorical variables), univariate analysis of variance (continuous variables), and the Kruskal-Wallis analysis of variance (costs). A multivariate regression model that used cost as the outcome was used to identify interaction between the variables presented. Over the six month study, 29,524 patients were triaged by using eTRIAGE. When compared with CTAS level 3, the odds ratios for consultation, CT scan, and admission were significantly higher in CTAS 1 and 2 and were significantly lower in CTAS 4 and 5 (p < 0.001). When compared with CTAS levels 2-5 combined, the odds ratio for death in CTAS 1 was 664.18 (p < 0.001). The length of stay also demonstrated significant correlation with CTAS score (p < 0.001). Costs to the ED and hospital also correlated significantly with increasing acuity (median costs for CTAS levels in Canadian dollars: CTAS 1 = 2,690 dollars, CTAS 2 = 433 dollars, CTAS 3 = 288 dollars, CTAS 4 = 164 dollars, CTAS 5 = 139 dollars, and p < 0.001). Significant interactions between the data collected were found in a multivariate regression model, although CTAS score remained highly associated with costs. Acuity measured by eTRIAGE demonstrates excellent predictive validity for resource utilization and ED and hospital costs. Future research should focus on specific presenting complaints and targeted resources to more accurately assess eTRIAGE validity.


A developmental study of the relationship between handedness and eyedness as applied to disappearing visual targets.
This study investigated differences between adult and children's perception of a disappearing, lateralized stimulus. In 20 trials, 23 first graders and 22 college students viewed a luminous target of parallel lines subtending a visual angle of 11 degrees 30' and reported whether a stimulus disappeared on either side of fixation or all at once. Both groups, regardless of handedness and eye dominance, had stronger right-field stability, therefore more left-field fragmentation.


Enhancement of Aflatoxin B1 induced liver carcinogenesis by portal diversion in the rat.
Conflicting results have been reported on the influence of portacaval anastomosis on liver carcinogenesis. The purpose of this investigation was to study the effect of portal diversion on liver carcinogenesis induced in the rat by a potent chemical liver carcinogen, Aflatoxin B1 (AFB1). Liver tumors appeared earlier and were significantly bigger in rats with shunts than in sham-operated controls. Portal diversion also induced in rats fed AFB1 a splenic atrophy with nearly complete disappearance of Malpighian corpuscles suggesting a profound immunodepression. This might be responsible for the enhancement of liver cancer by portacaval anastomosis in the rats fed AFB1. Thus, the influence of portal diversion on liver cancers appears to be multifactorial.


Runaway ornament diversity caused by Fisherian sexual selection.
Fisher's runaway process of sexual selection is potentially an important force generating character divergence between closely related populations. We investigated the evolution of multiple female preferences by Fisher's runaway process. There are two outcomes of runaway. The first is the evolution of mate preference to a stable equilibrium. This evolution occurs if the benefits of mate choice are sufficiently large relative to the cost of choice. Alternatively, mate preferences evolve cyclically. The rate and pattern of cyclic evolution depends primarily on the individual cost of choice and epistasis in the joint cost of choice. If there are small differences in natural selection (e.g., predation risk) between populations, cyclic evolution quickly leads to divergence in mate preferences and sexual ornaments and so to sexual isolation.


Adaptation and latent structure of the Brazilian version of the Ego Dissolution Inventory (EDI-BR): An exploratory study.
Existing scales that seek to measure alterations in self-experience were based on studies conducted in developed countries. Therefore, the aim of this study was to evaluate the psychometric properties of the Ego-Dissolution Inventory (EDI), translate and adapt it to the Brazilian context. Translation of the measure was made by two translators fluent in both English and Portuguese, with back-translation into English to ensure there was no loss of meaning. The scale was included in an online survey exploring substance use. A total of 528 participants answered the full scale. We calculated the Kaiser-Meyer-Olkin (KMO) measure to evaluate sampling adequacy, then ran Exploratory Analysis Factor (EFAs) to investigate the factor structure of the EDI. The scale showed acceptable psychometric properties, with excellent internal consistency and sampling adequacy for a factor analysis. Kaiser-Gutman's criteria and Hull's method pointed to a three-factor solution, while Parallel Analysis suggested a two-factor solution. All items showed salient loadings, with two items exhibiting cross-loading. Positive but weak correlations were found between EDI factors 1 and 2 and nature-relatedness. The validated scale showed solid psychometric properties, with potential differences in factor structure in relation to the English version. Considering validation as ongoing process, it is recommended to conduct studies comparing the scores of ego dissolution across distinct substances and different regions of the country.


Explaining modified 2-min walk test outcomes in male Veterans with traumatic or nontraumatic lower-limb amputation.
Little evidence exists to support the presence of differences in spatiotemporal gait parameters and ambulation ability between those individuals with traumatic and nontraumatic lower-limb amputation (LLA). We conducted an exploratory study of 81 male Veterans with unilateral amputation to quantify differences in spatiotemporal gait parameters and ambulatory mobility between Veterans with traumatic and nontraumatic LLA. Furthermore, we identified variables that significantly contributed to the explanation of variability in modified 2-min walk test distance. All participants completed the modified 2-min walk test and a spatiotemporal gait analysis using an instrumented walkway during a routine physical therapy visit. Veterans with nontraumatic LLA walked significantly shorter mean distances during a modified 2-min walk test than Veterans with traumatic LLA. Variables identified as significant contributors to modified 2-min walk test variability were amputated limb stance time, amputated limb step length, and percentage of the gait cycle spent in double support. These findings demonstrate that differences in spatiotemporal gait parameters and ambulatory mobility exist between Veterans with traumatic and nontraumatic LLA and identify important spatiotemporal parameters of gait contributing to this decline. These parameters should be considered as targets for intervention and future investigation.


Th1 and Th17 Cells and Associated Cytokines Discriminate among Clinically Isolated Syndrome and Multiple Sclerosis Phenotypes.
Multiple sclerosis (MS) is a chronic, inflammatory, and demyelinating disease of the central nervous system. It is a heterogeneous pathology that can follow different clinical courses, and the mechanisms that underlie the progression of the immune response across MS subtypes remain incompletely understood. Here, we aimed to determine differences in the immunological status among different MS clinical subtypes. Blood samples from untreated patients diagnosed with clinically isolated syndrome (CIS) (n = 21), different clinical forms of MS (n = 62) [relapsing-remitting (RRMS), secondary progressive, and primary progressive], and healthy controls (HCs) (n = 17) were tested for plasma levels of interferon (IFN)-γ, IL-10, TGF-β, IL-17A, and IL-17F by immunoanalysis. Th1 and Th17 lymphocyte frequencies were determined by flow cytometry. Our results showed that IFN-γ levels and the IFN-γ/IL-10 ratio were higher in CIS patients than in RRMS patients and HC. Th1 cell frequencies were higher in CIS and RRMS than in progressive MS, and RRMS had a higher Th17 frequency than CIS. The Th1/Th17 cell ratio was skewed toward Th1 in CIS compared to MS phenotypes and HC. Receiver operating characteristic statistical analysis determined that IFN-γ, the IFN-γ/IL-10 ratio, Th1 cell frequency, and the Th1/Th17 cell ratio discriminated among CIS and MS subtypes. A subanalysis among patients expressing high IL-17F levels showed that IL-17F and the IFN-γ/IL-17F ratio discriminated between disease subtypes. Overall, our data showed that CIS and MS phenotypes displayed distinct Th1- and Th17-related cytokines and cell profiles and that these immune parameters discriminated between clinical forms. Upon validation, these parameters might be useful as biomarkers to predict disease progression.


[Study on inhibition of coxsackievirus B3 infection in HeLa cell by short interfering RNA targeting 2B protein].
To study the inhibitory effect and function characteristics of small interfering RNA (siRNA) on cosxackievirus B3(CVB3) infection by RNA interference technique, siRNA-2B against the viral 2B region was synthesized and transfected into HeLa cell, which was then infected with CVB3. The efficiency of siRNA transfection was examined by FCM, the cell toxicity of siRNA-2B by MTT, and the antiviral ability of siRNA-2B by cytopathic effect (CPE), plaque reduction assay and RT-PCR. The results showed that siRNA-2B could be transfected efficiently into HeLa cell and lasted at least 48h. High concentration of siRNA-2B didn't show any sign of toxicity to cells. siRNA-2B exhibited a significant protective effect on cell viability by specific inhibition of viral replication. It showed a close relationship between the concentrations of siRNA-2B and the antiviral effects. siRNA-2B led to dramatical reduction of viral titers in supernatant of cell culture and weakened the reinfection ability of the virus. These data proposed that siRNA-2B, targeting 2B protein, can effectively inhibit CVB3 infection in HeLa cell and exhibits its transfection efficiency, viral inhibition specificity and adose-dependant manner, suggesting its potential role in prevention and treatement of CVB3 infection.


The Flint Food Store Survey: combining spatial analysis with a modified Nutrition Environment Measures Survey in Stores (NEMS-S) to measure the community and consumer nutrition environments.
The goal of the present study was to use a methodology that accurately and reliably describes the availability, price and quality of healthy foods at both the store and community levels using the Nutrition Environment Measures Survey in Stores (NEMS-S), to propose a spatial methodology for integrating these store and community data into measures for defining objective food access. Two hundred and sixty-five retail food stores in and within 2 miles (3·2 km) of Flint, Michigan, USA, were mapped using ArcGIS mapping software. A survey based on the validated NEMS-S was conducted at each retail food store. Scores were assigned to each store based on a modified version of the NEMS-S scoring system and linked to the mapped locations of stores. Neighbourhood characteristics (race and socio-economic distress) were appended to each store. Finally, spatial and kernel density analyses were run on the mapped store scores to obtain healthy food density metrics. Regression analyses revealed that neighbourhoods with higher socio-economic distress had significantly lower dairy sub-scores compared with their lower-distress counterparts (β coefficient=-1·3; P=0·04). Additionally, supermarkets were present only in neighbourhoods with <60 % African-American population and low socio-economic distress. Two areas in Flint had an overall NEMS-S score of 0. By identifying areas with poor access to healthy foods via a validated metric, this research can be used help local government and organizations target interventions to high-need areas. Furthermore, the methodology used for the survey and the mapping exercise can be replicated in other cities to provide comparable results.


Who does nutrition prevention work in Queensland? An investigation of structural and political workforce reforms.
This study aimed (i) to determine the change in the number of government-funded nutrition positions following structural and political reforms and (ii) to describe the remaining workforce available to do nutrition prevention work, including student placements, in Queensland. Positions funded by the Queensland government were counted using departmental human resource data and compared with data collected 4 years earlier. Positions not funded by the government were identified using formal professional networks and governance group lists. Both groups were sent an online survey that explored their position name, funding source, employer, qualifications, years of experience, work in prevention and ability to supervise students. There was a 90% reduction in the number of nutrition prevention positions funded by the government between 2009 (137 full time equivalents (FTE)) and 2013 (14 FTE). In 2013, 313 specialist (n = 92) and generalist (n = 221) practitioners were identified as potentially working in nutrition prevention throughout Queensland. A total of 30 permanent FTEs indicated over 75% of their work focused on prevention. This included the 14 FTE funded by the Queensland government and an additional 16 FTE from other sectors. Generalists did not consider themselves part of the nutrition workforce. Queensland experienced an extreme reduction in its nutrition prevention workforce as a result of political and structural reforms. This disinvestment by the Queensland government was not compensated for by other sectors, and has left marked deficits in public health nutrition capacity, including student placements.


Supersaturation of zafirlukast in fasted and fed state intestinal media with and without precipitation inhibitors.
Poor water solubility is a bottle neck in the development of many new drug candidates, and understanding and circumventing this is essential for a more effective drug development. Zafirlukast (ZA) is a leukotriene antagonist marketed for the treatment of asthma (Accolate®). ZA is poorly water soluble, and is formulated in an amorphous form (aZA) to improve its solubility and oral bioavailability. It has been shown that upon dissolution of aZa, the concentration of ZA in solution is supersaturated with respect to its stable crystalline form (ZA monohydrate), and thus, in theory, the bioavailability increases upon amorphization of ZA. The polymers hydroxypropylmethylcellulose (HPMC) and polyvinylpyrrolidone (PVP), often used as stabilizers of the supersaturated state, are in the excipient list of Accolate®. It is not recommended to take Accolate® with food, as this reduces the bioavailability by 40%. The aim of this study was to investigate the effect of simulated fasted and fed state intestinal media as well as the effect of HPMC and PVP on the supersaturation and precipitation of ZA in vitro. Supersaturation of aZA was studied in vitro in a small scale setup using the μDiss Profiler™. Several media were used for this study: One medium simulating the fasted state intestinal fluids and three media simulating different fed state intestinal fluids. Solid state changes of the drug were investigated by small angle x-ray scattering. The duration wherein aZA was maintained at a supersaturated state was prolonged in the presence of HPMC and lasted more than 20h in the presence of PVP in a fasted state intestinal medium. The presence of PVP increased the concentration of drug dissolved in the supersaturated state. The duration of supersaturation was shorter in fed than in a fasted state simulated intestinal media, but the concentration during supersaturation was higher. It was thus not possible to predict any positive or negative food effects from the dissolution/precipitation curves from different media. Lipolysis products in the fed state simulated media seemed to cause both a negative effect on the duration of supersaturation, and an increased drug concentration during supersaturation. In contrast, when testing the effect of a fed state simulated medium compared to the fasted state medium, in the presence of PVP, a clear negative effect was seen on the dissolution/precipitation curved of the fed state medium. The drug concentration during supersaturation was marginally different in the two media, but a precipitation of ZA was seen in the fed state medium, which was not observed in the fasted state medium. Solid state transformation from aZA to ZA monohydrate (mhZA) upon precipitation of the supersaturated solutions was confirmed by small angle x-ray scattering. All of these results can explain the described in vivo behavior of ZA. For ZA simple dissolution experiments in vitro can be used to examine supersaturation, effectiveness of PI and potential food effects on these.


Social contexts of trauma and healing.
The social contexts in which the mass trauma of thousands of people occur and in which their recovery should progress have qualities that distinguish it in important ways from individualised trauma in which a person is a victim of a violent attack, rape or a traffic accident. Organised violence, such as wars, oppression by dictatorships and massive terrorist attacks are extreme cases in which hundreds or thousands of people are exposed to trauma in a short period of time. As such, it has multiple consequences that extend beyond the affected individuals and the symptoms they suffer. Although the symptoms may be similar, the social contexts in which individual victimisation and exposure to organised violence happen are very different. The social milieu in which the survivors of individual trauma and survivors of mass trauma are embedded is likewise different, with important consequences for recovery. Understanding the social context of the trauma helps create the right social intervention for healing at social and personal levels.


Canonical BMP signaling is dispensable for hematopoietic stem cell function in both adult and fetal liver hematopoiesis, but essential to preserve colon architecture.
Numerous publications have described the importance of bone morphogenetic protein (BMP) signaling in the specification of hematopoietic tissue in developing embryos. Here we investigate the full role of canonical BMP signaling in both adult and fetal liver hematopoiesis using conditional knockout strategies because conventional disruption of components of the BMP signaling pathway result in early death of the embryo. By targeting both Smad1 and Smad5, we have generated a double-knockout mouse with complete disruption of canonical BMP signaling. Interestingly, concurrent deletion of Smad1 and Smad5 results in death because of extrahematopoietic pathologic changes in the colon. However, Smad1/Smad5-deficient bone marrow cells can compete normally with wild-type cells and display unaffected self-renewal and differentiation capacity when transplanted into lethally irradiated recipients. Moreover, although BMP receptor expression is increased in fetal liver, fetal liver cells deficient in both Smad1 and Smad5 remain competent to long-term reconstitute lethally irradiated recipients in a multilineage manner. In conclusion, canonical BMP signaling is not required to maintain either adult or fetal liver hematopoiesis, despite its crucial role in the initial patterning of hematopoiesis in early embryonic development.


[Arterial hypertension: adenocarcinoma of the kidney or bilateral renal artery stenosis$].
In a 71-year-old female with severe hypertension, bilateral renal artery stenosis and renal adenocarcinoma, a renal vein renin study revealed suppressed renin secretion from the kidney with carcinoma and contralateral ischemia. The hypertension was not cured by surgical removal of the kidney with carcinoma. Hypertension is frequently noted in patients with renal adenocarcinoma (28% of 603 patients reported in the literature). This type of hypertension is frequently improved after removal of the tumor (83% of 36 surgically treated patients). In certain patients the pathogenesis of hypertension associated with renal adenocarcinoma may be related to renin secretion from the tumor or to renin activation due to regional ischemia caused by vascular compression. In other patients the renin-angiotensin system does not appear to play a pathogenic role in the development of hypertension associated with renal adenocarcinoma.


Feasibility of training nurses in motivational interviewing to improve patient experience in mental health inpatient rehabilitation: a pilot study.
WHAT IS KNOWN ON THE SUBJECT?: Recently, concerns have been raised about how well United Kingdom National Health Service nurses care for their patients and their level of compassion. Motivational interviewing (MI) is an established approach to helping people make positive behaviour changes, through directive, person-centred counselling within a collaborative relationship between clinician and recipient. Based on evidence that MI may influence nursing practice positively, an investigation into the feasibility of training nurses on mental health inpatient rehabilitation wards ('rehabilitation') in MI to improve patient experience was reported. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: This pilot study demonstrates that training rehabilitation nurses in MI is feasible and provides preliminary evidence suggesting that a larger study to examine efficacy is warranted, including a calculation of sample size required to draw robust statistical conclusions. Nurses evaluated the training as highly relevant to their work. Patients responded well to interviews and focus groups with support from experts-by-experience; they were generally fairly satisfied with the rehabilitation ward and slight improvements in their experience were found following MI training for nurses but not at 6-month follow-up. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Rehabilitation nurses may face conflicting demands between ensuring patients with severe difficulties meet their basic needs and working with them to develop greater independence. Qualitative findings question whether nurse-patient interactions are fully valued as nursing interventions in inpatient rehabilitation. Learning MI might be a useful way of helping nurses think in detail about their interactions with patients and how to improve communications with their patients. The principles of MI should be incorporated into pre-registration training. Introduction There is limited research addressing the experiences of patients in inpatient rehabilitation (rehabilitation), who often spend long periods in hospital, and the nursing approaches utilized. Aim Based on evidence that motivational interviewing (MI) may improve nursing practice, this was a pilot study evaluating the feasibility of training rehabilitation nurses in MI and measuring patient experience. Method Nurses underwent training and supervision focusing on MI spirit. Quantitative and qualitative measures were taken pretraining, 2 months post-training and 8 months post-training. Expert-by-experience research assistants facilitated patients' participation in the study. Results This study showed that training rehabilitation nurses in MI was feasible and relevant to their work. Patients participated in interviews and focus groups with support and potential improvements that require further empirical investigation in patient experience were found following the MI training. Discussion This pilot study establishes the feasibility of a larger study addressing efficacy. Tentative qualitative findings question whether interactions between nurses and patients are valued in rehabilitation and support MI as a promising skill set for rehabilitation nurses. Implications for practice Bringing MI into inpatient rehabilitation provoked reflection on nursing practice. Dilemmas for nurses about balancing safety with promoting autonomy and communicating constructively with patients emerged as important.


Impact on reproductive performance and body condition in a small limpet parasitized by a large castrator pea crab.
Parasitic castrators utilize the energy reserves that the host allocates on reproduction resulting in sterilization of the host. However, whether other processes (e.g., growth) are also impaired depends on the balance between the castrator's energy requirements and the available resources that the castrated host does not use in reproduction. We investigated whether the castrator pea crab Calytraeotheres garthi alters body condition, reproductive performance, and occurrence of copulation in its limpet host Bostrycapulus odites. For this purpose, we examined the anatomy of the ovary, the seminal receptacles, and the body condition of parasitized and unparasitized limpets. The histology of the female gonad of parasitized limpets revealed the ovarian tubules are smaller and characterized by a greater proportion of intertubular and intratubular free space compared with non-parasitized individuals. The body condition of female limpets from all sizes (during summer) and those larger than ~16 mm (during spring and autumn) were impacted by the pea crab. These results are in contrast to that previously reported in the comparatively larger limpet species Crepidula cachimilla, in which the same pea crab species does not alter or even increase the host body weight. We concluded this pea crab species could drastically impair its host's reproduction and body condition although deleterious effects are species-specific and likely depend on limpet body size. The histology of seminal receptacles revealed an uncommon disposition of spermatozoa (i.e., excessive debris and acrosomes detached from epithelium) in seminal receptacles of some parasitized limpets. However, this analysis failed to determine whether sperm derived from present matings or previous pea crab infection. Further studies are needed to address whether pea crabs interfere with the mating behavior of limpets and if the alterations in sperm disposition are a consequence of castration.


[Schimke's immuno-osseous dysplasia as an explanation for the rare combination of disproportionately short stature and the nephrotic syndrome].
A 10-year-old Turkish boy with consanguineous parents was presented with a disproportionately short stature and a nephrotic syndrome. The mild form of Schimke's immuno-osseous dysplasia was diagnosed as the common cause. This rare, autosomal recessive osteochondrodysplasia is characterised by spondyloepiphyseal dysplasia, facial dysmorphism, T-cell immunodeficiency and progressive renal failure due to focal segmental glomerulosclerosis. In Schimke's immuno-osseous dysplasia, a severe early-onset form and a milder later-onset form can be distinguished on the basis of the clinical course. The patient was treated by fluid and salt restriction, enalapril and later also losartan, which led to a decrease in the proteinuria and an increase in serum albumin concentration. Two years later, the renal function was still normal.


Ontogenetic changes in the expression of immune related genes in response to immunostimulants and resistance against white spot syndrome virus in Litopenaeus vannamei.
In recent years, researchers have focused on viral and plant immunostimulants which could have beneficial effects in disease prevention and control in shrimp culture. At present, the application of the recombinant VP28 protein (r-VP28) and herbal immunostimulant has been considered as a more effective approach to prevent white spot syndrome (WSS) by enhancing the immune response in shrimp. In the present study, expression of selected immune related genes in response to r-VP28 and herbal immunostimulant mix (HIM) were separately studied qualitatively and quantitatively by RT-PCR and real time PCR, respectively during ontogenetic development from nauplius to juvenile stage in Litopenaeus vannamei. The mRNA expression level of immune related genes such as anti-lipopolysaccharides (ALF), Lysozyme, cMnSOD, Crustin, Prophenoloxidase, Tumor necrosis factor receptor-associated factor 6 (TRAF6) and Haemocyanin were found to be up-regulated significantly in different ontogenetic development stages of shrimp fed with r-VP28 and HIM formulated diets. Relative percent survival (RPS) was determined in shrimp fed with immunostimulants formulated diets after oral challenge with WSSV. The survival of WSSV challenged shrimp was found to be higher in immunostimulants treated groups when compared to untreated group. The results of PCR, ELISA and real time PCR revealed the absence of WSSV in WSSV-challenged shrimp after 20 days of treatment with immunostimulants. Among these immunostimulants, HIM was found to be more effective when compared to r-VP28. After a survey of literature, we are of the opinion that this might be the first report on the expression of immune genes during ontogenetic development of L. vannamei in response to immunostimulants.


Cytoplasmic targeting motifs control localization of toll-like receptor 9.
Toll-like receptors (TLRs) are essential for host defense. Although several TLRs reside on the cell surface, nucleic acid recognition of TLRs occurs intracellularly. For example, the receptor for CpG containing bacterial and viral DNA, TLR9, is retained in the endoplasmic reticulum. Recent evidence suggests that the localization of TLR9 is critical for appropriate ligand recognition. Here we have defined which structural features of the TLR9 molecule control its intracellular localization. Both the cytoplasmic and ectodomains of TLR9 contain sufficient information, whereas the transmembrane domain plays no role in intracellular localization. We identify a 14-amino acid stretch that directs TLR9 intracellularly and confers intracellular localization to the normally cell surface-expressed TLR4. Truncation or mutation of the cytoplasmic tail of TLR9 reveals a vesicle localization motif that targets early endosomes. We propose a model whereby modification of the cytoplasmic tail of TLR9 results in trafficking to early endosomes where it encounters CpG DNA.


Clinical and Apoptotic Factors Defining and Predicting Steroid Resistance in Nephrotic Syndrome in Children.
Introduction. Nephrotic syndrome (NS) is a kidney disease characterized by albuminuria, hyperlipidemia, edema, and hypoalbuminemia. Above 20 % of nephrotic children do not show response to steroid treatment. Molecular markers controlling apoptosis have not been studied as a predictors of steroid resistant NS (SRNS) and steroid sensitive NS (SSNS) in children. Aim of the Study. To identify clinical and molecular markers which define and predict the steroid-resistance phenomenon in children with NS. Methods. Fifty-six clinical cases of children hospitalized in Pediatric Hospital No. 7 (Kyiv, Ukraine) with NS (26 SSNS and 30 SRNS) studied. Stepwise logistic regression models used to analyze data. Data processed using GraphPad Prism 9.0 Software for Windows (USA, San Diego, CA). Results. Arterial hypertension, WBC and RBC count, serum creatinine, serum urea, serum cholesterol found to be factors defining and predicting SRNS. Apoptosis regulating BcL-xL, Bax but not caspase-8 found to be those defining SRNS. Among transcriptional factors HIF-1alfa selected as a factor predicting steroid resistance phenomenon. For SSNS group significant negative correlation observed between BcL-xL and Bax, BcL-xL and caspase-3, significant positive correlation observed between marker of cellular hypoxia HIF-1alfa and proapoptotic factor caspase-3. For SRNS group significant negative correlation observed between BcL-xL and Bax, BcL-xL and caspase-3 level, significant positive correlation observed between HIF-1alfa and proapoptotic factor caspase-3. Conclusions. Arterial hypertension, serum creatinine level, serum urea level, serum cholesterol level, WBC and RBC count, BcL-xL, Bax, caspase-3, and HIF-1alfa identified as candidate biomarkers to predict and define SRNS in pediatric NS.


Facile fabrication and upconversion luminescence enhancement of LaF3:Yb3+/Ln3+@SiO2 (Ln = Er, Tm) nanostructures decorated with Ag nanoparticles.
A novel hybrid nanostructure, that is a Ag nanoparticle decorated LaF(3):Yb(3+)/Ln(3+)@SiO(2) nanosphere (Ln=Er, Tm), was constructed by a facile strategy, and characterized by XRD, TEM, FTIR, XPS and UV-vis-NIR absorption. Obvious spectral broadening and red-shift on the surface plasmon resonance were obtained by adjusting the size and configuration of Ag nanoparticles. Effective upconversion luminescence enhancements for Er(3+) and Tm(3+) containing samples were obtained. It is suggested that the luminescence enhancement results from both the excitation and emission processes, and the configuration of the studied hybrid nanostructure is an efficient system to enhance the luminescence emission of rare earth doped nanomaterials. It is believed that the enhancement from the hybrid nanostructure will find great potential in the development of photovoltaic solar cells.


Solvent effects on the photoinduced charge separation dynamics of directly linked zinc phthalocyanine-perylenediimide dyads: a nonadiabatic dynamics simulation with an optimally tuned screened range-separated hybrid functional.
Herein, we have employed a combination of the optimally tuned screened range-separated hybrid (OT-SRSH) functional, the polarizable continuum model (PCM), and nonadiabatic dynamics (NAMD) simulations to investigate the photoinduced dynamics of directly linked donor-acceptor dyads formed using zinc phthalocyanine (ZnPc) and perylenediimide (PDI), in which ZnPc is the donor while PDI is the acceptor. Our simulations aim to analyze the behavior of these dyads upon local excitation of the ZnPc moiety in the gas phase and in benzonitrile. Our findings indicate that the presence of a solvent can significantly influence the excited state dynamics of ZnPc-PDI dyads. Specifically, the polar solvent benzonitrile effectively lowers the vertical excitation energies of the charge transfer (CT) state from ZnPc to PDI. As a result, the energetic order of the locally excited (LE) states of ZnPc and the CT states is reversed compared to the gas phase. Consequently, the photoinduced electron transfer (PET) dynamics from ZnPc to PDI, which is absent in the gas phase, takes place in benzonitrile with a time constant of 10.4 ps. Importantly, our present work not only qualitatively agrees with experimental results but also provides in-depth insights into the underlying mechanisms responsible for the photoinduced dynamics of ZnPc-PDI. Moreover, this study emphasizes the importance of appropriately considering solvent effects in NAMD simulation of organic donor-acceptor systems, taking into account the distinct excited state dynamics observed in the gas phase and benzonitrile. Furthermore, the combination of the OT-SRSH functional, the PCM solvent model, and nonadiabatic dynamics simulations shows promise as a strategy for investigating the complex excited state dynamics of organic donor-acceptor systems in solvents. These findings will be valuable for the future design of novel organic donor-acceptor structures with improved performance.


Patients with inflammatory bowel disease and post-inflammatory polyps have an increased risk of colorectal neoplasia: A meta-analysis.
Longstanding intestinal inflammation increases the risk of colorectal neoplasia in patients with inflammatory bowel disease (IBD). Accurately predicting the risk of colorectal neoplasia in the early stage is still challenging. Therefore, identifying visible warning markers of colorectal neoplasia in IBD patients is the focus of the current research. Post-inflammatory polyps (PIPs) are visible markers of severe inflammation under endoscopy. To date, there is controversy regarding the necessity of strengthened surveillance strategies for IBD patients with PIPs. To determine whether IBD patients with PIPs carryan increased risk of colorectal neoplasia. Researchers searched the following databases up to July 31, 2021: MEDLINE (PubMed), MEDLINE (Ovid), EMBASE, Cochrane Library, China National Knowledge Infrastructure, Wan-Fang Data, China Science and Technology Journal Database and Chinese BioMedical Literature Database. Cohort and case-control studies that compared the risk of colorectal neoplasia between IBD patients with or without PIPs and published in English or Chinese were included. Methodological quality was assessed using the Risk of Bias in Nonrandomized Studies-of Interventions assessment tool. The outcomes of interest were the rates of various grades of colorectal neoplasia. The pooled risk ratio (RR) and 95% confidence interval (95%CI) were calculated using the random-effects model. Begg's test and Egger's test were used to calculate the publication bias. Sensitivity and subgroup analyses were performed to verify the robustness of the results. The Grading of Recommendations, Assessment, Development and Evaluation approach was used to assess the overall quality of evidence supporting the outcomes of interest. Nine studies involving 5424 IBD patients (1944 with PIPs vs 3480 without PIPs) were included. The overall bias in each included study ranged from moderate to serious. Compared with nonconcurrent PIPs, patients with PIPs had a higher risk of colorectal neoplasia (RR = 1.74, 95%CI: 1.35-2.24, P < 0.001, I2 = 81.4%; aHR = 1.31, 95%CI: 1.01-1.70, P = 0.04, I 2 = 26.2%; aOR = 2.62, 95%CI: 1.77-3.88, P < 0.001, I 2 = 0%), advanced colorectal neoplasia (RR = 2.07, 95%CI: 1.49-2.87, P < 0.001, I 2 = 77.4%; aHR = 1.63, 95%CI: 1.05-2.53, P = 0.03, I 2 = 10.1%) and colorectal cancer (RR = 1.93, 95%CI: 1.32-2.82, P = 0.001, I 2 = 83.0%). Publication bias was not observed in Begg's test or Egger's test. Sensitivity and subgroup analyses showed that the results are robust. The overall quality of evidence was assessed as moderate to low. IBD patients with PIPs may have an increased incidence of colorectal neoplasia.


Anatomy of Landsmeer Ligaments-Redefined.
Introduction Landsmeer ligaments play a significant role in synchronizing the movements of the two distal phalanges of the fingers. However, there is considerable controversy in descriptions of its anatomy, function, presence, and clinical applications. Aim To ascertain and redefine the detailed anatomy of Oblique Retinacular (ORL) and Transverse Retinacular ligaments (TRL) and their applied features. Materials and Methods Anatomical dissection study was conducted in 100 cadaveric fingers in 42 cadavers (28 fresh specimens and remaining preserved specimens) under loupe magnification. The whole dorsal digital expansion with attached fibrous flexor sheath was dissected and specimen was examined after thorough saline wash. The dimensions, course, attachment, and configuration were noted in each specimen. The statistical mean was obtained for thickness of the ligaments. The measurements were made using a caliper at the level of the mid proximal phalanx, volar to the proximal interphalangeal (PIP) joint, and dorsal to the distal interphalangeal (DIP) joint. Results By anatomical dissection we have found the following: • The ORL was deep to the TRL. • The ORL had got a check rein effect at the PIP joint, in such a way that extension of the PIP joint causes extension of the DIP joint. • The ORL criss-crossed volar to the A3 pulley of fibrous flexor sheath and formed a good hammock for the PIP joint. This criss-crossing anatomical feature was found in all dissected fingers as an additional normal anatomical feature complementing the classical description of Landsmeer. • Variations in configuration of the Landsmeer ligaments were observed among various fingers. • The Landsmeer ligament was never absent as reported by several studies. Conclusion Contrary to several studies, the ORL was omnipresent in all dissected fingers with considerable variations in dimensions. Complementing the classical description of Landsmeer, we found that there was an additional normal criss-cross anatomical feature of the ORL in all fingers volar to A3 pulley and deep to the TRL. Also, the TRL was present in all the fingers.


Molecular characterization of metastatic osteosarcoma: Differentially expressed genes, transcription factors and microRNAs.
The present study aimed to understand the molecular mechanisms underlying osteosarcoma metastasis. Microarray dataset GSE49003 was downloaded from the Gene Expression Omnibus database and used for analysis. Raw expression data were preprocessed using the preprocessCore, impute and aggregate packages in R. Differentially expressed genes (DEGs) between metastatic and non‑metastatic osteosarcoma cell lines were screened using the limma package following exclusion of DEGs with a higher significance in intra‑groups compared with inter‑groups using the genefilter package. Enrichment analysis was performed on DEGs using TargetMine, followed by identification of transcription factors (TFs) and microRNAs (miRNAs). Regulatory networks were constructed using Cytoscape software. A total of 248 upregulated and 208 downregulated genes were obtained. The upregulated genes were significantly enriched in the following pathways: Downregulation of transforming growth factor β (TGF‑β) receptor signaling and TGF‑β receptor signaling activates SMADs; these upregulated genes included protein phosphatase 1, regulatory subunit 15A, transforming growth factor, β receptor II and ubiquitin carboxyl‑terminal hydrolase L5. In addition, some upregulated genes were enriched in lung cancer disease ontology, including epidermal growth factor receptor (EGFR), insulin‑like growth factor 2 mRNA binding protein 3 (IGF2BP3), runt‑related transcription factor 3 (RUNX3) and secreted frizzled‑related protein 1 (SFRP1). Conversely, the downregulated genes were significantly enriched in extracellular matrix‑associated pathways or functions, such as collagen, type XII, α 1; collagen, type I, α 1; collagen, type IV, α 1; and collagen, type V, α 1. In addition, some downregulated genes were significantly enriched in the TGF‑β signaling pathway, including bone morphogenetic protein 4, inhibitor of DNA binding 3 and SMAD family member 6. A total of 10 TFs and 84 miRNAs (e.g. miR-21-5p) were deemed to be associated with DEGs. In conclusion, DEGs enriched in the downregulation of TGF‑β receptor signaling, TGF‑β receptor signaling activates SMADs and TGF‑β signaling pathways, as well as the extracellular matrix may be implicated in the progression of osteosarcoma metastasis. Dysregulated EGFR, IGF2BP3, RUNX3 and SFRP1 may contribute to the metastasis of osteosarcoma to the lungs. In addition, screened TFs and miR-21-5p may be associated with metastasis via target genes.


Operations in spinal surgery are not always needed. Do we operate more than we should?
Lumbar disc herniation and low back pain are the main cause of sickness during labor life. The decision for operation is thought to be taken easily and as a result a lot of money is being spent for treatment and rehabilitation. The aim of this study was to evaluate whether conservative treatment is sufficient for treatment of lumbar disc herniation and low back pain and what percentage of the patients operated are satisfied with social and everyday life two years after operation. One hundred and twenty seven patients (67 male and 60 female) were treated because of lumbar disc herniation. No neurological deficiency or muscle weakness was observed. Seventy two patients underwent conservative treatment. Fifty five patients underwent microsurgical discectomy. Back and leg pain are reported on a visual analog scale (VAS) and with the Oswestry disability index (ODI). The Short Form-36 health survey (SF-36) and the European Quality of Life questionnaire (EQ-5D) should also be completed. Surgical data, including diagnosis, are recorded by the surgeon without access to the patient's questionnaires. Both groups (conservative and operative) improved from baseline with regard to SF-36 and ODI (all P<0.01). The results 2 years after surgery were similar for both groups, as measured with the SF-36 and the ODI. Both groups improved from baseline to follow-up with regard to both back pain and leg pain (all P<0.01). The frequency of returning to work was analyzed for those patients who were less than 65 years of age at the time of follow up, and who had been working before surgery. Statistical analysis indicates that there are no significant differences between the groups. The decision for operation is thought to be taken easily and as a result a lot of money is being spent for treatment and rehabilitation. In conclusion, this study shows that operative treatment is equal in outcome to conservative treatment and should follow, seen from an economic perspective, the conservative treatment.


Development of a Green Microwell Spectrofluorimetric Assay with High Analytical Throughput for the Determination of Selective Serotonin Reuptake Inhibitors in Pharmaceutical Dosage Forms and Plasma.
In this study, a new green microwell spectrofluorimetric assay (MW-SFA) with high throughput was developed and validated, for the first time, for the determination of three selective serotonin reuptake inhibitors (SSRIs) in pharmaceutical dosage forms and plasma. These SSRIs were fluoxetine (FLX), fluvoxamine (FXM), and paroxetine (PXT), which are commonly prescribed drugs for depression treatment. The MW-SFA is based on the condensation reaction of SSRIs with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) in alkaline media to form highly fluorescent derivatives. The MW-SFA procedures were conducted in 96-microwell white opaque assay plates with a flat bottom and the fluorescence signals were measured using a microplate reader at their maximum excitation and emission wavelengths. The calibration curves were generated with good correlation coefficients (0.9992-0.9995) between the relative fluorescence intensity (RFI) and the SSRI concentrations in the range of 35-800 ng/mL. The limits of detection were in the range of 11-25 ng/mL, and the precision and accuracy were satisfactory. The proposed MW-SFA was successfully applied to the analysis of the SSRIs in their pharmaceutical dosage forms. The statistical analysis for the comparison between the MW-SFA assay results and those of pharmacopeial assays showed no significant differences between the assays in terms of their accuracy and precision. The application of the proposed MW-SFA was extended to successfully analyze SSRIs in plasma samples. The greenness of the assay was confirmed using three different metric tools. The assay was characterized with high throughput properties, enabling the sensitive simultaneous analysis of many samples in a short time. This assay is valuable for rapid routine applications in pharmaceutical quality control units and clinical laboratories for the determination of SSRIs.


Cultural and Linguistic Diversity in Recent Verbal Behavior Research on Individuals with Disabilities: a Review and Implications for Research and Practice.
The number of individuals from various culture and language backgrounds who are receiving behavior-analytic services is growing. Therefore, a behavioral understanding of the role of cultural and linguistic diversity (CLD) in language acquisition may be warranted. We searched recent editions of The Analysis of Verbal Behavior and the Journal of Applied Behavior Analysis to determine the degree to which researchers report the CLD of individuals with disabilities who participate in verbal behavior research. Our results indicate that researchers in these journals rarely report the culture and language background of their participants. Given these results, we provide a conceptual analysis and describe implications for research and clinical practice. A further understanding of the role of CLD may aid in the development of better behavioral interventions and culturally sensitive treatments. Finally, research that explores the role of CLD in language acquisition may add to the generality of behavior-analytic research and practice.


Is Major Depression Linked to Alcohol-Impaired Driving?
Alcohol-impaired driving causes a substantial proportion of motor vehicle accidents. Depression is a prevalent psychiatric disorder among drinker-drivers. Few previous studies have investigated the relationship between major depression and alcohol-impaired driving. We investigated whether depression has a positive relationship with the probability of alcohol-impaired driving after controlling for the co-occurrence of binge drinking and alcohol dependence. Our data consisted of drinkers aged 21-64 years from two waves of the National Epidemiologic Survey of Alcohol and Related Conditions. Cross-sectional analysis investigated whether depression is an independent risk factor for drinking-driving. Longitudinal analysis distinguished the relationship of depression onset, continuance, and recovery with changes in drinking-driving behaviors between the waves. These dual approaches allowed comparisons with previous studies. Major depression was a small but statistically significant predictor of changes in alcohol-impaired driving behaviors among males but not females. Binge drinking and alcohol dependence were comparatively stronger predictors. Conclusions/Importance: There is limited empirical support that treating depression reduces drinking and driving in males who do not exhibit symptoms of alcohol use disorders. For persons with co-occurring depression and alcohol use disorders, depression treatment should be part of a strategy for treating alcohol use disorders which are highly related to drinking and driving.


Fluid-Solid Reaction in Porous Media as a Chaotic Restart Process.
Chemical and biological reactions at fluid-solid interfaces are central to a broad range of porous material applications and research. Pore-scale solute transport limitations can reduce reaction rates, with marked consequences for a wide spectrum of natural and engineered processes. Recent advances show that chaotic mixing occurs spontaneously in porous media, but its impact on surface reactions is unknown. We show that pore-scale chaotic mixing significantly increases reaction efficiency compared to nonchaotic flows. We find that reaction rates are well described in terms of diffusive first-passage times of reactants to the solid interface subjected to a stochastic restart process resulting from Lagrangian chaos. Under chaotic mixing, the shear layer at no-slip interfaces sets the restart rate and leads to a characteristic scaling of reaction efficiency with Péclet number, in excellent agreement with numerical simulations. Reaction rates are insensitive to the flow topology as long as flow is chaotic, suggesting the relevance of this process to a broad range of porous materials.


Synthesis of h-AIN nanowires via carbothermal reduction and nitridation method using acetylene black.
Using acetylene black as an assistant reagent in the ammonia atmosphere, one dimensional (1D) hexagonal single crystalline aluminum nitride (AIN) nanowires were successfully synthesized via carbothermal reduction and nitridation method. With smooth surface and uniform diameter, the wool-like product of AIN nanowires grow along [001] direction and are 80-120 nm in diameter and several tens micrometers in length. According to thermodynamic and kinetic analysis, AI2O3 initially was reduced to a volatile suboxide gas Al2O at 1800 degrees C. Then gaseous Al2O was transported by N2/NH3 mixtures to about 1200 degrees C, where 1D AIN nanowires formed by the reaction of Al2O gas, graphite and NH3. Due to high surface area, small particle size and amorphous structure, acetylene black maybe possess more active sites and more effective contact area, which benefits the first step reaction. The electrostatic polar charge model and crystallographic characteristics are employed to explain the growth mechanism of AIN nanowires. To our knowledge, acetylene black is the first time to be used for synthesizing 1D AIN nanostructures via carbothermal reduction and nitridation method, which would be an efficient, economical assistant reagent for fabricating nitride nanostructures.


Current role of perampanel in pediatric epilepsy.
Perampanel is among the latest AEDs approved, indicated for the treatment of partial-onset seizures with or without secondary generalization, and for primary generalized tonic-clonic seizures, in patients aged 12 years and older. This paper summarizes the clinical recommendations on the current role of perampanel in the treatment of pediatric epilepsies and future directions for research. The optimal dosage should be comprised between 4 and 12 mg/day, with 8 mg/day being the most common dosage used. The rate and severity of adverse events, including psychiatric symptoms, can be decreased by starting at low doses, and titrating slowly. Overall, perampanel presents an acceptable risk/benefit ratio, but special caution should be made to the risk of seizure aggravation and behavioral problems. The favorable cognitive profile, the ease of use of the titration scheme and the once-daily formulation offer advantage over other AEDs and make this drug particularly suitable for adolescent population. Perampanel is a welcome addition to the armamentarium of the existing AEDs, as it represents a new approach in the management of epilepsy, with a novel mechanism of action and a potential to have a considerable impact on the treatment of adolescents with epilepsy.


[Internal medicine in Italy and Europe: current realities and prospects].
The crisis of internal medicine may be viewed as a crisis of the image of the internist himself. If, however, we look to the future, this image has the potential to be viewed in a significantly improved light, provided the internist modifies his role and position within the health service structure and maintains his characteristic broad-minded approach to medical problems. He may play his essential role in patient management by utilizing his capacity to "fit together" diagnostic options, advice from specialists, and therapeutic choices--in short by acting as "case manager" and offering expert support to both individual patients and to the overall organizational setup of the clinical structure. Another important task of the internist is to train students and oversee continuing education of the medical community. The position of clinical and patient manager is particularly relevant to future health care scenarios that will be characterized by economic constraints, the need for new organizational models, populations on the move, and the necessity to involve patients directly in health-related decision making and to respect their opinions. To meet this challenge, the future internist must enhance his global approach to medical problems with specific training in management in order to offer multi-sector expert support to the health care structure.


Feasibility and Acceptability of e-Screening and Brief Intervention and Tailored Text Messaging for Marijuana Use in Pregnancy.
Background: There are at present no evidence-based interventions for marijuana use during pregnancy, despite it being by far the most commonly used illicit drug during pregnancy. Lack of treatment-seeking, combined with implementation challenges, has limited the extent to which at-risk women receive interventions of any kind. This study sought to evaluate the feasibility and acceptability of two high-reach technology-based interventions: electronic screening and brief intervention (e-SBI) and tailored text messaging, delivered either alone or in combination. Materials and Methods: In this exploratory feasibility trial, pregnant women seeking prenatal care services and scoring positive for marijuana use risk (n = 45) were randomly assigned to e-SBI, text messaging, or e-SBI plus text messaging. We examined completion rates and acceptability ratings as a function of intervention condition and participant characteristics. Results: All participants assigned to receive the e-SBI (n = 30) were able to complete it during the in-clinic baseline session. Participants assigned to text messaging (n = 30) received a median of 24 text messages before giving birth; 6 of 30 (20%) chose to end text messages before giving birth. Acceptability ratings for the e-SBI were high, with most being above 4.4 on a 5-point scale (e.g., for ease of use, respectfulness, and helpfulness). Acceptability ratings for some aspects of the texting intervention were also high (e.g., for ease of understanding and respectfulness). Participants in the combined e-SBI plus texting condition chose to stop messages at a rate of 13.3% (2 of 15), versus 26.7% (4 of 15) in the texting-only condition (p = 0.37). Conclusions: These two high-reach intervention elements showed strong feasibility and modest to high acceptability. Future efforts evaluating efficacy are warranted, and should specifically examine the possibility that combining text messaging with a brief intervention may promote retention.


Multiple endocrine neoplasia syndrome type IIb: a case report.
Multiple endocrine neoplasia type IIb (MEN IIb) is a syndrome, part of which can involve neoplastic change in the thyroid and adrenal glands. It has unusual oro-facial manifestations including mucosal neuromata on the lips, cheeks and tongue. A child aged 3 years and 10 months presented with mucosal tags at the corners of the mouth, early eruption of permanent teeth, malocclusion and facial asymmetry. Biopsy of the excess mucosal tissue suggested a diagnosis of either MEN type IIb or neurofibromatosis. Genetic testing eventually confirmed MEN type IIb. The patient has been followed up regularly for 9 years. He has developed modular lesions on his tongue and irregular enlargement of his lower lip, but to date there have been no signs of tumour development. This report emphasizes the importance of thorough examination of the oral mucosa and follow-up of any abnormalities.


Phencyclidine Intoxication Case Series Study.
Phencyclidine (PCP) is a synthetic compound derived from piperidine and used as an anesthetic and hallucinogenic. Little has been recently published regarding the clinical presentation of PCP intoxication. PCP use as a recreational drug is resurging. Our objective was to describe clinical findings in patients presenting to the emergency department (ED) under the influence of PCP. This was a case series study conducted at a tertiary care center with an annual census of 100,000 patients/year. Emergency physicians, residents, physician assistants, and research assistants identified patients with possible PCP intoxication. Self-reported PCP use, report by bystanders or Emergency Medical Services (EMS) staff, was used in this process. A structured data collection form was completed, documenting both clinical and behavioral events observed by the treating team during the ED visit. We collected data on 219 patients; 184 were analyzed; two patients were excluded secondary to incomplete data. The mean age of patients was 32.5 years (±7 years) with 65.2 % being males. PCP use was self-reported by 60.3 % of patients. Of the 184 patients, 153 (83.1 %) received a urine drug screen (UDS); 152 (98.7 %) were positive for PCP. On arrival, 78.3 % of patients were awake and alert, and 51.6 % were oriented to self, time/date, and place. Mean physiological parameters were the following: heart rate 101.1 bpm (±24.3), RR 18.9 bpm (±3.4), BP 146.3 (±19.4)/86.3 (±14.0) mmHg, 36.9° C (±0.5), and pulse oximetry 98.2 % (±1.9). Clinical findings were the following: retrograde amnesia in 46 (25 %), horizontal nystagmus in 118 (64.1 %), vertical nystagmus in 90 (48.9 %), hypertension in 87 (47.3 %), and agitation in 71 (38.6 %). Concomitant use of at least one other substance was reported by 99 (53.8 %) patients. The mean length of stay in the ED for all subjects was 261.1 (±172.8) minutes. Final disposition for 152 (82.6 %) patients was to home. Of the 184 patients, 14 (7.6 %) required admission; 12 were referred to Crisis Response Center. Patients with PCP intoxication tended to be young males. The prevalent clinical signs and symptoms were the following: retrograde amnesia, nystagmus, hypertension, and psychomotor agitation. Co-use of other substances was the norm. Most patients presenting to the ED with PCP intoxication do well and can be discharged home after a period of observation.


99MTc-diphosphonate bone imaging and uptake in healing rat extraction sockets.
Clinically positive bone scans of the jaws may result from a variety of benign dental conditions. An experimental system for studying radionuclide imaging and uptake in the jaws of rats was developed. Sequential 99mTc-diphosphonate bone scans and radionuclide uptake determinations were performed on rats after standardized extractions of their mandibular left first molars. Positive bone scans were seen 4-16 days after molar extraction, and increased radionuclide uptake was found in the healing extraction wounds 4-42 days after the extraction. Conventional radiography and histology fail to show unusual bony architecture in extraction sockets at such times. These results correlate with clinical findings in patients and suggest that human beings may have positive bone scans for several months after dental extraction.


The biological pump in the Costa Rica Dome: an open-ocean upwelling system with high new production and low export.
The Costa Rica Dome is a picophytoplankton-dominated, open-ocean upwelling system in the Eastern Tropical Pacific that overlies the ocean's largest oxygen minimum zone. To investigate the efficiency of the biological pump in this unique area, we used shallow (90-150 m) drifting sediment traps and 234Th:238U deficiency measurements to determine export fluxes of carbon, nitrogen and phosphorus in sinking particles. Simultaneous measurements of nitrate uptake and shallow water nitrification allowed us to assess the equilibrium balance of new and export production over a monthly timescale. While f-ratios (new:total production) were reasonably high (0.36 ± 0.12, mean ± standard deviation), export efficiencies were considerably lower. Sediment traps suggested e-ratios (export/14C-primary production) at 90-100 m ranging from 0.053 to 0.067. ThE-ratios (234Th disequilibrium-derived export) ranged from 0.038 to 0.088. C:N and N:P stoichiometries of sinking material were both greater than canonical (Redfield) ratios or measured C:N of suspended particulates, and they increased with depth, suggesting that both nitrogen and phosphorus were preferentially remineralized from sinking particles. Our results are consistent with an ecosystem in which mesozooplankton play a major role in energy transfer to higher trophic levels but are relatively inefficient in mediating vertical carbon flux to depth, leading to an imbalance between new production and sinking flux.


A critical role for ecdysone response genes in regulating egg production in adult female Rhodnius prolixus.
Ecdysteroids control ovary growth and egg production through a complex gene hierarchy. In the female Rhodnius prolixus, a blood-gorging triatomine and the vector of Chagas disease, we have identified the ecdysone response genes in the ovary using transcriptomic data. We then quantified the expression of the ecdysone response gene transcripts (E75, E74, BR-C, HR3, HR4, and FTZ-F1) in several tissues, including the ovary, following a blood meal. These results confirm the presence of these transcripts in several tissues in R. prolixus and show that the ecdysone response genes in the ovary are mostly upregulated during the first three days post blood meal (PBM). Knockdown of E75, E74, or FTZ-F1 transcripts using RNA interference (RNAi) was used to understand the role of the ecdysone response genes in vitellogenesis and egg production. Knockdown significantly decreases the expression of the transcripts for the ecdysone receptor and Halloween genes in the fat body and the ovaries and reduces the titer of ecdysteroid in the hemolymph. Knockdown of each of these transcription factors typically alters the expression of the other transcription factors. Knockdown also significantly decreases the expression of vitellogenin transcripts, Vg1 and Vg2, in the fat body and ovaries and reduces the number of eggs produced and laid. Some of the laid eggs have an irregular shape and smaller volume, and their hatching rate is decreased. Knockdown also influences the expression of the chorion gene transcripts Rp30 and Rp45. The overall effect of knockdown is a decrease in number of eggs produced and a severe reduction in number of eggs laid and their hatching rate. Clearly, ecdysteroids and ecdysone response genes play a significant role in reproduction in R. prolixus.


Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity.
In mammalian systems RNA can move between cells via vesicles. Here we demonstrate that the gastrointestinal nematode Heligmosomoides polygyrus, which infects mice, secretes vesicles containing microRNAs (miRNAs) and Y RNAs as well as a nematode Argonaute protein. These vesicles are of intestinal origin and are enriched for homologues of mammalian exosome proteins. Administration of the nematode exosomes to mice suppresses Type 2 innate responses and eosinophilia induced by the allergen Alternaria. Microarray analysis of mouse cells incubated with nematode exosomes in vitro identifies Il33r and Dusp1 as suppressed genes, and Dusp1 can be repressed by nematode miRNAs based on a reporter assay. We further identify miRNAs from the filarial nematode Litomosoides sigmodontis in the serum of infected mice, suggesting that miRNA secretion into host tissues is conserved among parasitic nematodes. These results reveal exosomes as another mechanism by which helminths manipulate their hosts and provide a mechanistic framework for RNA transfer between animal species.


Factors governing the quality of aqueous CdTe nanocrystals: calculations and experiment.
The aqueous synthesis of thiol-stabilized semiconductor CdTe colloidal nanocrystals has been revisited. We found optimal conditions for the synthesis of high-quality CdTe NCs through a study of the influence of the initial conditions (structure and concentration of Cd-thiol complexes) on the quality of the CdTe nanocrystals. A numerical calculation shows a clear correlation between the concentration of CdL (where L is (SCH(2)COO)(2-)) in the initial solution and the photoluminescence quantum efficiency of the CdTe nanocrystals.


Molecular diagnosis of viral hepatitis.
Molecular biology-based assays are invaluable tools for the management of chronic viral hepatitis. They can be used to test blood donations, diagnose active infection, help to establish the prognosis, guide treatment decisions, and assess the virological response to therapy. This article reviews current molecular biology-based techniques and assays, and their practical use in the management of hepatitis B and C virus infection.


Resin composites in dentistry: the monomer systems.
The present review outlines the history of monomers used in resin composites, motivates further development, and highlights recent and ongoing research reported in the field of dental monomer systems. The monomer systems of most present-day resin composites are based on BisGMA, developed some 40 years ago, or derivatives of BisGMA. In the remaining resin composites, urethane monomers or oligomers are used as the basis of the monomer system. The main deficiencies of current resin composites are polymerization shrinkage and insufficient wear resistance under high masticatory forces. Both factors are highly influenced by the monomer system, and considerable efforts are being made around the world to reduce or eliminate these undesirable properties. The use of fluoride-releasing monomer systems, some of which are under investigation, has been suggested to mitigate the negative effects of marginal gaps formed in consequence of polymerization shrinkage. The very crux of the problem has also been approached with the synthesis of potentially low-shrinking/non-shrinking resin composites involving ring opening or cyclopolymerizable monomers. By the use of additives with a supposed chain transfer agent function, monomer systems have been formulated that improve the degree of conversion of methacrylate double bonds and mechanical properties. Many promising monomer systems have been devised, the implementation of which may be expected to improve the longevity of resin composite fillings and expand the indications for resin composites.