Food intake does not differ between obese women who are metabolically healthy or abnormal.
Metabolically healthy obesity may confer lower risk of adverse health outcomes compared with abnormal obesity. Diet and race are postulated to influence the phenotype, but their roles and their interrelations on healthy obesity are unclear. We evaluated food intakes of metabolically healthy obese women in comparison to intakes of their metabolically healthy normal-weight and metabolically abnormal obese counterparts. This was a cross-sectional study in 6964 women of the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Participants were aged 45-98 y with a body mass index (BMI; kg/m(2)) ≥18.5 and free of cardiovascular diseases, diabetes, and cancer. Food intake was collected by using a food-frequency questionnaire. BMI phenotypes were defined by using metabolic syndrome (MetS) and homeostasis model assessment of insulin resistance (HOMA-IR) criteria. Mean differences in food intakes among BMI phenotypes were compared by using ANCOVA. Approximately one-half of obese women (white: 45%; black: 55%) as defined by MetS criteria and approximately one-quarter of obese women (white: 28%; black: 24%) defined on the basis of HOMA-IR values were metabolically healthy. In age-adjusted analyses, healthy obesity and normal weight as defined by both criteria were associated with lower intakes of sugar-sweetened beverages compared with abnormal obesity among both white and black women (P < 0.05). HOMA-IR-defined healthy obesity and normal weight were also associated with higher fruit and low-fat dairy intakes compared with abnormal obesity in white women (P < 0.05). Results were attenuated and became nonsignificant in multivariable-adjusted models that additionally adjusted for BMI, marital status, residential region, education, annual income, alcohol intake, multivitamin use, cigarette smoking status, physical activity, television viewing, high-sensitivity C-reactive protein, menopausal status, hormone therapy, and food intakes. Healthy obesity was not associated with a healthier diet. Prospective studies on relations of dietary patterns, which may be a better indicator of usual diet, with the phenotype would be beneficial.


Synthesis of a Sm3+-doped YGa1.5Al1.5(BO3)4 phosphor via a mechanical activation-assisted solid-state reaction.
A Sm3+-doped YGa1.5Al1.5(BO3)4 (abbreviated as YGAB) phosphor was synthesized via a solid-state reaction with mechanical activation assistance in a high-energy density stirred bead mill. The samples were characterized by laser particle size analysis, specific surface area analysis, powder X-ray diffraction (XRD), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and fluorescence spectroscopy. In addition, the photoluminescence characteristics, luminescence decay, thermal stability, and LED application of the phosphors were also investigated. The results show that the mechanical activation of mixed raw materials before calcination can reduce the particle size and the activation energy of crystallization, resulting in the formation of the YGAB crystal phase at a lower calcination temperature. The mechanical activation in grinding can accelerate the subsequent solid-phase reaction, make Sm3+ ions more easily diffuse into the YGAB lattice, and improve the crystal structure of the synthesized phosphor, thus enhancing the optical properties of the phosphor. According to the photoluminescence emission (PL) and excitation (PLE) spectra, Sm3+ doped in the YGAB lattice can provide an efficient emission under 405 nm excitation. The optimum doping concentration of Sm3+ ions is 0.03 mol%. The optimum photoluminescence intensity, quantum yield, and fluorescence lifetime of the phosphor synthesized from mixed raw materials ground for 45 min can be obtained. The temperature-dependent PL spectra show that the emission intensity of the YGAB:0.03Sm3+ phosphor at 425 K is 84.7% of its initial intensity at room temperature. It is indicated that the YGAB:0.03Sm3+ phosphor synthesized could be used as one of the promising LED lighting materials.


Nutrient Starvation Sensitizes Human Ovarian Cancer SKOV3 Cells to BH3 Mimetic via Modulation of Mitochondrial Dynamics.
The aberrant proliferation of tumor cells necessitates compensatory changes in tumor metabolic processes. Previous studies on tumor growth and metabolism have established a relationship between nutrient stress and Bcl-2 anti-apoptotic proteins, although the mechanisms connecting these processes remain unclear. We induced nutrient deprivation in human ovarian cancer SKOV3 cells by culturing cells in Earle's balanced salt solution (EBSS) as a starvation model. We used EBSS treatment with the BH3 domain of Bcl-2 family proteins (BH3) mimetic ABT737, which targets Bcl-2/Bcl-xL, to examine mitochondrial dynamics and the interactive regulatory mechanisms between nutrition and Bcl-2 proteins. We found that EBSS combined with ABT737 can promote SKOV3 cells to undergo apoptosis and convert tubular mitochondria into small, fragmented morphologies. Bcl-2 family proteins participated in the regulation of mitochondrial fusion and fission through apoptosis, and the decrease of Mcl-1 expression was the key to ABT737 sensitization. Our findings showed that nutrient stress could sensitize SKOV3 cells to ABT737 via regulation of the mitochondrial dynamic balance and interaction of Bcl-2 family proteins. Our data suggest that nutrient starvation combined with the BH3 mimetic ABT737 could reduce the required effective dose of ABT737, and that inhibition of Bcl-2 and Mcl-1 together with nutrient starvation could serve as an effective strategy for the treatment of human ovarian cancer. Anat Rec, 300:326-339, 2017. © 2016 Wiley Periodicals, Inc.


[Urinary incontinence in women--diagnostic and therapeutic guidelines].
The pathophysiology and the most common clinical features of female urinary incontinence were presented. The practical diagnostic and therapeutic approach to urinary incontinence in patients was discussed. New surgical techniques including endoscopy and modified sling operation (TVT) were analysed in terms of clinical efficacy. The pivotal role of educational programme aimed at rational treatment of female urinary incontinence, including both physicians and patients, was emphasized.


On the position of Archigetes and its bearing on the early evolution of the tapeworms.
The tapeworm Archigetes sieboldi Leuckart, 1878 (Platyhelminthes: Cestoda: Caryophyllidea) has been cited as a likely representative of the "protocestode" condition, owing to its lack of segmentation and ability to attain sexual maturity in the invertebrate host (aquatic oligochaetes). The idea has been variously amplified or rejected in the literature, although the actual phylogenetic position of the species has not been investigated until now. New collections of Archigetes sp. from both its vertebrate and invertebrate hosts provided the opportunity to estimate its phylogenetic position with the use of molecular systematics, while prompting new analyses aimed at assessing the early diversification of the Cestoda. Additional collections representing the Amphilinidea, Caryophyllidea, and Gyrocotylidea were combined with published gene sequences to construct data sets of complete 18S (110 taxa) and partial (D1-D3) 28S (107 taxa) rDNA sequences, including 8 neodermatan outgroup taxa. Estimates resulting from Bayesian inference, maximum likelihood, and maximum parsimony analyses of the separate and combined data sets supported a derived position of the genus within the Caryophyllidea, and thus reject the idea that Archigetes sp. may exemplify a "primitive" condition. Topological constraint analyses rejected the hypothesis that Archigetes represents the most basal lineage of the Eucestoda, but did not rule out that it could represent the earliest branching taxon of the Caryophyllidea. In all analyses, the Eucestoda were monophyletic and supported basal positions of the nonsegmented Caryophyllidea and Spathebothriidea relative to other major lineages of the Eucestoda, implying that segmentation is a derived feature of the common ancestor of the di- and tetrafossate eucestodes. However, constraint analyses could not provide unequivocal evidence as to the precise branching patterns of the cestodarian, spathebothriidean, and caryophyllidean lineages. Phylogenetic analyses favor the interpretation that sexual maturity of Archigetes sp. in the invertebrate host, and similar examples in members of the Spathebothriidea, are the result of progenesis and have little if any bearing on understanding the protocestode condition.


Diagnostic accuracy of diffusion weighted MRI in differentiating benign and malignant meningiomas.
To determine the diagnostic accuracy of DWI in differentiating benign and malignant meningiomas keeping histopathology as gold standard. This was a descriptive analytical study conducted at Radiology Department, DUHS/Dr. Ruth K. M. Pfau Civil Hospital Karachi, from August 2016 to March 2018.It included152 patients clinically suspected of meningioma on conventional neuroimaging. Imaging features of DWI were compared with histopathology findings. The diagnostic accuracy of DWI was calculated in terms of sensitivity, specificity, accuracy, PPV and NPV using histopathology as gold standard. There were 59 male and 93 female patients with mean age of 55.38±9.8 years. Mean duration of sign and symptoms was 5.67±2.57 months. Out of 152 patients, 117(77%) and 35(23%) were differentiated into benign and malignant meningiomas respectively by DWI while 135(88.82%) and17(11.18%) patients were diagnosed respectively on histopathology. The sensitivity, specificity, PPV, NPV and accuracy of DWI of 84.4%, 82.3%, 97.4%, 40%, and 84.2% respectively keeping histopathology as gold standard. DWI features along with calculation of ADC values is a reliable non-invasive technique for differentiating benign and malignant meningiomas. However the low negative predictive value necessitates the use of histopathology.


Stem cell-based treatments against stroke: observations from human proof-of-concept studies and considerations regarding clinical applicability.
Ischemic stroke remains a heavy burden for industrialized countries. The only causal therapy is the recanalization of occluded vessels via thrombolysis, which due to a narrow time window still can be offered only to a minority of patients. Since the majority of patients continues to exhibit neurological deficits even following successful thrombolysis, restorative therapies are urgently needed that promote brain remodeling and repair once stroke injury has occurred. Due to their unique properties of action, stem cell-based strategies gained increasing interest during recent years. Using various stroke models in both rodents and primates, the transplantation of stem cells, namely of bone marrow derived mesenchymal stem cells (MSCs) or neural progenitor cells (NPCs), has been shown to promote neurological recovery most likely via indirect bystander actions. In view of promising observations, clinical proof-of-concept studies are currently under way, in which effects of stem and precursor cells are evaluated in human stroke patients. In this review we summarize already published studies, which due to the broad experience in other medical contexts mostly employed bone marrow-derived MSCs by means of intravenous transplantation. With the overall number of clinical trials limited in number, only a fraction of these studies used non-treated control groups, and only single studies were adequately blinded. Despite these limitations, first promising results justify the need for more elaborate clinical trials in order to make stem cell transplantation a success for stroke treatment in the future.


A novel role for D-alanylation of lipoteichoic acid of enterococcus faecalis in urinary tract infection.
Enterococci are the third most common cause of healthcare-associated infections, which include urinary tract infections, bacteremia and endocarditis. Cell-surface structures such as lipoteichoic acid (LTA) have been poorly examined in E. faecalis, especially with respect to urinary tract infections (UTIs). The dlt operon is responsible for the D-alanylation of LTA and includes the gene dltA, which encodes the D-alanyl carrier protein ligase (Dcl). The involvement of LTA in UTI infection by E. faecalis has not been studied so far. Here, we examined the role of teichoic acid alanylation in the adhesion of enterococci to uroepithelial cells. In a mouse model of urinary tract infection, we showed that E. faecalis 12030ΔdltA mutant colonizes uroepithelial surfaces more efficiently than wild type bacteria. We also demonstrated that this mutant adhered four fold better to human bladder carcinoma cell line T24 compared to the wild type strain. Bacterial adherence could be significantly inhibited by purified lipoteichoic acid (LTA) and inhibition was specific. In contrast to bacteraemia model and adherence to colon surfaces, E. faecalis 12030ΔdltA mutant colonized uroepithelial surfaces more efficiently than wild-type bacteria. In the case of the uroepithelial surface the adherence to specific host cells could be prevented by purified LTA. Our results therefore suggest a novel function of alanylation of LTA in E. faecalis.


Do class 1 antiarrhythmic drugs impair myocardial contractility? The class 1A example of ajmaline (conductance catheter technique).
Antiarrhythmic drug effects may include cardiodepression. This risk is theoretically well recognized but clinically rather poorly defined. To evaluate the risks of ajmaline treatment, we monitored hemodynamic parameters and end-systolic pressure-volume relations (ES-PVR) to evaluate potential negative inotropic effects. Twelve patients (nonischemic CAD) underwent hemodynamic analysis with and without the influence of ajmaline, 1 mg/kg i.v., both (a) at rest (paced constant heart rate of 90 beats/min) and (b) during tachycardia of 160 beats/min. With ajmaline, LV pump function was found to have diminished moderately; ejection fraction by 23 and 10%, stroke volume by 10 and 0%, cardiac work by 5 and 16%, and dP/dtmax by 14 and 19%, respectively. While preload increased under the influence of ajmaline (LVEDP by 17 and 30%, respectively), the LV volumes increased (EDV by 18 and 12%, and ESV by 58 and 21%, respectively), and afterload remained unchanged. Ajmaline caused the loops of the ESPVR to move rightward and the slope k to decrease, thus indicating loss of inotropy under the influence of the antiarrhythmic agent. In essence, ajmaline's negative inotropic components were defined by the conductance technique, but they failed to induce clinically relevant cardiodepression in the above NYHA class II patients. This technique proved to be sensitive, useful, and safe in the assessment of inotropic effects by analyzing the ESPVR within the routine of the catheterization laboratory.


Heparin and LPS-induced COX-2 expression in airway cells: a link between its anti-inflammatory effects and GAG sulfation.
Previous studies have indicated that the sulfated polysaccharide heparin has anti-inflammatory effects. However, the mechanistic basis for these effects has not been fully elucidated. NCI-H292 (mucoepidermoid) and HBE-1 (normal) human bronchial epithelial cells were treated with LPS alone or in the presence of high-molecular-weight (HMW) fully sulfated heparin or desulfated HMW heparin. Cells were harvested to examine the phosphorylation levels of ERK1/2, p38, and NF-kB p65 and COX-2 protein expression by Western blot and gene expression of both COX-2 and CXCL-8 by TaqMan qRT-PCR. Heparin is known to exert an influence on receptor-mediated signaling through its ability to both potentiate and inhibit the receptor-ligand interaction, depending upon its concentration. In H292 cells, fully-sulfated HMW heparin significantly reduced LPS-induced gene expression of both COX-2 and CXCL-8 for up to 48 hours, while desulfated heparin had little to no significant suppressive effect on signaling or on COX-2 gene or protein expression. Desulfated heparin, initially ineffective at preventing LPS-induced CXCL8 up-regulation, reduced CXCL8 transcription at 24 hours. In contrast, in normal HBE-1 cells, fully sulfated heparin significantly suppressed only ERK signaling, COX-2 gene expression at 12 hours, and CXCL-8 gene expression at 6 and 12 hours, while desulfated heparin had no significant effects on LPS-stimulated signaling or on gene or protein expression. Sulfation determines heparin's influence and may reflect the moderating role of GAG sulfation in lung injury and health. Heparin's anti-inflammatory effects result from its nonspecific suppression of signaling and gene expression and are determined by its sulfation.


[Rheumatoid arthritis developing into systemic lupus erythematosus during long-term treatment with penicillamine and sulfasalazine].
A female patient with IgM RF seropositive rheumatoid arthritis according to criteria of the American Rheumatism Association was treated for 133 months with Penicillamine and for 17 months also with Sulfasalazine. Both types of treatment were discontinued because the patient developed symptoms meeting diagnostic criteria of systemic lupus erythematosus, as defined by the same society. Early recognition of this diagnosis was made possible by regular follow up of clinical and laboratory data (ANA, anti DNP, anti dsDNA, C3, C4 and others). Marked improvement, incl. improvement of the nephropathy, was recorded after pulsed treatment with methylprednisolone.


Multivariate model for predicting postoperative blood loss in children undergoing cardiac surgery: a preliminary study.
Postoperative bleeding and blood product transfusion increase morbidity, mortality, and costs after cardiac surgery. However, factors that could accurately predict bleeding have not been well studied in children undergoing cardiac surgery. This study aims at determining factors that could be used to predict postoperative bleeding in this paediatric population. We included 182 children undergoing congenital heart surgery. Significant bleeding was defined as a blood loss that exceeds 10% of total blood volume within the first 6 postoperative hours. Univariate and multivariate logistic regression analyses were performed to determine variables independently associated with bleeding. These variables were used to calculate a probability for each individual child to develop postoperative bleeding. According to the definition of bleeding, 44 patients were included into the 'bleeder' group and 138 into the 'non-bleeder' group. Factors independently associated with postoperative bleeding were preoperative body weight, the presence of a cyanotic disease, and the time required for wound closure. Based on these three parameters, we calculated the probability of bleeding and found a significant relationship with postoperative bleeding. Finally, a calculated probability of 0.59 can predict significant postoperative blood loss with a sensitivity of 84% and a specificity of 64%. This study shows that preoperative body weight, cyanotic disease, and wound closure duration are best predictors of bleeding in the paediatric population after cardiac surgery. The combination of these three factors could be used at the end of the surgery to estimate the probability of postoperative bleeding.


[Research advances in mathematical model of coniferous trees cold hardiness].
Plant cold hardiness has complicated attributes. This paper introduced the research advances in establishing the dynamic models of coniferous trees cold hardiness, with the advantages and disadvantages of the models presented and the further studies suggested. In the models established initially, temperature was concerned as the only environmental factor affecting the cold hardiness, and the concept of stationary level of cold hardiness was introduced. Due to the obvious prediction errors of these models, the stationary level of cold hardiness was modeled later by assuming the existence of an additive effect of temperature and photoperiod on the increase of cold hardiness. Furthermore, the responses of the annual development phases for cold hardiness to environment were considered. The model researchers have paid more attention to the additive effect models, and run some experiments to test the additivity principle. However, the research results on Scots pine (Pinus sylvestris) indicated that its organs did not support the presumption of an additive response of cold hardiness by temperature and photoperiod, and the interaction between environmental factors should be taken into account. The mathematical models of cold hardiness need to be developed and improved.


Iridoid glycosides from Saprosma ternatum.
Three new iridoid glycosides, epiasperuloside (1), epipaederosidic acid (2), and epipaederoside (3), together with 7 known compounds, were isolated from the 85% ethanol extract of the leaves of Saprosma ternatum Hook. f. Their structures were determined by application of spectroscopic (NMR, MS) and chemical methodologies. The antioxidant activity was evaluated for all isolates in terms of both DPPH and ABTS bioassays. Epiasperuloside (1) showed some antioxidant activity.


Cell replacement with stem cell-derived retinal ganglion cells from different protocols.
Glaucoma, characterized by a degenerative loss of retinal ganglion cells, is the second leading cause of blindness worldwide. There is currently no cure for vision loss in glaucoma because retinal ganglion cells do not regenerate and are not replaced after injury. Human stem cell-derived retinal ganglion cell transplant is a potential therapeutic strategy for retinal ganglion cell degenerative diseases. In this review, we first discuss a 2D protocol for retinal ganglion cell differentiation from human stem cell culture, including a rapid protocol that can generate retinal ganglion cells in less than two weeks and focus on their transplantation outcomes. Next, we discuss using 3D retinal organoids for retinal ganglion cell transplantation, comparing cell suspensions and clusters. This review provides insight into current knowledge on human stem cell-derived retinal ganglion cell differentiation and transplantation, with an impact on the field of regenerative medicine and especially retinal ganglion cell degenerative diseases such as glaucoma and other optic neuropathies.


Evaluation and Management of Convergence Insufficiency in Adults.
A search was performed of the literature published in peer-reviewed journals from disciplines related to eye care and rehabilitation between 2000 and 2022. The purpose was to discover new thinking on the topic of the evaluation and management of convergence insufficiency in adults. Ninety-one papers were reviewed and summarized. The etiology, identification, evaluation, and management of convergence insufficiency in this population, as reported in the literature, is presented in this paper. Many publications addressing rehabilitation after traumatic head injury addressed the management of convergence insufficiency. There was consensus in the importance of complete patient examination, to include a complete sensorimotor examination and careful refraction, prior to initiating any therapy. A chronic issue continues in the paucity of large, placebo-controlled studies to provide clear best practice for providers. Additionally, healthcare professionals from eye care and other professions are working with patients who have convergence insufficiency without significant interprofessional collaboration.


Retroviral integrase protein and intasome nucleoprotein complex structures.
Retroviral replication proceeds through the integration of a DNA copy of the viral RNA genome into the host cellular genome, a process that is mediated by the viral integrase (IN) protein. IN catalyzes two distinct chemical reactions: 3'-processing, whereby the viral DNA is recessed by a di- or trinucleotide at its 3'-ends, and strand transfer, in which the processed viral DNA ends are inserted into host chromosomal DNA. Although IN has been studied as a recombinant protein since the 1980s, detailed structural understanding of its catalytic functions awaited high resolution structures of functional IN-DNA complexes or intasomes, initially obtained in 2010 for the spumavirus prototype foamy virus (PFV). Since then, two additional retroviral intasome structures, from the α-retrovirus Rous sarcoma virus (RSV) and β-retrovirus mouse mammary tumor virus (MMTV), have emerged. Here, we briefly review the history of IN structural biology prior to the intasome era, and then compare the intasome structures of PFV, MMTV and RSV in detail. Whereas the PFV intasome is characterized by a tetrameric assembly of IN around the viral DNA ends, the newer structures harbor octameric IN assemblies. Although the higher order architectures of MMTV and RSV intasomes differ from that of the PFV intasome, they possess remarkably similar intasomal core structures. Thus, retroviral integration machineries have adapted evolutionarily to utilize disparate IN elements to construct convergent intasome core structures for catalytic function.


Single cell analysis reveals a biophysical aspect of collective cell-state transition in embryonic stem cell differentiation.
In the stem cell research field, the molecular regulatory network used to define cellular states has been extensively studied, however, the general driving force guiding the collective state dynamics remains to be identified from biophysical aspects. Here we monitored the time-development of the cell-state transition at the single-cell and colony levels, simultaneously, during the early differentiation process in mouse embryonic stem cells. Our quantitative analyses revealed that cellular heterogeneity was a result of spontaneous fluctuation of cellular state and cell-cell cooperativity. We considered that the cell state is like a ball fluctuating on a potential landscape, and found that the cooperativity affects the fluctuation. Importantly, the cooperativity temporarily decreased and increased in the intermediate state of cell differentiation, leading to cell-state transition in unison. This process can be explained using the mathematical equation of flashing-ratchet behaviour, which suggests that a general mechanism is driving the collective decision-making of stem cells.


Psychometric Assessments of Three Self-Report Autism Scales (AQ, RBQ-2A, and SQ) for General Adult Populations.
This study assesses the psychometric properties of three self-report measures of autistic-like tendencies in the general adult population: autistic spectrum quotient (AQ), adult repetitive behaviours questionnaire-2 (RBQ-2A), and systemizing quotient (SQ). Three rounds of development and testing using different U.S. and global samples led to three instruments that are psychometrically sound, parsimonious, and generalizable across populations. The resulting AQ-9, consisting of two factors: social communication and attention to detail, now mirrors the current dual diagnostic criteria in the DSM-5. The RBQ-2A-R has now been refined through CFA for the first time. The new SQ-7 scale also has updated content. All three refined scales demonstrate satisfactory psychometric validity and parsimony and now provide evidence of their appropriateness for empirical research.


Comorbidity between balance and anxiety disorders: verification in a normal population.
Comorbidity between balance and anxiety disorders has been documented in clinical psychiatric and neurological samples. The authors aimed to determine whether the comorbidity of balance and anxiety disorders has an analogous representation in the normal population. Participants were 20 undergraduate students ages 22-29 years. The authors assigned them to high or low trait anxiety groups and performed a balance task in 3 experimental stages: baseline, training, and test. The baseline and test stages consisted of 4 wobbly and 4 stable trials each. The authors measured state anxiety in the form of auditory startle responses (ASRs) during the stable trials. In the baseline stage, the ASR amplitudes were higher in the high trait anxiety participants. In the test stage, the low trait anxiety participants performed the balance task better than the high trait anxiety participants did. These data suggest that the clinical entity designated as a comorbidity of balance and anxiety disorders has an analogous representation in the normal population.


Achieving antihyperglycemic treatment goals with incretin-related therapies.
The management of type 2 diabetes mellitus (T2DM) remains challenging. Limitations associated with many current therapies include hypoglycemia and weight gain. An increased understanding of the pathophysiology of T2DM has led to the development of incretin-related antihyperglycemic therapies. These agents enhance insulin secretion and inhibit inappropriate glucagon secretion, both in a glucose-dependent manner. As a result, they can lower blood glucose levels with a low risk of hypoglycemia or weight gain. Incretin-based therapies, the dipeptidyl peptidase 4 inhibitors and the glucagonlike peptide-1 receptor agonists, are now integrated into T2DM treatment algorithms. Trial data and clinical experience have shown that these agents are efficacious and generally well tolerated.


Brief Submotor-Threshold Electrical Stimulation Applied Synchronously Over Wrist Flexor and Extensor Muscles does Not Suppress Essential Tremor, Independent of Stimulation Frequency.
Electrical stimulation of muscles below motoneuron threshold has shown potential as a low-cost and minimally invasive treatment for Essential Tremor (ET). Prior studies have stimulated wrist flexor and extensor muscles synchronously with diverging results, calling for further investigation. Also, prior studies have only used a narrow range of stimulation parameters, so stimulation parameters have not been optimized. Our purpose was to further investigate synchronous submotor stimulation and identify the effect of stimulation frequency on tremor suppression. We quantified the effect of brief, synchronous stimulation at 15 different frequencies from 10-150 Hz applied over wrist flexors and extensors on both tremor power and frequency in 20 ET patients. We compared tremor power and frequency from hand acceleration and sEMG between pre-, per-, and post-stimulation phases. Our stimulation paradigm did not result in significant tremor suppression or tremor frequency changes at any tested stimulation frequency, showing no significant interaction between phase and stimulation frequency for tremor power measured by either hand acceleration (p = 0.69) or sEMG (p = 0.07). Additionally, the effect of phase interacting with stimulation frequency on tremor frequency was statistically insignificant for acceleration (p = 0.64) and sEMG (p = 0.37). We conclude that brief synchronous submotor-threshold stimulation does not reduce tremor in ET patients, independent of stimulation frequency (from 10 to 150 Hz). Our results are consistent with the hypothesis that brief submotor-threshold stimulation suppresses tremor via reciprocal inhibition, which requires asynchronous stimulation. In contrast, it is hypothesized that synchronous stimulation might require longer stimulation durations to affect supraspinal tremor networks. We studied the effects of synchronous submotor electrical stimulation over wrist flexor and extensor muscles on Essential Tremor. Our results indicate that suppressing tremor with brief synchronous stimulation is ineffective. Based on recently hypothesized mechanisms of peripheral tremor suppression, we hypothesize that asynchronous stimulation or long-duration synchronous stimulation are more effective approaches to peripheral tremor suppression.


Interferon-gamma inhibits cell replication, but not pp60src activity of RSV-transformed fibroblasts.
The present study analyzes the effect of murine IFN-gamma on DNA synthesis, ornithine decarboxylase activity and phosphorylation of pp60src of Rouse sarcoma virus transformed cells. When natural or recombinant IFN-gamma was added to quiescent SR-BALB or L1210 cells, stimulated with fetal calf serum, only the highest IFN-gamma concentrations (2000 U/ml) inhibited DNA synthesis of both tumor lines. By contrast, lower IFN-concentrations (20-200 U/ml) inhibited the DNA synthesis of L1210 but not of SR-BALB tumor cells. A similar pattern of inhibition was observed when ornithine decarboxylase activity was analyzed. Finally, when the levels of phosphorylation in SR-BALB cells were analyzed after IFN-gamma treatment, no difference with untreated controls was observed, even at the highest concentrations. These results suggest that SR-BALB tumor cells are insensitive to IFN-gamma and that src oncogene activity is not affected at IFN-concentrations inhibiting cell growth.


Surface tension and the Mori-Tanaka theory of non-dilute soft composite solids.
Eshelby's theory is the foundation of composite mechanics, allowing calculation of the effective elastic moduli of composites from a knowledge of their microstructure. However, it ignores interfacial stress and only applies to very dilute composites-i.e. where any inclusions are widely spaced apart. Here, within the framework of the Mori-Tanaka multiphase approximation scheme, we extend Eshelby's theory to treat a composite with interfacial stress in the non-dilute limit. In particular, we calculate the elastic moduli of composites comprised of a compliant, elastic solid hosting a non-dilute distribution of identical liquid droplets. The composite stiffness depends strongly on the ratio of the droplet size, R, to an elastocapillary lengthscale, L. Interfacial tension substantially impacts the effective elastic moduli of the composite when [Formula: see text]. When R<3L/2 (R=3L/2) liquid inclusions stiffen (cloak the far-field signature of) the solid.


Hyperinsulinemia in rats with ventromedial hypothalamic lesions: role of hyperphagia.
The relation of hyperinsulinemia to hyperphagia was examined in rats with lesions of the ventromedial hypothalamus (VMH). Plasma insulin and glucose levels were assayed after a 4-hr fast and 17 min after the initiation of a meal (6 ml of sweetened milk in 7 min) in animals with sham lesions, VMH animals maintained at preoperative body weight by food restriction, and VMH animals fed ad lib. Both VMH groups displayed basal and postabsorptive hyperinsulinemia, compared with the sham-operated control group, but insulin levels were greatest under the ad lib feeding condition. It is suggested that VMH hyperinsulinemia is due both to a primary effect of the lesion and to hyperphagia and that marked obesity can result in the absence of basal hyperinsulinemia as a result of hyperphagia with consequent postabsorptive hyperinsulinemia.


International variations in surgical practice for spontaneous intracerebral hemorrhage.
Spontaneous intracerebral hemorrhage is a major cause of death and disability, yet there is no convincing evidence of the benefit of any medical treatment and the role of surgery remains controversial. The international randomized Surgical Trial in Intracerebral Hemorrhage (STICH) provided an opportunity to assess the role of surgery within the centers taking part. Screening logs were completed to record details of all patients assessed by the department, whether they were included in the trial, the reasons if they were not included, and whether they underwent surgery. Logs were returned by 42 centers and cover 704 months. They include details on 1578 patients with characteristics comparable to STICH inclusion criteria. Neurosurgeons were more likely to express clinical certainty about treatment for older patients, patients with a higher Glasgow Coma Score scale, and patients in whom the hematoma was located on the right or in the basal ganglia or thalamus. Patients for whom the neurosurgeon was certain about treatment were more likely to have the hematoma removed if they were younger (62 versus 68 years of age), had a lower Glasgow Coma Scale score (10 versus 13), and had a lobar hematoma (49% versus 40%). The operation rate varied between 74% in Lithuania and 2% in Hungary. The difference in operation rates could not be explained by differences in patient characteristics alone. This finding demonstrates the need for further evidence to ensure that treatment for intracerebral hemorrhage is not governed by local custom.


Biased mutagenesis in the N-terminal region by degenerate oligonucleotide gene shuffling enhances secretory expression of barley alpha-amylase 2 in yeast.
Recombinant barley alpha-amylase 1 (rAMY1) and 2 (rAMY2), despite 80% sequence identity, are produced in very different amounts of 1.1 and <0.05 mg/l, respectively, by Saccharomyces cerevisiae strain S150-2B. The low yield of AMY2 practically excludes mutational analysis of structure-function relationships and protein engineering. Since different secretion levels of AMY1/AMY2 chimeras were previously ascribed to the N-terminal sequence, AMY1 residues were combinatorially introduced at the 10 non-conserved positions in His14-Gln49 of AMY2 using degenerate oligonucleotide gene shuffling (DOGS) coupled with homologous recombination in S.cerevisiae strain INVSc1. Activity screening of a partial library of 843 clones selected six having a large halo size on starch plates. Three mutants, F21M/Q44H, A42P/A47S and A42P rAMY2, also gave higher activity than wild-type in liquid culture. Only A42P showed wild-type stability and enzymatic properties. The replacement is located to a beta-->alpha loop 2 that interacts with domain B (beta-->alpha loop 3) protruding from the catalytic (beta/alpha)(8)-barrel. Most remarkably Pichia pastoris strain GS115 secreted 60 mg/l A42P compared with 3 mg/l of wild-type rAMY2. The crystal structure of A42P rAMY2 was solved and found to differ marginally from the AMY2 structure, suggesting that the high A42P yield stems from stabilization of the mature and/or intermediate form owing to the introduced proline residue. Moreover, the G to C substitution for the A42P mutation might have a positive impact on protein translation.


Relationship between Pyruvate Kinase Activity and Cariogenic Biofilm Formation in Streptococcus mutans Biotypes in Caries Patients.
Streptococcus mutans (MS) and its biotype I are the strains most frequently found in dental plaque of young children. Our results indicate that in children pyruvate kinase (PK) activity increases significantly in dental plaque, and this corresponds with caries progression. The MS strains isolated in this study or their main glycolytic metabolism connected with PK enzymes might be useful risk factors for studying the pathogenesis and target points of novel therapies for dental caries. The relationship between PK activity, cariogenic biofilm formation and selected biotypes occurrence was studied. S. mutans dental plaque samples were collected from supragingival plaque of individual deciduous molars in 143 subjects. PK activity was measured at different time points during biofilm formation. Patients were divided into two groups: initial stage decay, and extensive decay. Non-parametric analysis of variance and analysis of covariance were used to determine the connections between S. mutans levels, PK activity and dental caries biotypes. A total of 143 strains were derived from subjects with caries. Biotyping data showed that 62, 23, 50, and 8 strains were classified as biotypes I, II, III, IV, respectively. PK activity in biotypes I, II, and IV was significantly higher in comparison to that in biotype III. The correlation between the level of S. mutans in dental plaque and PK activity was both statistically significant (p < 0.05) and positive. The greater the level of S. mutans in the biofilm (colony count and total biomass), the higher the PK activity; similarly, a low bacterial count correlated with low PK activity.


Prevention and management of antibiotic associated acute kidney injury in critically ill patients: new insights.
Drug associated kidney injury (D-AKI) occurs in 19-26% of hospitalized patients and ranks as the third to fifth leading cause of acute kidney injury (AKI) in the intensive care unit (ICU). Given the high use of antimicrobials in the ICU and the emergence of new resistant organisms, the implementation of preventive measures to reduce the incidence of D-AKI has become increasingly important. Artificial intelligence is showcasing its capabilities in early recognition of at-risk patients for acquiring AKI. Furthermore, novel synthetic medications and formulations have demonstrated reduced nephrotoxicity compared to their traditional counterparts in animal models and/or limited clinical evaluations, offering promise in the prevention of D-AKI. Nephroprotective antioxidant agents have had limited translation from animal studies to clinical practice. The control of modifiable risk factors remains pivotal in avoiding D-AKI. The use of both old and new antimicrobials is increasingly important in combating the rise of resistant organisms. Advances in technology, such as artificial intelligence, and alternative formulations of traditional antimicrobials offer promise in reducing the incidence of D-AKI, while antioxidant medications may aid in minimizing nephrotoxicity. However, maintaining haemodynamic stability using isotonic fluids, drug monitoring, and reducing nephrotoxic burden combined with vigilant antimicrobial stewardship remain the core preventive measures for mitigating D-AKI while optimizing effective antimicrobial therapy.


Women and men of mafia between traditional cultural contexts and new social roles.
The Italian mafia organizations represent a subculture with values, beliefs, and goals that are antithetical to and undermining of the predominant society. The conduct of individual members includes such extreme violence for material gain, it may at least superficially suggest a severe personality disorder. Since the first edition of the DSM and into the 21st century, various terms have been used, sometimes interchangeably, but over time inconsistently, to designate the mentality and practices of mafia members. Only recently has the psychology of mafia members become a focus of serious scientific study. For the first time, investigators for the present study applied instruments, including the PCL-R, to examine for character psychopathology and specifically degrees of psychopathy in male and female mafia members, 20 female and 21 male members. Results showed some gender difference with the women having a higher score on Factor 1, in contrast to men who showed a lower score. Psychopathy and personality disorder were not found to be associated with membership in the mafia for either gender. Some psychopathic traits and gender differences warrant further research. Meanwhile these findings are consistent with a mentality characterized by beliefs and practices determined by a deviant culture rather than psychopathology.


Effect of the rifamycin dimers on the activities of nucleic acid polymerases from various sources. Relation between lipophily and toxicity.
The chemical dimers of rifamycin SV resembled the corresponding monomeric analogs with respect to the inhibitory properties versus the nucleic acid polymerases. At low doses, such compounds blocked the initiation step of the DNA transcription catalyzed by the bacterial RNA polymerase, as observed for the parental antibiotic and its derivative rifampicin which are largely used in therapy. At concentrations one to two orders of magnitude higher, the chemically modified rifamycins inhibited also other nucleotidyltransferases. The widespread toxicity of the dimeric and monomeric semisynthetic rifamycins versus these enzymes was not causally related with an enhancement of their lipophily. The observed effects might be due to a loss of selectivity in the inhibition mechanism which was originally specific for the RNA polymerase from E. coli at the beginning of its catalysis. The rifamycin derivatives might then react with the catalytic portion of other nucleotidyltransferases interfering adversely with the enzyme activity in a number of ways and/or at different levels.


Cationic Defect Engineering for Controlling the Infrared Absorption of Hexagonal Cesium Tungsten Bronze Nanoparticles.
Cesium tungsten bronzes (Cs0.32WO3) have attracted much attention as a near-infrared absorbing material. We report the successful synthesis of highly crystalline and high purity Cs0.32WO3 nanoparticles through a spray pyrolysis route. Careful analyses disclosed the presence of cationic defects, that is, a tungsten deficiency and insufficient Cs doping in the Cs0.32WO3 nanoparticles. These cationic defects can be controlled by facile heat treatment in a mildly reducing atmosphere. In particular, we clarify that the tungsten deficiency is a key factor among the cationic defects to obtain high near-infrared absorption properties. Furthermore, this study clearly demonstrates the precise tunability of the optical properties by means of the lattice constants of the Cs0.32WO3 crystal. The realized range of lattice constants is significantly wider than those previously reported. These findings should contribute to the engineering of Cs0.32WO3 structure and properties.


[Maxillary and upper airway changes immediately after mini-screw assisted rapid maxillary expansion in class Ⅲ patients].
Objective: To assess maxillary sagittal and vertical as well as upper airway changes immediately after mini-screw assisted rapid maxillary expansion (MARME) in class Ⅲ patients. Method: A consecutive sample of 48 class Ⅲ patients with maxillary transverse deficiency who visited the Department of Orthodontics, School & Hospital of Stomatology, Wuhan University between January 2013 and March 2023 was retrospectively collected. The sample was comprised of 24 growing patients (cervical vertebra maturation, CVM 1-4) and 24 nongrowing patients (CVM 5-6). Cone-beam CT scans before (T0) and immediately after MARME (T1) were imported into Dolphin Imaging software, and then voxel-based superimposition was conducted on the basis of the anterior cranial base. Sagittal and vertical changes of the maxillary landmarks (A, ANS, PNS, UI and Spr), as well as upper airway changes after MARME were measured on multiplanar reconstruction views. Wilcoxon signed-rank test was employed to analyze the changes after MARME. Mann-Whitney U test was employed to compare the changes between growing and non-growing patients. Results: Some class Ⅲ patients exhibited significant maxillary sagittal and vertical changes immediately after MARME. The amount of changes in midpalatal suture was 4.03 (2.99, 4.87) mm in growing patients, significantly larger than that in non-growing patients [2.27 (1.49, 3.64) mm] (U=3.18, P=0.001). In growing class Ⅲ patients, the forward changes of A, ANS, PNS, UI and Spr were 0.35 (0.06, 0.80), 0.48 (0.11, 0.88), 0.48 (0.13, 0.99), 0.53 (-0.33, 1.04) and 0.40 (0.03, 0.69) mm, respectively. Vertically, the downward changes of A, ANS, PNS, UI and Spr were 1.45 (0.99, 2.13), 1.18 (0.61, 1.95), 1.30 (0.91, 1.96), 1.20 (0.71, 1.83) and 1.30 (0.81, 1.73) mm, respectively. All changes were significantly different from 0 after treatment (P<0.05). In nongrowing patients, PNS moved forward by 0.18 (-0.08, 0.39) mm while other sagittal changes were statistically insignificant (P>0.05); vertically, the downward changes of A, ANS, PNS, UI and Spr were 0.90 (0.51, 1.39), 0.73 (0.41, 1.21), 0.70 (0.55, 1.08), 0.60 (0.36, 1.19) and 0.70 (0.55, 1.23) mm, respectively. Significant immediate increase of the nasopharynx volume and nasal width was obtained in both groups (P<0.05), and the changes of oropharynx volume and minimum cross-sectional area (MCA) presented as statistically insignificant (P>0.05). Conclusions: For growing class Ⅲ patients, besides transverse expansion, significant forward and downward changes of maxilla were obtained immediately after MARME. For non-growing patients, significant downward changes were observed, while sagittal changes were negligible. The nasopharynx volume increased in both growing and nongrowing class Ⅲ patients immediately after MARME, whereas, the changes of oropharynx volume and MCA presented as statistically insignificant.


The effect of a paced auditory serial addition test (PASAT) intervention on the profile of volatile organic compounds in human breath: a pilot study.
This study sought to identify if detectable changes in human breath profiles may be observed following a psychological intervention designed to induce stress, a paced auditory serial addition test (PASAT). Breath samples were collected from 22 participants (10 male and 12 female) following a double cross-over randomized design with two experimental interventions. One intervention required participants to listen to classical music chosen to be neutral. The other intervention required participants to undertake a PASAT that induced cardiovascular responses consistent with acute stress. Both interventions also involved two sequences of cognitive function tests. Blood-pressure and heart-rate were recorded throughout each intervention and distal breath samples were collected onto Tenax® TA/Carbograph 1 thermal desorption tubes, using an adaptive breath sampler. Samples were collected before and after the PASAT. Breath samples were analysed by thermal desorption gas chromatography-mass spectrometry. Data registration using retention indexing and peak deconvolution followed by partial least-squares discriminant analysis identified six stress sensitive compounds. A principal components analysis model based on these components generated a model that predicted post-PASAT versus post-neutral intervention samples with a sensitivity of 83.3% and a selectivity of 91.6% for females, compared to 100% sensitivity and 90% selectivity for males. Of the six compounds indole, 2-hydroxy-1-phenylethanone, benzaldehyde, and 2-ethylhexan-1-ol were identified on the basis of mass spectral, retention indexing and confirmation against pure standards. 2-methylpentadecane was tentatively identified from mass spectral and retention indexing, whilst one component has yet to be assigned, although the mass spectrum is indicative of a terpene. Indole and 2-methylpentadecane concentrations increased in response to the PASAT intervention, while the other compounds reduced in their abundance in human breath, possibly as a result of ventilation effects.


Administration of a Nutraceutical Mixture Composed by Aloe arborescens, Annona muricata, Morinda citrifolia, Beta rubra, Scutellaria baicalensis, and Vaccinium myrtillus Reduces Doxorubicin-Induced Side Effects.
The antibiotic doxorubicin is often used as an anti-neoplastic drug; however, many patients showed very unpleasant side-effects. Previous studies have demonstrated that dietary substances such as Aloe arborescens, Annona muricata, Morinda citrifolia, Beta rubra, Scutellaria baicalensis, and Vaccinium myrtillus may have anti-oxidant, anti-proliferative, and anti-inflammatory effects. The purpose of this study was to investigate the protective effects of a mixture of these components in an experimental model of doxorubicin toxicity. Rats (n = 30) received doxorubicin (5 mg/kg/day) for 4 weeks and were randomized to receive the dietary mixture 2 hours following the first doxorubicin injection and until the end of the experiment. Animals were killed following 4 weeks, and blood, liver, and heart were collected for further analysis. The dietary supplement improved the depressed body weight and food consumption induced by DOX. In addition, the nutraceutical mixture reduced oxidative stress, ameliorated the morphological score, and preserved liver and heart structure, demonstrating a protective effect. These data show for the first time that the mixture of Aloe arborescens, Annona muricata, Morinda citrifolia, Beta rubra, Scutellaria baicalensis, and Vaccinium myrtillus may be useful to reduce the side effects following treatment with doxorubicin, and might ameliorate the quality of life of patients following chemotherapy.


Enhanced fermentative performance under stresses of multiple lignocellulose-derived inhibitors by overexpression of a typical 2-Cys peroxiredoxin from Kluyveromyces marxianus.
Bioethanol from lignocellulosic materials is of great significance to the production of renewable fuels due to its wide sources. However, multiple inhibitors generated from pretreatments represent great challenges for its industrial-scale fermentation. Despite the complex toxicity mechanisms, lignocellulose-derived inhibitors have been reported to be related to the levels of intracellular reactive oxygen species (ROS), which makes oxidoreductase a potential target for the enhancement of the tolerance of yeasts to these inhibitors. A typical 2-Cys peroxiredoxin from Kluyveromyces marxianus Y179 (KmTPX1) was identified, and its overexpression was achieved in Saccharomyces cerevisiae 280. Strain TPX1 with overexpressed KmTPX1 gene showed an enhanced tolerance to oxidative stresses. Serial dilution assay indicated that KmTPX1 gene contributed to a better cellular growth behavior, when the cells were exposed to multiple lignocellulose-derived inhibitors, such as formic acid, acetic acid, furfural, ethanol, and salt. In particular, KmTPX1 expression also possessed enhanced tolerance to a mixture of formic acid, acetic acid, and furfural (FAF) with a shorter lag period. The maximum glucose consumption rate and ethanol generation rate in KmTPX1-expressing strain were significantly improved, compared with the control. The mechanism of improved tolerance to FAF depends on the lower level of intracellular ROS for cell survival under stress. A new functional gene KmTPX1 from K. marxianus is firstly associated with the enhanced tolerance to multiple lignocellulose-derived inhibitors in S. cerevisiae. We provided a possible detoxification mechanism of the KmTPX1 for further theoretical research; meanwhile, we provided a powerful potential for application of the KmTPX1 overexpressing strain in ethanol production from lignocellulosic materials.


[Avian pathogenic Escherichia coli (APEC)].
Infections with avian pathogenic Escherichia coli (APEC) cause colibacillosis, an acute and mostly systemic disease resulting in significant economic losses in poultry industry worldwide. Avian colibacillosis is a complex syndrome characterized by multiple organ lesions with airsacculitis and associated pericarditis, perihepatitis and peritonitis being most typical. Environmental factors as well as the constitution of poultry or initial viral infections influence the outcome of APEC-infections. However, several challenge experiments in chickens proofed the role of virulent APEC strains as the single aetiological agent. Currently serotypes O1:K1, O2:K1 and O78:K80 are recognized as the most prevalent, however the number of published serotypes is increasing. In addition, single APEC isolates vary profoundly in virulence, and knowledge about the molecular basis of this variability is still scarce. Known virulence factors of APEC are adhesins (F1- and P-fimbriae), iron acquisition systems (aerobactin and yersiniabactin), hemolysins (hemolysinE and temperaturesensitive hemagglutinin), resistance to the bactericidal effects of serum and phagocytosis (outer membrane protein, iss protein, lipopolysaccharide, K/1)-capsule and colilcin production) as well as toxins and cytotoxins (heat stable toxin, cyto-/verotoxin and flagella toxin). Esperimental studies have shown that the respiratory tract, principally the gas-exchange region of the lung and the interstitium of the air sacs are the most important sites of entry for avian pathogenic E. coli. APEC strains adhere to the epithelial cells of air sacs presumably through F1-fimbriae. After colonization and multiplication the bacteria enter the bloodstream, and the temperature-sensitive hemagglutinin (tsh) seems to be important int his step. After invading the bloodstream APEC cause a septicemia resulting in massive lesins in multiple internal organs and in sudden death of the birds. The ability of the bacteria to acquire iron and the resistance to the bactericidal effects of serum, predominantly conferred by the increased serum survival (iss)--protein, enables APEC to multiply quickly in their hosts. Iss is regarded a specific genetic marker for avian pathogenic E. colistrains. A critical review of the literature published so far on APEC reveals, that these pathotypes are not defined appropriately. This findings urge investigations on the population structure of APEC, enabling the establishment of appropriate diagnostic tools and avoiding the obsolete use of serotyping for APEC diagnosis. So far more than 20 APEC strains have been investigated in animal experiments, explaining contrary published results. Thus, the lack of knowledge in pathogenicity and in immunity of APEC infections urges further experimental studies. As APEC share not only identical serotypes with human pathogens but also specific virulence factors, their zoonotic potential is under consideration.


Arboviral survey of mosquitoes in two northern Italian regions in 2007 and 2008.
Recently, Italy-particularly the Emilia-Romagna region-was the location of consecutive outbreaks of human diseases caused by the arboviruses chikungunya virus and West Nile virus. The two outbreaks, spread by different species of mosquitoes, were not related, but pointed out the lack of an arboviral surveillance program in this region. Beginning in 2007 entomological surveillance was initiated in the Emilia-Romagna region, and in 2008 the program was improved and extended at Lombardia region. Using CO(2)-baited traps, 65,292 mosquitoes were collected; pooled by date of collection, location, and species; macerated manually; and tested by reverse transcription (RT)-polymerase chain reaction for the presence of alphaviruses, orthobunyaviruses, and flaviviruses. Amplicons were sequenced and employed for identification of viral RNA by basic local alignment search tool search in GenBank. Results of these assays showed (1) the presence of West Nile virus in two pools of Culex pipiens mosquitoes, (2) the presence of RNA of two orthobunyaviruses, Tahyna virus in a pool of Ochlerotatus caspius mosquitoes and Batai virus in a pool of Anopheles maculipennis mosquitoes, and (3) the presence of flavivirus RNAs in pools of Oc. caspius, Aedes albopictus, and Aedes vexans mosquitoes; the sequences of these amplicons were most closely related to flaviviruses that have been detected only in mosquitoes and had no recognized vertebrate host (Aedes flavivirus, Culex flavivirus, and Kamiti River virus).


Thioredoxin-1, chemokine (C-X-C motif) ligand-9 and interferon-γ expression in the neoplastic cells and macrophages of Hodgkin lymphoma: clinicopathologic correlations and potential prognostic implications.
Expression of thioredoxin-1 (TXN) and CXCL9 is not restricted to THRLBCL macrophages, but may be observed in histiocytes and neoplastic (HRS) cells of EBV + mixed cellularity (MC) classical Hodgkin lymphoma (cHL) and nodular lymphocyte predominant HL. We aimed to validate and extend the above observations in 174 cHL patients evaluating the immunohistochemical expression of TXN, CXCL9 and IFN-γ. HRS-cell CXCL9 expression was higher in latent membrane protein-1 (LMP1)+, MC and Stage IV. TXN and CXCL9 expression by cHL histiocytes was more frequent in LMP1+, MC and older patients (only for CXCL9). TXN expression by HRS cells (≥80%) was independently associated with better failure-free survival. In conclusion, markers of TCHRLBCL histiocytes (TXN, CXCL9), as well as IFN-γ are also expressed by histiocyte subsets and neoplastic cells of cHL. The expression of some of them is more prominent in EBV + MC, but not restricted to this subtype. The prognostic implication of TXN needs further evaluation.


The Development of Non-Enzymatic Glucose Biosensors Based on Electrochemically Prepared Polypyrrole-Chitosan-Titanium Dioxide Nanocomposite Films.
The performance of a modified electrode of nanocomposite films consisting of polypyrrole-chitosan-titanium dioxide (Ppy-CS-TiO₂) has been explored for the developing a non-enzymatic glucose biosensors. The synergy effect of TiO₂ nanoparticles (NPs) and conducting polymer on the current responses of the electrode resulted in greater sensitivity. The incorporation of TiO₂ NPs in the nanocomposite films was confirmed by X-ray photoelectron spectroscopy (XPS) spectra. FE-SEM and HR-TEM provided more evidence for the presence of TiO₂ in the Ppy-CS structure. Glucose biosensing properties were determined by amperommetry and cyclic voltammetry (CV). The interfacial properties of nanocomposite electrodes were studied by electrochemical impedance spectroscopy (EIS). The developed biosensors showed good sensitivity over a linear range of 1-14 mM with a detection limit of 614 μM for glucose. The modified electrode with Ppy-CS nanocomposite also exhibited good selectivity and long-term stability with no interference effect. The Ppy-CS-TiO₂ nanocomposites films presented high electron transfer kinetics. This work shows the role of nanomaterials in electrochemical biosensors and describes the process of their homogeneous distribution in composite films by a one-step electrochemical process, where all components are taken in a single solution in the electrochemical cell.


[Mini-PCNL, micro-PCNL or RIRS: comparative efficacy and safety in renal stones up to 2 cm].
One of the main trends in the evolution of endoscopic treatment of urolithiasis is the miniaturization of instruments. This is obvious in the development of minimally invasive percutaneous nephro-lithotomy (PCNL) and retrograde intrarenal surgery (RIRS). However, there are few studies comparing the efficiency and safety of these methods. To evaluate and compare the efficiency and safety of mini-PCNL, micro-PCNL and RIRS in the treatment of kidney stones up to 2 cm in size. Between October 2020 and December 2022, a total 72 patients underwent minimally invasive endoscopic procedures in two centers, including RIRS (n=30), mini-PCNL (n=26) and micro-PCNL (n=16) using thulium fiber laser FiberLase U2. The efficiency of procedure (stone free rate [SFR]) was assessed using non-contrast-enhanced CT. SFR was considered as the absence of residual fragments > 4 mm. Complications (safety) were evaluated based on the Clavien-Dindo classification. The mean age of all patients was 47.7 (22-84) years. There were no significant differences between three groups in stone characteristics according to CT (maximum diameter, density, volume and number of stones, the presence of pelvicalyceal dilation). SFR was significantly different between the groups (p=0.034). The overall SFR was 81.9% (n=59). After RIRS, mini-PCNL, and micro-PCNL the SFR was 93.3%, 80.8%, and 62.5%, respectively. A significant difference was found between the RIRS and micro-PNL groups, with 2 out of 30 and 6 out of 16 patients requiring repeat procedure, respectively (p=0.026). The overall rate of complication of grades I-II, IIIa and IIIb according to Clavien-Dindo was 6.9%, 9.7% and 6.9%, respectively. A significant difference was found between the RIRS and micro-PCNL (p=0.021) for grade I-II complications. A rate of grade III complications was not differed between the groups. The operation time was higher for mini-PNL (79.8 (30-145) min), and it was shorter for RIRS (55.7 (30-155) min). The length of stay was lower in RIRS group (4.5 (1-12) days). The highest SFR was achieved in the RIRS group. In terms of the number of complications of I-II grades according to Clavien-Dindo, the duration of the procedure and the length of stay, RIRS also showed the advantage. There were no significant differences in efficiency and safety between the micro-PNL and mini-PNL. There are not enough studies comparing minimally invasive methods for treating kidney stones. It is necessary to continue research in this area in order to develop an optimal algorithm for choosing the method of endoscopic treatment.


[Highly expressed CHAF1A and PCNA are positively associated with malignancy of cervical squamous cell carcinoma].
Objective To investigate the expressions of chromatin assembly factor 1 subunit A (CHAF1A) and proliferating cell nuclear antigen (PCNA) in cervical squamous cell carcinoma (CSCC) and their clinical implication. Methods Real-time quantitative PCR was performed to detect the mRNA levels of CHAF1A and PCNA in CSCC and corresponding paracancerous tissues. Immunohistochemistry was used to detect the expressions of CHAF1A and PCNA proteins in normal cervical epithelium tissues (NC), cervical intraepithelial neoplasia tissues (CIN), and CSCC. The correlation between CHAF1A and PCNA expressions and the relationship of the two proteins to the clinical pathological features of cervical cancer were analyzed. Results The expressions of CHAF1A and PCNA in CIN and CSCC were significantly higher than those in NC. In addition, CHAF1A and PCNA expressions were positively correlated in the CSCC tissues. Furthermore, overexpression of CHAF1A was significantly associated with the degree of differentiation, tumor size, depth of cancer invasion and HPV infection. Finally, the up-regulated expression of PCNA was correlated with the degree of differentiation, International Federation of Gynecology and Obstetrics (FIGO) grade, lymph node metastasis, depth of cancer invasion and HPV infection. Conclusion CHAF1A and PCNA are highly expressed in CSCC and associated with the malignancy.


Cultural competence of baccalaureate nursing faculty: are we up to the task?
Reported low levels of cultural competence among baccalaureate nursing students, as well as professional nurses, have raised questions about nursing faculty's readiness to prepare culturally competent graduates. This study examined cultural competence among faculty of baccalaureate nursing programs in Louisiana. Using a five-point Likert-type scale, the respondents were asked to express their level of agreement with statements addressing the components of cultural competence. The data analysis revealed the respondents' rating of their cultural awareness (4.14), desire (3.67) knowledge (3.65), skills (3.65), and encounters (3.56). Overall cultural competence was rated as 3.73. When the overall cultural competence index was regressed on the index of each subscale, the cultural knowledge index and the cultural encounter index significantly explained 87% of the variance in the model. These findings suggest that faculty should be encouraged to attend continuing education programs on cultural competence to improve their knowledge in this area. This continuing education, coupled with more local and/or international cross-cultural encounters should significantly improve the overall cultural competence of the respondents.


Loading Efficiency of Polymersomes with Contrast Agents and their Intracellular Delivery: Quantum Dots Versus Organic Dyes.
Contrast nanocarriers as drug-delivery systems, capable of selective delivery to cancer cells and solid tumors, are essential for the development of new diagnostic and therapeutic (theranostic) strategies. The present study aimed to investigate the loading efficiency of chitosan-based polymersomes with fluorescent contrast substances [quantum dots (QDs) and conventional organic dyes] and the possibility to control their release from the polymer matrix into cells by chemical modifications and electroporation. All investigated fluorophores were retained within the polymer globule via electrostatic and hydrophilic-hydrophobic interactions, without conjugation with the polymer. The fluorophore-loaded polymersomes were characterized by dynamic light scattering, zeta-potential titration, and fluorescence spectroscopy. The release of fluorophore from the polymersomes, passively or after electroporation, was detected by 5-step spin-ultrafiltration, combined with fluorescence spectroscopy of the upper phase (supernatant) of the filter unit. Passive intracellular delivery of the nanoparticles to HeLa cells was detected by fluorescence confocal microscopy. The QDs were retained tightly and continuously in the polymer matrix, while the organic fluorophores [fluorescein isothiocyanate (FITC), FITC-dextran10,000 and FITC-dextran70,000] were released rapidly from the polymersomes. The detergent Brij significantly increased the retention of FITC-dextran10,000 in the polymer globule. Electroporation up to 1000 V/cm did not induce release of QDs from the polymersomes, but accelerated the release of Brij-treated FITC-dextran10,000 B from the polymer matrix. High-voltage pulses (over 750 V/cm) induced also fragmentation or aggregation of the nanoparticles. QD_labeled polymersomes penetrated passively in cancer cells after 24-hour incubation. The results suggest that QD-labeled polymersomes are appropriate fluorescent probes and a nano-drug delivery system with high tracing opportunities for in vitro and in vivo applications. Furthermore, loading polymersomes with organic dyes with different molecular weights (such as FITC-dextrans) is a simple model for visualizing and predicting the rate of release of small organic molecules (e.g. conventional drugs, other contrasts, stabilizers, and supplements) from the polymer matrix.


A school-, hospital- and university-based adolescent pregnancy prevention program. A cooperative design for service and research.
Based upon prior service and research findings, a program was designed to reduce the incidence of early childbearing among a high-risk, inner-city junior and senior high school population. Combining a strong research design with medical and educational service in a school- and clinic-based program, the project team sought to develop a replicable model the individual components of which could be evaluated against baseline data collected from 1,709 male and female students before the program began. This paper reports levels of sexual activity, contraceptive use and pregnancy in the student population, using data from anonymous, self-administered questionnaires, and outlines the program's objectives and major features. It also suggests variables that can be used in the measurement of program impact.


Efficacy and tolerance of femoxetine and imipramine in the treatment of depressive states. A randomized, double-blind study.
Fifty-two patients with depressive illness characterized by four symptoms (periodical course, psychomotor retardation, diurnal variation, unrealistic self-depreciation) and a score of at least 18 on the Hamilton Depression Scale 1-17 (HDS) were allocated to a double-blind randomized study with femoxetine and imipramine. Patients were diagnosed according to RDC and further classified according to the Newcastle-II index. During the six weeks of treatment, efficacy was evaluated by means of HDS and a global evaluation. Side-effect symptoms were recorded on a check-list by questioning. After six weeks of treatment with femoxetine or imipramine (recommended daily standard dosages are 600 mg femoxetine and 150 mg imipramine (b.i.d.); in the present study, dosages were flexible and could be adjusted according to effect/side-effects) evaluation of efficacy based on HDS, a six-item subscale, groups of HDS items as well as single items showed no statistically significant differences between the treatment groups except with regard to the factor for sleep disturbances in the HDS, where greatest reduction was seen in the femoxetine group. No statistically significant differences regarding side-effect profile were seen. However, in the imipramine group, higher frequencies of such moderate to severe symptoms as dry mouth, constipation and urination difficulties were observed (the greatest difference was seen for dry mouth, p 0.1, while p-values for the remaining two symptoms were greater than 0.1). Moreover, based on the patients' own opinion on side-effects, femoxetine seemed to be better tolerated. One patient took an overdosage of approx. 26 g femoxetine; half of the intake was removed by gastric emptying at the hospital.(ABSTRACT TRUNCATED AT 250 WORDS)


Complement-mediated bactericidal system: evidence for a new pathway of complement action.
The early components of human complement (C1, C4, and C2) plus certain serum euglobulins will kill pathogenic strains of Shigella sonnei. Serum from patients with hereditary C3 deficiencies and specific antiserums to C3, C5, and C6 were utilized to demonstrate the absence of requirements for late-acting complement components in this unusual bactericidal system.


Dityrosine formation in calmodulin: conditions for intermolecular cross-linking.
The pattern and extent of photoactivated dityrosine formation in bovine brain calmodulin are strongly affected by the presence of superoxide dismutase during UV irradiation. The addition of the enzyme to Ca(2+)-containing solutions of calmodulin results in an altered distribution of the dityrosine-containing photoproducts, from a predominance of cross-linked monomer to a mixture of products with inter- and intramolecular cross-linking. When Ca2+ is absent, significant dityrosine formation occurs only in the presence of superoxide dismutase. Fractionation of the latter reaction mixture yields a dimer of calmodulin, corresponding to a single component in sedimentation equilibrium, a smaller amount of a more highly polymerized material, and virtually no cross-linked monomer--as was found in the absence of the enzyme [Malencik, D.A., & Anderson, S.R. (1987) Biochemistry 26, 695]. Although it is homogeneous in terms of molecular weight, the purified dimer contains three electrophoretic components. Chemical characterization demonstrates intermolecular cross-linking of Tyr-99 to Tyr-138 and probably of Tyr-99 to Tyr-99. On the average, 85-90% of the dimeric calmodulin molecules bind two molecules of smooth muscle myosin light chain kinase. Catalytic activity determinations with this enzyme detect no difference between the dimer and the native protein. Fluorescence anisotropy measurements of Ca2+ binding give a Hill coefficient of < or = 0.73 and a free Ca2+ concentration of approximately 11 microM at 50% saturation. The average pKa of the dityrosine cross-link in the dimeric calmodulin is 8.5-8.6 (+/- Ca2+). Sedimentation velocity experiments show that the average Ca(2+)-liganded dimer has an elongated structure, with a relative frictional ratio approximately 30% greater than that of the native monomer. In terms of functional properties, the dimeric calmodulin preparation is more like the native protein than it is like the previously reported cross-linked monomer.


Rous sarcoma virus is integrated but not expressed in chicken early embryonic cells.
We have developed a protocol that allows us to infect chicken early embryonic (CEE) cells with high efficiency. This was achieved by exposing the CEE cells to a semicontinuous dose of Rous sarcoma virus (RSV) for a period of 20 hr. Southern blot analysis indicated that an average of one proviral copy is integrated per embryonic cell. However, there was no production of infectious viral particles by the cells containing the proviral genome, although low levels of full-length genomic RNA could be detected by RNA transfer blot analysis. These low RNA levels contrast with the 100- to 1000-fold higher levels found in RSV-infected chicken embryo fibroblasts. We conclude that in cells derived from pregastrulating chicken embryos, RSV DNA is integrated into the cell genome but fails to be expressed in an efficient manner. These primary cells can therefore be used to identify factors involved in regulation of retroviral gene expression in normal cells. Such factors may also be instrumental in elucidating basic mechanisms involved in gene regulation during early development in higher vertebrates.


Blood pressure variability and urinary electrolyte excretion in normotensive adults.
The principal aim of the present study was to determine the relationship of ambulatory blood pressure (BP) to urinary electrolyte excretion in normotensives. Twenty-five young adults underwent ambulatory BP and heart rate monitoring while collecting urine over 24 h. The correlations of 24 h urine sodium excretion and the ratio of sodium/potassium excretion with systolic BP in the laboratory (r = 0.12 and 0.24), ambulatory awake (r = 0.11 and 0.24), and ambulatory asleep (r = 0.24 and 0.31) settings were all in the positive direction but not significant. However, 24 h sodium excretion did correlate significantly and positively with awake and asleep ambulatory systolic (r = 0.45 and 0.41, P < .05) and diastolic (r = 0.42 and 0.43, P < .05) coefficients of variability. Thus, in normotensives on an unlimited diet, 24 h urinary sodium was more closely related to ambulatory BP variability than to BP level.


Association of Neuroimaging Markers on Clinical CT Scans With Domain-Specific Cognitive Impairment in the Early and Later Poststroke Stages.
Poststroke cognitive impairment (PSCI) is associated with neuroimaging markers, including cortical atrophy and white matter lesions (WMLs), on clinically acquired CT neuroimaging. The objective was to investigate the association between cortical atrophy/WMLs and PSCI in specific cognitive domains in the acute/subacute and chronic stages after stroke, to provide clarity on the relationship between these neuroimaging markers and the temporal evolution of PSCI. We visually assessed cortical atrophy using the Global Cortical Atrophy (GCA) scale and WMLs using the Fazekas scale. Oxford Cognitive Screen or Birmingham Cognitive Screen assessed PSCI at 2 time points (acute/subacute and chronic) in 6 domains (language, memory, number processing, executive function, attention, and praxis). We binarized domain-specific performance as impaired/unimpaired using normative cutoffs. Multivariable linear and logistic regression analyses evaluated associations between GCA/Fazekas scores with acute/subacute and chronic global and domain-specific PSCI, and ANCOVAs examined whether these scores were significantly different in patients with recovered vs persistent PSCI. Age, sex, education, NIHSS, lesion volume, and recurrent stroke were covariates in these analyses. Among 411 stroke patients (Mdn/IQR age = 76.16/66.84-83.47; 193 female; 346 ischemic stroke; 107 recurrent stroke), GCA and Fazekas scores were not associated with global cognitive impairment in the acute/subacute stage after stroke, but GCA score was associated with chronic global PSCI (B = 0.01, p < 0.001, 95% CI 0.00-0.01). In domain-specific analyses, GCA score was associated with chronic impairment in the memory (B = 0.06, p < 0.001, 95% CI 0.03-0.10) and attention (B = 0.05, p = 0.003, 95% CI 0.02-0.09) domains, and in patients with persistent PSCI, these domains showed significantly higher GCA scores than patients who had recovered (memory: F(1, 157) = 6.63, p = 0.01, η 2 G = 0.04; attention: F(1, 268) = 10.66, p = 0.001, η 2 G = 0.04). This study highlights the potential effect of cortical atrophy on the cognitive recovery process after stroke and demonstrates the prognostic utility of CT neuroimaging for poststroke cognitive outcomes. Clinical neuroimaging could help identify patients at long-term risk of PSCI during acute hospitalization.


Removal of bacteriophages with different surface charges by diverse ceramic membrane materials in pilot spiking tests.
This study examines mechanisms for removal of bacteriophages (MS2 and phiX174) by ceramic membranes without application of flocculants. The ceramic membranes considered included ultra- and microfiltration membranes of different materials. Phages were spiked into the feed water in pilot scale tests in a waterworks. The membranes with pore sizes of 10 nm provided a 2.5-4.0 log removal of the phages. For pore sizes of 50 nm, the log removal dropped to 0.96-1.8. The membrane with a pore size of 200 nm did not remove phages. So, the removal of both MS2- and phiX174-phages depended on the pore size of the membranes. But apart from pore size also other factors influence the removal of phages. Removal was 0.5-0.9 log higher for MS2-phages compared with phiX174-phages. Size exclusion seems to be the major but not the only mechanism which influences the efficiency of phage removal by ceramic membranes.


[The issue of autonomy in medical ethics: philosophy of Karol Wojtyła].
The issue of autonomy seems to play a very central and fundamental role in contemporary medical ethics. However, it should be emphasized, that there is no agreement on how the concept of autonomy ought to be understood. Although as the main intellectual framework to describe the meaning of "autonomy" is the use of philosophical system of John St. Mill or Immanuel Kant, one could identify the tendency to redefine the concept under study. The aim of this article was to find out if the philosophy of Karol Wojtyla could provide--interesting from the bioethical point of view--insights into understanding of the idea of autonomy. The Wojtyla's critique of Kant's and Mill's understanding of autonomy was shortly described and the main elements of Wojtyla's concept of autonomy were analyzed. On the basis of these considerations it was assumed that philosophical background of Wojtyla is so different from those which are used in the contemporary, especially so called Anglo-American, bioethics that introducing it "elements" of his thinking would lead to misunderstandings and indeed even serious errors. On the other hand, however, philosophical works of Wojtyla seems to be very influential in developing 'personalistic' bioethics. But this bioethics could be accepted only by people who share Wojtyla's ontological and probably also theological or religious assumptions.


Quantification of Cell-to-Cell Connectivity Using Particle Bombardment.
Plant cells are connected by cytoplasmic bridges called plasmodesmata. Plasmodesmata are lined by the plasma membrane, essentially forming tunnels that directly connect the cytoplasm of adjacent cells through which soluble molecules can move from cell to cell. This cell-to-cell mobility is underpinned by cytoplasmic advection and diffusion in a manner dependent on molecular size. This movement of molecules is regulated by the aperture of plasmodesmata. GREEN FLUORESCENT PROTEIN (GFP) is a 27 kDa soluble protein that can move passively between cells via plasmodesmata. Thus, it serves as an ideal probe to assess plasmodesmal aperture. GFP can be transgenically produced in single cells by microprojectile bombardment-mediated transformation, and its cell-to-cell mobility can be measured by live-cell imaging and counting the number of cells (or cell layers) to which it has moved. Thus, the number of cells in which GFP is visible serves as a measure of plasmodesmal aperture and functional cell-to-cell connectivity. Here we present methods for microprojectile bombardment of GFP into leaf epidermal cells and statistical analysis of resulting data.


Phospholipid membrane composition affects EGF receptor and Notch signaling through effects on endocytosis during Drosophila development.
The role of phospholipids in the regulation of membrane trafficking and signaling is largely unknown. Phosphatidylcholine (PC) is a main component of the plasma membrane. Mutants in the Drosophila phosphocholine cytidylyltransferase 1 (CCT1), the rate-limiting enzyme in PC biosynthesis, show an altered phospholipid composition with reduced PC and increased phosphatidylinositol (PI) levels. Phenotypic features of dCCT1 indicate that the enzyme is not required for cell survival, but serves a role in endocytic regulation. CCT1- cells show an increase in endocytosis and enlarged endosomal compartments, whereas lysosomal delivery is unchanged. As a consequence, an increase in endocytic localization of EGF receptor (Egfr) and Notch is observed, and this correlates with a reduction in signaling strength and leads to patterning defects. A further link between PC/PI content, endocytosis, and signaling is supported by genetic interactions of dCCT1 with Egfr, Notch, and genes affecting endosomal traffic.


The Glasgow prognostic score: Useful information when prescribing palliative radiotherapy.
The purpose of the present retrospective study was to investigate whether a score reflecting systemic inflammatory processes [the Glasgow Prognostic Score (GPS)] provides relevant information for radiation oncologists. GPS is a three-tiered score [0: normal C-reactive protein (CRP) and albumin; 1: one abnormal result; 2: increased CRP and low albumin]. Correlations between disease type and extent, resource utilization, survival and GPS were analyzed in 703 patients. In the subgroup with GPS 2, significantly higher rates of lung, adrenal gland and liver metastases were observed. An increasing GPS score was associated with a higher likelihood of anemia, leukocytosis and thrombocytosis. Comparable findings were made regarding utilization of palliative care resources, need for blood transfusion and intravenous administration of antibiotics. Compared with GPS 0 or 1, more patients with GPS 2 did not complete their prescribed course of radiotherapy. One-third of patients with GPS 2 received treatment during the final month of life. Multivariate analysis demonstrated that GPS was a significant prognostic factor for overall survival (median, 479, 136, and 61 days, for GPS 0, 1 and 2, respectively). In patients with GPS 2 and additional leukocytosis, the median survival was 38 days. In conclusion, GPS provides important prognostic information. This biomarker-based score may be considered for deciding fractionation, and should be validated further.


[Effect of dopamine and met-enkephalin on the background and evoked spike activity of rat neostriatal neurons].
Extracellular recordings of 191 neostriatum neurons revealed the effects of ionophoretically applied dopamine, met-enkephalin and morphine on spontaneous and glutamate- and acetylcholine-evoked unit activity. Dopamine either depressed or enhanced the spontaneous and glutamate-evoked activities depending on the firing rate. Met-enkephalin depressed the spontaneous, glutamate- and acetylcholine evoked activities. These findings suggest that dopamine exerts a modulatory effect on glutamatergic synaptic neurotransmission in the rat neostriatum.


[Comparison of classic simulation and virtual simulation in breast irradiation: prospective study on 14 patients].
To compare conventional 2D simulation and virtual simulation on 14 patients with breast cancer. Patients were simulated for treatment using standard procedure. They subsequently underwent CT scan in the treatment position. The CTV was defined as breast tissue. The PTV was obtained by adding a 3D margin of 1 cm around CTV. Organs at risk (lungs and heart) were outlined. Ballistics and dose distribution obtained with the two planning methods were compared. With conventional simulation, 95% of CTV received 95% of the dose prescribed. Virtual simulation significantly improved dosimetric coverage of PTV without increasing irradiation volume of lung and heart. In 2D simulation, using three slices allowed optimisation by adjusting wedge angle. The five-slice plan was a much better predictor of the maximum dose regions when compared to the three-slice plan. Using entire CT data didn't give any benefit. Variations in CTV delineation and PTV definition limit interest of virtual simulation. In classic simulation, a 5 CT slice-plan can be used to optimise dose distribution.


Analysis of the incidence and factors predictive of outcome in patients with head and neck cancer with pulmonary nodules.
The management of pulmonary nodules is challenging; unfortunately, little is known about the incidence and significance of pulmonary nodules in patients with head and neck cancer. A review was conducted of 400 consecutive patients with head and neck cancer. Imaging was reviewed to identify the incidence of nodules and patient, tumor, and radiological factors associated with the risk of malignancy. Nodules were found in 58% of patients, with a malignant rate of 6%. Age was the only predictor of having a nodule and advanced-stage III + IV was a predictor of malignancy (P = .023; odds ratio [OR] 10.64; confidence interval 1.33-84.98). Patients presenting with head and neck cancer have a higher incidence of pulmonary nodules and a higher risk of malignancy. In contrast to the British Thoracic Society (BTS) guidelines, which use size to guide the need for serial scans, we would recommend follow-up imaging in all patients with head and neck cancer with nodules, irrespective of size.


Mechanistic investigation of mixing and segregation of ordered mixtures: experiments and numerical simulations.
Pulmonary delivery of cohesive and micronized drugs through dry powder inhalers (DPIs) is traditionally achieved through the formation of ordered mixtures. In order to improve the mechanistic understanding of formation of ordered mixtures, the system consisting of micronized lactose (AZFL, representative of an active pharmaceutical ingredient) and a coarse particle carrier (LH100) is investigated as a function of different process and material variables in a high shear mixer (HSM) and in a low shear double cone (DCN) blender, using both experimental and numerical methods. Process insight is developed using a Discrete Element Method (DEM) based numerical model which could predict the formation of ordered mixtures in the two blenders and was verified against experimental determinations. Spatial and temporal evolution of granular flow are visualized and quantified in silico to reveal distinguishing features of both blenders to aid in rational selection of blenders and process parameters.


A Bayesian Poisson-lognormal Model for Count Data for Multiple-Trait Multiple-Environment Genomic-Enabled Prediction.
When a plant scientist wishes to make genomic-enabled predictions of multiple traits measured in multiple individuals in multiple environments, the most common strategy for performing the analysis is to use a single trait at a time taking into account genotype × environment interaction (G × E), because there is a lack of comprehensive models that simultaneously take into account the correlated counting traits and G × E. For this reason, in this study we propose a multiple-trait and multiple-environment model for count data. The proposed model was developed under the Bayesian paradigm for which we developed a Markov Chain Monte Carlo (MCMC) with noninformative priors. This allows obtaining all required full conditional distributions of the parameters leading to an exact Gibbs sampler for the posterior distribution. Our model was tested with simulated data and a real data set. Results show that the proposed multi-trait, multi-environment model is an attractive alternative for modeling multiple count traits measured in multiple environments.


Unusual Stepwise Protonation and J-Aggregation of meso-Tetrakis(N-methylpyridinium-4-yl)porphine on Binding Poly(sodium vinylsulfonate).
The binding of a tetracationic porphyrin to a highly charged polymer like poly(sodium vinylsulfonate) has been investigated over a wide pH range and under various experimental conditions. We present evidence that, depending on the pH, the high electrostatic field exerted by the polymer stabilizes the diprotonated form of the free base porphyrin at unusual pH values or otherwise causes the formation of H-type aggregates. In particular, at a low polymer concentration, lowering the pH at first allows the formation of the diacid species then it determines its reorganization in close-packed J-type aggregates. The employment of various metallo-derivatives of the title porphyrin enables a better insight into the nature of all the detected species.


Effects of reduced mobility on trabecular bone density in captive big cats.
Bone responds to elevated mechanical loading by increasing in mass and density. Therefore, wild animals should exhibit greater skeletal mass and density than captive conspecifics. This expectation is pertinent to testing bone functional adaptation theories and to comparative studies, which commonly use skeletal remains that combine zoo and wild-caught specimens. Conservationists are also interested in the effects of captivity on bone morphology as it may influence rewilding success. We compared trabecular bone volume fraction (BVF) between wild and captive mountain lions, cheetahs, leopards and jaguars. We found significantly greater BVF in wild than in captive felids. Effects of captivity were more marked in the humerus than in the femur. A ratio of humeral/femoral BVF was also lower in captive animals and showed a positive relationship to home range size in wild animals. Results are consistent with greater forelimb than hindlimb loading during terrestrial travel, and possibly reduced loading of the forelimb associated with lack of predatory behaviour in captive animals. Thus, captivity among felids has general effects on BVF in the postcranial skeleton and location-specific effects related to limb use. Caution should be exercised when identifying skeletal specimens for use in comparative studies and when rearing animals for conservation purposes.


Mitochondrial DNA Copy Number and Heteroplasmy in Monozygotic Twins Discordant for Schizophrenia.
Schizophrenia (SZ) is a severe, complex, and common mental disorder with high heritability (80%), an adult age of onset, and high discordance (∼50%) in monozygotic twins (MZ). Extensive studies on familial and non-familial cases have implicated a number of segregating mutations and de novo changes in SZ that may include changes to the mitochondrial genome. Yet, no single universally causal variant has been identified, highlighting its extensive genetic heterogeneity. This report specifically focuses on the assessment of changes in the mitochondrial genome in a unique set of monozygotic twins discordant (MZD) for SZ using blood. Genomic DNA from six pairs of MZD twins and two sets of parents (N = 16) was hybridized to the Affymetrix Human SNP Array 6.0 to assess mitochondrial DNA copy number (mtDNA-CN). Whole genome sequencing (WGS) and quantitative polymerase chain reaction (qPCR) was performed for a subset of MZD pairs and their parents and was also used to derive mtDNA-CN estimates. The WGS data were further analyzed to generate heteroplasmy (HP) estimates. Our results show that mtDNA-CN estimates for within-pair and mother-child differences were smaller than comparisons involving unrelated individuals, as expected. MZD twins showed discordance in mtDNA-CN estimates and displayed concordance in directionality of differences for mtDNA-CN across all technologies. Further, qPCR performed better than Affymetrix in estimating mtDNA-CN based on relatedness. No reliable differences in HP were detected between MZD twins. The within-MZD differences in mtDNA-CN observed represent postzygotic somatic changes that may contribute to discordance of MZ twins for diseases, including SZ.


Yeast methylotrophy: metabolism, gene regulation and peroxisome homeostasis.
Eukaryotic methylotrophs, which are able to obtain all the carbon and energy needed for growth from methanol, are restricted to a limited number of yeast species. When these yeasts are grown on methanol as the sole carbon and energy source, the enzymes involved in methanol metabolism are strongly induced, and the membrane-bound organelles, peroxisomes, which contain key enzymes of methanol metabolism, proliferate massively. These features have made methylotrophic yeasts attractive hosts for the production of heterologous proteins and useful model organisms for the study of peroxisome biogenesis and degradation. In this paper, we describe recent insights into the molecular basis of yeast methylotrophy.


The public health dashboard: a surveillance model for bioterrorism preparedness.
The City of Milwaukee Health Department piloted a short-term, near real-time syndromic surveillance and communication tool by using an existing secure regional Internet infrastructure. Voluntary, active syndromic case reporting by hospital Emergency Departments was combined with other data streams, including clinical laboratory reports of communicable disease, hospital emergency room diversions, ambulance runs, medical examiner reports of unusual or suspicious deaths, poison control and nursing hotline call volumes, and pharmacy over-the-counter sales. These data were aggregated into a "Surveillance Dashboard" format that was used to communicate community syndromic health trends to hospitals, Emergency Departments, and other providers using a secure Internet technology. Emergency Departments at 8 area hospitals reported a total of 314 cases meeting syndromic criteria from 26,888 patient encounters. Participants were satisfied with data entry and communications. All participating Emergency Departments received e-mail and text pager alerts sent by the Milwaukee Health Department. No unexplained findings or suggestions of an early outbreak were reported through syndrome surveillance for the 4-week duration of the project. Similar surveillance and communications systems could provide multiple benefits to Emergency Department workflow and management, as well as to public health and emergency response.


The Effect of Access to Information on Beliefs Surrounding Breast Cancer in South Africa.
Breast cancer is the most common cancer affecting women in South Africa. There is little knowledge of beliefs to help identify key areas to improve support and education in this demographically and culturally diverse population. Women with a variety of demographic and socioeconomic characteristics accessing care for breast cancer were asked their agreement to statements of knowledge and beliefs about breast cancer. Of the 259 participants, positive statements of medical cure (87.9%) and family support (90.5%) were most commonly believed. Beliefs in faith-based cure and alternative treatments were also present (79.5 and 24.9%, respectively). Negative beliefs were initially more likely in black patients (RR: 11.57, 95%CI: 1.37-97.69) as was belief of cancer as a punishment (RR: 6.85, 95%CI: 1.41-33.21). However, in multivariate analysis adjusting for age, education and access to information (by newspaper, Internet and confidence in reading and writing), there was no difference between racial groups or hospital attended. Reading a newspaper or accessing the Internet was the most protective against belief that cancer was a punishment or curse (Internet use: aRR: 0.12, 95%CI: 0.02-0.99), belief in alternative methods of cure (newspaper use: aRR: 0.51, 95%CI: 0.27-0.96) and the negative beliefs of death and disfigurement (Internet use: aRR: 0.00, 95%CI: 0.00-0.00). Positive expressions of cure and beating cancer were found equally in all women. Attitudes and beliefs about cancer showed little independent demographic or socioeconomic variance. Negative beliefs were mitigated by access to information and confidence in literacy.