Cyclists' perceived safety on intersections and roundabouts - A qualitative bicycle simulator study.
Although cycling provides both individual and societal benefits, the mode share in Germany remains at a relatively low level. One reason described in literature is the lack of perceived safety due to the cycling infrastructure, especially at junctions. The study addresses the influence of junction design on cyclists' perceived safety. Three intersections (BS: Berlin Standard, PI: protected intersection, CbC: cycle lanes between car lanes) and one roundabout were modeled in a virtual environment. Using a bicycle simulator, n = 46 participants cycled through each junction design, followed by a qualitative interview. We conducted a structured content analysis on the interview transcripts. Regarding the quality of statements, PI provides the highest level of perceived safety whereas CbC provides the lowest level. Both roundabout and BS provide medium to low perceived safety. Specific design features, such as continuous cycling infrastructure, physical separation and elements enhancing cyclists' visibility improve participants' perceived safety. On the other hand, curbs, bends, and elements obstructing visibility decrease perceived safety. Our findings also point towards a difference between overextending and manageable interactions between cars and cyclists. While manageable interactions raise attention to an appropriate extent, overextending interactions diminish the quality of the cycling experience so that some cyclists rather violate rules instead of using the designated cycling infrastructure. Furthermore, three factors influence participants' perception of infrastructure design: comprehensibility, comfort, and perceived safety. To provide a cycling friendly infrastructure, planners should consider cyclists' perceived safety as well as comfort and comprehensibility. Furthermore, in contrast to isolated segments, a continuous high-quality cycling infrastructure network should be implemented. Lastly, infrastructure might focus on manageable interactions rather than cause overextending interactions. The findings should be considered in future cycling infrastructure planning. Planners may test and modify temporary solutions to find appropriate designs for each junction.


Multiplex Analysis of Adipose-Derived Stem Cell (ASC) Immunophenotype Adaption to In Vitro Expansion.
In order to enhance the therapeutic potential, it is important that sufficient knowledge regarding the dynamic changes of adipose-derived stem cell (ASC) immunophenotypical and biological properties during in vitro growth is available. Consequently, we embarked on a study to follow the evolution of highly defined cell subsets from three unrelated donors in the course of eight passages on tissue culture polystyrene. The co-expression patterns were defined by panels encompassing seven and five cell surface markers, including CD34, CD146, CD166, CD200, CD248, CD271, and CD274 and CD29, CD31, CD36, CD201, and Stro-1, respectively. The analysis was performed using multichromatic flow cytometry. We observed a major paradigm shift, where the CD166-CD34+ combination which was found across all cell subsets early in the culture was replaced by the CD166+ phenotype as the population homogeneity increased with time. At all analysis points, the cultures were dominated by a few major clones that were highly prevalent in most of the donors. The selection process resulted in two predominant clones in the larger panel (CD166+CD34-CD146-CD271- CD274-CD248-CD200- and CD166+CD34+ CD146-CD271-CD274-CD248-CD200-) and one clone in the smaller panel (CD29+CD201+CD36- Stro-1- CD31-). The minor subsets, including CD166+CD34-CD146-CD271+CD274-CD248-CD200- and CD166+CD34+CD146+CD271-CD274-CD248-CD200-, and CD29+CD201-CD36-Stro-1-CD31-, CD29+CD201+CD36-Stro-1+CD31-, and CD29+CD201+CD36+Stro-1-CD31-, in the seven and five marker panels, respectively, were, on the other, hand highly fluctuating and donor-dependent. The results demonstrate that only a limited number of phenotypical repertoires are possible in ASC cultures. Marked differences in their relative occurrence between distinct individuals underscore the need for potency standardization of different ASC preparation to improve the clinical outcome.


Are human embryos Kantian persons?: Kantian considerations in favor of embryonic stem cell research.
One argument used by detractors of human embryonic stem cell research (hESCR) invokes Kant's formula of humanity, which proscribes treating persons solely as a means to an end, rather than as ends in themselves. According to Fuat S. Oduncu, for example, adhering to this imperative entails that human embryos should not be disaggregated to obtain pluripotent stem cells for hESCR. Given that human embryos are Kantian persons from the time of their conception, killing them to obtain their cells for research fails to treat them as ends in themselves. This argument assumes two points that are rather contentious given a Kantian framework. First, the argument assumes that when Kant maintains that humanity must be treated as an end in itself, he means to argue that all members of the species Homo sapiens must be treated as ends in themselves; that is, that Kant regards personhood as co-extensive with belonging to the species Homo sapiens. Second, the argument assumes that the event of conception is causally responsible for the genesis of a Kantian person and that, therefore, an embryo is a Kantian person from the time of its conception. In this paper, I will present challenges against these two assumptions by engaging in an exegetical study of some of Kant's works. First, I will illustrate that Kant did not use the term "humanity" to denote a biological species, but rather the capacity to set ends according to reason. Second, I will illustrate that it is difficult given a Kantian framework to denote conception (indeed any biological event) as causally responsible for the creation of a person. Kant ascribed to a dualistic view of human agency, and personhood, according to him, was derived from the supersensible capacity for reason. To argue that a Kantian person is generated due to the event of conception ignores Kant's insistence in various aspects of his work that it is not possible to understand the generation of a person qua a physical operation. Finally, I will end the paper by drawing from Allen Wood's work in Kantian philosophy in order to generate an argument in favor of hESCR.


Involvement of H-ras in erythroid differentiation of TF1 and human umbilical cord blood CD34 cells.
To investigate the role of the ras gene in erythroid differentiation, a human erythroleukemic cell line, TF1, was transduced with a selectable retroviral vector carrying a mammalian wild type H-ras gene or a cytoplasmic dominant negative RAS1 gene. Transduction of TF1 cells with the wild type H-ras gene resulted in changes of cell types and up-regulation of erythroid-specific gene expression similar to that seen in differentiating erythroid cells. The number of red blood cell containing colonies derived from TF1 cells transduced with wild type H-ras cDNA was significantly increased and the cells in the colonies were more hemoglobinized as estimated by a deeper red color compared to those colony cells from mock or dominant negative RAS1 gene transduced TF1 cells, suggesting increased erythroid differentiation of TF1 cells after transduction of wild type H-ras in vitro. The mRNA levels of beta- and gamma-, but not alpha-, globin genes were significantly higher in H-ras transduced TF1 cells than those in TF1 cells transduced with mock or dominant negative RAS1 gene. Moreover, a 4kb pre-mRNA of the Erythropoietin receptor (EpoR) was highly expressed only in H-ras transduced TF1 cells. Additionally, human umbilical cord blood (CB) CD34 cells which are highly enriched for hematopoietic stem/progenitor cells were transduced with the same retroviral vectors to evaluate in normal primary cells the activities of H-ras in erythroid differentiation. Increased numbers of erythroid cell containing colonies (BFU-E and CFU-GEMM) were observed in CD34 cells transduced with the H-ras cDNA, compared to that from mock transduced cells. These data suggest a possible role for ras in erythroid differentiation.


Modified Wicomb's apparatus for preservation of heart for 24 hours.
To prolong the time of heart preservation, we modified the Wicomb's perfusion apparatus, in which oxygen flow acts as the source of power and provides oxygenation for the perfused myocardium. Ten adult porcine hearts which had been preserved for 24 hours were resuscitated successfully and continued to beat steadily for more than 1.5-3 hours after reperfusion. Myocardial ultrastructure was observed at the end of preservation and 15-120 minutes after reperfusion. The damages of the myocardial ultrastructure at the end of preservation were reversible.


Highly efficient and consistent gene transfer into dendritic cells utilizing a combination of ultraviolet-irradiated adenovirus and poly(L-lysine) conjugates.
Dendritic cells (DCs) are capable of presenting tumor-associated antigens and subsequently play an essential role in T-cell activation. The aim of this study was to develop an efficient method for gene transfer into DCs. These genetically transduced DCs can then be used as potent inducers of specific cell-mediated immune response. When compared with physical methods for gene transfer (lipofection and calcium phosphate precipitation), adenovirus (AdV) vectors proved to be highly efficient for gene transfer into DCs. To overcome concomitant AdV gene expression and potential immunogenicity, AdVs were irradiated with UV. The UV dose was optimized to block AdV transcription without altering AdV receptor binding and endocytosis capacity. We subsequently used a polycationic amino acid compound, poly(L-lysine), to conjugate the irradiated AdVs to transgenes. The resulting complexes were found to mediate a highly efficient transfer of transgenes into DCs, without concomitant expression of AdV gene products. Low titers of irradiated AdVs were sufficient for a consistent gene transfer into DCs. This is the first study to demonstrate efficient, consistent, and practical gene transfer using an UV approach to irradiated AdV-poly(L-lysine) conjugates and should be useful for the development of DC-based tumor vaccine therapies.


Ultrasound for Venous Local Pulse Wave Velocity: Comparison of Pulse Transit Time Methods.
Venous pulse wave velocity (vPWV) is a potential marker for determining the state of venous hemodynamics, venosclerosis, and vascular filling. Although there have been several studies on pulse wave velocity through blood vessels, the majority have focused on arteries, with only limited studies on veins. To our knowledge, this study is the first to compare the local vPWV estimation metrices. An in vivo study was conducted on 10 participants where the jugular venous pulses (JVP) from two proximal sites were simultaneously acquired using a dual-element high frame rate system. The local vPWV was computed using different transit time-based techniques. The study demonstrates the comparison between vPWV ranges computed using thresholding, fiduciary point (c and v) and correlation-based approaches indicated as vPWV|th, vPWV|c, vPWV|v and vPWV|Xcorr respectively. High fidelity echo frames were acquired from the jugular vein (JV) at a temporal resolution of 2 ms and an amplitude resolution of 10 µm. The study findings indicated that the vPWV computed using various transit time metrics were comparable without significant bias (p > 0.05). Among the VPWV metrices, vPWV|th had the lowest beat-to-beat variation (CoV = 18 %). The mean deviations in vPWV|c, vPWV|v and vPWV|Xcorr values from vPWV|th were 0.28, 0.17 and 0.22 m/s respectively, where the average beat-to-beat variation was minimal. The results suggested that the thresholding and cross-correlation metrices offered better performance in comparison with the fiduciary point techniques for vPWV estimation.Clinical Relevance- The study demonstrated the potential of direct transit time methods to reliably estimate the local vPWV on the internal jugular vein.


The exposure of mom-influencers on social media: a potential threat to public health awareness.
The potential threat to public health awareness posed by mom-influencers on social media must be taken into account. In the meantime, the concept of fostering partnerships between health experts, the government and mom-influencers must be made accessible in order to promote the immediate availability of appropriate, accurate and trustworthy information to the public and adequate health education practices.


Attentional bias in depression: understanding mechanisms to improve training and treatment.
One of the most common symptoms of depression is the tendency to attend to negative stimuli in the world and negative thoughts in mind. This symptom is especially nefarious because it is also a cause - biasing processing to negatively valenced information, thus worsening mood, and exacerbating the condition. Here we attempt to systematize the diverse body of recent research on the negative attentional bias from across cognitive and clinical psychology in order to identify recurring themes and devise potential mechanistic explanations. We leverage theoretical progress in our understanding of healthy attention systems in terms of internal versus external components. With this lens, we review approaches to training attention that might reduce the negative attentional bias, including behavioral interventions and real-time neurofeedback. Although extant findings are somewhat mixed, these approaches provide hope and clues for the next generation of treatments.


Recognition of Fibrotic Infarct Density by the Pattern of Local Systolic-Diastolic Myocardial Electrical Impedance.
Myocardial electrical impedance is a biophysical property of the heart that is influenced by the intrinsic structural characteristics of the tissue. Therefore, the structural derangements elicited in a chronic myocardial infarction should cause specific changes in the local systolic-diastolic myocardial impedance, but this is not known. This study aimed to characterize the local changes of systolic-diastolic myocardial impedance in a healed myocardial infarction model. Six pigs were successfully submitted to 150 min of left anterior descending (LAD) coronary artery occlusion followed by reperfusion. 4 weeks later, myocardial impedance spectroscopy (1-1000 kHz) was measured at different infarction sites. The electrocardiogram, left ventricular (LV) pressure, LV dP/dt, and aortic blood flow (ABF) were also recorded. A total of 59 LV tissue samples were obtained and histopathological studies were performed to quantify the percentage of fibrosis. Samples were categorized as normal myocardium (<10% fibrosis), heterogeneous scar (10-50%) and dense scar (>50%). Resistivity of normal myocardium depicted phasic changes during the cardiac cycle and its amplitude markedly decreased in dense scar (18 ± 2 Ω·cm vs. 10 ± 1 Ω·cm, at 41 kHz; P < 0.001, respectively). The mean phasic resistivity decreased progressively from normal to heterogeneous and dense scar regions (285 ± 10 Ω·cm, 225 ± 25 Ω·cm, and 162 ± 6 Ω·cm, at 41 kHz; P < 0.001 respectively). Moreover, myocardial resistivity and phase angle correlated significantly with the degree of local fibrosis (resistivity: r = 0.86 at 1 kHz, P < 0.001; phase angle: r = 0.84 at 41 kHz, P < 0.001). Myocardial infarcted regions with greater fibrotic content show lower mean impedance values and more depressed systolic-diastolic dynamic impedance changes. In conclusion, this study reveals that differences in the degree of myocardial fibrosis can be detected in vivo by local measurement of phasic systolic-diastolic bioimpedance spectrum. Once this new bioimpedance method could be used via a catheter-based device, it would be of potential clinical applicability for the recognition of fibrotic tissue to guide the ablation of atrial or ventricular arrhythmias.


Diagnostic Accuracy of the INSHI Consensus Case Definition for the Diagnosis of Paradoxical Tuberculosis-IRIS.
The diagnosis of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) relies on characteristic clinical features synthesized as the International Network for the Study of HIV-associated IRIS (INSHI) case definition. There is no confirmatory laboratory test. Site B HIV-TB clinic in Khayelitsha, Cape Town, South Africa. Using data of participants with HIV-associated tuberculosis starting antiretroviral treatment from a prospective trial evaluating prednisone for TB-IRIS prevention, we applied latent class analysis to model a gold standard for TB-IRIS. The model-predicted probability of TB-IRIS for each participant was used to assess the performance of the INSHI case definition and compare its diagnostic accuracy with several adapted case definitions. Data for this analysis were complete for 217 participants; 41% developed TB-IRIS. Our latent class model included the following parameters: respiratory symptoms; night sweats; INSHI major criteria 1, 2, and 4; maximum C-reactive protein >90 mg/L; maximum heart rate >120/min; maximum temperature >37.7°C; and preantiretroviral therapy CD4 count <50 cells/µL. The model estimated a TB-IRIS incidence of 43% and had optimal goodness of fit (χ2 = 337, P = 1.0). The INSHI case definition displayed a sensitivity of 0.77 and a specificity of 0.86. Replacing all the minor INSHI criteria with objectives measures (C-reactive protein elevation, fever, and/or tachycardia) resulted in a definition with better diagnostic accuracy, with a sensitivity of 0.89 and a specificity of 0.88. The INSHI case definition identifies TB-IRIS with reasonable accuracy. Amending the case definition by replacing INSHI minor criteria with objective variables improved sensitivity without loss of specificity.


Ascorbate in plasma as measured by liquid chromatography and by dichlorophenolindophenol colorimetry.
Ascorbic acid was measured in 125 plasma samples by an automated colorimetric method involving dichlorophenolindophenol and by a "high-performance" liquid-chromatographic procedure with electrochemical detection. The two methods gave comparable results for samples with ascorbate concentrations of 1 to 20 mg/L (r = 0.97). We also measured the amount of total ascorbate (ascorbic acid + dehydroascorbic acid) in the same samples by a liquid-chromatographic procedure with precolumn derivitization of ascorbic acid. We confirmed that plasma contains little dehydroascorbic acid.


Autologus stem cell transplatation as a care option in elderly patients. A review.
The ageing population and the increase in life expectancy have put new social and health questions into the public health agenda of western countries. Hematological cancer incidence peaks in older population as a logical consequence of a longer lifespan promoting prolonged exposure to carcinogens and accumulation of genetic alterations. Hematological cancer represents a major cause of mortality in this age group despite recent progress observed in the management of cancer in the general population. Autologous stem cell transplantation (ASCT) represents a therapeutic option in the treatment of a large proportion of lymphomas and multiple myeloma, but their role in the onco-geriatric setting remains an open question, due to the presence of chronic disease. Ageing is characterized by progressive decrements in physiologic reserves and abilities to compensate for physical and/or functional limitations, which increase the risk of developing morbidity and disability. These events explains the extreme diversity of ageing individuals in terms of clinical and functional status. As a consequence, life expectancy in the elderly is influenced not only by the neoplastic diseases itself but also by the various co-morbidities common to this age group. The management of elderly people with hematological diseases potentially curative, should therefore combine both geriatric and tumor assessments. Among the elderly patients identified as being candidates for AHSCT, after the mobilization of progenitor cells from the bone marrow into the peripheral blood, the aphaeresis procedure is the most common method for collecting an adequate number of stem cells. The proper selection of patients may greatly improve the results and the toxicity related to cancer treatment in the elderly. We recommend the adoption of some form of geriatric assessment in the evaluation of any patient who is 70 years and older, this review intends to offer an overview of the state of art in ASCT in elderly patients.


Oral administration of Lactobacillus gasseri SBT2055 is effective in preventing Porphyromonas gingivalis-accelerated periodontal disease.
Probiotics have been used to treat gastrointestinal disorders. However, the effect of orally intubated probiotics on oral disease remains unclear. We assessed the potential of oral administration of Lactobacillus gasseri SBT2055 (LG2055) for Porphyromonas gingivalis infection. LG2055 treatment significantly reduced alveolar bone loss, detachment and disorganization of the periodontal ligament, and bacterial colonization by subsequent P. gingivalis challenge. Furthermore, the expression and secretion of TNF-α and IL-6 in gingival tissue was significantly decreased in LG2055-administered mice after bacterial infection. Conversely, mouse β-defensin-14 (mBD-14) mRNA and its peptide products were significantly increased in distant mucosal components as well as the intestinal tract to which LG2055 was introduced. Moreover, IL-1β and TNF-α production from THP-1 monocytes stimulated with P. gingivalis antigen was significantly reduced by the addition of human β-defensin-3. These results suggest that gastrically administered LG2055 can enhance immunoregulation followed by periodontitis prevention in oral mucosa via the gut immune system; i.e., the possibility of homing in innate immunity.


Service change and innovation in community end-of-life care during the COVID-19 pandemic: Qualitative analysis of a nationwide primary care survey.
Primary healthcare teams (general practice and community nursing services) within the United Kingdom provided the majority of community end-of-life care during COVID-19, alongside specialist palliative care services. As international healthcare systems move to a period of restoration following the first phases of the pandemic, the impact of rapidly-implemented service changes and innovations across primary and specialist palliative care services must be understood. To provide detailed insights and understanding into service changes and innovation that occurred in UK primary care to deliver end-of-life care during the first phase of the COVID-19 pandemic. Cross-sectional online survey. Responses were analysed using descriptive statistics and thematic analysis. United Kingdom survey of general practitioners and community nurses, circulated via regional and national professional networks. A total of 559 valid responses were received from 387 community nurses, 156 general practitioners and 16 'other'. Over a third of respondents (n = 224; 40.8%) experienced changes in the organisation of their team in order to provide end-of-life care in response to the COVID-19 pandemic. Three qualitative themes were identified: COVID-19 as a catalyst for change in primary palliative care; new opportunities for more responsive and technological ways of working; and pandemic factors that improved and strengthened interprofessional collaboration. Opportunity has arisen to incorporate cross-boundary service changes and innovations, implemented rapidly at the time of crisis, into future service delivery. Future research should focus on which service changes and innovations provide the most benefits, who for and how, within the context of increased patient need and complexity.


Successful mental health promotion with men: the evidence from 'tacit knowledge'.
There remains significant concern about men's mental health, particularly in terms of personal and societal barriers to help-seeking, negative coping mechanisms and high suicide rates. This article presents findings from a multi-phase study looking at 'what works' in mental health promotion for men. Work here reports the collection and analysis of the tacit knowledge of those working within mental health promotion interventions for men. A 'multiple hub and spoke' approach was used to assist data collection. Thirteen key players, active in the men's mental health field, half from the UK and half beyond, formed an Investigative Network collecting data, mainly through interviews, from wider geographical and professional community contexts where they had networks. The focus of data collection was on 'what works' in mental health promotion for men. Data was analysed using thematic analysis techniques. Findings suggest that settings which created safe male spaces acted to promote trust, reduce stigma and normalize men's engagement in interventions. Embedding interventions within the communities of men being engaged, fully involving these men, and holding 'male-positive' values engendered familiarity and consolidated trust. Using 'male-sensitive' language and activity-based approaches allowed for positive expressions of emotions, facilitated social engagement, and provided a base for open communication. Appropriate partnerships were also seen as a necessary requirement for success and as crucial for maximizing intervention impact. The importance of gender and 'masculinity' was apparent throughout these findings and taking time to understand gender could facilitate positive ways of working alongside men, increasing levels of engagement and successful outcomes.


Hepatic concentration of heat shock protein 70 kD (Hsp70) in broilers subjected to different thermal treatments.
1. The relationship between repeated thermal treatments and hepatic synthesis of Hsp 70 was studied in broiler chickens. 2. Sixty broilers were submitted to 5 different treatments (12 birds each) from day 1 to day 42. Four groups were kept in a thermoneutral environment and subjected to 0, 1, 2 and 3 heat stress episodes at 35 degrees C for 4 h per week (TN-0, TN-1, TN-2 and TN-3, respectively). The last group (HT-35) was reared at a room temperature of 35 degrees C. 3. From 39 to 42 old, the birds experienced acute heat stress at 41 degrees C. Resistance to heat stress was evaluated by the time taken for rectal temperature to increase by 3 degrees C above the pre-treatment value. Livers were collected (before and after heat stress) and Hsp70 was determined using Western Blot analysis with monoclonal anti-Hsp70 antibody. 4. Resistance to heat stress and concentration of Hsp70 were higher in those birds subjected to more heat stress episodes during the experimental period (TN-3) and HT-35. A positive correlation was observed between Hsp70 concentration and the time taken for a 3 degrees C increase in rectal temperature (r = 0.42; P<0.01). 5. Exposing birds to episodes of heat stress (35 degrees C) during rearing may improve their resistance to acute heat stress, but the previous thermal history did not seem to influence the hepatocyte Hsp70 content after exposure to more severe heat stress (41 degrees C).


Increased cerebral blood flow after single dose of antipsychotics in healthy volunteers depends on dopamine D2 receptor density profiles.
As a result of neuro-vascular coupling, the functional effects of antipsychotics in human brain have been investigated in both healthy and clinical populations using haemodynamic markers such as regional Cerebral Blood Flow (rCBF). However, the relationship between observed haemodynamic effects and the pharmacological action of these drugs has not been fully established. Here, we analysed Arterial Spin Labelling (ASL) rCBF data from a placebo-controlled study in healthy volunteers, who received a single dose of three different D2 receptor (D2R) antagonists and tested the association of the main effects of the drugs on rCBF against normative population maps of D2R protein density and gene-expression data. In particular, we correlated CBF changes after antipsychotic administration with non-displaceable binding potential (BPND) template maps of the high affinity D2-antagonist Positron Emission Tomography (PET) ligand [18F]Fallypride and with brain post-mortem microarray mRNA expression data for the DRD2 gene from the Allen Human Brain Atlas (ABA). For all antipsychotics, rCBF changes were directly proportional to brain D2R densities and DRD2 mRNA expression measures, although PET BPND spatial profiles explained more variance as compared with mRNA profiles (PET R2 range = 0.20-0.60, mRNA PET R2 range 0.04-0.20, pairwise-comparisons all pcorrected<0.05). In addition, the spatial coupling between ΔCBF and D2R profiles varied between the different antipsychotics tested, possibly reflecting differential affinities. Overall, these results indicate that the functional effects of antipsychotics as measured with rCBF are tightly correlated with the distribution of their target receptors in striatal and extra-striatal regions. Our results further demonstrate the link between neurotransmitter targets and haemodynamic changes reinforcing rCBF as a robust in-vivo marker of drug effects. This work is important in bridging the gap between pharmacokinetic and pharmacodynamics of novel and existing compounds.


Oral Scutellarin Treatment Ameliorates Retinal Thinning and Visual Deficits in Experimental Glaucoma.
Purpose: Intraocular pressure (IOP) is currently the only modifiable risk factor for glaucoma, yet glaucoma can continue to progress despite controlled IOP. Thus, development of glaucoma neurotherapeutics remains an unmet need. Scutellarin is a flavonoid that can exert neuroprotective effects in the eye and brain. Here, we investigated the neurobehavioral effects of scutellarin treatment in a chronic IOP elevation model. Methods: Ten adult C57BL/6J mice were unilaterally injected with an optically clear hydrogel into the anterior chamber to obstruct aqueous outflow and induce chronic IOP elevation. Eight other mice received unilateral intracameral injection of phosphate-buffered saline only. Another eight mice with hydrogel-induced unilateral chronic IOP elevation also received daily oral gavage of 300 mg/kg scutellarin. Tonometry, optical coherence tomography, and optokinetics were performed longitudinally for 4 weeks to monitor the IOP, retinal nerve fiber layer thickness, total retinal thickness, visual acuity, and contrast sensitivity of both eyes in all three groups. Results: Intracameral hydrogel injection resulted in unilateral chronic IOP elevation with no significant inter-eye IOP difference between scutellarin treatment and untreated groups. Upon scutellarin treatment, the hydrogel-injected eyes showed less retinal thinning and reduced visual behavioral deficits when compared to the untreated, hydrogel-injected eyes. No significant difference in retinal thickness or optokinetic measures was found in the contralateral, non-treated eyes over time or between all groups. Conclusion: Using the non-invasive measuring platform, oral scutellarin treatment appeared to preserve retinal structure and visual function upon chronic IOP elevation in mice. Scutellarin may be a novel neurotherapeutic agent for glaucoma treatment.


Peripheral T lymphocyte cytokine profile (IFNgamma, IL-2, IL-4) and CD30 expression/release during measles infection.
Measles virus infection (MVI) has been reported to be characterized by an imbalanced Th(1/2)-type cytokine profile. CD30 has been proposed as a receptor preferentially associated with the Th(0/2)-type cytokine pattern. The aim of this study was therefore to define the peripheral T lymphocyte cytokine profile and to test which CD30 expression pattern it was associated with in MVI. The design of the study was a prospective evaluation with comparative analysis. The serum levels of the soluble form of CD30 (sCD30) were determined at diagnosis and at weekly intervals up to 4 weeks, using an ELISA, in 23 males (median age 19), who developed MVI while serving in the Italian army and who were admitted to the Infectious Disease Unit of the Military Hospital in Padua. In 10 of the patients at diagnosis we studied the lymphoid immunophenotype and, after non-specific ex vivo stimulation, the expression of IFNgamma, IL-2 and IL-4 by peripheral T cells using flow cytometry single cell analysis. In 3 patients such evaluations were also performed 7 weeks later. At diagnosis, we found (i) reduction of IFNgamma+/CD4+ T cells (p=0.048 vs controls) in the absence of substantial variation of IL-2+ and IL-4+ T cells (p=ns vs controls); (ii) expansion of CD30+/ CD4+ and CD30+/CD8+ T cell subsets (p<0.01 vs controls); (iii) high sCD30 values (median 61 U/mL; p<0.001 vs controls); (iiii) a context of lymphopenia (0. 728+/-0.292 lymph x10(9)/L). sCD30 remained elevated up to 4 weeks from MVI onset [median values 53, 49, 50, 34 U/mL after 1, 2, 3 and 4 weeks, respectively (p=ns between different time points)]. In 3 patients tested 7 weeks after diagnosis, we still observed decreased IFNgamma production by CD4+ and CD8+ T cells (p=0.05 and <0.01, respectively vs controls) and reduction of CD4+ and CD8+/IL-2+ T cells (p<0.01). MVI was characterized by featuresof inadequate Th/Tc(1) activation associated with increased circulating CD30+ T cells and elevated sCD30 levels, supporting a correlation between Th/Tc status and CD30 expression/release pattern in vivo.


A Review of Mid-Infrared and Near-Infrared Imaging: Principles, Concepts and Applications in Plant Tissue Analysis.
Plant cells, tissues and organs are composed of various biomolecules arranged as structurally diverse units, which represent heterogeneity at microscopic levels. Molecular knowledge about those constituents with their localization in such complexity is very crucial for both basic and applied plant sciences. In this context, infrared imaging techniques have advantages over conventional methods to investigate heterogeneous plant structures in providing quantitative and qualitative analyses with spatial distribution of the components. Thus, particularly, with the use of proper analytical approaches and sampling methods, these technologies offer significant information for the studies on plant classification, physiology, ecology, genetics, pathology and other related disciplines. This review aims to present a general perspective about near-infrared and mid-infrared imaging/microspectroscopy in plant research. It is addressed to compare potentialities of these methodologies with their advantages and limitations. With regard to the organization of the document, the first section will introduce the respective underlying principles followed by instrumentation, sampling techniques, sample preparations, measurement, and an overview of spectral pre-processing and multivariate analysis. The last section will review selected applications in the literature.


Quality of care for myocardial infarction at academic and nonacademic hospitals.
Whether academic hospitals provide better quality of care for patients with acute myocardial infarction is widely debated. The aim of this study was to compare processes of care and mortality between academic and nonacademic hospitals in the contemporary era of acute myocardial infarction management. We analyzed the original data from a prospective cohort study of 3059 patients, including 1714 with ST-segment elevation and 1345 with non-ST-segment elevation myocardial infarction, enrolled at 39 and 183 academic and nonacademic hospitals, respectively, in France. Unadjusted 1-year mortality for academic and nonacademic hospitals was 10% versus 15% for patients with ST-segment elevation myocardial infarction (P=.01) and 13% versus 14% for patients with non-ST-segment elevation myocardial infarction (P=.75). Patients treated in academic or nonacademic hospitals with percutaneous coronary intervention capability were more likely to receive reperfusion and recommended drug therapies than those treated in nonacademic hospitals without percutaneous coronary intervention capability. After adjusting for baseline characteristics, the hazards of death associated with admission to nonacademic hospitals with and without percutaneous coronary intervention capability relative to academic hospitals were 1.13 (95% confidence interval [CI], 0.79-1.62) and 1.65 (95% CI, 1.09-2.49) for those with ST-segment elevation myocardial infarction and 0.95 (95% CI, 0.66-1.36) and 1.06 (95% CI, 0.72-1.58) for those with non-ST-segment elevation myocardial infarction, respectively. Further adjustment for receipt of acute reperfusion and recommended drug therapies eliminated all differences in mortality between the study groups. Admission to academic hospitals was associated with a more frequent use of recommended therapies, conveying a survival advantage for patients with ST-segment elevation myocardial infarction.


Use of the long tube in the management of patients with small-intestinal obstruction due to adhesions.
A retrospective analysis was performed of all patients admitted to our hospital over a six-year period with a diagnosis of small-intestinal obstruction due to adhesions, to assess the efficacy of treatment with long-tube decompression. Of 127 episodes of obstruction, two thirds responded to nonoperative treatment. Factors that were associated with a greater likelihood of success with long-tube decompression included incomplete obstruction, recurrent obstruction, and passage of the tube beyond the pylorus. Clinical findings were relatively reliable as diagnostic indicators of strangulation. The overall mortality was 1.5%, with no deaths due to a delay in operative intervention. A trial of long-tube decompression is recommended in patients presenting with a diagnosis of small-intestinal obstruction due to adhesions in the absence of clinical evidence of strangulation.


Anatomical predictors of successful prism adaptation in chronic visual neglect.
Visual neglect is a frequent and disabling consequence of right hemisphere damage. Previous work demonstrated a probable role of posterior callosal dysfunction in the chronic persistence of neglect signs. Prism adaptation is a non-invasive and convenient technique to rehabilitate chronic visual neglect, but it is not effective in all patients. Here we aimed to assess the hypothesis that prism adaptation improves left neglect by facilitating compensation through the contribution of the left, undamaged hemisphere. We assessed the relationship between prism adaptation effects, cortical thickness and white matter integrity in a group of 14 patients with unilateral right-hemisphere strokes and chronic visual neglect. Results showed that patients who benefitted from prism adaptation had thicker cortex in temporo-parietal, prefrontal and cingulate areas of the left, undamaged hemisphere. Additionally, these patients had a higher fractional anisotropy value in the body and genu of the corpus callosum. Results from normal controls show that these callosal regions connect temporo-parietal, sensorimotor and prefrontal areas. Finally, shorter time intervals from the stroke tended to improve patients' response to prism adaptation. We concluded that prism adaptation may improve left visual neglect by promoting the contribution of the left hemisphere to neglect compensation. These results support current hypotheses on the role of the healthy hemisphere in the compensation for stroke-induced, chronic neuropsychological deficits, and suggest that prism adaptation can foster this role by exploiting sensorimotor/prefrontal circuits, especially when applied at early stages post-stroke.


Mesencephalic microinjections of neurotensin-(1-13) and its C-terminal fragment, neurotensin-(8-13), potentiate brain stimulation reward.
Using the curve shift method, we assessed the effects of ventromedial mesencephalic tegmental (VMT) microinjections of an equimolar concentration of neurotensin-(1-13) (NT-(1-13)) and of its C-terminal fragment, neurotensin-(8-13) (NT-(8-13)), on operant responding for rewarding electrical stimulation of the caudal mesencephalic central gray. The effects of NT-(1-13) and NT-(8-13) on brain stimulation reward (BSR) were also compared to those of systemically administered quinpirole (0.1 and 0.2 mg/kg, s.c.), a direct dopamine agonist, and GBR-12909 (10 and 20 mg/kg, i.p.), a selective dopamine uptake blocker. At the concentration injected, NT-(8-13) was as effective as NT-(1-13) at facilitating BSR, producing significant leftward shifts of the function relating the rate of responding to the stimulation frequency (R/F function); neither form of the peptide was effective when injected in regions dorsal to the VMT. Similarly, GBR-12909 produced a parallel leftward shift of the R/F function, but, unlike NT-(1-13), also significantly increased the asymptotic rates of responding. In contrast, the high dose of quinpirole produced non-parallel leftward shifts of the R/F function and suppressed the asymptote. The similarity between the effects of neurotensin and GBR-12909 on one hand, and the differences between those of neurotensin and quinpirole on the other, suggest that activation VMT neurotensin receptors potentiate BSR by enhancing increases in dopamine neurotransmission that are contingent upon operant responding or rewarding brain stimulation, or both.(ABSTRACT TRUNCATED AT 250 WORDS)


Pathological classification of human iPSC-derived neural stem/progenitor cells towards safety assessment of transplantation therapy for CNS diseases.
The risk of tumorigenicity is a hurdle for regenerative medicine using induced pluripotent stem cells (iPSCs). Although teratoma formation is readily distinguishable, the malignant transformation of iPSC derivatives has not been clearly defined due to insufficient analysis of histology and phenotype. In the present study, we evaluated the histology of neural stem/progenitor cells (NSPCs) generated from integration-free human peripheral blood mononuclear cell (PBMC)-derived iPSCs (iPSC-NSPCs) following transplantation into central nervous system (CNS) of immunodeficient mice. We found that transplanted iPSC-NSPCs produced differentiation patterns resembling those in embryonic CNS development, and that the microenvironment of the final site of migration affected their maturational stage. Genomic instability of iPSCs correlated with increased proliferation of transplants, although no carcinogenesis was evident. The histological classifications presented here may provide cues for addressing potential safety issues confronting regenerative medicine involving iPSCs.


Interleukin-1 and acute brain injury.
Inflammation is the key host-defense response to infection and injury, yet also a major contributor to a diverse range of diseases, both peripheral and central in origin. Brain injury as a result of stroke or trauma is a leading cause of death and disability worldwide, yet there are no effective treatments, resulting in enormous social and economic costs. Increasing evidence, both preclinical and clinical, highlights inflammation as an important factor in stroke, both in determining outcome and as a contributor to risk. A number of inflammatory mediators have been proposed as key targets for intervention to reduce the burden of stroke, several reaching clinical trial, but as yet yielding no success. Many factors could explain these failures, including the lack of robust preclinical evidence and poorly designed clinical trials, in addition to the complex nature of the clinical condition. Lack of consideration in preclinical studies of associated co-morbidities prevalent in the clinical stroke population is now seen as an important omission in previous work. These co-morbidities (atherosclerosis, hypertension, diabetes, infection) have a strong inflammatory component, supporting the need for greater understanding of how inflammation contributes to acute brain injury. Interleukin (IL)-1 is the prototypical pro-inflammatory cytokine, first identified many years ago as the endogenous pyrogen. Research over the last 20 years or so reveals that IL-1 is an important mediator of neuronal injury and blocking the actions of IL-1 is beneficial in a number of experimental models of brain damage. Mechanisms underlying the actions of IL-1 in brain injury remain unclear, though increasing evidence indicates the cerebrovasculature as a key target. Recent literature supporting this and other aspects of how IL-1 and systemic inflammation in general contribute to acute brain injury are discussed in this review.


Bile Acid-Induced Toxicity in HepaRG Cells Recapitulates the Response in Primary Human Hepatocytes.
Cholestatic liver injury is a pathological component of numerous disease states. Much of the current literature on cholestatic liver injury is derived from in vitro studies using rodent hepatocytes or cell lines transfected with bile acid (BA) uptake transporters. While these studies demonstrate BA-driven apoptosis, it is debatable whether these models reflect the human pathophysiology, as primary human hepatocytes undergo primarily necrosis. HepaRG cells are a bipotential, human hepatoma line that express apical and basolateral BA transporters. Thus, we sought to determine whether HepaRG cells could replicate the response of primary human hepatocytes to BA exposure in vitro. HepG2 cells, primary murine hepatocytes (PMH) or HepaRG cells, were exposed to taurocholic acid (TCA), or glycochenodeoxycholate (GCDC) and lactate dehydrogenase release were measured to determine cell death. Cell death occurred dose-responsively in HepaRG cells when exposed to GCDC; however, HepG2 cells died acutely only at very high concentrations of GCDC. In HepaRG cells, pre-treatment with the caspase inhibitor z-VD-FMK had no effect on cell death, indicating a lack of apoptotic cell death, and while c-jun N-terminal kinase (JNK) protein was activated by GCDC treatment in HepaRG cells, the inhibition of JNK did not protect. Although previous data indicate that TCA stimulates pro-inflammatory gene induction in PMH, there was no change in gene expression after TCA stimulation in HepaRG cells, which mimicked previous data found in primary human hepatocytes. These data provide evidence for HepaRG cells as a new model for the study of the effect of BA on human hepatocytes.


Synergistic cytotoxicity using 2'-deoxy-5-azacytidine and cisplatin or 4-hydroperoxycyclophosphamide with human tumor cells.
The combined use of 2'-deoxy-5-azacytidine with cisplatin or 4-hydroperoxycyclophosphamide in vitro frequently resulted in synergistic cytotoxicity against a panel of six human cell lines. This enhanced cell killing occurred at drug concentrations that are clinically achievable. Synergy was also seen if the sequence of drug administration was altered, implying that a temporal overlap between the drugs was necessary, but that the actual biochemical lesions induced by each agent were probably unique, and interacted in an as yet undefined manner. Of further interest was the observation that at least one of the synergistic pairs was active against five of the six cell lines tested. 2'-Deoxy-5-azacytidine incorporation as assessed by the level of gross genomic DNA methylation did not appear to correlate with the synergistic cytotoxicity observed. Thus, we could not discern a clear relationship between the degree of DNA hypomethylation and the observed synergies, although DNA hypomethylation frequently occurred when synergy was demonstrated. The practical usefulness of these drug combinations has not yet been tested and awaits appropriate clinical trials both to assess the tumoricidal effects and possible increased toxicity.


Hydrological analysis of single and dual storage systems for stormwater harvesting.
As stormwater flows are intermittent, the requirement to store urban runoff is important to the design of a stormwater re-use scheme. In many urban areas, the space available to provide storage is limited and thus the need to optimise the storage volume becomes critical. This paper will highlight the advantages and disadvantages of two different approaches of providing storage: 1) a single shallow storage (0.5 m depth) in which stormwater capture and a balanced release to supply users is provided by the one unit; and 2) a dual system in which the functions of stormwater capture and supply release are provided by two separate deeper storage units (2 m depth). The comparison between the two strategies is supported by water balance modelling assessing the supply reliability and storage volume requirements for both options. Above a critical volumetric capacity, the supply yield of a dual storage system is higher than that from a single storage of equal volume mainly because of a smaller assumed footprint. The single storage exhibited greater evaporation loss and is more susceptible to algae blooms due to long water residence times. Results of the comparison provide guidance to the design of more efficient storages associated with stormwater harvesting systems.


A positive donor gram stain does not predict outcome following lung transplantation.
Many potential lung donors are excluded on the basis of a positive donor gram stain (DGS). We examined the association between a positive DGS and the probability of post-operative recipient pneumonia in the first 30 days. Ninety lung transplants (80 with a non-septic pre-transplant diagnosis) from 60 consecutive donors were evaluated for post-operative pneumonia (defined as a compatible clinical syndrome with fever, leukocytosis, chest X-ray abnormalities or histologic evidence obtained by transbronchial biopsy). DGS, white blood cell quantity, CXR and PaO(2)/FIO(2) (P/F) ratio were compared with immediate and 24-hour P/F ratio, length of mechanical ventilation and incidence of pneumonia. All recipients received standard prophylactic anti-bacterial coverage. Patients not surviving 30 days (n = 3) were excluded from this study, but none had evidence of pneumonia either by bronchoalveolar lavage (BAL), transbronchial biopsy or autopsy. Fourteen (16%) of our 87 recipients developed pneumonia in the first 30 days after transplant. Of the 43 patients with a positive DGS, 5 (12%) developed pneumonia, compared to 9 of 44 (20%) with a negative DGS (p = 0.26). The mean post-operative P/F ratio (315 +/- 47 with a positive DGS, p = 0.3) and length of mechanical ventilation (2 days in each group) did not differ significantly between the negative and positive DGS groups. In the current era of lung transplantation, DGS does not predict the development of early post-operative pneumonia and does not affect oxygenation or duration of mechanical ventilation; therefore, its role should be diminished when judging donor lung suitability.


Postoperative Care of Patients with High-grade Glioma: Is There a Real Need for the Neurocritical ICU and Early CT Scan?
Pressure on economic resources now requires a careful rationalization of services. For adult patients with supratentorial gliomas, there is no consensus on the real need for care in a postoperative neurocritical intensive care unit (NICU) and on the timing of a postsurgical computed tomography (CT) scan. In this retrospective nonrandomized study, we assessed if and when there is a real need for NICU and if an early CT scan could be justified in the absence of neurologic worsening. Of 264 patients, 21 were admitted to the NICU after the procedure as planned before the surgery for their clinical features (Karnofsky performance status < 70, American Society of Anesthesiologists score > 2, or Charlson Comorbidity Index > 5). The mean stay in the NICU was 19.7 hours. One of these patients had developed a postoperative hematoma that was subsequently removed, and died afterward. The other 243 patients were followed clinically after the procedure: 219 underwent a cerebral CT scan 24 hours after the procedure and were discharged in good condition. The other 24 patients had a cerebral CT scan within 24 hours after the procedure. The early CT showed the presence of a local edema in five cases and a hematoma surgically treated with a subsequent admission to the NICU in two cases. Considering our data, we suggest that NICU should not always be used after craniotomy for supratentorial gliomas. Clinical observation was sufficient to predict early postoperative complications. A CT scan before 24 hours after surgery is not recommended in the absence of clinical worsening.


Characterization of the electrically evoked release of substance P from dorsal root ganglion neurons: methods and dihydropyridine sensitivity.
The mechanism by which dihydropyridines (DHPs) modulate the electrically evoked or KCI-induced release of substance P (SP) from embryonic chick dorsal root ganglion (DRG) neurons was investigated in the present study. The release of SP, as measured by radioimmunoassay (RIA), was characterized in terms of its dependence on extracellular calcium ion, its stimulus-response relationship, its sensitivity to the calcium-channel blocker omega conus toxin (omega-CgTx), and its modulation by the DHPs Bay K 8644 and nifedipine. Here it is reported that omega-CgTx (1 microM) blocked the electrically evoked release of SP. In contrast, the calcium-channel agonist Bay K 8644 (5 microM) facilitated the release of SP (by 45%), whereas the calcium-channel antagonist nifedipine (5 microM) was without effect. When the release of SP was triggered by depolarization of cultures with 60 mM KCI, the actions of the DHPs became much more pronounced. Under these conditions, Bay K 8644 facilitated (by 115%), whereas nifedipine inhibited (by 58%), peptide secretion. Voltage-clamp analysis of DRG cell calcium currents demonstrated that these actions of omega-CgTx, Bay K 8644, and nifedipine are explicable in terms of their effects on the slowly inactivating (L-type) calcium current. On the basis of these findings, it is suggested that the SP release mechanism exhibits DHP sensitivity due to the involvement of L-type calcium channels in the neurosecretory process. This model predicts that the voltage and time-dependent antagonist actions of nifedipine are sufficient to explain its failure to inhibit the electrically evoked release of SP.


Comparison between visit-to-visit office and 24-h blood pressure variability in treated hypertensive patients.
In any treated hypertensive patient office blood pressure (BP) values may differ between visits and this variability (V) has an adverse prognostic impact. However, little information is available on visit-to-visit 24-h BPV. In 1114 hypertensives of the ELSA and PHYLLIS trials we compared visit-to-visit office and 24-h mean BPV by coefficient of variation (CV) of the mean systolic (S) and diastolic (D) BP obtained from yearly measurements during a 3-4 year treatment period. Visit-to-visit BPV during daytime and night-time were also compared. Twenty-four-hour SBP-CV was about 20% less than office SBP-CV ( P < 0.0001). SBP-CV was considerably greater for the night-time than for the daytime period (20%, P < 0.0001). Results were similar for DBP and in males and females, older and younger patients, patients under different antihypertensive drugs or with different baseline or achieved BP values. In the group as a whole and in subgroups there was significant correlations between office and 24-h BP-CV but the correlation coefficients was weak, indicating that office SBP or DBP CV accounted for only about 1-4% of 24-h SBP or DBP-CV values. Twenty-four-hour mean BP across visits is more stable than across visit office BP. Visit-to-visit office and 24-h BPV are significantly related to each other, but correlation coefficients are low, making visit-to-visit office BP variations poorly predictive of the concomitant 24-h BP variations and thus of on-treatment ambulatory BP stability.


Jumping Hurdles: Peptides Able To Overcome Biological Barriers.
The cell membrane, the gastrointestinal tract, and the blood-brain barrier (BBB) are good examples of biological barriers that define and protect cells and organs. They impose different levels of restriction, but they also share common features. For instance, they all display a high lipophilic character. For this reason, hydrophilic compounds, like peptides, proteins, or nucleic acids have long been considered as unable to bypass them. However, the discovery of cell-penetrating peptides (CPPs) opened a vast field of research. Nowadays, CPPs, homing peptides, and blood-brain barrier peptide shuttles (BBB-shuttles) are good examples of peptides able to target and to cross various biological barriers. CPPs are a group of peptides able to interact with the plasma membrane and enter the cell. They display some common characteristics like positively charged residues, mainly arginines, and amphipathicity. In this field, our group has been focused on the development of proline rich CPPs and in the analysis of the importance of secondary amphipathicity in the internalization process. Proline has a privileged structure being the only amino acid with a secondary amine and a cyclic side chain. These features constrain its structure and hamper the formation of H-bonds. Taking advantage of this privileged structure, three different families of proline-rich peptides have been developed, namely, a proline-rich dendrimer, the sweet arrow peptide (SAP), and a group of foldamers based on γ-peptides. The structure and the mechanism of internalization of all of them has been evaluated and analyzed. BBB-shuttles are peptides able to cross the BBB and to carry with them compounds that cannot reach the brain parenchyma unaided. These peptides take advantage of the natural transport mechanisms present at the BBB, which are divided in active and passive transport mechanisms. On the one hand, we have developed BBB-shuttles that cross the BBB by a passive transport mechanism, like diketoperazines (DKPs), (N-MePhe)n, or (PhPro)n. On the other hand, we have investigated BBB-shuttles that utilize active transport mechanisms such as SGV, THRre, or MiniAp-4. For the development of both groups, we have explored several approaches, such as the use of peptide libraries, both chemical and phage display, or hit-to-lead optimization processes. In this Account, we describe, in chronologic order, our contribution to the development of peptides able to overcome various biological barriers and our efforts to understand the mechanisms that they display. In addition, the potential use of both CPPs and BBB-shuttles to improve the transport of promising therapeutic compounds is described.


DE1, a 12-base pair cis-regulatory element sufficient to confer dark-inducible and light down-regulated expression to a minimal promoter in pea.
We found a cis-regulatory element of 12 base pairs (bp) (GGATTTTACAGT) capable of conferring light responsiveness to a minimal promoter, CaMV 35S46, in pea. The 12-bp sequence is located in the 5' upstream region of the light down-regulated gene pra2, which encodes a small GTPase belonging to the YPT/rab family. Here we examined gain-of-function analyses using synthetic promoter-luciferase constructs in a transient assay and found that the 12-bp element alone was sufficient to confer dark induction, as well as light down-regulation on the minimal promoter. We named this dark inducible element DE1. Effects of various light conditions on the reporter gene activity showed that DE1 received signals from phytochrome A, phytochrome B, and blue light photoreceptors. Using phytochrome-deficient mutants, we showed that the pra2 protein level in seedlings was also regulated by these photoreceptors. The changes in the immunoblotting pattern of the pra2 protein in these mutants were correlated with the changes in epicotyl elongation. Results from transient assays using these mutants showed that the DE1 received signals from phytochromes A and B, demonstrating that this element is indeed a light-responsive element. To our knowledge, this is the first cis-element that by itself confers light responsiveness to a minimal promoter.


Mevastatin suppresses lipopolysaccharide-induced Rac activation in the human monocyte cell line THP-1.
Rac is a member of the Rho family of small guanosine triphosphatases that regulate the actin cytoskeleton. Activation of Rac requires lipid modification that can be blocked by statins. Lipopolysaccharide-induced rearrangements in the actin cytoskeleton lead to changes in cell adhesion and motility that play a role in the cellular response to infection. The lipid products of phosphatidylinositol-3 kinase (PI3K) modulate Rac effector pathways and have been linked to the activation of the Rac-guanosine triphosphatase. We hypothesize that lipopolysaccharide stimulation leads to Rac activation and that this may be inhibited by statin pretreatment. Furthermore, signaling downstream of Rac is linked to PI3K; therefore, we hypothesize that a signaling complex between PI3K and Rac may be involved. THP-1 cells were maintained in 1% fetal calf serum with or without 20 micromol/L mevastatin for 24 hours, followed by lipopolysaccharide stimulation. Active Rac was precipitated from THP-1 total cell lysate and then detected by immunoblotting. The PI3K-Rac complex was immunoprecipitated from total cell lysate, and the p85 regulatory subunit of PI3K was detected by immunoblotting. Lipopolysaccharide stimulation activated Rac. Rac activation was suppressed by pretreatment with mevastatin. The p85 subunit of PI3K was associated with Rac. Lipopolysaccharide stimulation leads to Rac activation in THP-1 cells, which may be suppressed with mevastatin pretreatment. There is an association between Rac and PI3K that demonstrates a role for PI3K in the activation of downstream Rac effector pathways.


Training and Competition Readiness in Triathlon.
Triathlon is characterized by the multidisciplinary nature of the sport where swimming, cycling, and running are completed sequentially in different events, such as the sprint, Olympic, long-distance, and Ironman formats. The large number of training sessions and overall volume undertaken by triathletes to improve fitness and performance can also increase the risk of injury, illness, or excessive fatigue. Short- and medium-term individualized training plans, periodization strategies, and work/rest balance are necessary to minimize interruptions to training due to injury, illness, or maladaptation. Even in the absence of health and wellbeing concerns, it is unclear whether cellular signals triggered by multiple training stimuli that drive training adaptations each day interfere with each other. Distribution of training intensity within and between different sessions is an important aspect of training. Both internal (perceived stress) and external loads (objective metrics) should be considered when monitoring training load. Incorporating strength training to complement the large body of endurance work in triathlon can help avoid overuse injuries. We explore emerging trends and strategies from the latest literature and evidence-based knowledge for improving training readiness and performance during competition in triathlon.


Performance of the MTBDRsl assay in Georgia.
The country of Georgia has a high burden of multi- (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). To assess the performance of the GenoType® MTBDRsl assay in the detection of resistance to kanamycin (KM), capreomycin (CPM) and ofloxacin (OFX), and of XDR-TB. Consecutive acid-fast bacilli smear-positive sputum specimens identified as MDR-TB using the MTBDRplus test were evaluated with the MTBDRsl assay and conventional second-line drug susceptibility testing (DST). Among 159 specimens, amplification was adequate in 154 (97%), including 9 of 9 culture-negative and 2 of 3 contaminated specimens. Second-line DST revealed that 17 (12%) Mycobacterium tuberculosis isolates were XDR-TB. Compared to DST, the MTBDRsl had 41% sensitivity and 98% specificity in detecting XDR-TB and 81% sensitivity and 99% specificity in detecting OFX resistance. Sensitivity was low in detecting resistance to KM (29%) and CPM (57%), while specificity was respectively 99% and 94%. Median times from sputum collection to second-line DST and MTBDRsl results were 70-104 vs. 10 days. Although the MTBDRsl assay had a rapid turnaround time, detection of second-line drug resistance was poor compared to DST. Further genetic mutations associated with resistance to second-line drugs should be included in the assay to improve test performance and clinical utility.


Controlling mechanisms for expression of the bacteriophage T4 beta-glucosyltransferase gene.
The plasmid pTHF3047 carries a 2200 bp fragment containing the phage T4 beta-glucosyltransferase (beta gt) gene and part of the upstream gene 42 cloned in pBR313 under the control of the amp promoter P1. In T4-infected cells the beta gt gene may be expressed by a mechanism antagonizing Rho action. The plasmid pTHF3047 expressed about threefold higher beta-glucosyltransferase activity in a strain carrying the polarity-suppressing rho-102 mutation than in an otherwise isogenic rho+ strain, and production of T4 alpha gt- beta gt- phage was strongly stimulated. The plasmid copy number and the total T4-specific transcription was the same in the two strains. Two T4-specific transcripts from the plasmid, 600 bases and 1850 bases, were identified by Northern hybridization. Comparison with the T4 and plasmid maps suggested that both transcripts were initiated at P1, the 600 base transcript ending at the Rho-dependent terminator t42 between gene 42 and beta gt, and the 1850 base transcript reading through this terminator to the end of the beta gt gene. This analysis places t42 at position 25.1 on the T4 map, and a Rho-independent beta gt terminator at position 23.8. The three-fold higher beta gt expression in the rho- strain may be partially accounted for by Rho control of transcription. In the rho+ strain about half of the transcripts stopped at t42, while in the rho- strain readthrough appeared slightly higher. Thus, the t42 terminator was observed also on the plasmid, but appeared considerably less effective there than in the phage DNA in infected cells.


Alan Frederick Williams 25 May 1945 - 9 April 1992.
Alan WIlliams is noted for his seminal contributions to the field of leucocyte membrane glycoproteins (that is, differentiation antigens). He played a leading role in the development of approaches to the purification and structural analysis of cell surface antigens. His comprehensive characterization of the structure of the rat Thy-1 antigen, as well as the application of monoclonal antibodies to the designation and subsequent isolation of multiple new leucocyte antigens, were exemplary. His discovery that Thy-1 is structurally related to immunoglobulin led directly to the concept of the immunoglobulin (Ig) superfamily, which embraced a spectrum of cell surface molecules involved in a variety of cell recognition systems. He was a very strong advocate in support of the rat as a model animal in the study of immunological phenomena. He was energetic and courageous, as well as radiating enthusiasm for immunological research, inspiring others, critically analysing accepted dogmas and setting high standards. In short, he was a brilliant research scientist.


The endo-lysosomal system as an NAADP-sensitive acidic Ca(2+) store: role for the two-pore channels.
Accumulating evidence suggests that the endo-lysosomal system provides a substantial store of Ca(2+) that is tapped by the Ca(2+)-mobilizing messenger, NAADP. In this article, we review evidence that NAADP-mediated Ca(2+) release from this acidic Ca(2+) store proceeds through activation of the newly described two-pore channels (TPCs). We discuss recent advances in defining the sub-cellular targeting, topology and biophysics of TPCs. We also discuss physiological roles and the evolution of this ubiquitous ion channel family.


Effect of albumin on glomerular ultrafiltration coefficient in isolated perfused dog glomerulus.
To evaluate the direct effect of albumin concentration on the glomerular capillary ultrafiltration coefficient (Kf), we compared the effect of "normal" (3.4 g/100 ml), "low" (0.1 g/100 ml), and "no albumin" (less than 0.005 g/100 ml) concentration on the determinants of single-nephron glomerular filtration rate (SNGFR) as measured with the isolated perfused glomerulus technique. When the albumin concentration was decreased from normal to low concentrations, the afferent flow rate increased from 318 +/- 147 (mean +/- SE) to 450 +/- 174 nl/min, the filtration fraction increased from 0.19 +/- 0.04 to 0.35 +/- 0.08, and the SNGFR increased from 49 +/- 21 to 126 +/- 34 nl/min. These changes were associated with a small though significant increase in Kf from 2.79 +/- 1.01 to 3.74 +/- 0.98 nl/(min X mmHg) (P less than 0.05). When the albumin concentration was decreased from low to no albumin the filtration fraction and SNGFR increased even further and were associated with a marked increase in Kf to a value of 27.04 +/- 11.43 nl/min X mmHg). We conclude that there is very little effect of decreases in albumin concentration on Kf until extremely low levels are reached, and at that point there is a marked increase in the ultrafiltration coefficient. Furthermore, when these extremely low concentrations of albumin are reached an important role for albumin in the basic function of the ultrafiltration barrier is demonstrable.


The role of diet in susceptibility to rheumatoid arthritis: a systematic review.
Many studies have examined the role of diet in the management of established rheumatoid arthritis (RA), warranting several recent reviews. However, none have considered the possible link between diet and the onset of RA in detail. Studies investigated a possible effect of individual components of diet and the development of RA, but the lack of a systematic review means there is no unbiased assessment of the evidence. We systematically reviewed studies with comparison groups that examined dietary intake or biological markers prior to the onset of RA. Four electronic databases were searched to identify relevant reports. Six quality criteria were agreed, against which the studies were assessed. The main outcome measure was a diagnosis of RA according to the ARA 1958 or revised ACR 1987 classification criteria. Fourteen reports were included in the review. There was evidence of a protective effect of higher consumption of olive oil, oil-rich fish, fruit, vegetables and beta-cryptoxanthin. Lower serum concentrations of antioxidants were associated with an increased risk of RA in 3 studies. Due to the heterogeneity of study designs and analyses, the results could not be pooled. Evidence exists that diet may play a role in the etiology of RA, but it is inconclusive due to the small number of studies available and variation in study design.


Glucose-targeted niosomes deliver vasoactive intestinal peptide (VIP) to the brain.
The aim of this study was to evaluate glucose-bearing niosomes as a brain targeted delivery system for the vasoactive intestinal peptide (VIP). To this end, VIP/125I-VIP-loaded glucose-bearing niosomes were intravenously injected to mice. Brain uptake was determined by measuring the radioactivity of 125I-labeled VIP using gamma-counting, after intravenous administration of VIP in solution or encapsulated in glucose-bearing niosomes or in control niosomes. VIP integrity was assessed by reversed-phase HPLC analysis of brain extracts. Distribution of 125I-VIP derived radioactivity was examined from serial brain slices. HPLC analysis confirmed the presence of intact VIP in brain after administration of VIP-loaded niosomes, but not after administration of VIP solution. Encapsulation within glucose-bearing niosomes mainly allowed a significantly higher VIP brain uptake compared to control niosomes (up to 86%, 5min after treatment). Brain distribution of intact VIP after injection of glucose-bearing niosomes, indicated that radioactivity was preferentially located in the posterior and the anterior parts of the brain, whereas it was homogeneously distributed in the whole brain after the administration of control vesicles. In conclusion, this novel vesicular formulation of VIP delivers intact VIP to particular brain regions in mice. Glucose-bearing vesicles might be therefore a novel tool to deliver drugs across the blood-brain barrier (BBB).


Identification of Diseases in Newborns Using Advanced Acoustic Features of Cry Signals.
Our challenge in the current study is to extend research on the cries of newborns for the early diagnosis of different pathologies. This paper proposes a recognition system for healthy and pathological cries using a probabilistic neural network classifier. Two different kinds of features have been used to characterize newborn cry signals: 1) acoustic features such as fundamental frequency glide (F0glide) and resonance frequencies dysregulation (RFsdys); 2) conventional features such as mel-frequency cestrum coefficients. This paper describes the automatic estimation of the proposed characteristics and the performance evaluation of these features in identifying pathological cries. The adopted methods for F0glides and RFsdys estimation are based on the derived function of the F0 contour and the jump "J" of the RFs between two subsequent tunings, respectively. The database used contains 3250 cry samples of full-term and preterm newborns, and includes healthy and pathologic cries. The obtained results indicate the important association between the quantified features and some studied pathologies, and also an improvement in the identification of pathologic cries. The best result obtained is 88.71% for the correct identification of health status of preterm newborns, and 82% for the correct identification of full-term infants with a specific disease. We conclude that using the proposed characteristics improves the diagnosis of pathologies in newborns. Moreover, the method applied in the estimation of these characteristics allows us to extend this study to other uninvestigated pathologies.


[Injury to visceral organs by ischemia and reperfusion. Processes in pathogenetic networks].
The injury of the visceral organs liver, stomach/intestine and pancreas by ischemia and reperfusion can be understood as a process, the events of which represent junctions in pathogenetic networks. In the phase of ischemia, damage of cells by oxygen deficiency is the center of the injurious process. The initial event is the decreased mitochondrial energy supply. Changes in ion homeostasis, activation of hydrolases as well as formation of large pores in the mitochondrial membranes, the so-called mitochondrial permeability transition, are other decisive events in the network of the hypoxic cell injury. Cell damage in the phase of reperfusion is either a consequence of changes in the cells, originating from the phase of ischemia, or the result of an inflammatory tissue reaction. In both cases reactive oxygen species are important triggers of the cell damage. Disturbances of the glutathione equilibrium and of the calcium balance as well as again the mitochondrial permeability transition and the activation of hydrolases belong to the events in the network of cell injury in this phase. Even more than the intracellular events of the cell damage, the events of the inflammatory tissue reaction are linked net-like with one another. Initiated by cells already damaged, an increased release of reactive oxygen species, nitrogen monoxide and other mediators, activation of macrophages, neutrophils, endothelial cells, lymphocytes and the complement system as well as disturbances of the microcirculation form a network of interacting events, which leads to a perpetuation of the tissue damage. A multiplicity of injurious pathways can be designed due to the net-like linkage of the events of the cell and tissue damage. An important consequence, which results from the construct of the pathogenetic networks, is therefore the demand that an effective therapy of the ischemia-reperfusion injury of visceral organs can be attained only by blockade of several central junctions.


Cardiovascular reactivity and left ventricular mass: an integrative review.
Left ventricular hypertrophy has been shown to be an independent predictor of risk for cardiovascular morbidity and mortality. Behavioral scientists have focused on how hemodynamic factors influenced by psychosocial stress may be associated with left ventricular mass (LVM). We reviewed existing studies examining stress-related cardiovascular reactivity (CVR) and LVM, with a goal of examining the moderating role of population (age and hypertensive status) and methodological factors (task type, sample size, and study design) explaining the observed results. Twenty-one studies met the criteria for this review. Results showed only a modestly consistent relationship between CVR and LVM. Forty-three percent of the studies reported 1 or more significant results linking systolic blood pressure reactivity with LVM, and 14% of the studies showed that diastolic blood pressure reactivity was significantly related to LVM. Hypertensive status, task type, and sample size did not play a major role in moderating the relationship between LVM and CVR. A somewhat larger percentage of positive results was shown in prospective and adult studies. The association between CVR and LVM may be real, although the effect size is modest, and we discuss methodological strategies for enhancing statistical power in future investigations. Additional sampling factors (e.g., race, gender) may also impact this relationship. Finally, greater attention is warranted to the role of the psychosocial environment, as this may interact with reactivity to influence LVM.


Rank-based inverse normal transformations are increasingly used, but are they merited?
Many complex traits studied in genetics have markedly non-normal distributions. This often implies that the assumption of normally distributed residuals has been violated. Recently, inverse normal transformations (INTs) have gained popularity among genetics researchers and are implemented as an option in several software packages. Despite this increasing use, we are unaware of extensive simulations or mathematical proofs showing that INTs have desirable statistical properties in the context of genetic studies. We show that INTs do not necessarily maintain proper Type 1 error control and can also reduce statistical power in some circumstances. Many alternatives to INTs exist. Therefore, we contend that there is a lack of justification for performing parametric statistical procedures on INTs with the exceptions of simple designs with moderate to large sample sizes, which makes permutation testing computationally infeasible and where maximum likelihood testing is used. Rigorous research evaluating the utility of INTs seems warranted.


OptoDyCE-plate as an affordable high throughput imager for all optical cardiac electrophysiology.
We present a simple low-cost system for comprehensive functional characterization of cardiac function under spontaneous and paced conditions, in standard 96 and 384-well plates. This full-plate actuator/imager, OptoDyCE-plate, uses optogenetic stimulation and optical readouts of voltage and calcium from all wells in parallel. The system is validated with syncytia of human induced pluripotent stem cell derived cardiomyocytes, iPSC-CMs, grown as monolayers, or in quasi-3D isotropic and anisotropic constructs using electrospun matrices, in 96 and 394-well format. Genetic modifications, e.g. interference CRISPR (CRISPRi), and nine compounds of acute and chronic action were tested, including five histone deacetylase inhibitors (HDACis). Their effects on voltage and calcium were compared across growth conditions and pacing rates. We also demonstrated deployment of optogenetic cell spheroids for point pacing to study conduction in 96-well format, and the use of temporal multiplexing to register voltage and calcium simultaneously on a single camera in this stand-alone platform. Opto-DyCE-plate showed excellent performance even in the small samples in 384-well plates, in the various configurations. Anisotropic structured constructs may provide some benefits in drug testing, although drug responses were consistent across tested configurations. Differential voltage vs. calcium responses were seen for some drugs, especially for non-traditional modulators of cardiac function, e.g. HDACi, and pacing rate was a powerful modulator of drug response, highlighting the need for comprehensive multiparametric assessment, as offered by OptoDyCE-plate. Increasing throughput and speed and reducing cost of screening can help stratify potential compounds early in the drug development process and accelerate the development of safer drugs.


[Microbial flora and sensitivity to antibiotics in surgical abdominal infection].
The paper contains the data of 394 microbiological tests made in 205 patients with different-type nosological surgical infection of the abdominal cavity. The prevailing flora was determined in the above infection; its dynamic structure was defined in complicated pathological variations. The derived microflora was demonstrated to be susceptible to the most frequently used antibacterial drugs.


Scoring functions for computational algorithms applicable to the design of spiked oligonucleotides.
Protein engineering by inserting stretches of random DNA sequences into target genes in combination with adequate screening or selection methods is a versatile technique to elucidate and improve protein functions. Established compounds for generating semi-random DNA sequences are spiked oligonucleotides which are synthesised by interspersing wild type (wt) nucleotides of the target sequence with certain amounts of other nucleotides. Directed spiking strategies reduce the complexity of a library to a manageable format compared with completely random libraries. Computational algorithms render feasible the calculation of appropriate nucleotide mixtures to encode specified amino acid subpopulations. The crucial element in the ranking of spiked codons generated during an iterative algorithm is the scoring function. In this report three scoring functions are analysed: the sum-of-square-differences function s, a modified cubic function c, and a scoring function m derived from maximum likelihood considerations. The impact of these scoring functions on calculated amino acid distributions is demonstrated by an example of mutagenising a domain surrounding the active site serine of subtilisin-like proteases. At default weight settings of one for each amino acid, the new scoring function m is superior to functions s and c in finding matches to a given amino acid population.


Bacterial adhesion to conventional hydrogel and new silicone-hydrogel contact lens materials.
As bacterial adhesion to contact lenses may contribute to the pathogenesis of keratitis, the aim of our study was to investigate in vitro adhesion of clinically relevant bacteria to conventional hydrogel (standard HEMA) and silicone-hydrogel contact lenses using a bioluminescent ATP assay. Four types of unworn contact lenses (Etafilcon A, Galyfilcon A, Balafilcon A, Lotrafilcon B) were incubated with Staphylococcus epidermidis (two different strains) and Pseudomonas aeruginosa suspended in phosphate buffered saline (PBS). Lenses were placed with the posterior surface facing up and were incubated in the bacterial suspension for 4 hours at 37 degrees C. Bacterial binding was then measured and studied by bioluminescent ATP assay. Six replicate experiments were performed for each lens and strain. Adhesion of all species of bacteria to standard HEMA contact lenses (Etafilcon A) was found to be significantly lower than that of three types of silicone-hydrogel contact lenses, whereas Lotrafilcon B material showed the highest level of bacterial binding. Differences between species in the overall level of adhesion to the different types of contact lenses were observed. Adhesion of P. aeruginosa was typically at least 20 times greater than that observed with both S. epidermidis strains. Conventional hydrogel contact lenses exhibit significantly lower bacterial adhesion in vitro than silicone-hydrogel ones. This could be due to the greater hydrophobicity but also to the higher oxygen transmissibility of silicone-hydrogel lenses.


Microarray analysis of RpoS-mediated gene expression in Escherichia coli K-12.
The alternative sigma factor RpoS controls the expression of many stationary-phase genes in Escherichia coli and other bacteria. Though the RpoS regulon is a large, conserved system that is critical for adaptation to nutrient deprivation and other stresses, it remains incompletely characterized. In this study, we have used oligonucleotide arrays to delineate the transcriptome that is controlled by RpoS during entry into stationary phase of cultures growing in rich medium. The expression of known RpoS-dependent genes was confirmed to be regulated by RpoS, thus validating the use of microarrays for expression analysis. The total number of positively regulated stationary-phase genes was found to be greater than 100. More than 45 new genes were identified as positively controlled by RpoS. Surprisingly, a similar number of genes were found to be negatively regulated by RpoS, and these included almost all genes required for flagellum biosynthesis, genes encoding enzymes of the TCA cycle, and a physically contiguous group of genes located in the Rac prophage region. Negative regulation by RpoS is thus much more extensive than has previously been recognized, and is likely to be an important contributing factor to the competitive growth advantage of rpoS mutants reported in previous studies.


Varenicline for smoking cessation: nausea severity and variation in nicotinic receptor genes.
This study evaluated association between common and rare sequence variants in 10 nicotinic acetylcholine receptor subunit genes and the severity of nausea 21 days after initiating the standard, Food and Drug Administration-approved varenicline regimen for smoking cessation. A total of 397 participants from a randomized clinical effectiveness trial with complete clinical and DNA resequencing data were included in the analysis (mean age=49.2 years; 68.0% female). Evidence for significant association between common sequence variants in CHRNB2 and nausea severity was obtained after adjusting for age, gender and correlated tests (all P(ACT)<0.05). Individuals with the minor allele of CHRNB2 variants experienced less nausea than did those without the minor allele, consistent with previously reported findings for CHRNB2 and the occurrence of nausea and dizziness as a consequence of first smoking attempt in adolescents, and with the known neurophysiology of nausea. As nausea is the most common reason for discontinuance of varenicline, further pharmacogenetic investigations are warranted.


Sound speeds vision through preparation, not integration.
In manual choice reaction time (RT) tasks, people respond faster to a visual target stimulus when it is accompanied by a task-irrelevant tone than when it is presented alone. This intersensory facilitation effect is often attributed to multisensory integration, but here we show it to be a reflection of temporal preparation. According to this view, the more rapidly processed tone serves as a warning signal (S1), which initiates preparation for the more sluggish visual target (S2). To test this view, we varied the delay between S1 and S2 in conjunction with the modality of S1 (auditory or visual). For brief delays, responses to S2 were faster when S1 was auditory than when it was visual. Crucially, however, this intersensory facilitation effect disappeared after correction for the difference in S1-detection time, equating the effective preparation period. This shows that sound speeds response to a visual target only through preparation.


Electrical stimulation of the nervous system.
Twenty-seven patients with chronic pain had dorsal column stimulators implanted for pain control over a period of three years. Technical factors of electrode placement and type of unit were not found to correlate with the degree of pain relief. The preoperative psychological attitude of the patient correlated highly with the degree of pain relief and was the single most important factor in patient selection and evaluation. Theoretical concepts of pain psychophysiology in relation to the gate theory and areas for more extensive investigation of pain are discussed.


Fentanyl and the Evolving Opioid Epidemic: What Strategies Should Policy Makers Consider?
Major policy efforts are being aimed at combating the epidemic of opioid addiction and overdose deaths. In response to the epidemic, the medical community and policy makers have attempted to intervene; to date, these varied approaches have done little to reverse the increase in mortality related to opioid overdose. One factor that has complicated efforts to control overdose deaths has been the emergence of a public health crisis related to illicit fentanyl. The rise in fentanyl-related overdose deaths means that new approaches are needed to combat the opioid epidemic, including adoption of harm reduction strategies. Specific strategies that should be considered as part of efforts to combat the opioid crisis include safe drug consumption sites, anonymous drug-checking services, updated naloxone distribution policies, harm reduction-oriented policing, expansion of evidence-based pharmacological treatments in criminal justice and emergency department settings, and stigma-reduction messaging emphasizing the risks of fentanyl.


The protective effect of propofol on erythrocytes during cardiopulmonary bypass.
To evaluate the relationship between erythrocyte injury and intracellular calcium ion overload, and the protective effect of propofol on erythrocytes during cardiopulmonary bypass (CPB). 40 children with congenital heart diseases who underwent surgical repair under CPB were included. The patients were randomly divided into two groups: control group (group C) and propofol group (group P). Anesthesia was maintained in the patients with 6 mg/kg/h propofol in Group P, and those in the Group C inhaled 1%-2% isoflurane. The blood samples were taken before CPB, 30 min after CPB, at the end of CPB, and 2 h and 24 h after CPB to measure the content of erythrocyte intracellular calcium ion (E-Ca2+), Ca2+-Mg2+-ATPase and Na+-K+-ATPase activities, index filtration of erythrocytes (IF), mean corpuscular volume (MCV) and the concentration of plasma free hemoglobin (F-Hb). Results showed that in the control group, E-Ca2+, IF, MCV and F-Hb were gradually increased and Ca2+-Mg2+-ATPase and Na+-K+-ATPase activities were decreased. The increase of E-Ca2+ was linearly paralleled to IF, MCV and F-Hb. In propofol group, all the above-mentioned parameters were significantly improved (P<0.05). This study suggests that erythrocyte injury is related to elevation of intracellular calcium during CPB and propofol has a protective effect on erythrocyte injury.


Moving Beyond Collaboration: A Model for Enhancing Social Work's Organizational Empathy.
Many first-year field students and new practitioners enter the "fog of practice" seeking a strong mentor who will teach them to survive and thrive in the practice world. They are armed with much social work-related ideology but perhaps too little organizational knowledge and savvy. This challenge may be traced back to another historical professional debate: the imbalance between micro and macro social work education and training. This article addresses the challenge by introducing the overarching competency of organizational empathy, defined as an understanding of the practice environment one occupies. The major objective of this article is to help bridge an academe-practice knowledge gap, thereby giving the social work practitioner enhanced opportunities for broader organizational influence, collaboration, and leadership.


Structural and germination defects of Bacillus subtilis spores with altered contents of a spore coat protein.
The start sites for transcription and translation of a Bacillus subtilis spore coat protein gene, cotT, were determined. The CotT protein was synthesized as a 10.1-kDa precursor which was processed to a coat polypeptide of 7.8 kDa. Insertional inactivation of the cotT gene resulted in spores with an altered appearance of the inner coat layers and slow germination in response to a germination solution containing fructose, glucose, and asparagine. Rates of germination in L-alanine and in Penassay broth were the same as that of the wild type. A strain containing the cotT gene on a low-copy-number plasmid produced spores with an excess of CotT precursor and a thickening of the striated inner coat. These spores responded poorly to all of the germinants mentioned above. A site-directed mutation of the codon at the processing site of CotT resulted in the accumulation of the precursor in sporulating cells and on the spores, but there was no effect on the germination rates or solvent resistance of these spores. Both the lack and the overproduction of CotT led to subtle alterations in the structure of the inner spore coat and in the capacity of spores to respond to particular germinants.


Nonpharmacologic Therapies in Patients With Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review With Meta-Analysis.
To evaluate the effectiveness and adverse events of nonpharmacologic interventions in patients with exacerbation of chronic obstructive pulmonary disease (COPD). We searched Embase, MEDLINE, Cochrane databases, Scopus, and clinicaltrials.gov from database inception to January 2, 2019, for randomized controlled trials that enrolled adults with exacerbation of COPD and evaluated the effect of nonpharmacologic interventions on clinical outcomes and/or lung function. We included 30 randomized controlled trials with 2643 participants. Improvement in 6-minute walking test distance was associated with resistance training (weighted mean difference [WMD], 74.42; 95% CI, 46.85 to 101.99), pulmonary rehabilitation (WMD, 20.02; 95% CI, 12.06 to 28.67), whole body vibration (WMD, 89.42; 95% CI, 45.18 to 133.66), and transcutaneous electrical nerve stimulation (WMD, 64.54; 95% CI, 53.76 to 75.32). Improvement in quality of life was associated with resistance training (WMD, 18.7; 95% CI, 5.06 to 32.34), combined breathing technique and range of motion exercises (WMD, 14.89; 95% CI, 5.30 to 24.50), whole body vibration (WMD, -12.02; 95% CI, -21.41 to -2.63), and intramuscular vitamin D (WMD, -4.67; 95% CI, -6.00 to -3.35 at the longest follow-up). Oxygen titration with a target oxygen saturation range of 88% to 92% was associated with reduced mortality compared with high flow oxygen (odds ratio, 0.36; 95% CI, 0.14 to 0.88). All findings were based on low strength of evidence. In patients hospitalized for exacerbation of COPD, exercise interventions and pulmonary rehabilitation programs may ameliorate functional decline. Oxygen should be titrated with a target oxygen saturation of 88% to 92% in these patients. PROSPERO Identifier: CRD42018111609.


Structural rocking filters in highly birefringent photonic crystal fiber.
We report what we believe is the first example of efficient rocking filter formation in polarization-maintaining photonic crystal fiber. Very high coupling efficiencies (as much as -23.5-dB suppression of the input polarization) and loss of < 0.02 dB were achieved for fibers as short as 11 mm. The filters, which we prepared by periodic mechanical twisting and heating with a scanned CO2 laser beam, are highly compact, and they are expected to be temperature stable.


Proteolysis and antiproteolysis associated with toxemia of pregnancy.
Ten pregnancy toxemia patients, 10 pregnant patients with essential arterial hypertension and 12 normal pregnant women were studied between the weeks 37 and 40 of gestation. From them blood samples were obtained 24 hours before and 24 hours and three months after the delivery. In these samples proteolytic (P) and antiproteolytic (AP) activities and alpha-1-antitrypsin (A1-AT) concentration were determined. The P and the AP were measured by hydrolysis of BAPNA, and the A1-AT by radial immunodiffusion. The most interesting results were observed 24 hours before the delivery. Toxemic patients presented increase of P and AP, and hypertensive patients diminution of A1-AT when compared with normal controls. These results demonstrated that in toxemia and essential hypertension during pregnancy maladjustments in mechanisms of serum proteolysis and antiproteolysis, perhaps related with the activation of complement, clotting and circulating immune complexes formation systems, exist.


MPTM: A tool for mining protein post-translational modifications from literature.
Due to the importance of post-translational modifications (PTMs) in human health and diseases, PTMs are regularly reported in the biomedical literature. However, the continuing and rapid pace of expansion of this literature brings a huge challenge for researchers and database curators. Therefore, there is a pressing need to aid them in identifying relevant PTM information more efficiently by using a text mining system. So far, only a few web servers are available for mining information of a very limited number of PTMs, which are based on simple pattern matching or pre-defined rules. In our work, in order to help researchers and database curators easily find and retrieve PTM information from available text, we have developed a text mining tool called MPTM, which extracts and organizes valuable knowledge about 11 common PTMs from abstracts in PubMed by using relations extracted from dependency parse trees and a heuristic algorithm. It is the first web server that provides literature mining service for hydroxylation, myristoylation and GPI-anchor. The tool is also used to find new publications on PTMs from PubMed and uncovers potential PTM information by large-scale text analysis. MPTM analyzes text sentences to identify protein names including substrates and protein-interacting enzymes, and automatically associates them with the UniProtKB protein entry. To facilitate further investigation, it also retrieves PTM-related information, such as human diseases, Gene Ontology terms and organisms from the input text and related databases. In addition, an online database (MPTMDB) with extracted PTM information and a local MPTM Lite package are provided on the MPTM website. MPTM is freely available online at http://bioinformatics.ustc.edu.cn/mptm/ and the source codes are hosted on GitHub: https://github.com/USTC-HILAB/MPTM .