Cation-dependent gating of the hyperpolarization-activated cation current in the rabbit sino-atrial node cells.
1. The gating properties of the hyperpolarization-activated cation current (I(f) or Ih) were investigated in single pacemaker cells dissociated from the rabbit sino-atrial node. 2. The whole-cell I(f) was recorded in the presence of different external cations. The inward I(f) was increased when external Na+ was replaced with K+, and was decreased in Li+ or Rb+ solution. In Tris+ and Cs+ solutions, the inward I(f) was negligible. The outward tail current recorded upon depolarization was largest in Li+ solution and smaller in a sequence of Na+, Tris+ and K+ solutions. In Rb+ and Cs+ solutions, only a small tail current was recorded. 3. The outward tail current had a 'shoulder' in Na+ solution, which was much delayed by replacing Na+ with Li+. In K+ solution, the decay of the tail current was much faster, and no obvious shoulder was recorded. The tail current was slowest in Li(+)-rich and 0 mM K+ solution, and was progressively accelerated by adding K+ over the range from 0 to 3 mM. The tail current at 30 mM [K+]o showed only a small shoulder. A common binding site to modulate the I(f) deactivation was suggested for monovalent cations. 4. The shoulder of the I(f) tail became more evident as I(f) was activated to a larger extent either by prolonging the duration or by increasing the amplitude of the preceding hyperpolarization in both Na+ and Li+ solutions. 5. The I(f) was first activated by hyperpolarizing the membrane to -110 mV, and then deactivated by depolarization. The inward tail current at -50 mV showed a single exponential decay. At more positive potentials, the shoulder of the outward tail currents became more evident and the rate of the final decay was increased. 6. The time course of I(f) activation was well fitted with the sum of two exponential functions. Time constants of both components were not affected by the external cation (Na+, K+ or Li+) replacement. Likewise, the quasi-steady state activation was conserved when external Na+ was replaced with Li+. 7. Two closed and three open states were assumed in a sequential state model of the I(f) channel. The cation effects were well simulated by assuming that the deactivation rate was selectively modulated. The flow of I(f) during the spontaneous action potential was calculated. The activation of I(f) started on repolarization to the maximum diastolic potential and reached a maximum in the middle of the diastolic period. Its peak amplitude was 14% of the net inward current during the diastolic period.


Detection of Low Adherence in Rural Tuberculosis Patients in China: Application of Morisky Medication Adherence Scale.
The detection and analysis of cases of low medication adherence is important for helping to control tuberculosis (TB). The purpose of this study was to detect low adherence in rural TB patients by using the eight-item Morisky Medication Adherence Scale of Chinese version (C-MMAS-8) and to further analyze the adherence-related variables. A total of 358 rural TB patients recruited through multi-stage randomized sampling participated in the survey. Data were collected by the use of interviewer-led questionnaires. First, the reliability and validity of the C-MMAS-8 were determined. Second, the adherence level was assessed, and factors related to low adherence were analyzed by using Pearson's chi-square test and then in multiple logistic regression model. Finally, the prediction of the logistic model was assessed with Receiver Operating Characteristic (ROC) curves. The C-MMAS-8 could be used to detect low adherence in TB patients with good reliability and validity. By using the referred cutoff points of MMAS-8, it was found that more than one-third of the participants had low medication adherence. Further analysis revealed the variables of being older, a longer treatment time, and being depressive were significantly related to low adherence. The ROC of the model was assessed as good using the cutoff point. We conclude that appropriately tailored strategies are needed for health-care providers to help rural TB patients cope with low medication adherence.


Group psychotherapy with bipolar patients: a review and synthesis.
Contrary to traditional thinking, a review of the recent literature has suggested that bipolar patients can be treated in homogeneous therapy groups in conjunction with concomitant lithium management. Important psychodynamic and interpersonal features are reviewed that have received empirical support and have enhanced our understanding of these patients. Goals for bipolar groups include educating patients on the nature of the disease, helping them learn ways of coping with its symptoms, and encouraging them to discuss relevant psychodynamic and interpersonal issues. To achieve these goals, therapists have used techniques involving education, support, and facilitation of group discussions. Further clinical and empirical work needs to be done to evaluate the effectiveness and process of these bipolar groups, particularly in the inpatient setting.


Thyroglobulin measurement in the management of patients with differentiated thyroid cancer.
The post-operative management of patients with differentiated thyroid carcinoma (DTC) relies on serial measurements of serum thyroglobulin. Current methodologies for thyroglobulin quantitation vary in their analytical and clinical performance. For years, thyroglobulin radioimmunoassays (RIA) and immunometric assays (IMA) have been used despite analytical interferences from anti-thyroglobulin autoantibodies (TgAb) as well as heterophile antibodies (HAb). TgAb interference limits Tg utility as a tumor marker in ∼30% of TgAb-positive patients. Consequently, additional studies are necessary to rule out persistent or recurrent disease in these patients. Recently, thyroglobulin mass spectrometry assays have been introduced as a solution to the interference problems observed in immunoassays. However, their analytical sensitivity is inferior to the high sensitivity immunoassays. The aims of this review are to: (i) review current thyroglobulin assays; (ii) discuss technical limitations of each assay; and (iii) discuss the clinical uses of thyroglobulin in serum and fine-needle aspirate biopsy washouts for the management of DTC patients. An understanding of the technical advantages and disadvantages of Tg assays is critical for clinicians and laboratorians to effectively use and interpret this test in the management of DTC patients.


Triggering of RNA interference with RNA-RNA, RNA-DNA, and DNA-RNA nanoparticles.
Control over cellular delivery of different functionalities and their synchronized activation is a challenging task. We report several RNA and RNA/DNA-based nanoparticles designed to conditionally activate the RNA interference in various human cells. These nanoparticles allow precise control over their formulation, stability in blood serum, and activation of multiple functionalities. Importantly, interferon and pro-inflammatory cytokine activation assays indicate the significantly lower responses for DNA nanoparticles compared to the RNA counterparts, suggesting greater potential of these molecules for therapeutic use.


Unbalance of intestinal microbiota in atopic children.
Playing a strategic role in the host immune function, the intestinal microbiota has been recently hypothesized to be involved in the etiology of atopy. In order to investigate the gastrointestinal microbial ecology of atopic disease, here we performed a pilot comparative molecular analysis of the faecal microbiota in atopic children and healthy controls. Nineteen atopic children and 12 healthy controls aged 4-14 years were enrolled. Stools were collected and the faecal microbiota was characterized by means of the already developed phylogenetic microarray platform, HTF-Microbi.Array, and quantitative PCR. The intestinal microbiota of atopic children showed a significant depletion in members of the Clostridium cluster IV, Faecalibacterium prausnitzii, Akkermansia muciniphila and a corresponding increase of the relative abundance of Enterobacteriaceae. Depleted in key immunomodulatory symbionts, the atopy-associated microbiota can represent an inflammogenic microbial consortium which can contribute to the severity of the disease. Our data open the way to the therapeutic manipulation of the intestinal microbiota in the treatment of atopy by means of pharmaceutical probiotics.


BDNF regulates the expression and distribution of vesicular glutamate transporters in cultured hippocampal neurons.
BDNF is a pro-survival protein involved in neuronal development and synaptic plasticity. BDNF strengthens excitatory synapses and contributes to LTP, presynaptically, through enhancement of glutamate release, and postsynaptically, via phosphorylation of neurotransmitter receptors, modulation of receptor traffic and activation of the translation machinery. We examined whether BDNF upregulated vesicular glutamate receptor (VGLUT) 1 and 2 expression, which would partly account for the increased glutamate release in LTP. Cultured rat hippocampal neurons were incubated with 100 ng/ml BDNF, for different periods of time, and VGLUT gene and protein expression were assessed by real-time PCR and immunoblotting, respectively. At DIV7, exogenous application of BDNF rapidly increased VGLUT2 mRNA and protein levels, in a dose-dependent manner. VGLUT1 expression also increased but only transiently. However, at DIV14, BDNF stably increased VGLUT1 expression, whilst VGLUT2 levels remained low. Transcription inhibition with actinomycin-D or α-amanitine, and translation inhibition with emetine or anisomycin, fully blocked BDNF-induced VGLUT upregulation. Fluorescence microscopy imaging showed that BDNF stimulation upregulates the number, integrated density and intensity of VGLUT1 and VGLUT2 puncta in neurites of cultured hippocampal neurons (DIV7), indicating that the neurotrophin also affects the subcellular distribution of the transporter in developing neurons. Increased VGLUT1 somatic signals were also found 3 h after stimulation with BDNF, further suggesting an increased de novo transcription and translation. BDNF regulation of VGLUT expression was specifically mediated by BDNF, as no effect was found upon application of IGF-1 or bFGF, which activate other receptor tyrosine kinases. Moreover, inhibition of TrkB receptors with K252a and PLCγ signaling with U-73122 precluded BDNF-induced VGLUT upregulation. Hippocampal neurons express both isoforms during embryonic and neonatal development in contrast to adult tissue expressing only VGLUT1. These results suggest that BDNF regulates VGLUT expression during development and its effect on VGLUT1 may contribute to enhance glutamate release in LTP.


[The thoracoscopic thymectomy for myasthenia gravis].
Myasthenia gravis (MG) is a chronic autoimmune disease that usually responds positively to treatment with thymectomy. Standard surgical procedures have been shown to result in a favorite outcome. The optimal surgical access, however, is under discussion. In a prospective study conducted between 8/97 and 4/05, 173 patients with MG underwent thoracoscopic thymectomy, for which a left-sided approach was generally applied. An analysis of the intraoperative and postoperative course was performed in 137 patients (8/97 and 12/03), as well as of the impact of the surgical procedure on further development of the disease. The results obtained were compared with those published in the literature, with particular reference to results obtained with open surgery. In 8 patients, the procedure was converted to an anterolateral thoracotomy or sternotomy, so we examined 129 patients, which were operated thoracoscopically. The patients in this study were 93 females and 36 males, with a mean age of 35.8 (range: 9-83) years. The mean preoperative duration of the disease was 22.9 (range: 1-140) months. The duration of operation was 50 to 85 minutes, the blood loss was lower than 100 ml. The mean follow up was 24.7 (range: 1-57) months. Complete remission was noted in 30 patients (23.3 %), and improvements reflected either in a reduction of the required medication, or a decrease in symptom severity, were seen in a total of 86 patients (66.6 %). Complete thoracoscopic thymectomy is a technically feasible operation, and as effective as conventional open surgery. Remissions or symptomatic improvements were observed in more than 89 % of the patients. The low morbidity rate, in combination with excellent cosmetic results, has led to increasing acceptance of the operation both by patients and neurologists. Therefore, thoracoscopic thymectomy represents a new, alternative method for treatment of patients with MG.


Vape Shop Employees: Public Health Advocates?
E-cigarettes have increased in popularity and given rise to a new type of sales outlet-the vape shop. Expanding on work examining vape shop employee e-cigarette and tobacco attitudes and behaviors1, this study examined key messages that vape shop employees communicate to customers. Using informal interviews, observations, and a cross-sectional survey, we examined vape shop employees' (n=16) perceptions and e-cigarette use. Data were collected in nine vape shops in Louisville, Kentucky. We used open coding to analyze the qualitative interviews, observation notes, and open-ended survey responses. Descriptive statistics were used to analyze survey data. The findings revealed that nearly all employees were former smokers (93.8%), who now only use e-cigarettes. Over one-third of the employees (37.5%) began using e-cigarettes as a replacement for traditional cigarettes, and 93.8% reported better health (e.g., easier breathing, less coughing) since starting to use e-cigarettes. Although most employees believed e-cigarettes should be regulated, 56.3% thought regulations should be different from those governing traditional cigarettes. Analysis of qualitative data revealed that employees see themselves as health advocates who: 1) provide instructions on vaping and promote a vape community, 2) encourage cessation of traditional cigarettes, and 3) support some regulations. The findings reveal that vape shop employees regard e-cigarettes as viable smoking cessation tools and relish their role in assisting others in taking what employees view as positive health actions. Future research addressing communication between vape shop employees and customers, especially related to smoking cessation and health, is needed.


Temperature and pH control on lipid composition of silica sinters from diverse hot springs in the Taupo Volcanic Zone, New Zealand.
Microbial adaptations to environmental extremes, including high temperature and low pH conditions typical of geothermal settings, are of interest in astrobiology and origin of life investigations. The lipid biomarkers preserved in silica deposits associated with six geothermal areas in the Taupo Volcanic Zone were investigated and variations in lipid composition as a function of temperature and pH were assessed. Lipid analyses reveal highly variable abundances and distributions, reflecting community composition as well as adaptations to extremes of pH and temperature. Biomarker profiles reveal three distinct microbial assemblages across the sites: the first in Champagne Pool and Loop Road, the second in Orakei Korako, Opaheke and Ngatamariki, and the third in Rotokawa. Similar lipid distributions are observed in sinters from physicochemically similar springs. Furthermore, correlation between lipid distributions and geothermal conditions is observed. The ratio of archaeol to bacterial diether abundance, bacterial diether average chain length, degree of GDGT cyclisation and C31 and C32 hopanoic acid indices typically increase with temperature. At lower pH, the ratio of archaeol to bacterial diethers, degree of GDGT cyclisation and C31 and C32 hopanoic acid indices are typically higher. No trends in fatty acid distributions with temperature or pH are evident, likely reflecting overprinting due to population influences.


Brain Ultrasonography Findings in Neonatal Seizure; a Cross-sectional Study.
Screening of newborns with seizure, who have curable pathologic brain findings, might be able to improve their final outcome by accelerating treatment intervention. The present study aimed to evaluate the brain ultrasonography findings of newborns hospitalized with complaint of seizure. The present cross-sectional study designed to evaluate brain ultrasonography findings of hospitalized newborns complaining seizure. Neonatal seizure was defined as presence of tonic, clonic, myoclonic, and subtle attacks in 1 - 28 day old newborns. 100 newborns with the mean age of 5.82 ± 6.29 days were evaluated (58% male). Most newborns were in the < 10 days age range (76%), term (83%) and with normal birth weight (81%). 22 (22%) of the ultrasonography examinations showed a pathologic finding. A correlation was only found between birth age and probability of the presence of a pathologic problem in the brain as the frequency of these problems was significantly higher in pre-term newborns (p = 0.023). Based on the findings of the present study, frequency of pathologic findings in neonatal brain ultrasonography was 22%. Hemorrhage (12%) and hydrocephaly (7%) were the most common findings. The only factor correlating with increased probability of positive findings was the newborns being pre-term.


Highly Fluorescent Dianionic Polymethines with a 1,3,2-Dioxaborine Core.
The difluoroboron β-diketonate ring is ever more used for creating bright polymethine-type fluorophores for the visible and NIR range. Here, we report the synthesis and spectral properties of a series of dianionic cyanine dyes of the rare A1-π-A-π-A1 type, with the central dioxaborine ring (A) embedded into the polymethine chain and various electron-acceptor terminal groups A1. Depending on the nature of the end group, the maxima of their intensive (with molar extinctions up to 380 000 M-1 cm-1) and narrow long-wavelength absorption band lie in the range of 530-770 nm. Their absorption and fluorescence bands are nearly mirror-like and characterized by weak solvatochromism; the marked hypsochromic shifts are observed only when going from polar aprotic solvents to methanol. The designed dianionic dyes have fluorescence quantum yields up to 92 % in the visible range, and even for the NIR dyes, the values of 18-37 % are observed in DMF.


[Determination and the significance of three types of GGT mRNA in human liver tissues].
To explore the relationship between the alteration in GGT mRNA expression and the development of HCC. Three GGT mRNA types (F, H, and P) in normal liver tissues, diseased liver tissues without HCC, cancerous and noncancerous tissues from livers with HCC, and noncancerous tissues from livers with metastatic tumor were tested by RT-PCR. In normal livers, the main type of GGT mRNA was type F. In liver diseases but not HCC, the distribution of the type GGT mRNA was nearly the same as in normal livers. The prevalence of type H was significantly higher in both cancerous and noncancerous tissues of livers with HCC than in livers without HCC (P<0.05). The prevalence of type F in cancerous tissues was significantly lower than that in livers without HCC (P<0.05). The GGT mRNA expression in the human liver will shift from type F to type H during the development of HCC. The fragment analysis of GGT genes may be a sensitive assay to detect hepatic cell canceration.


Continuous Erector Spinae Plane Block for Rescue Analgesia in Thoracotomy After Epidural Failure: A Case Report.
The ultrasound-guided erector spinae plane (ESP) block is a newly described technique for providing thoracic analgesia. It is simple to perform and relatively noninvasive compared with thoracic epidural analgesia. In addition, the anatomy lends itself well to catheter insertion for continuous blockade. In this report, we describe the use of the ESP block as a rescue analgesic technique for postthoracotomy analgesia in a patient with failed thoracic epidural analgesia.


Mapping the Dynamics of the Glucocorticoid Receptor within the Nuclear Landscape.
The distribution of the transcription machinery among different sub-nuclear domains raises the question on how the architecture of the nucleus modulates the transcriptional response. Here, we used fluorescence fluctuation analyses to quantitatively explore the organization of the glucocorticoid receptor (GR) in the interphase nucleus of living cells. We found that this ligand-activated transcription factor diffuses within the nucleus and dynamically interacts with bodies enriched in the coregulator NCoA-2, DNA-dependent foci and chromatin targets. The distribution of the receptor among the nuclear compartments depends on NCoA-2 and the conformation of the receptor as assessed with synthetic ligands and GR mutants with impaired transcriptional abilities. Our results suggest that the partition of the receptor in different nuclear reservoirs ultimately regulates the concentration of receptor available for the interaction with specific targets, and thus has an impact on transcription regulation.


Epidemiology of paediatric injury.
Thousands of young lives are lost every year as a result of accidents, and trauma remains the number one cause of paediatric death. There is a pattern and regularity to children's injury: boys are more often victims than the girls, most injuries occur during the summer months, the pedestrian child has usually been the victim of a road traffic accident (RTA) and, in 75% of these cases, has suffered head injury. The research into paediatric trauma is still very young. For instance, socio-economic and ethnic factors play a significant role in the statistics of accidental death. In order to take effective preventative measures more factors must be determined.


A comparison of language deficits in learning-disabled, head-injured, and nondisabled young adults: results from an abbreviated Aphasia Screening Test.
This study used an Aphasia Screening Test (AST) abbreviated to its naming, pronunciation, and sentence interpretation items to compare groups of 60 learning-disabled (LD), 30 head-injured (HI), and 30 nondisabled (ND) young adults matched for FISQ and balanced for gender composition. The LD and HI, who did not differ, made significantly more AST errors than the ND. One-quarter to one-third of the LD and HI subjects exhibited language deficits. For the clinical groups only, AST errors, particularly pronunciation errors, were related negatively to WRAT reading and spelling scores. The Reitan and Wolfson (1988) severity ratings for AST items did not improve group discrimination.


Increased adipogenesis of human adipose-derived stem cells on polycaprolactone fiber matrices.
With accelerating rates of obesity and type 2 diabetes world-wide, interest in studying the adipocyte and adipose tissue is increasing. Human adipose derived stem cells--differentiated to adipocytes in vitro--are frequently used as a model system for white adipocytes, as most of their pathways and functions resemble mature adipocytes in vivo. However, these cells are not completely like in vivo mature adipocytes. Hosting the cells in a more physiologically relevant environment compared to conventional two-dimensional cell culturing on plastic surfaces, can produce spatial cues that drive the cells towards a more mature state. We investigated the adipogenesis of adipose derived stem cells on electro spun polycaprolactone matrices and compared functionality to conventional two-dimensional cultures as well as to human primary mature adipocytes. To assess the degree of adipogenesis we measured cellular glucose-uptake and lipolysis and used a range of different methods to evaluate lipid accumulation. We compared the averaged results from a whole population with the single cell characteristics--studied by coherent anti-Stokes Raman scattering microscopy--to gain a comprehensive picture of the cell phenotypes. In adipose derived stem cells differentiated on a polycaprolactone-fiber matrix; an increased sensitivity in insulin-stimulated glucose uptake was detected when cells were grown on either aligned or random matrices. Furthermore, comparing differentiation of adipose derived stem cells on aligned polycaprolactone-fiber matrixes, to those differentiated in two-dimensional cultures showed, an increase in the cellular lipid accumulation, and hormone sensitive lipase content. In conclusion, we propose an adipocyte cell model created by differentiation of adipose derived stem cells on aligned polycaprolactone-fiber matrices which demonstrates increased maturity, compared to 2D cultured cells.


Low levels of estrogen significantly diminish axonal sprouting after entorhinal cortex lesions in the mouse.
This study tested the hypothesis that estrogen enhances axonal sprouting in the hippocampal formation in the female mouse. The entorhinal cortex was unilaterally lesioned with ibotenic acid in control mice and in ovariectomized mice that were treated with a high dose of, a moderate dose of, or zero estrogen supplementation pellets. Four weeks later the density of staining for synaptophysin immunoreactivity and acetylcholinesterase (AChE) histochemistry was measured in the molecular layer of the dentate gyrus. In control mice, lesions of the lateral part of the entorhinal cortex increased synaptophysin and acetylcholinesterase staining (i.e., indicative of axonal sprouting) in the outer one-third of the molecular layer of the dentate gyrus. Mice receiving high and moderate estrogen supplementation displayed the same sprouting response; however, in ovariectomized mice the sprouting response was significantly reduced (to nearly nothing). Thus, in ovariectomized compared with control mice the lesion-induced sprouting response is severely blunted, and this effect is reversed by estrogen supplementation. Together, these findings suggest that estrogen plays a prominent role in promoting neuronal plasticity and remodeling in the dentate gyrus.


Production of rice straw hydrolysis enzymes by the fungi Trichoderma reesei and Humicola insolens using rice straw as a carbon source.
Rice straw was evaluated as a carbon source for the fungi, Trichoderma reesei and Humicola insolens, to produce enzymes for rice straw hydrolysis. The enzyme activity of T. reesei and H. insolens cultivated in medium containing non-treated rice straw were almost equivalent to the enzyme of T. reesei cultivated in Avicel medium, a form of refined cellulose. The enzyme activity of T. reesei cultivated in medium containing NH4OH-treated rice straw was 4-fold higher than enzyme from cultures grown in Avicel medium. In contrast, H. insolens enzyme from cultures grown in NH4OH-treated rice straw had significantly lower activity compared with non-treated rice straw or Avicel. The combined use of T. reesei and H. insolens enzymes resulted in a significant synergistic enhancement in enzymatic activity. Our data suggest that rice straw is a promising low-cost carbon source for fungal enzyme production for rice straw hydrolysis.


Characteristics of Circulating CD4+ T Cell Subsets in Patients with Mycobacterium avium Complex Pulmonary Disease.
Although prevalence of Mycobacterium avium complex pulmonary disease (MAC-PD) is increasing, limited data are available regarding vulnerability to Mycobacterium avium complex (MAC) infections. To understand the pathobiology of interaction between MAC and host-immunity, it is important to understand the characteristics for circulating T cells in terms of the immunological phenotype and functional correlates in MAC-PD. We aimed to characterize immunophenotype, cytokine profile, and immune inhibitory receptors of circulating CD4+ T cells in MAC-PD patients. We enrolled 71 MAC-PD and 20 control individuals. Flow cytometric analysis was performed to determine T cell subsets and immune checkpoint markers. Ex vivo cytokine productions in response to MAC were determined using enzyme-linked immunosorbent assay. The frequencies of CD4+ T cells and CD4+IL-17+ T cells decreased, while CD4+IL-4+ T cells and CD4+CD25+Foxp3+ T cells increased in peripheral blood mononuclear cells (PBMCs) of MAC-PD individuals upon MAC stimulation compared with those cells in healthy donor-PBMCs. Additionally, we found increased PD-1, CTLA-4, and TIM-3-expressing T cells in MAC- PD individuals in response to MAC-stimulation, indicating that suppressed T cell-mediated response is associated with the susceptibility to MAC infection. These results may help to explain impaired T cell-mediated responses and pave the way for better strategies to achieve protective immunity against MAC infection.


Impairment of brain vessels may contribute to mortality in patients with Parkinson's disease.
The effect of brain-vessel pathology on mortality in 57 consecutive PD patients was studied. Baseline clinical, neuropsychological, ultrasonographic (US), and MR data obtained from patients who died (n = 18) during a 4-year follow-up period were compared with the data of patients who survived. US/MRI data displayed a more-severe vascular impairment in deceased patients. Differences were significant between both groups with respect to age, clinical and cognitive status, intima-media thickness, and resistance index (indicators of large and small vessel impairment). The sum score of white-matter hyperintensities was significantly higher among decedents. A cluster analysis displayed two clusters that differed in the two parameters (i.e. in age and in sum score). This study provides evidence that comorbid atherosclerosis and otherwise subclinical impairment of brain vessels may contribute to mortality in PD. The vascular pathology may act in association with other comorbidities on the terrain of progressive neurodegenerative pathology.


Comparative effects of captopril and nifedipine on diastolic and systolic cardiac function in elderly hypertensive patients.
Both nifedipine and captopril are effective in the treatment of systemic hypertension in the elderly, but their effects on cardiac function in this age group have not been evaluated. We studied the effects of acute oral administration of 20 mg nifedipine and 12.5 mg captopril on systolic and diastolic cardiac function, as evaluated by a radionuclide method, in 14 elderly hypertensives, mean age 73.4 +/- 3.9 years. The radionuclide studies were performed 1 h after ingestion of nifedipine and 1.5 h after captopril, on separate days. Nifedipine accelerated the heart rate whereas captopril slowed it. Nifedipine increased the ejection fraction by 2.6 +/- 14.6% but captopril increased it by 13 +/- 15.3%. Nifedipine reduced the left ventricular peak ejection rate by 4.8 +/- 21.7% whereas captopril increased it by 18 +/- 24.3%. Nifedipine increased the peak filling rate by 14.3 +/- 41.6% and captopril increased it by 27.6 +/- 32.6%. Nifedipine reduced the time to peak filling rate by 24.9 +/- 27.0%, but captopril reduced it by 68.8 +/- 59.6%. All these differences were statistically significant. Therefore, captopril improves some diastolic and systolic parameters of cardiac function more than nifedipine does. Other parameters are impaired by nifedipine but improved by captopril.


The effect of mechanical stimulation on the keratinization of sulcular epithelium.
This study was designed to evaluate the effect of mechanical stimulation on the keratinization of the sulcular epithelium in four adult Rhesus monkeys. Each animal received a thorough prophylaxis. One week later, each monkey received one of the following modalities of plaque control: (a) daily intravenous tetracycline and rubber cup prophylaxis, (b) daily rubber cup prophylaxis, (c) daily intravenous tetracycline injections; (d) no treatment, as a control. After sacrifice and tissue processing the histologic sections were evaluated for the presence of sulcular keratinization. The keratin width and length were measured, and an Inflammatory Index determined. It was found that all treatment modalities reduced inflammation significantly, when compared to the control. No differences among the three procedures tested were found. Although all permitted keratinization to develop, sulcular keratinization was significantly increased when daily prophylaxes were performed. It was concluded that mechanical stimulation of the sulcular epithelium, seemingly plays a role in promoting its keratinization.


Selective Convolutional Descriptor Aggregation for Fine-Grained Image Retrieval.
Deep convolutional neural network models pre-trained for the ImageNet classification task have been successfully adopted to tasks in other domains, such as texture description and object proposal generation, but these tasks require annotations for images in the new domain. In this paper, we focus on a novel and challenging task in the pure unsupervised setting: fine-grained image retrieval. Even with image labels, fine-grained images are difficult to classify, letting alone the unsupervised retrieval task. We propose the selective convolutional descriptor aggregation (SCDA) method. The SCDA first localizes the main object in fine-grained images, a step that discards the noisy background and keeps useful deep descriptors. The selected descriptors are then aggregated and the dimensionality is reduced into a short feature vector using the best practices we found. The SCDA is unsupervised, using no image label or bounding box annotation. Experiments on six fine-grained data sets confirm the effectiveness of the SCDA for fine-grained image retrieval. Besides, visualization of the SCDA features shows that they correspond to visual attributes (even subtle ones), which might explain SCDA's high-mean average precision in fine-grained retrieval. Moreover, on general image retrieval data sets, the SCDA achieves comparable retrieval results with the state-of-the-art general image retrieval approaches.


AIE Nanoassemblies for Discrimination of Glycosaminoglycans and Heparin Quality Control.
The discrimination of glycosaminoglycans (GAGs) is a challenging task but of great importance to ensure their safe use in clinics. Herein, four supramolecular AIE nanoassemblies denoted as PDDA-TPE100, PDDA-TPE75, PDDA-TPE50, and PDDA-TPE25 were synthesized by loading different amounts of the negatively charged AIEgen TPE onto the surface of the positively charged polymer PDDA. These AIE nanoassemblies were utilized for the construction of a fluorescent sensor array, which was able to discriminate various GAGs on the basis of a compaction to displacement reaction mechanism. LDA and HCA results revealed that GAGs including Hep, Chs, HA, CTS, DS, and OSCS can be discriminated with 100% accuracy. The four-sensor array was then simplified to a three-sensor array using PDDA-TPE100, PDDA-TPE75, and PDDA-TPE50 as the sensors, which was determined to be still powerful in discrimination of various GAGs, accurate identification of unknown GAG samples, sensitive detection of trace OSCS contaminant in Hep, and identification of Hep and other biologically abundant anions. Moreover, the three-sensor array was even successfully applied for differentiating GAGs in serum media.


[Reconstruction of large external nose defect with forehead flap].
To discuss the role of forehead flap in large external nasal defect reconstruction. We retrospectively reviewed the clinical and follow-up data of 11 patients with large or full-thickness external nasal defects, which were reconstructed with single-or two-stage interpolated or island forehead flaps from January 2007 to June 2011. All patients were male,defects of 9 cases were resulted from resection of skin malignant tumor and traumatic defect in 2 cases. The average diameter of defects was 3.3 cm (2.5-5.0 cm). Four cases had alar full thickness defect. The supratrochlear and angular artery of the elders (>70 yrs) and patients with suspicious peripheral blood vessel lesions were scanned before the surgery by Doppler ultrasonic. The defects were reconstructed by two-stage interpolated flap in 7 cases; five cases were reconstructed by single-stage island flap technique. A nasolabial flap based on piriform aperture was turned into the nasal cavity to reconstruct the lining. All defects were repaired successfully. All tissue flap survived and the scar was not conspicuous. One patient had nostril stenosis with mild nasal congestion complain at the 6th postoperative month. The forehead flap, interpolated or island, can be used safely and effectively to repair the large external nasal defect in experienced hands.


Defects formation and spiral waves in a network of neurons in presence of electromagnetic induction.
Complex anatomical and physiological structure of an excitable tissue (e.g., cardiac tissue) in the body can represent different electrical activities through normal or abnormal behavior. Abnormalities of the excitable tissue coming from different biological reasons can lead to formation of some defects. Such defects can cause some successive waves that may end up to some additional reorganizing beating behaviors like spiral waves or target waves. In this study, formation of defects and the resulting emitted waves in an excitable tissue are investigated. We have considered a square array network of neurons with nearest-neighbor connections to describe the excitable tissue. Fundamentally, electrophysiological properties of ion currents in the body are responsible for exhibition of electrical spatiotemporal patterns. More precisely, fluctuation of accumulated ions inside and outside of cell causes variable electrical and magnetic field. Considering undeniable mutual effects of electrical field and magnetic field, we have proposed the new Hindmarsh-Rose (HR) neuronal model for the local dynamics of each individual neuron in the network. In this new neuronal model, the influence of magnetic flow on membrane potential is defined. This improved model holds more bifurcation parameters. Moreover, the dynamical behavior of the tissue is investigated in different states of quiescent, spiking, bursting and even chaotic state. The resulting spatiotemporal patterns are represented and the time series of some sampled neurons are displayed, as well.


The effect of magnesium depletion on thyroid function in rats.
The effects of dietary magnesium (Mg) depletion on thyroid function were studied in young male rats. The rats were fed a semipurified diet containing either 12 ppm Mg (deficient rats) or 662 ppm Mg (control rats) for 14 to 28 days. Results showed that the Mg-deficient rats had decreased body weight gain, lowered concentrations of plasma thyroxine (T4) and Mg, but increased weight of the thyroid gland when expressed in proportion to the body weight (milligrams/100 g). There was no difference in the accumulation (uptake) of 131I, 24 hours after Na131I injection, between the Mg-deficient and Mg-supplemented rats. The protein-bound 131I (PB131I) level and the ratio of PB131I to total 131I in plasma was significantly reduced in Mg-deficient rats. Serum thyroid-stimulating hormone (TSH) levels after thyrotropin-releasing hormone injection (TRH, 50 ng/100 g body weight) increased fivefold at 30 minutes, but declined to near the basal level at 2 hours in both groups. No consistent difference in TSH response was observed between the two treatments. Serum T4 response to TRH challenge was significantly reduced in Mg-deficient as compared to Mg-adequate rats at all time intervals. The reduction of T4 level could be due to an impaired T4 synthesis or release in Mg-deficient rats.


[Contents of free amino acids and water-soluble carbohydrates in safflower plant at different stages of growth].
As closely related to the development of plant organs, the contents of free amino acids and water-soluble carbohydrates in safflower plant vary with the course of growth. The ratio of the two contents rise with the growing periods, reaching maxima in the later stages of growth.


Why is mammalian thioredoxin reductase 1 so dependent upon the use of selenium?
Cytosolic thioredoxin reductase 1 (TR1) is the best characterized of the class of high-molecular weight (Mr) thioredoxin reductases (TRs). TR1 is highly dependent upon the rare amino acid selenocysteine (Sec) for the reduction of thioredoxin (Trx) and a host of small molecule substrates, as mutation of Sec to cysteine (Cys) results in a large decrease in catalytic activity for all substrate types. Previous work in our lab and others has shown that the mitochondrial TR (TR3) is much less dependent upon the use of Sec for the reduction of small molecules. The Sec-dependent substrate utilization behavior of TR1 may be the exception and not the rule as we show that a variety of high-Mr TRs from other organisms, including Drosophila melanogaster, Caenorhabditis elegans, and Plasmodium falciparum, do not require Sec to reduce small molecule substrates, including 5,5'-dithiobis(2-nitrobenzoic acid), lipoic acid, selenite, and selenocystine. The data show that high-Mr TRs can be divided into two groups based upon substrate utilization patterns: a TR1 group and a TR3-like group. We have constructed mutants of TR3-like enzymes from mouse, D. melanogaster, C. elegans, and P. falciparum, and the kinetic data from these mutants show that these enzymes are less dependent upon the use of Sec for the reduction of substrates. We posit that the mechanistic differences between TR1 and the TR3-like enzymes in this study are due to the presence of a "guiding bar", amino acids 407-422, found in TR1, but not TR3-like enzymes. The guiding bar, proposed by Becker and co-workers [Fritz-Wolf, K., Urig, S., and Becker, K. (2007) The structure of human thioredoxin reductase 1 provides insights into C-terminal rearrangements during catalysis. J. Mol. Biol. 370, 116-127], restricts the motion of the C-terminal tail containing the C-terminal Gly-Cys-Sec-Gly, redox active tetrapeptide so that only this C-terminal redox center can be reduced by the N-terminal redox center, with the exclusion of most other substrates. This makes TR1 highly dependent upon the use of Sec because the selenium atom is responsible for both accepting electrons from the N-terminal redox center and donating them to the substrate in this model. Loss of both Se-electrophilicity and Se-nucleophilicity in the Sec → Cys mutant of TR1 greatly reduces catalytic activity. TR3-like enzymes, in contrast, are less dependent upon the use of Sec because the absence of the guiding bar in these enzymes allows for greater access of the substrate to the N-terminal redox center and because they can make use of alternative mechanistic pathways that are not available to TR1.


Membranes to achieve immunoprotection of transplanted islets.
Transplantation of islet or beta cells is seen as the cure for type 1 diabetes since it allows physiological regulation of blood glucose levels without requiring any compliance from the patients. In order to circumvent the use of immunosuppressive drugs (and their side effects), semipermeable membranes have been developed to encapsulate and immunoprotect transplanted cells. This review presents the historical developments of immunoisolation and provides an update on the current research in this field. A particular emphasis is laid on the fabrication, characterization and performance of membranes developed for immunoisolation applications.


Effect of heat treatment on hepatitis A virus and norovirus in New Zealand greenshell mussels (Perna canaliculus) by quantitative real-time reverse transcription PCR and cell culture.
Quantitative real-time reverse transcription PCR (qRT-PCR) and cell culture (50% tissue culture infectious dose [TCID50]) were used to determine the effect of heat treatments on norovirus and hepatitis A virus (HAV) in the New Zealand Greenshell mussel (Perna canaliculus). Since it is common practice to cook mussels until the shells open, internal temperatures and opening times of mussels on boiling and steaming were determined at regular time intervals. Fifty mussels in batches of six were exposed to boiling and steaming. A mean internal temperature of 90 degrees C (recommended for virus inactivation when maintained for 90 s) was reached after boiling for 170 s, with all 50 mussels open at 210 s. For steaming, the mean internal temperature achieved was only 83 degrees C after 300 s, and all 50 mussels were open. When mussels were steamed for 180 s (mean internal temperature of 63 degrees C), a significant 1.5-log decrease in the HAV titer (log TCID50) was observed. Following the immersion of mussels in boiling water for 180 s (mean internal temperature of 92 degrees C), no viable HAV was detected. For both boiling and steaming experiments, there was no significant change in the norovirus or HAV qRT-PCR titers compared with the controls. Our results show that when New Zealand Greenshell mussels open on heating, their internal temperature may not reach the parameters required for virus inactivation. Immersion for a minimum of 3 min in boiling water rather than steaming is recommended to reduce the risk of viral foodborne illness from contaminated shellfish.


Influence of electrode positioning on accuracy and reproducibility of electrical velocimetry cardiac output measurements.
Electrical velocimetry (EV) is one of the most recent adaptions of impedance cardiography. Previous studies yielded diverging results identifying several factors negatively influencing accuracy. Although electrode arrangement is suspected to be an influencing factor for impedance cardiography in general, no data for EV is available. We aimed to prospectively assess the influence of electrode position on the accuracy and reproducibility of cardiac output (CO) measurements obtained by EV. Two pairs of standard electrocardiographic electrodes were placed at predefined positions of the thorax in 81 patients. The inter-electrode gap was varied between either 5 or 15 cm by caudal movement of the lowest electrode. Measurements were averaged over 20 s and performed twice at each electrode position. Reference values were determined using cardiac magnetic resonance imaging (CMR). Mean bias was 1.2 ± 1.6 l min(-1) (percentage error 22 ± 28%) between COCMR and COEV at the 5 cm gap significantly improving to 0.5 ± 1.6 l min(-1) (8 ± 28%) when increasing the gap (p < 0.0001). The mean difference between repeated measurements was 0.0 ± 0.3 l min(-1) for the 5 cm and 0.1 ± 0.3 l min(-1) for the 15 cm gap, respectively (p = 0.3). The accuracy of EV can be significantly improved when increasing the lower inter-electrode gap still exceeding the Critchley and Critchley recommendations. Therefore, absolute values should not be used interchangeably in clinical routine. As the reproducibility was not negatively affected, serial hemodynamic measurements can be reliably acquired in stable patients when the electrode position remains unchanged.


Structures of the cyanobacterial circadian oscillator frozen in a fully assembled state.
Cyanobacteria have a robust circadian oscillator, known as the Kai system. Reconstituted from the purified protein components KaiC, KaiB, and KaiA, it can tick autonomously in the presence of adenosine 5'-triphosphate (ATP). The KaiC hexamers enter a natural 24-hour reaction cycle of autophosphorylation and assembly with KaiB and KaiA in numerous diverse forms. We describe the preparation of stoichiometrically well-defined assemblies of KaiCB and KaiCBA, as monitored by native mass spectrometry, allowing for a structural characterization by single-particle cryo-electron microscopy and mass spectrometry. Our data reveal details of the interactions between the Kai proteins and provide a structural basis to understand periodic assembly of the protein oscillator.


Ciclosporin monitoring in kidney-transplanted children: high-performance liquid chromatography versus radioimmunoassay.
Due to large individual differences in absorption, utilization and metabolism of the predominantly used drug ciclosporin (CsA) for selective immunosuppression in kidney graft recipients, therapeutic blood levels (immunosuppression/toxicity) can be maintained only by frequent measurements of the CsA concentrations in blood samples and dosage readjustments. The purpose of the present study was to investigate the usefulness of a high-performance liquid chromatography (HPLC) method for native CsA and a radioimmunoassay (RIA) method for CsA and metabolites measuring simultaneously using both HPLC and RIA and creatinine serum levels (Crea) in whole blood samples from 19 kidney-transplanted children over a 3-year observation period. By comparison of the results of HPLC, RIA and Crea determinations (n = 1,284) we found a highly variable metabolization rate (RIA/HPLC ratio) of 5.25 +/- 2.33 (range 1.37-12.9). No direct correlation was found between changes in RIA/HPLC ratios and kidney function, rejection and infection periods. Dosage/HPLC and dosage/RIA showed no significant correlation. A higher correlation between HPLC, Crea and nephrotoxicity was found than between RIA and Crea. Because of rapid and large variations of CsA metabolization rates in young allograft recipients, we recommend measurements of CsA blood concentrations with any HPLC method specific for unchanged drug, since CsA metabolites detected by RIA, at least those which are most abundant, have less immunosuppressive and toxic effects.


Evaluation of the neck mass.
The differential diagnosis of a neck mass is extensive and varies with the age of the patient at presentation. A thorough work-up including an accurate history and complete head and neck examination often narrows the diagnostic possibilities. The fine needle aspiration biopsy has become an invaluable tool to aid clinicians in the evaluation of the neck mass and is safe, accurate, and cost-effective with minimal complications. The possibility of malignancy in any age group, especially in the late adult group, should never be overlooked. Close follow-up and aggressive pursuit of a diagnosis with appropriate work-up facilitates a timely and accurate treatment plan, which is essential to a favorable outcome.


Breaking a Dogma: High-Throughput Live-Cell Imaging in Real-Time with Hoechst 33342.
Automated high-throughput live cell imaging (LCI) enables investigation of substance effects on cells in vitro. Usually, cell number is analyzed by phase-contrast imaging, which is reliable only for a few cell types. Therefore, an accurate cell counting method, such as staining the nuclei with Hoechst 33342 before LCI, will be desirable. However, since the mid-1980s, the dogma exists that Hoechst can only be used for endpoint analyses because of its cytotoxic properties and the potentially phototoxic effects of the excitation light. Since microscopic camera sensitivity has significantly improved, this study investigates whether this dogma is still justified. Therefore, exposure parameters are optimized using a 4× objective, and the minimum required Hoechst concentration is evaluated, allowing LCI at 30-min intervals over 5 days. Remarkably, a Hoechst concentration of only 57 × 10-9 m significantly inhibits proliferation and thus impairs cell viability. However, Hoechst concentrations between 7 × 10-9 and 28 × 10-9 m can be determined, which are neither cytotoxic nor impacting cell viability, proliferation, or signaling pathways. The method can be adapted to regular inverted fluorescence microscopes and allows, for example, to determine the cytotoxicity of a substance or the transduction efficiency, with the advantage that the analysis can be repeated at any desired time point.


A Stoichiometric Solvent-Free Protocol for Acetylation Reactions.
Considering the remarkable relevance of acetylated derivatives of phenols, alcohols, and aryl and alkyl thiols in different areas of biology, as well as in synthetic organic chemistry, a sustainable solvent-free approach to perform acetylation reactions is proposed here. Acetylation reactions are classically performed using excess of acetic anhydride (Ac2O) in solvent-free conditions or by eventually working with stoichiometric amounts of Ac2O in organic solvents; both methods require the addition of basic or acid catalysts to promote the esterification. Therefore, they usually lead to the generation of high amounts of wastes, which sensibly raise the E-factor of the process. With the aim to develop a more sustainable system, a solvent-free, stoichiometric acetylation protocol is, thus, proposed. The naturally occurring phenol, thymol, can be converted to the corresponding-biologically active-ester with good yields, in the presence of 1% of VOSO4. Interestingly, the process can be efficiently adopted to synthesize other thymyl esters, as well as to perform acetylation of alcohols and aryl and alkyl thiols. Remarkably, a further improvement has been achieved replacing Ac2O with its greener alternative, isopropenyl acetate (IPA).


Deep Venous Thrombosis in a Patient with a Moderate Pretest Probability and a Negative D-Dimer Test: A Review of the Diagnostic Algorithms.
Modern diagnostic strategies of venous thromboembolism (VTE) have been developed. In this review, the diagnostic algorithms for deep-vein thrombosis (DVT) and their parameters are discussed individually in the context of reporting a case of DVT in a 43-year-old Caucasian female with a moderate pretest probability stratified by Wells' score and a negative high quality D-dimer test. The patient was on treatment with Xarelto (rivaroxaban), 20 mg PO daily at the time of presentation. The diagnosis was verified through a complete lower limb ultrasound (US). This case highlights the diagnostic challenges and pitfalls of the current algorithms, especially those seen in a subgroup of patients such as patients with cancer, pregnancy, recurrent VTE or are on anticoagulation therapy at the time of presentation. The diagnosis of DVT is less plausible in a patient who is on anticoagulation therapy, but physicians should be aware of such a possibility. Physicians should also know in advance the numerous clinically relevant limitations of D-dimer testing before interpreting the results. Unifying the current diagnostic strategies, modifying the current Wells' score and using the protocol of a whole-leg compression US instead of the limited US protocol are among the several cautious suggestions that have been proposed based on this review to possibly decrease the incidence of missed DVT.


Modified Nucleosides of Escherichia coli Ribosomal RNA.
The modified nucleosides of RNA are chemically altered versions of the standard A, G, U, and C nucleosides. This review reviews the nature and location of the modified nucleosides of Escherichia coli rRNA, the enzymes that form them, and their known and/or putative functional role. There are seven Ψ (pseudouridines) synthases to make the 11 pseudouridines in rRNA. There is disparity in numbers because RluC and RluD each make 3 pseudouridines. Crystal structures have shown that the Ψ synthase domain is a conserved fold found only in all five families of Ψ synthases. The conversion of uridine to Ψ has no precedent in known metabolic reactions. Other enzymes are known to cleave the glycosyl bond but none carry out rotation of the base and rejoining to the ribose while still enzyme bound. Ten methyltransferases (MTs) are needed to make all the methylated nucleosides in 16S RNA, and 14 are needed for 23S RNA. Biochemical studies indicate that the modes of substrate recognition are idiosyncratic for each Ψ synthase since no common mode of recognition has been detected in studies of the seven synthases. Eight of the 24 expected MTs have been identified, and six crystal structures have been determined. Seven of the MTs and five of the structures are class I MTs with the appropriate protein fold plus unique appendages for the Ψ synthases. The remaining MT, RlmB, has the class IV trefoil knot fold.


Blood-specific isotopic discrimination factors in the Magellanic penguin (Spheniscus magellanicus).
The use of stable isotopes for ecological studies has increased exponentially in recent years. Isotopic trophic studies are based on the assumption that animals are what they eat plus a discrimination factor. The discrimination factor is affected by many variables and can be determined empirically. The Magellanic penguin is a highly abundant marine bird that plays a key role in the southern oceans. This study provides the first estimation of the Magellanic penguin blood discrimination factor for (13) C and (15) N. A two and a half month feeding experiment was performed, in which ten captive penguins were fed their main natural prey (anchovy Engraulis anchoita). The discrimination factors were estimated by comparing anchovy δ(13) C and δ(15) N values (obtained with isotope ratio mass spectrometry using lipid-extracted and bulk anchovy muscle) with penguin blood δ(13) C and δ(15) N values. Penguin blood was shown to be enriched, compared with anchovies, for (13) C and (15) N. No changes were observed in the stable isotope ratios of anchovies and discrimination factors during the experiment. The overall discrimination factors were 0.93 ± 0.12 (bulk) and 0.41 ± 0.12 (lipid-free) for (13) C; and 2.81 ± 0.17 (bulk) and 2.31 ± 0.17 (lipid-free) for (15) N. Having an accurate discrimination factor for the studied species is key in any trophic or food web isotopic study. Comparisons of estimated diet-to-blood discrimination factors with published values of aquatic piscivore birds showed that the (13) C discrimination factor is particularly variable, and therefore ecologists should be cautious when using a surrogate value from other species. In this study, the Magellanic penguin discrimination factor of a tissue that does not require euthanasia was obtained, a fundamental input for trophic isotopic modeling of the species. Copyright © 2016 John Wiley & Sons, Ltd.


Role of BiPAP applied through endotracheal tube in unconscious patients suffering from acute exacerbation of COPD: a pilot study.
Mechanical ventilation is the recommended treatment in unconscious patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) and hypercapenic respiratory failure. But, in resource-poor countries, many of these patients are not able to afford this treatment due to financial constraints. The main aim of this study was to evaluate the usefulness, safety and cost-effectiveness of bilevel positive airway pressure (BiPAP) applied via endotracheal tube in such patients. Twenty patients with acute exacerbation of COPD and altered sensorium, who were unable to afford ventilatory support, were intubated and BiPAP therapy was provided to these patients through the endotracheal tube. The outcome of these patients was studied. The BiPAP success rate and hospital mortality were 85% (17/20) and 15% (3/20) respectively. BiPAP failure was associated with high sequential organ failure assessment (SOFA) score at the time of admission (P = 0.002). Improvement in Glasgow coma scale (GCS) score (P < 0.001), pH (P = 0.001), PaCO(2) (partial pressure of carbon dioxide) (P < 0.001), respiratory rate (P < 0.001), and SOFA score (P = 0.001) was observed among the responders following 2 hours of therapy. Only one of the responders developed aspiration pneumonitis, as a complication. The daily cost of BiPAP therapy was 8.75 times lower than the average cost of mechanical ventilation. This pilot study reveals that this treatment modality could be a safe, cost-effective and efficacious method of treatment in unconscious patients with acute exacerbation of COPD.


Highly Dispersed Ru Nanoparticles on Boron-Doped Ti3 C2 Tx (MXene) Nanosheets for Synergistic Enhancement of Electrocatalytic Hydrogen Evolution.
2D-layered materials have attracted increasing attention as low-cost supports for developing active catalysts for the hydrogen evolution reaction (HER). In addition, atomically thin Ti3 C2 Tx (MXene) nanosheets have surface termination groups (Tx : F, O, and OH), which are active sites for effective functionalization. In this work, heteroatom (boron)-doped Ti3 C2 Tx (MXene) nanosheets are developed as an efficient solid support to host ultrasmall ruthenium (Ru) nanoparticles for electrocatalytic HER. The quantum-mechanical first-principles calculations and electrochemical tests reveal that the B-doping onto 2D MXene nanosheets can largely improve the intermediate H* adsorption kinetics and reduce the charge-transfer resistance toward the HER, leading to increased reactivity of active sites and favorable electrode kinetics. Importantly, the newly designed electrocatalyst based on Ru nanoparticles supported on B-doped MXene (Ru@B-Ti3 C2 Tx ) nanosheets shows a remarkable catalytic activity with low overpotentials of 62.9 and 276.9 mV to drive 10 and 100 mA cm-2 , respectively, for the HER, while exhibiting excellent cycling stabilities. Moreover, according to the theoretical calculations, Ru@B-Ti3 C2 Tx exhibits a near-zero value of Gibbs free energy (ΔGH* = 0.002 eV) for the HER. This work introduces a facile strategy to functionalize MXene for use as a solid support for efficient electrocatalysts.


Patients' and their family members' experiences of participation in care following an acute exacerbation in chronic obstructive pulmonary disease: A phenomenological-hermeneutic study.
To explore the experiences of patients with chronic obstructive pulmonary disease and their family members relating both to participation in care during hospitalisation for an acute exacerbation in chronic obstructive pulmonary disease, and to the subsequent day-to-day care at home. When recovering from an exacerbation, the challenges associated with an unpredictable health condition dominate everyday life for patients and can involve their family members. Proper patient and family participation in care during discharge and follow-up can help patients to improve self-management. However, knowledge of the significance of patient and family participation for recovery and subsequent everyday life is still limited. This study adopted a longitudinal design informed by ethnographic fieldwork principles. Participant observations and interviews with 15 patients and 12 family members were conducted on a Danish hospital ward and twice at the participants' homes. A phenomenological-hermeneutic approach inspired by Ricoeur's theory of interpretation guided the data analysis. Participation in care was perceived as valuable, but could be associated with tensions and increased uncertainty. While patients mostly demonstrated a reactive approach to care, family members strived to be more proactive. In hospital, preparing for discharge included an effort to find a balance between powerlessness and influence during interactions with healthcare professionals. At home, managing further recovery and self-management were characterised by navigating between mutual pressure and consideration within the family. Family members play an important role in ensuring that patients are seen, heard and understood, but want to be acknowledged more by healthcare professionals. Appropriate interactions with healthcare professionals are crucial in order to support discharge and daily self-management. Knowledge of the challenges that patients with chronic obstructive pulmonary disease and their family members face in participating in care activities could inform future development of family-centred care approaches tailored to individual needs.


[Therefore force, when obsession is present?].
To force somebody means inflict pressure on him. Obsessive-compulsive behaviour (OCB) is a feature of relationships. In early infancy, repetitive biological functions rapidly become automatic psychic functions. Small children often try to relate to their surrounding in a constrained manner in order to re-establish their omnipotence. Play and transitional space are opposites of OCB. Anxiety and constraints show an inverse relation to each other. In many cases, OCB in infants and small children has no clinical relevance. OCB is characterised by a high intrapsychic persistence during the whole period of psychophysic development. Obsessive-compulsive diseases (OCD) may serve as defence against oedipal strivings or against psychotic functioning. It is addressed against the self, an inner object or a relevant person of the surrounding. OCD correspond to a relational illness. In this situation an involved person becomes rapidly involved in the constraint problem. To maintain an adequate form of relationship within such transferential movements, a continuous "unchaining" is necessary. During transference, regressive anxieties and rages are expressed in a personalised form. Verbalised by the therapist, they become ready for transformation. The relationship may now open up to allow the inclusion of a third person.


Supported Lipid Bilayer Platform To Test Inhibitors of the Membrane Attack Complex: Insights into Biomacromolecular Assembly and Regulation.
Complement activation plays an important role in innate immune defense by triggering formation of the membrane attack complex (MAC), which is a biomacromolecular assembly that exhibits membrane-lytic activity against foreign invaders including various pathogens and biomaterials. Understanding the details of MAC structure and function has been the subject of extensive work involving bulk liposome and erythrocyte assays. However, it is difficult to characterize the mechanism of action of MAC inhibitor drug candidates using the conventional assays. To address this issue, we employ a biomimetic supported lipid bilayer platform to investigate how two MAC inhibitors, vitronectin and clusterin, interfere with MAC assembly in a sequential addition format, as monitored by the quartz crystal microbalance-dissipation (QCM-D) technique. Two experimental strategies based on modular assembly were selected, precincubation of inhibitor and C5b-7 complex before addition to the lipid bilayer or initial addition of inhibitor followed by the C5b-7 complex. The findings indicate that vitronectin inhibits membrane association of C5b-7 via a direct interaction with C5b-7 and via competitive membrane association onto the supported lipid bilayer. On the other hand, clusterin directly interacts with C5b-7 such that C5b-7 is still able to bind to the lipid bilayer, and clusterin affects the subsequent binding of other complement proteins involved in the MAC assembly. Taken together, the findings in this study outline a biomimetic approach based on supported lipid bilayers to explore the interactions between complement proteins and inhibitors, thereby offering insight into MAC assembly and regulation.


[Detection rate of organochlorine pesticides and viral hepatitis B markers in patients with pulmonary tuberculosis].
Three hundred and fifty six patients with active forms of pulmonary tuberculosis were studied for organochlorine pesticides (OCP) and viral hepatitis B markers (VHBM) in their body. A combination of OCP and VHBM was detected in 37.4%, 63.2 and 61.5% had OCP and VHBM, respectively. Detection rates for pesticides and VHBM were not related to the place of residence (town or village) or the clinical type of pulmonary tuberculosis. However, the blood levels of OCP were significantly higher in rural patients and in patients with advanced pulmonary tuberculosis than in urban patients and in patients with restrictive pulmonary tuberculosis.


Making hybrids of two-hybrid systems.
Two-hybrid systems are powerful tools to find new partners for a protein of interest. However, exchange of material between two-hybrid users has been handicapped by the various versions of two-hybrid systems available and by the widely accepted idea that they are not compatible. In the present paper we show that, contrary to the dogma, the most often used two-hybrid systems may be combined by either transformation or mating assays. The protocol to be followed in each case is provided. This will greatly increase the prospects of the growing network of interacting proteins, by reconciling the "two-hybrid systems" and the "interaction trap".


Environmental chemicals active as human antiandrogens do not activate a stickleback androgen receptor but enhance a feminising effect of oestrogen in roach.
Sexual disruption is reported in wild fish populations living in freshwaters receiving discharges of wastewater treatment works (WwTW) effluents and is associated primarily with the feminisation of males by exposure to oestrogenic chemicals. Antiandrogens could also contribute to the feminisation of male fish, but there are far less data supporting this hypothesis and almost nothing is known for the effects of oestrogens in combination with antiandrogens in fish. We conducted a series of in vivo exposures in two fish species to investigate the potency on reproductive-relevant endpoints of the antiandrogenic antimicrobials triclosan (TCS), chlorophene (CP) and dichlorophene (DCP) and the resin, abietic acid (AbA), all found widely in WwTW effluents. We also undertook exposures with a mixture of antiandrogens and a mixture of antiandrogens in combination with the oestrogen 17α-ethinyloestradiol (EE2). In stickleback (Gasterosteus aculeatus), DCP showed a tendency to reduce spiggin induction in females androgenised by dihydrotestosterone (DHT), but these findings were not conclusive. In roach (Rutilus rutilus), exposures to DCP (178 days), or a mixture of TCS, CP and AbA (185 days), or to the model antiandrogen flutamide (FL, 178 days) had no effect on gonadal sex ratio or on the development of the reproductive ducts. Exposure to EE2 (1.5ng/L, 185 days) induced feminisation of the ducts in 17% of the males and in the mixture of antiandrogens (TCS, CP, AbA) in combination with EE2, almost all (96%) of the males had a feminised reproductive ducts. In stickleback androgen receptor (ARα and ARβ) transactivation assays, the model antiandrogens, FL and procymidone inhibited 11-ketotestosterone (11-KT) induced receptor activation, but none of the human antiandrogens, TCS, CP, DCP and AbA had an effect. These data indicate that antimicrobial antiandrogens in combination can contribute to the feminisation process in exposed males, but they do not appear to act through the androgen receptor in fish.


Interdependency of Reactive Oxygen Species generating and scavenging system in salt sensitive and salt tolerant cultivars of rice.
Salinity stress is a major constrain in the global rice production and hence serious efforts are being undertaken towards deciphering its remedial strategies. The comparative analysis of differential response of salt sensitive and salt tolerant lines is a judicious approach to obtain essential clues towards understanding the acquisition of salinity tolerance in rice plants. However, adaptation to salt stress is a fairly complex process and operates through different mechanisms. Among various mechanisms involved, the reactive oxygen species mediated salinity tolerance is believed to be critical as it evokes cascade of responses related to stress tolerance. In this background, the present paper for the first time evaluates the ROS generating and the scavenging system in tandem in both salt sensitive and salt tolerant cultivars of rice for getting better insight into salinity stress adaptation. Comparative analysis of ROS indicates the higher level of hydrogen peroxide (H2O2) and lower level of superoxide ions (O(2-)) in the salt tolerant as compared to salt sensitive cultivars. Specific activity of ROS generating enzyme, NADPH oxidase was also found to be more in the tolerant cultivars. Further, activities of various enzymes involved in enzymatic and non enzymatic antioxidant defence system were mostly higher in tolerant cultivars. The transcript level analysis of antioxidant enzymes were in alignment with the enzymatic activity. Other stress markers like proline were observed to be higher in tolerant varieties whereas, the level of malondialdehyde (MDA) equivalents and chlorophyll content were estimated to be more in sensitive. The present study showed significant differences in the level of ROS production and antioxidant enzymes activities among sensitive and tolerant cultivars, suggesting their possible role in providing natural salt tolerance to selected cultivars of rice. Our study demonstrates that the cellular machinery for ROS production and scavenging system works in an interdependent manner to offer better salt stress adaptation in rice. The present work further highlights that the elevated level of H2O2 which is considered as a key determinant for conferring salt stress tolerance to rice might have originated through an alternative route of photocatalytic activity of chlorophyll.


Differential binding of SARS-CoV-2 Spike protein variants to its cognate receptor hACE2 using molecular modeling based binding analysis.
The current emergence of novel coronavirus, SARS-CoV-2 and its ceaseless expansion worldwide has posed a global health emergency that has adversely affected the humans. With the entire world striving to understand the newly emerged virus, differences in morbidity and infection rate of SARS-CoV-2 have been observed across varied geographic areas, which have been ascribed to viral mutation and evolution over time. The homotrimeric Spike (S) glycoprotein on the viral envelope surface is responsible for binding, priming, and initiating infection in the host. Our phylogeny analysis of 1947 sequences of S proteins indicated there is a change in amino acid (aa) from aspartate (Group-A) to glycine (Group-B) at position 614, near the receptor- binding domain (RBD; aa positions 331-524). The two variants are reported to be in circulation, disproportionately across the world, with Group-A dominant in Asia and Group-B in North America. The trimeric, monomeric, and RBD of S protein of both the variant groups (A & B) were modeled using the Swiss-Model server and were docked with the human receptor angiotensin-converting enzyme 2 (hACE2) employing the PatchDock server and visualized in PyMol. Group-A S protein's RBD bound imperceptibly to the two binding clefts of the hACE2 protein, on the other hand, Group-B S protein's RBD perfectly interacted inside the binding clefts of hACE2, with higher number of hydrogen and hydrophobic interactions. This implies that the S protein's amino acid at position 614 near the core RBD influences its interaction with the cognate hACE2 receptor, which may induce its infectivity that should be explored further with molecular and biochemical studies.


Fatty acids derived from a marine crustacean Diogenes avarus (Heller) and their antiangiogenic activity.
An organic extract from a marine crustacean D. avarus was examined for antiangiogenic activity by using the chick embryo chorioallantoic membrane (CAM) assay. The methanol extract (HCM) inhibited angiogenesis in a dose dependent manner. The extract was further fractionated by bioactivity-guided separation to purify the active fractions successively. This resulted in three fractions HCM1, HCM2 and HCM3. The 50% inhibition shown by HCM was 600 ng/disc, HCM1 was 100 ng/disc and of HCM3 was 2.7ng/disc. HCM3 which was separated by column chromatography and showed single spot on TLC was analysed by GLC and showed the presence of saturated and unsaturated fatty acids such as lauric, myristic, palmitic, stearic, oleic, linoleic. The antiangiogenic activity of the fatty acids obtained from a marine crustacean is reported for the first time.


Qualitative analysis of patient-centered decision attributes associated with initiating hepatitis C treatment.
In this era of a constantly changing landscape of antiviral treatment options for chronic viral hepatitis C (CHC), shared clinical decision-making addresses the need to engage patients in complex treatment decisions. However, little is known about the decision attributes that CHC patients consider when making treatment decisions. We identify key patient-centered decision attributes, and explore relationships among these attributes, to help inform the development of a future CHC shared decision-making aid. Semi-structured qualitative interviews with CHC patients at four Veterans Health Administration (VHA) hospitals, in three comparison groups: contemplating CHC treatment at the time of data collection (Group 1), recently declined CHC treatment (Group 2), or recently started CHC treatment (Group 3). Participant descriptions of decision attributes were analyzed for the entire sample as well as by patient group and by gender. Twenty-nine Veteran patients participated (21 males, eight females): 12 were contemplating treatment, nine had recently declined treatment, and eight had recently started treatment. Patients on average described eight (range 5-13) decision attributes. The attributes most frequently reported overall were: physical side effects (83%); treatment efficacy (79%), new treatment drugs in development (55%); psychological side effects (55%); and condition of the liver (52%), with some variation based on group and gender. Personal life circumstance attributes (such as availability of family support and the burden of financial responsibilities) influencing treatment decisions were also noted by all participants. Multiple decision attributes were interrelated in highly complex ways. Participants considered numerous attributes in their CHC treatment decisions. A better understanding of these attributes that influence patient decision-making is crucial in order to inform patient-centered clinical approaches to care (such as shared decision-making augmented with relevant decision-making aids) that respond to patients' needs, preferences, and circumstances.


Volumetric Modulated Arc (Radio) Therapy in Pets Treatment: The "La Cittadina Fondazione" Experience.
Volumetric Modulated Arc Therapy (VMAT) is a modern technique, widely used in human radiotherapy, which allows a high dose to be delivered to tumor volumes and low doses to the surrounding organs at risk (OAR). Veterinary clinics takes advantage of this feature due to the small target volumes and distances between the target and the OAR. Sparing the OAR permits dose escalation, and hypofractionation regimens reduce the number of treatment sessions with a simpler manageability in the veterinary field. Multimodal volumes definition is mandatory for the small volumes involved and a positioning device precisely reproducible with a setup confirmation is needed before each session for avoiding missing the target. Additionally, the elaborate treatment plan must pursue hard constraints and objectives, and its feasibility must be evaluated with a per patient quality control. The aim of this work is to report results with regard to brain meningiomas and gliomas, trigeminal nerve tumors, brachial plexus tumors, adrenal tumors with vascular invasion and rabbit thymomas, in comparison with literature to determine if VMAT is a safe and viable alternative to surgery or chemotherapy alone, or as an adjuvant therapy in pets.


Preliminary investigation of air bubbling and dietary sulfur reduction to mitigate hydrogen sulfide and odor from swine waste.
When livestock manure slurry is agitated, the sudden release of hydrogen sulfide (H(2)S) can raise concentrations to dangerous levels. Low-level air bubbling and dietary S reduction were evaluated as methods for reducing peak H(2)S emissions from swine (Sus scrofa) manure slurry samples. In a first experiment, 15-L slurry samples were stored in bench-scale digesters and continuously bubbled with air at 0 (control), 5, or 10 mL min(-1) for 28 d. The 5-L headspace of each digester was also continuously ventilated at 40 mL min(-1) and the mean H(2)S concentration in the outlet air was <10 microL L(-1). On Day 28, the slurry was agitated suddenly. The peak H(2)S concentration exceeded instrument range (>120 microL L(-1)) from the control treatment, and was 47 and 3.4 microL L(-1) for the 5 and 10 mL min(-1) treatments, respectively. In a second experiment, individually penned barrows were fed rations with dietary S concentrations of 0.34, 0.24, and 0.15% (w/w). Slurry derived from each diet was bubbled with air in bench-scale digesters, as before, at 10 mL min(-1) for 12 d and the mean H(2)S concentration in the digester outlet air was 11 microL L(-1). On Day 12, the slurry was agitated but the H(2)S emissions did not change significantly. Both low-level bubbling of air through slurry and dietary S reduction appear to be viable methods for reducing peak H(2)S emissions from swine manure slurry at a bench scale, but these approaches must be validated at larger scales.


Ferroelastic n-butylammonium dihydrogenphosphate.
Crystals of n-butylammonium dihydrogenphosphate, C(4)H(9)NH(3)(+).H(2)PO(4)(-), reveal ferroelasticity at room temperature and a number of phase transitions when heated up to approximately 373 K. Some of these phase transitions show hysteresis effects. All atoms except two H atoms exist in pairs linked by the lost symmetry operations derived from the prototypic space group P2/b2(1)/n2(1)/a. Each of these two different H atoms is involved in an asymmetric hydrogen bond between an oxygen pair. Ferroelastic switching is concomitant with jumps of these hydrogen species from donor to acceptor O atoms. The studied structure belongs to the structural family of n-hexyl- to n-decylammonium dihydrogenphosphates and differs by localization of alternating layers from n-propyl- and n-pentylammonium dihydrogenphosphates. The studied crystal was slightly twinned; the minor domain constituted approximately 2%.


Sandstones of unexpectedly high diffusibility.
Measurements have been made of diffusion coefficients (D(i)=-mass flux/concentration gradient) using a double reservoir, steady-state method with two tracers, CaBr(2) and amino-G-acid, on intact samples of Triassic red-bed sandstone from northwest England. Diffusibility (D'=D(i)/diffusion coefficient in water) averages 0.124, ranging between 0.075 and 0.215 (porosity 0.1 to 0.24), very similar for the two tracers. Implied tortuosities (actual path length/straight line length) average 1.21 (range 1.06 to 1.47), with constrictivities close to 1. In comparison with limited red-bed sandstone data from elsewhere, these D' values are up to 4 times greater, and tortuosity correspondingly lower. Re-interpretation of formation factor data from previous studies on shallow sandstone samples also from northwest England confirms that diffusibility is significantly higher in these sandstones than others from similar palaeoenvironment/stratigraphic units. The lower tortuosities appear to result from the relatively high permeability, open fabric of the rock, properties likely to be present in shallow sandstone systems used for water supply. It is concluded that diffusion rates may, in some shallow freshwater-containing continental sandstone systems, be significantly greater than is implied by estimates of sandstone diffusibility current in the literature.


[Effect of gas-lift device on nitrogen removal efficiency of ANAMMOX reactor ].
The effect of air-lift device on the nitrogen removal efficiency of ANAMMOX reactor was studied by increasing the substrate concentration to improve nitrogen load rate and inoculate ANAMMOX sludge. The results showed that the effluent recirculation was achieved by using nitrogen gas produced from the ANAMMOX process as power in the air-lift room. With the increase of nitrogen removal rate, the rate of effluent recirculation was increased, which diluted influent substrate concentration and alleviated the inhibition of ANAMMOX bacteria,. After 183 d operation, the effluent NH4+ -N and NO2- -N concentrations were increased to 46. 3 mg L-1 and 53.21 mg.L-1, and the nitrogen removal rate was kept stable at 28.3 kg (m3.d)-1, when the influent NH4+ -N and NO2- -N concentrations were increased to 700 mg.L-1 and 840 mgL-1, respectively. The effluent recirculation system formed by gas-lift devices is an economic and effective solution to the inhibition caused by high substrate concentration in traditional reactor, meanwhile, the power consumption of the external reflux pump was reduced.


Sargassopenillines A-G, 6,6-spiroketals from the alga-derived fungi Penicillium thomii and Penicillium lividum.
Seven new 6,6-spiroketals, sargassopenillines A-G (1-7) were isolated from the alga-derived fungi Penicillium thomii KMM 4645 and Penicillium lividum KMM 4663. The structures of these metabolites were determined by HR-MS and 1D and 2D NMR. The absolute configurations of compounds 1, 5 and 6 were assigned by the modified Mosher's method and by CD data. Sargassopenilline C (3) inhibited the transcriptional activity of the oncogenic nuclear factor AP-1 with an IC50 value of 15 µM.


An interpretative phenomenological analysis of the experiences of older people self-managing cancer pain at home.
Cancer is predominantly an illness affecting older people, yet there is a higher risk of under-treated pain in this age group. Many older people are required to self-manage their cancer pain at home but this is currently an under-researched and poorly understood area. We explored the experiences of older adults who self-manage cancer pain at home using an Interpretative Phenomenological Analytic approach. Eight older adults (aged 72-85 years) were recruited from a hospital in the United Kingdom and interviewed using a semi-structured questionnaire. Themes which emerged from the analysis suggest the self-management of cancer pain involves a perceived loss of control followed by a temporal process of gaining control over pain. Subordinate themes reflected the physical and social restrictions caused by pain; leading to fears regarding familial burden. Participants utilized inner strengths, past experiences, and social support to cope. Successful self-management of cancer pain in late life is conceptualized utilizing a positive psychology framework.


EFNA3 Is a Prognostic Biomarker Correlated With Immune Cell Infiltration and Immune Checkpoints in Gastric Cancer.
Background: Ephrin A3 (EFNA3), like most genes in the ephrin family, plays a central role in embryonic development and can be dysregulated in a variety of tumors. However, the relationship between EFNA3 and gastric cancer (GC) prognosis and tumor-infiltrating lymphocytes remains unclear. Methods: Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) were used to analyze the expression of EFNA3. Kaplan-Meier plots and GEPIA2 were used to evaluate the relationship between EFNA3 expression and GC prognosis. Univariable survival and multivariate Cox analyses were used to compare various clinical characteristics with survival. LinkedOmics database was used for gene set enrichment analysis (GSEA). TIMER database and CIBERSORT algorithm were used to examine the relationship between EFNA3 expression and immune infiltration in GC and to explore cumulative survival in GC. The relationship between EFNA3 and immune checkpoints was examined using cBioPortal genomics analysis. Finally, EFNA3 expression in GC cells and tissues was assayed using quantitative real-time polymerase chain reaction. Results: EFNA3 expression differs in a variety of cancers, and EFNA3 expression was higher in GC tissue than normal gastric tissue. GC patients with high expression of EFNA3 had worse overall survival, disease-free survival, and first progression. Multivariate analysis identified EFNA3 as an independent prognostic factor for GC. GSEA identified ribosome, cell cycle, ribosome biogenesis in eukaryotes, and aminoacyl-tRNA biosynthesis pathways as differentially enriched in patients with high EFNA3 expression. B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells were significantly negatively correlated with a variety of immune markers. EFNA3 participates in changes in GC immune checkpoint markers in a collinear manner. EFNA3 expression in HGC-27, AGS, MKN45, and NCI-N87 was cell lines higher than that in GES-1, and patients with high expression of EFNA3 had a worse prognosis. Conclusion: EFNA3 can be used as a prognostic and immune infiltration and checkpoint marker in GC patients.


Blood flow to the haemopoietic bone marrow.
In order to maintain an adequate haemopoiesis, the bone marrow is dependent on a sufficient blood supply. Our understanding of the regulation of marrow perfusion remained patchy for several decades, mainly because of technological difficulties. Recent advances in methodology have permitted more detailed analyses of bone marrow perfusion. Enhanced stimulation of erythropoietic or leucopoietic activity leads to increased blood flow to the bone marrow. There is evidence that this vasodilatory effect is mediated by the cytokines erythropoietin and granulocyte colony-stimulating factor; however, a direct link has yet to be firmly established. The presence of receptors for several other cytokines on vascular endothelial and smooth muscle cells suggests that these may also have a regulatory role. The vasodilating factor nitric oxide (NO) regulates bone marrow blood flow both under normal conditions and during accelerated haemopoiesis, and NO is possibly induced via activation of cytokine receptors. There are conflicting reports as to how catecholamines affect marrow vascular tone. Although there is firm evidence that the bone marrow vasculature is innervated, no definite role of this innervation in vasoregulation has been documented. Advances in bone marrow/blood stem cell transplantation technology and the development of other therapeutic strategies for bone marrow failure may in part be dependent on optimization of the blood supply to the haemopoietic bone marrow.


Does a specialist voice clinic change ENT clinic diagnosis?
General ENT clinics lack the high quality diagnostic equipment and multidisciplinary advice that is available in the voice clinic. We wished to find out if referral to a specialist voice clinic from general ENT consultant clinics resulted in a change in diagnosis. Lists of voice clinic attendees were reviewed between January 2003 and May 2004. Notes were obtained for 20 patients who attended voice clinic after referral from a general ENT clinic: 3 had no diagnosis on referral to voice clinic, a diagnosis was given after attendance; 8 had their referring diagnosis changed by attendance; and 9 had no change. The voice clinic adds diagnostic value to the service available in general ENT clinics.


A Framework of Industrialized Building Assessment in China Based on the Structural Equation Model.
Compared with the conventional building, the industrialized building (IB) promotes the sustainable development of the construction industry, which will become a growth trend in the future. Nevertheless, the progress of industrialized building is intimately affected through the scientific evaluating mechanism, which still requires more research. Thus, this study establishes a conceptual framework of industrialized building assessment (IBA), which is validated through exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). The impact between efficiency and the other five dimensions are studied by the structural equations model (SEM). The findings indicated that the conceptual framework is valid, and the efficiency has a positive impact on economic factors, livability, safety, environmental factors, and social benefits. Consequently, the improvement of efficiency has turned out to be the primary issue for improving the growth of the industrialized building. This research explores the basic framework of industrialized building assessment and provides a basis to establish a comprehensive and precise industrial building evaluation mechanism in the near future.


Efficacy of oral pyronaridine for the treatment of acute uncomplicated falciparum malaria in African children.
Pyronaridine is a new antimalarial agent developed in China. In this randomized, unblinded study, the safety, tolerance, and clinical efficacy of pyronaridine (n = 44) were evaluated and compared with those of chloroquine (n = 44), the standard first-line antimalarial drug in most of Africa, in 88 Cameroonian children with acute uncomplicated falciparum malaria. The target sample size was determined to detect a 35% difference in in vivo resistance between the two treatment groups, with 95% power. Clinical and parasitological responses were monitored for 14 days on an outpatient basis. Seven children (3 treated with pyronaridine and 4 treated with chloroquine) were lost to follow-up and were excluded from the analysis. All 41 patients treated with pyronaridine were cured. Treatment failure was observed in 16 (40%) of the 40 children treated with chloroquine. In vitro assays indicated that 23 of 40 clinical isolates obtained from patients treated with pyronaridine were resistant in vitro to chloroquine. Side effects associated with pyronaridine intake were minor and transient. Pyronaridine is safe and well tolerated by symptomatic Cameroonian children, and it is highly efficacious in Africa, where chloroquine resistance is well established.


Nuclear factors binding to the human immunoglobulin heavy-chain gene enhancer.
The human immunoglobulin heavy chain (IgH) gene contains at least two tissue-specific regulatory regions, which are similar to the mouse IgH gene. One is the J-C enhancer and another is located in the 5' promoter region. Using an electrophoretic mobility shift assay and DNase I footprint, we have examined the interaction of factors in B cell nuclear extracts with the two regulatory regions of the human IgH gene. We have identified a nuclear factor in mouse B cell nuclear extracts which bound to specific sequence in the human IgH enhancer. This factor is apparently not present in mouse fibroblast nuclear extracts. We also found factor(s) which bound to the highly conserved octanucleotide sequence within the human IgH enhancer and 5' promoter regions.


Factors affecting decision concerning influenza vaccination among students of medical faculties.
Influenza is one of the most common cyclic respiratory diseases in humans. Methods of prevention are multidirectional, but the most effective and most efficacious way to prevent influenza and its complications is through preventive vaccination. This work aims to determine different factors affecting the decision concerning influenza vaccine. The percentage of people vaccinated against the flu was evaluated, as well as their knowledge of post-influenza complications, etc. among full-time students and bridging studies of nursing and physiotherapy (full-time and part-time) at the University of Technology and Life Sciences in Radom, and students of medicine and pharmacy at the Medical University of Łódź. The research tool was the authors' questionnaire with 18 questions. The surveys conducted, consisting of multiple choice questions, were anonymous. In total, the survey involved 470 students. Overall, the number of people who were vaccinated against influenza in the 2012/13 epidemic season numbered 15 respondents, representing 5.84% of the total group of respondents. For the group of nursing students it was 6%, for physiotherapy students 5%, for students of medicine and pharmacy 14%. The percentage of respondents who said they would get vaccinated if the vaccinaton was free of charge was also low. Increasing the percentage of people vaccinated against influenza (immunization coverage) is a very important measure in preventing influenza epidemics. Therefore, it is necessary to identify the reasons why people are reluctant to be vaccinated against influenza, particularly among students who will work in the future in the health care services sector.


Size and physical map of the chromosome of Haemophilus influenzae.
A variation of pulse-field electrophoresis, field-inversion gel electrophoresis, was used to determine the size and physical map of the chromosome of Haemophilus influenzae. The DNA of H. influenzae had a low G + C content (39%) and no restriction sites for the enzymes NotI or SfiI. However, a number of restriction enzymes (SmaI, ApaI, NaeI, and SacII) that recognized 6-base-pair sequences containing only G and C nucleotides were found to generate a reasonable number of DNA fragments that were separable in agarose gels by field-inversion gel electrophoresis. The sizes of the DNA fragments were calibrated with a lambda DNA ladder and lambda DNA restriction fragments. The sum of fragment sizes obtained with restriction digests yielded a value for the chromosome of 1,980 kilobase pairs. Hybridization of a labeled fragment with two or more fragments from a digest with a different restriction enzyme provided the information needed to construct a circular map of the H. influenzae chromosome.


Strengthening spatial reasoning: elucidating the attentional and neural mechanisms associated with mental rotation skill development.
Spatial reasoning is a critical skill in many everyday tasks and in science, technology, engineering, and mathematics disciplines. The current study examined how training on mental rotation (a spatial reasoning task) impacts the completeness of an encoded representation and the ability to rotate the representation. We used a multisession, multimethod design with an active control group to determine how mental rotation ability impacts performance for a trained stimulus category and an untrained stimulus category. Participants in the experimental group (n = 18) showed greater improvement than the active control group (n = 18) on the mental rotation tasks. The number of saccades between objects decreased and saccade amplitude increased after training, suggesting that participants in the experimental group encoded more of the object and possibly had more complete mental representations after training. Functional magnetic resonance imaging data revealed distinct neural activation associated with mental rotation, notably in the right motor cortex and right lateral occipital cortex. These brain areas are often associated with rotation and encoding complete representations, respectively. Furthermore, logistic regression revealed that activation in these brain regions during the post-training scan significantly predicted training group assignment. Overall, the current study suggests that effective mental rotation training protocols should aim to improve the encoding and manipulation of mental representations.