A differential involvement of the shell and core subterritories of the nucleus accumbens of rats in attentional processes.
The nucleus accumbens comprises of two anatomically distinct subterritories: an inner core and an outer shell region. The distinct pattern of the core and shell input and output targets suggests that these two regions may mediate different behavioral processes. Using N-methyl-D-aspartate excitotoxic lesions in either the core or shell region, we investigated whether we can dissociate functionally these two subterritories. N-Methyl-D-aspartate-lesioned, sham-lesioned and non-operated animals were tested for locomotor activity in an open field and in two behavioral paradigms known to evaluate attentional deficits, namely the pre-pulse inhibition of the acoustic startle reflex and latent inhibition, measured in a two-way active avoidance paradigm. The shell-lesioned animals showed a small but significant hyperactivity in the open field when compared to the core-lesioned and to control animals. In the pre-pulse inhibition paradigm, core-lesioned animals demonstrated reduced pre-pulse inhibition to the two high pre-pulse intensities (80 dB[A], 84 dB[A]). In the active avoidance paradigm, whereas no lesion effects were detected in the non-pre-exposed groups, clear attenuation of latent inhibition was found in the shell-lesioned rats, in comparison to both core-lesioned and control rats, due to improved avoidance performance of the shell-pre-exposed group. From these results we suggest that the two subterritories of the nucleus accumbens are differentially involved in attention-related processes: the core lesion leads to significant disruption of pre-pulse inhibition while the shell lesion leads to heightened activity and significant attenuation of latent inhibition.


Regulation of cholesterol synthesis in skin fibroblasts derived from old people.
Sterol synthesis from radioactive acetate and the suppression of this synthesis by human low density lipoprotein (LDL) have been investigated in skin fibroblast strains derived from infant donors and from donors over the age of 70 years. The activity of the enzyme hydroxymethylglutaryl-CoA reductase and its repression by LDL has also been investigated in these fibroblast strains and in senescent cells of the foetal lung cell strain MRC-5. No age-related differences could be detected either in repression of [3H]acetate incorporation by LDL, or in repression of HMG-CoA reductase activity.


[Two cases of minimally invasive reoperative coronary artery bypass].
Reoperative coronary artery bypass grafting (CABG) are still associated with higher mortality than primary CABG. This is due in part to the potential for cardiac and patent graft injury during their dissection and the reopening of the sternum. Therefore, in two patients with recurrent angina attributable to occlusion of the old vein graft to the LAD, we performed reoperative CABG by the minimally invasive direct coronary artery bypass (MIDCAB) procedures. The left internal thoracic artery was anastomosed to the LAD through small anterolateral thoracotomy without cardiopulmonary bypass. Both patients recovered fast and underwent postoperative angiogram, showing the new grafts widely patent. About two weeks later, both discharged in the conditions of nearly normal activities. The reoperative MIDCAB grafting might be expected to be as safe and promising as the primary one.


Divergent in vitro effects of recombinant interferons on human osteosarcoma cells.
We investigated the in vitro effects of human recombinant interferon alpha (rIFN alpha) and interferon gamma (rIFN gamma) on the proliferation and MCH class II antigen expression of two human osteosarcoma cell lines SAOS-2 and U2-OS. Addition of low concentrations of either rIFN alpha (10 U/mL) or rIFN gamma (100 U/mL) to the cultures almost completely inhibited the 3H-thymidine incorporation in SAOS-2 cells while even high amounts (10,000 U/mL) of rIFN alpha or rIFN gamma did not affect the growth rate of U2-OS cells. This difference was not caused by lack of IFN receptors in U2-OS cells since both cell lines responded to rIFN gamma treatment with rapid accumulation of HLA class II mRNA and de novo surface expression of HLA-DR, -DP and -DQ antigens. The induced HLA class II antigens were functionally intact. Osteosarcoma cells treated with rIFN gamma stimulated a mixed lymphocyte culture (MLC) response in allogeneic T-lymphocytes while untreated osteosarcoma cells were unable to provoke T-lymphocyte proliferation. These findings indicate that IFNs display divergent effects on two phenotypically closely related tumor cell lines. This should be appreciated also when therapeutic effects of IFNs are evaluated.


Temperature-pressure correlations of cryoprotective additives for the design of constant volume cryopreservation protocols.
In the recent years, the use of constant volume (isochoric) cryopreservation, in medicine and biotechnology has captured more attention from the research community and now there is an increasing interest in the use of this new technology. It has been established that the thermodynamics of isochoric freezing is different from that of isobaric (constant pressure) freezing. This study provides researchers in the field experimental results for various compositions of cryoprotectants commonly used in isobaric cryopreservation, in terms of temperature-pressure-molar concentration correlation. It also reveals experimental isochoric thermodynamic data for the following cryoprotectants, commonly used in isobaric cryopreservation: dimethyl sulfoxide, trehalose, ethylene glycol and diethylene glycol. Currently, the data on the pressure-temperature correlation in an isochoric system of cryoprotectants used in isobaric cryopreservation is not available. Our new experimental results indicate that the studied concentrations for each of the CPAs, lower and expands the range of temperatures in which cryopreservation by isochoric freezing can be safely practiced. We consider that these experiments will aid researchers developing new isochoric cryopreservation protocols.


Activation of natural resistance against lung metastasis of an adenocarcinoma in T-cell depressed spontaneously hypertensive rats by infection with Listeria monocytogenes.
We report here our study of the role of natural host defense mechanisms mediated by macrophages and natural killer (NK) cells in an experimental model of spontaneous pulmonary metastases of a mammary adenocarcinoma SST-2 in spontaneously hypertensive rats (SHR) with congenital T-cell depression. To activate macrophages and NK cells, Listeria monocytogenes (LM) was injected IV into SHR which had received a transplantation of SST-2. To assess the antimetastatic responses induced by LM, the number of lung nodules and the lung weight in SHR were evaluated 30 days after tumor inoculation. The growth of lung metastases, though not of primary tumors, was significantly reduced if 10(7) LM were injected IV into SHR 2, 10 and 20 days after the SC transplantation of 5 X 10(4) or 5 X 10(5) SST-2. An inhibitory effect of LM on pulmonary metastases was also observed in tumor-excised rats, in which the number of lung metastases and the lung weight were enhanced as compared with those in tumor-bearing rats which had not undergone surgery. Peritoneal resident cells which were harvested from rats injected with LM showed a significant augmentation of tumoricidal activity against SST-2 cells as measured by in vitro cytotoxicity. Similarly, the NK activity of spleen cells of SHR injected with LM increased significantly when compared with untreated SHR. These data suggest that the inhibition of metastatic growth, though not of primary tumor growth, was accomplished by the, possibly T-cell independent, activation of macrophages and NK cells.


Assessment of ropinirole as a reinforcer in rhesus monkeys.
Ropinirole, a D(2)/D(3)/5-HT(1A) agonist, is used for the treatment of Parkinson's disease and restless leg syndrome, and is currently being evaluated as a treatment for cocaine dependence. However, there is little information available on ropinirole's reinforcing effects. The current study tested ropinirole in monkeys (n=7) trained to self administer cocaine on a fixed-ratio 25 (FR 25) schedule of reinforcement to determine if it would function as a reinforcer. In addition, a behavioral economics approach was used in four monkeys to compare the reinforcing effectiveness of ropinirole to cocaine. Cocaine (0.01-0.3 mg/kg/injection) functioned as a reinforcer in all monkeys under the FR 25 schedule, and ropinirole (0.01-0.1mg/kg/injection) functioned as a reinforcer in all but one. Furthermore, cocaine was a more effective reinforcer than ropinirole as indexed by demand functions. The current data indicate that ropinirole has reinforcing effects in monkeys, although its effectiveness as a reinforcer is relatively weak.


Integrated real-time Raman system for clinical in vivo skin analysis.
Raman spectroscopy is a non-invasive optical technique that can probe the molecular structure and conformation of biochemical constituents. The probability of Raman scattering is exceedingly low ( approximately 10(-10)), and consequently up to now the practical application of Raman spectroscopy to clinical medicine has been limited by either the weak spectral signal or by the long data acquisition times. Recent advances in Raman hardware and probe design have reduced spectral acquisition times, paving the way for clinical applications. We present an integrated real-time Raman spectroscopy system for skin evaluation and characterization, which combines customized hardware features and software implementation. Real-time data acquisition and processing includes CCD dark-noise subtraction, wavelength calibration, spectral response calibration, intensity calibration, signal saturation detection, cosmic ray rejection, fluorescence background removal, and composition modeling. Real-time in vivo Raman measurement of volar forearm skin is presented to illustrate the methods and modeling. The system design implemented full-chip vertical hardware binning to improve the signal-to-noise ratio by 16-fold. The total time for a single in vivo measurement with analysis can be reduced to 100 ms with this implementation. Human skin was well modeled using the base Raman spectra. In vivo real-time Raman can be a very promising research and practical technique for skin evaluation.


7S domain constitutes the amino-terminal end of type IV collagen: an immunochemical study.
The collagenous material from bovine kidney cortex was prepared by pepsin digestion of cortex homogenates. The 7S collagen was isolated after bacterial collagenase digestion of collagenous basement membrane material and was further purified by molecular sieve and ion exchange chromatography. The antibodies were raised in rabbits against a purified 7S collagen preparation. The pepsin-derived collagenous fragments alpha 1(IV)130K, 95K and alpha 2(IV)120K prepared from bovine cortex were tested for their cross-reactivity with the antiserum. The fragment alpha 1(IV)130K was found to be significantly cross-reactive. The results show the presence of common structural antigenic determinants between 7S collagen and alpha 1(IV)130K fragment, thus indicating that 7S collagen is located at the amino-terminal end of type IV collagen.


Quantitative analysis of JAK/STAT signaling pathway in patients of inflammatory skin disorders.
Inflammatory skin diseases (ISDs), are characterized by dysregulated activation of innate and adaptive immune systems, with inflammatory cytokines playing a crucial role in their pathogenesis. This study aimed to investigate the involvement of Janus kinase/signal transduction and activator of transcription (JAK/STAT) signaling pathway in the pathogenesis of ISDs. The study analyzed a total of 117 skin biopsies, comprising 31 from pyoderma gangrenosum (PG), 25 from hidradenitis suppurativa (HS), 35 from psoriasis patients, and 26 from control subjects. To assess the expression levels of JAK/STAT pathway components, immunohistochemical staining was performed on both the dermal and epidermal layers of the skin. The Histo score (H score) was utilized as the immunoexpression score to evaluate the staining intensity. The results indicated that all components of the JAK/STAT signaling pathway, except JAK2 and STAT6 in PG, JAK1, STAT4, and STAT6 in HS, and JAK1 in psoriasis, were overexpressed in the dermal skin compared to the control group (p < 0.05). Psoriatic skin had higher expression of STAT6 than both PG and HS and higher expression of JAK2 than PG (p < 0.05). Additionally, HS biopsies had higher expression of JAK2 and STAT6 compared to PG (p < 0.05). JAK1 expression was higher in PG than in HS, psoriasis, and the control group (mean H score was 265.8, 184.8, 191.4, and 113.1, p < 0.05, respectively). This study provides new insights into the potential contribution of the JAK/STAT pathway to the pathogenesis of ISDs. The findings suggest that targeting this pathway could be a promising therapeutic strategy for treating these disorders.


Assessment of Anxiety, Depression, and Sleep Quality in Mothers of Children with Atopic Dermatitis: A Qualitative Questionnaire Study.
To compare the anxiety, depression and sleep quality of mothers of healthy control children and mothers of children with atopic dermatitis (AD) of varying severity, both before and after treatment. A total of 120 parent-child dyads participated in the study. These dyads were divided into four subgroups of 30 patients each: mild AD, moderate AD, severe AD, and control groups. The children's symptoms, their mothers' psychological status, and their mothers' sleep quality were evaluated using the Scoring of Atopic Dermatitis (SCORAD), the Hospital Anxiety and Depression Scale (HADS), and the Pittsburgh Sleep Quality Index (PSQI), respectively, before and after a one-month comprehensive treatment. SCORAD, representing differences in severity of children's AD, decreased significantly after one month's treatment (p < 0.001). Anxiety in mothers significantly decreased in all AD severity groups after treatment (p < 0.05). However, for depression, only the mothers in the mild and moderate AD groups showed a decrease after treatment (p < 0.05). The PSQI total score also decreased in the mild AD group after treatment (p < 0.05). The most severe effect was seen in the psychology and sleep quality of mothers of children with severe AD. After one month of treatment, the psychological health and sleep quality of the mothers in the mild AD group significantly improved, while those of mothers in the moderate and severe AD groups showed partial improvement.


Endoscopy in Inflammatory Bowel Disease.
The roles of flexible endoscopy in the setting of inflammatory bowel disease include diagnosis, surveillance, and determining response to treatment and monitoring for the development of recurrence, dysplasia, or malignancy. Advanced techniques, such as chromoendoscopy and narrow band imaging, can be useful adjuncts when performing endoscopy in patients with inflammatory bowel disease. There are several roles for therapeutic endoscopy in the setting of inflammatory bowel disease, including endoscopic balloon dilation and endoscopic stricturotomy.


Risk-based stratified primary care for common musculoskeletal pain presentations (STarT MSK): a cluster-randomised, controlled trial.
Risk-based stratified care shows clinical effectiveness and cost-effectiveness versus usual primary care for non-specific low back pain but is untested for other common musculoskeletal disorders. We aimed to test the clinical effectiveness and cost-effectiveness of point-of-care risk stratification (using Keele's STarT MSK Tool and risk-matched treatments) versus usual care for the five most common musculoskeletal presentations (back, neck, knee, shoulder, and multi-site pain). In this cluster-randomised, controlled trial in UK primary care with embedded qualitative and health economic studies we recruited patients from 24 general practices in the West Midlands region of England. Eligible patients were those aged 18 years or older whose general practitioner (GP) confirmed a consultation for a musculoskeletal presentation. General practices that consented to participate via a representative of the cluster were randomly assigned (1:1) to intervention or usual care, using stratified block randomisation. Researchers involved in data collection, outcome data entry, and statistical analysis were masked at both the cluster and individual participant level. Participating patients were told the study was examining GP treatment of common aches and pains and were not aware they were in a randomised trial. GPs in practices allocated to the intervention group were supported to deliver risk-based stratified care using a bespoke computer-based template, including the risk-stratification tool, and risk-matched treatment options for patients at low, medium, or high risk of poor disability or pain outcomes. There were 15 risk-matched treatment options. In the usual care group, patients with musculoskeletal pain consulting their GP received treatment as usual, typically including advice and education, medication, referral for investigations or tests, or referral to other services. The primary outcome was time-averaged pain intensity over 6 months. All analyses were done by intention to treat. The trial is registered with ISRCTN, ISRCTN15366334. Between May 1, 2018, and April 30, 2019, 104 GPs from 24 practices (12 per study group) identified 2494 patients with musculoskeletal pain. 1211 (49%) participants consented to questionnaires (534 in the intervention group and 677 in the usual care group), with 1070 (88%) completing the follow-up questionnaire at 6 months. We found no significant difference in time-averaged pain intensity (mean(SD) mean 4·4 [SD 2·3] in the intervention group vs 4·6 [2·5] in the control group; adjusted mean difference -0·16, 95% CI -0·65 to 0·34) or in standardised function score (mean -0·06 [SD 0·94] in the intervention group vs 0·05 [1·04]; adjusted mean difference -0·07, 95% CI -0·22 to 0·08). No serious adverse events or adverse events were reported. Risk stratification received positive patient and clinician feedback. Risk stratification for patients in primary care with common musculoskeletal presentations did not lead to significant improvements in pain or function, although some aspects of GP decision making were affected, and GP and patients had positive experiences. The costs of risk-based stratified care were similar to usual care, and such a strategy only offers marginal changes in cost-effectiveness outcomes. The clinical implications from this trial are largely inconclusive. National Institute for Health Research.


Applying the Ugandan Sexual Health and Pastoral Education whole institution approach at the Ugandan UK Health Alliance Summit 2018.
The Ugandan UK Health alliance (UUKHA) promotes collaboration between UK- and Uganda-based organisations working in health in order to further global learning and the sharing of best practice. On 22-23 March 2018, the UUKHA held the third East African Health Improvement and Investment Summit in Kampala, Uganda. This is the report of a dynamic workshop which was aimed at encouraging thought and discussion on an innovative approach to tackling common health problems such as family planning, alcohol and malnutrition.


Evaluation of anti-proliferative activity of Eryngium caucasicum on melanoma cancer cells.
The genus Eryngium is a member of the Apiaceae family that has shown different pharmacological effects mainly including anti-inflammatory, analgesic, anti-cancer, hepatoprotective, and anti-oxidant. Previous research on the anti-cancer activity of Eryngium in some cancer cell lines has led us to explore the anti-proliferative activity of E. caucasicum in the B16F10 cell line. In this study, the antiproliferative activity of E. caucasicum on melanoma cancer cells (B16F10) and non-cancerous cells (HFFF2) were evaluated in vitro. The dried plant sample of E. caucasicum was extracted by Soxhlet apparatus with n-Hexane, dichloromethane, and methanol solvents. The effects of cytotoxicity of the extracts by the MTT method on melanoma cancer cells (B16F10) and noncancerous cells (HFFF2) was investigated for 24 and 48 hours. Then, the cytotoxicity of different fractions of the strong extract against normal and cancer cells was evaluated by this method. Annexin V/PI assay was used to study the induction apoptosis via the fractions in cancer cells. According to the results of the MTT test, n-Hexane extract is the most effective extract against the B16F10 cell line and is a candidate for fractionation with VLC. Among the fractions, 40 and 60% VLC fractions of n-Hexan extract inhibited the growth of B16F10 cells at 24 and 48 hours while, these fractions at IC50 concentration had no cytotoxic effects on normal cells. Treatment of cancer cells with effective extract caused apoptosis and necrosis and 40 and 60% more fractions induced apoptosis in these cells. The n-Hexane extract of E. caucasicum and its 40 and 60% fractions showed the highest cytotoxic effect against the B16F10 cell line compared to other extracts and control groups. This inhibition was made through induction of apoptosis.


Strategies to optimize implementation of novel preceptorship models: Peer-assisted learning and near-peer teaching.
Hospital experiential placements have traditionally used a 1:1 (student to preceptor) ratio. Two models, peer-assisted learning (PAL) and near-peer teaching (NPT), have been described in the literature for education of health professions. This research explored the use of PAL and NPT, as well as advantages, challenges, and strategies to address challenges for implementation. This study used an anonymous survey to solicit feedback from staff pharmacists and pharmacy leaders about their use of PAL and NPT models in hospital settings in Alberta, Canada. Using closed and open-ended questions, experience with each model and implementation considerations were explored. The survey was completed by 115 hospital pharmacists (11% response rate). PAL and NPT were utilized by 25% and 8% of respondents, respectively, and 10% had experience with both models. Advantages of these models include promoting teamwork and clinical independence, learners supporting each other, and fostering active learning. The highest ranked challenges were space/technology/computer access limitations and additional time to complete learner assessments. Many strategies were provided to address challenges, and facilitate implementation and utilization. In the hospital setting, pharmacists used PAL more commonly than NPT. Feedback from pharmacists and leaders affirmed the advantages and challenges associated with use of these precepting models. Strategies to facilitate and optimize use were provided, which will guide faculty, pharmacy leaders, and preceptors in efforts to support implementation to increase capacity and expand the practice of precepting.


Purified inner membrane protease I of yeast mitochondria is a heterodimer.
Inner membrane protease I is bound to the outer face of the yeast mitochondrial inner membrane and mediates the proteolytic maturation of cytochrome b2 and cytochrome oxidase subunit II. We have previously shown that one of its subunits is a 21.4-kDa integral membrane protein encoded by the nuclear IMP1 gene. We have now purified the active protease approximately 300-fold from yeast mitochondria. It has an apparent molecular weight of 35,000 and contains not only Imp1p but also a previously unrecognized 19-kDa subunit. Partial amino acid sequencing identifies this subunit as the product of the recently described IMP2 gene (Nunnari, J., Fox, T., and Walter, P. (1993) Science 262, 1997-2004).


Adsorption recovery of phosphate from aqueous solution by CaO-biochar composites prepared from eggshell and rice straw.
CaO-biochar composites were prepared by mixed ball milling and pyrolysis of agricultural wastes eggshell and rice straw. The resulting CaO-biochar composites (E-C) showed excellent performance for phosphate adsorption from aqueous solution in a wide range of solution pH (5-11), and a maximum adsorption capacity of 231 mg/g could be obtained by E-C sample that was prepared from the eggshell and rice straw with a mass ratio of 1:1 (E-C 1:1). The adsorption of phosphate onto the E-C samples could be well described by pseudo-second-order (R2 > 0.975) and Langmuir models (R2 > 0.979). Thermodynamic analysis revealed that the adsorption process was spontaneous (ΔG0 < 0) and endothermic (ΔH0 > 0). This work provides a promising method to prepare functionalized biochar adsorbents from agricultural wastes for the recovery of phosphate from aqueous solution, and the phosphate adsorbed CaO-biochar composites can be directly applied as a slow-release fertilizer to farmland soil, which have the functions of improving soil physical structure, increasing soil fertility, and regulating soil pH.


Reye's syndrome: preservation of mitochondrial enzymes in brain and muscle compared with liver.
The activities of five mitochondrial enzymes tested in liver from patients with Reye's syndrome were measured. Citrate synthase, glutamic dehydrogenase, succinic dehydrogenase, pyruvate carboxylase, and pyruvate dehydrogenase were all outside of the range shown by control samples and well below them in activity. The activity of two extramitochondrial enzymes, glucose-6-phosphatase, which is a microsomal enzyme, and fructose-1,6-diphosphatase, which is a soluble enzyme, were in the normal range in samples from Reye's syndrome patients. In both muscle and brain the activities of the mitochondrial enzyme, citrate synthase, glutamic dehydrogenase, and succinic dehydrogenase were all within the control range. Pyruvate dehydrogenase was found to be normal in muscle from these patients.


Morpholine-based immonium and halogenoamidinium salts as coupling reagents in Peptide synthesis1.
Here we describe a new family of N-form immonium-type coupling reagents that differ in their carbocation skeleton structure. The N-methylpiperazine derivative failed to form immonium salts, while the thiomorpholine derivative did not give better results than the coupling reagents currently used. The presence of the morpholine had a marked influence on the solubility and stability as well as the reactivity of the reagent. Finally, the fluoroamidinium salt performed extremely well in the presence of only 1 equiv of base, thereby confirming the effect of the proton acceptor in the reaction.


Occurrence in brain lysosomes of a sialidase active on ganglioside.
A lysosomal preparation, obtained from brain homogenate of 17-day-old C57BL mice by centrifugation on a self-generating Percoll linear density gradient, showed relative specific activity (RSA) values for typical lysosomal enzymes of 40-120 and for mitochondria, plasma membrane, and cytosol markers of much lower than 1, a result indicating a high degree of homogeneity. The lysosomal preparation contained a sialidase activity that was assayed radiometrically with ganglioside [3H]GD1a and fluorimetrically with 4-methylumbelliferyl-1-alpha-D-N-acetylneuraminic acid (MUB-NeuAc). The properties of the lysosomal enzyme were compared with those of the plasma membrane-bound sialidase contained in a purified synaptosomal plasma membrane fraction that was prepared from the same homogenate and assayed with the same substrates. The optimal pH was 4.2 for the lysosomal and 5.1 for the plasma membrane-bound enzyme. The apparent Km values for GD1a and MUB-NeuAc were 1.5 X 10(-5) and 4.2 X 10(-5) M, respectively, for the lysosomal enzyme and 2.7 X 10(-4) and 6.3 X 10(-5) M for the plasma membrane-bound one. Triton X-100 had a predominantly inhibitory effect on the lysosomal enzyme, whereas it strongly activated the plasma membrane-bound one. The lysosomal enzyme was highly unstable on storage and freezing and thawing cycles, whereas the plasma membrane-bound one was substantially stable. The RSA value of the lysosomal sialidase in the lysosomal fraction closely resembled that of authentic lysosomal enzymes, whereas the RSA value of plasma membrane-bound sialidase in the plasma membrane fraction was very similar to that of typical plasma membrane markers.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of solar proton events on test mass for gravitational wave detection in the 24th solar cycle.
Free-falling cubic Test Masses (TMs) are a key component of the interferometer used for low-frequency gravitational wave (GW) detection in space. However, exposure to energetic particles in the environment can lead to electrostatic charging of the TM, resulting in additional electrostatic and Lorentz forces that can impact GW detection sensitivity. To evaluate this effect, the high-energy proton data set of the Geostationary Operational Environmental Satellite (GOES) program was used to analyze TM charging due to Solar Proton Events (SPEs) in the 24th solar cycle. Using the Geant4 Monte Carlo toolkit, the TM charging process is simulated in a space environment for SPEs falling into three ranges of proton flux: (1) greater than 10 pfu and less than 100 pfu, (2) greater than 100 pfu and less than 1000 pfu, and (3) greater than 1000 pfu. It is found that SPEs charging can reach the threshold within 535 s to 18.6 h, considering a reasonable discharge threshold of LISA and Taiji. We demonstrate that while there is a somewhat linear correlation between the net charging rate of the TM and the integrated flux of [Formula: see text] 10 MeV SPEs, there are many cases in which the integrated flux is significantly different from the charging rate. Therefore, we investigate the difference between the integral flux and the charging rate of SPEs using the charging efficiency assessment method. Our results indicate that the energy spectrum structure of SPEs is the most important factor influencing the charging rate. Lastly, we evaluate the charging probability of SPEs in the 24th solar cycle and find that the frequency and charging risk of SPEs are highest in the 3rd, 4th, 5th, 6th, and 7th years, which can serve as a reference for future GW detection spacecraft.


Temporal stability of symptom dimensions in adult patients with obsessive-compulsive disorder.
Although symptoms of obsessive-compulsive disorder (OCD) are heterogeneous, considerable advances have been made in subtyping OCD based on factor-analysed symptom dimensions. However, there is very little empirical data on the longitudinal course of symptom dimensions in adult OCD. We examined prospectively the temporal symptom stability in adult OCD patients. Of 54 baseline OCD inpatients, 43 (80%) were re-assessed with the Yale-Brown Obsessive-Compulsive Scale symptom checklist after 6 years on average. Significant changes occurred within the symptom dimensions aggressive/checking, symmetry/ordering, and contamination/cleaning, whereas the others (hoarding, sexual/religious) remained unchanged from baseline to follow-up. Shifts between different dimensions from baseline to follow-up were rare, the score of each dimension at follow-up was most strongly predicted from the score of the same dimension at baseline. The main limitation of the present study is the relatively small sample size. Furthermore, not the same raters conducted the baseline and follow-up assessments. Symptom dimensions seem to be remarkably stable over several years in adult OCD, despite various treatments and significant improvements in symptom severity. This underlines the usefulness of these symptom dimensions for studies of biological and genetic markers, comorbidity and treatment response predictors.


Nicardipine versus nitroprusside for deliberate hypotension during idiopathic scoliosis repair.
To compare coagulation, blood loss, and transfusion requirements between patients receiving nicardipine and nitroprusside for deliberate hypotension during idiopathic scoliosis repair. Prospective, randomized study. University hospital. 51 ASA physical status I patients presenting for spine fusion for idiopathic adolescent scoliosis. Patients were randomized to two groups to receive nicardipine or nitroprusside to maintain mean arterial pressure (MAP) between 55 and 65 mmHg. Blood loss, blood transfusions, and coagulation studies (thromboelastogram and platelet aggregation) before starting vasodilator, 30 minutes and 90 minutes after starting vasodilator, and 30 minutes after stopping vasodilator, were all recorded. There was no difference between the groups in blood loss [nicardipine = 1,129 cc (893 to 1,480), nitroprusside = 960 cc (704 to 1,473)] and only one patient required a nonautologous transfusion. There were no differences in prothrombin time (pT, partial thromboplastin time (pTT), platelet count, or platelet aggregation between groups. There were more episodes of severe hypotension (MAP <45 mmHg) in the nitroprusside group (0% vs. 28%, p = 0.0175). On average, patients in the nicardipine group spent 21 minutes less in the recovery room than did the nitroprusside group (p = 0.043). Nitroprusside's effect on platelet aggregation produces no increase in blood loss compared with nicardipine. Nicardipine causes less transient severe hypotension than nitroprusside, although both drugs are acceptable choices for obtaining the goals of deliberate hypotension.


Neuronal F-Box protein FBXO41 regulates synaptic transmission and hippocampal network maturation.
FBXO41 is a neuron-specific E3 ligase subunit implicated in epileptic encephalopathies. Fbxo41 null mutant (KO) mice show behavioral deficits and early lethality. Here, we report that loss of FBXO41 causes defects in synaptic transmission and brain development. Cultured Fbxo41 KO neurons had normal morphology and showed no signs of degeneration. Single-cell electrophysiology showed a lower synaptic vesicle release probability in excitatory neurons. Inhibitory neurons exhibited reduced synaptophysin expression, a smaller readily releasable pool, and decreased charge transfer during repetitive stimulation. In Fbxo41 KO hippocampal slices at postnatal day 6, the dentate gyrus was smaller with fewer radial-glial-like cells and immature neurons. In addition, neuronal migration was delayed. Two-photon calcium imaging showed a delayed increase in network activity and synchronicity. Together, our findings point toward a role for FBXO41 in synaptic transmission and postnatal brain development, before behavioral deficits are detected in Fbxo41 KO mice.


COPD: A stepwise or a hit hard approach?
Current guidelines differ slightly on the recommendations for treatment of Chronic Obstructive Pulmonary Disease (COPD) patients, and although there are some undisputed recommendations, there is still debate regarding the management of COPD. One of the hindrances to deciding which therapeutic approach to choose is late diagnosis or misdiagnosis of COPD. After a proper diagnosis is achieved and severity assessed, the choice between a stepwise or "hit hard" approach has to be made. For GOLD A patients the stepwise approach is recommended, whilst for B, C and D patients this remains debatable. Moreover, in patients for whom inhaled corticosteroids (ICS) are recommended, a step-up or "hit hard" approach with triple therapy will depend on the patient's characteristics and, for patients who are being over-treated with ICS, ICS withdrawal should be performed, in order to optimize therapy and reduce excessive medications. This paper discusses and proposes stepwise, "hit hard", step-up and ICS withdrawal therapeutic approaches for COPD patients based on their GOLD group. We conclude that all approaches have benefits, and only a careful patient selection will determine which approach is better, and which patients will benefit the most from each approach.


Stanniocalcin 2 promotes cell proliferation and cisplatin resistance in cervical cancer.
Cervical cancer is one of the most common carcinomas in the female reproductive system. Treatment of cervical cancer involves surgical removal and chemotherapy. Resistance to platinum-based chemotherapy drugs including cisplatin has increasingly become an important problem in the treatment of cervical cancer patients. We found in this study that stanniocalcin 2 (STC2) expression was upregulated in both cervical cancer tissues and cell lines. The levels of STC2 expression in cervical cancer cell lines were positively correlated with the rate of cell proliferation. Furthermore, in cisplatin resistant cervical cancer cells, the levels of STC2 expression were significantly elevated. Modulation of STC2 expression by siRNA or overexpression in cisplatin resistant cells resulted in altered cell survival, apoptosis, and cisplatin resistance. Finally, we found that there was significant difference in the activity of the MAPK signaling pathway between cisplatin sensitive and resistant cervical cancer cells, and that STC2 could regulate the activity of the MAPK signaling pathway.


Subdural hemorrhage rebleeding in abused children: frequency, associations and clinical presentation.
Limited documentation exists about how frequently radiologically visible rebleeding occurs with abusive subdural hemorrhages (SDH). Likewise, little is known about rebleeding predispositions and associated symptoms. To describe the frequency of subdural rebleeding after abusive head trauma (AHT), its predispositions and clinical presentation. We evaluated children with SDHs from AHT who were reimaged within a year of their initial hospitalization, retrospectively reviewing clinical details and imaging. We used the available CT and MR images. We then performed simple descriptive and comparative statistics. Fifty-four of 85 reimaged children (63.5%) with AHT-SDH rebled. No child had new trauma, radiologic evidence of new parenchymal injury or acute neurologic symptoms from rebleeding. From the initial presentation, macrocephaly was associated with subsequent rebleeding. Greater subdural depth, macrocephaly, ventriculomegaly and brain atrophy at follow-up were associated with rebleeding. No other radiologic findings at initial presentation or follow-up predicted rebleeding risk, although pre-existing brain atrophy at initial admission and initial chronic SDHs barely missed significance. Impact injuries, retinal hemorrhages and clinical indices of initial injury severity were not associated with rebleeding. All rebleeding occurred within chronic SDHs; no new bridging vein rupture was identified. The mean time until rebleeding was recognized was 12 weeks; no child had rebleeding after 49 weeks. Subdural rebleeding is common and occurs in children who have brain atrophy, ventriculomegaly, macrocephaly and deep SDHs at rebleed. It usually occurs in the early months post-injury. All children with rebleeds were neurologically asymptomatic and lacked histories or clinical or radiologic findings of new trauma. Bleeds did not occur outside of chronic SDHs. We estimate the maximum predicted frequency of non-traumatic SDH rebleeding accompanied by acute neurological symptoms in children with a prior abusive SDH is 3.5%.


CT appearance of giant renal angiomyolipoma.
Renal angiomyolipomas are rare benign tumors readily identified by computed tomography due to their high fat content. When they attain giant proportions other fatty neoplasms, specifically liposarcomas, cannot be excluded based on the radiographic findings. A case in which a notch defect in the lateral border of the kidney was the single most important clue as to the intrarenal origin of the mass and led to the correct pre-operative diagnosis is presented.


Optimization of the scanning technique and diagnosis of pulmonary nodules with first-pass 64-detector-row perfusion VCT.
The aims of this study were to optimize the scanning technique of first-pass 64-detector-row perfusion volume computed tomography imaging, to evaluate the effectiveness and stability of this scan protocol, and lastly to evaluate the differential diagnosis ability of perfusion imaging in solitary pulmonary nodules (SPNs). A total of 144 patients with SPNs underwent perfusion scan with 64-slice spiral CT scanner. The CT perfusion imaging was analyzed for time-density curve, perfusion parametric maps, and the respective perfusion parameters. We then analyzed the main factors concerning the imaging quality and evaluated the effectiveness of scan protocol by determining the receiver operating characteristic (ROC) curve, diagnostic efficacy, and odds ratio as well as the stability of scan protocol by consistency analysis. Immunohistochemical findings of microvessel density measurement and vascular endothelial growth factor expression were evaluated. The total sensitivity, specificity, accuracy, positive predictive value, negative predictive value, likelihood ratio, and the area under ROC curve during 5-45-s scan period were 78.95%, 82.4%, 80.6%, 83.3%, 77.8%, 4.620, 0.280, and 0.840, respectively, and Kappa value was 0.894. The diagnostic efficacy of CT pulmonary perfusion was significantly higher than during 0-40-s scan period. The parameter values in different nodules were different. The optimized 5-45-s scan period of CT pulmonary perfusion imaging is effective in pathologic diagnosis and has good stability, worthy of being popularized. Lung perfusion CT could be a promising and feasible method for differentiation of SPNs.


Effects of warm and cold ischemia on mitochondrial functions in brain, liver and kidney.
The purpose of this work was to study the effects of warm (37 degrees C) and cold (4 degrees C) ischemia on different mitochondrial functions in rat brain, liver and kidney. After 10 to 60 minutes of ischemia at 37 degrees C the energy coupled respiration as well as the ADP-induced malate-aspartate shuttle activity in brain and liver mitochondria or the rate of mitochondrial ATP synthesis in kidney were significantly decreased. However, the respiratory rates and the shuttle activity in the absence of ADP remained unchanged. These data suggest that ischemia primarily affects electron transport in the respiratory chain rather than the hydrogen shuttle and the energy coupling system. When the temperature during the indicated ischemic periods was decreased to 4 degrees C, in brain and liver no significant alterations of these mitochondrial functions were found in comparison with the non-ischemic controls. When rat kidneys were stored for 36 hours at 4 degrees C according to Collins mimicking transplantation conditions, the mitochondrial respiration and ATP synthesis were only slightly decreased. It therefore appears that hypothermia can prevent effectively mitochondrial dysfunction due to ischemia.


CLEFT RR- New app to Calculate Recurrence Risk in Cleft lip and Palate.
To describe the Cleft Recurrence Risk (Cleft RR) App, designed to be used on genetic counseling for cleft lip and/ or palate. A validation study, single cohort. Tertiary care children's Hospital. The manual obtained the results of 100 cases undergoing genetic counseling at the cleft lip and palate treatment center. The application for genetic counseling for cleft lip and/ or palate is designed to calculate quickly the recurrence risk considering the ancestry, cleft type, sex, and family history and thus encourage the implementation of genetic counseling in cleft lip and palate centers around the world. The data were submitted to the Bland-Altman statistics. After defining parameters the application development follows the steps: development, prototyping, and documentation. The validation of the calculated data was performed by comparing the results of 100 cases undergoing genetic counseling at the cleft lip and palate treatment center obtained by the manual method with the results obtained by the mobile app method; the data were submitted to the Bland-Altman statistics and a high concordance was found. The mobile app for use by healthcare professionals proved to be simple to use, easy to apply, and provided accurate results. Cleft Recurrence Risk is an application for smartphones developed for genetic counseling in cleft lip and palate, supplementary use by health professionals, and should not replace professional performance.


Spectral characterization and crystal structure of 2-benzoylpyridine nicotinoyl hydrazone.
The synthesis, spectral characterization and crystal structure of 2-benzoylpyridine nicotinoyl hydrazone (HL) is reported. Spectral techniques employed include 1H NMR, COSY homonuclear, HSQC heteronuclear correlation techniques, electronic and IR. The infrared spectrum suggests the existence of the compound in keto form in solid state, which is further established by the single crystal X-ray analysis. The compound crystallizes into a triclinic lattice with P-1 symmetry with two molecules per unit cell.


Ultra-sensitive detection of pyridine in water using zinc porphyrin incorporated in a transparent hydrophobic film.
In this study, we investigated the axial coordination reaction between pyridine and zinc meso-tetra(4-sulfonatophenyl)porphyrin (ZnTPPS) incorporated in a transparent layered double hydroxide (LDH) film modified with 1-decanesulfonate (C10S) in an aqueous solution. The apparent equilibrium constant ([Formula: see text]) of the axial coordination reaction between pyridine and ZnTPPS incorporated in the transparent ZnTPPS/C10S/LDH film was approximately 260 times that of the corresponding reaction in an aqueous solution. The hydrophobisation of the LDH interlayer space by C10S, which led to the elimination of water molecules surrounding ZnTPPS and enabled the accumulation of pyridine molecules, was responsible for such a significant increase in the apparent [Formula: see text] value. The developed film can detect pyridine in aqueous solutions with ultra-high sensitivity in the order of 10-5 mol/L through changes in the colour tone, which is comparable to the molecular detection ability of insect antennae. The sensing response was also observed at pyridine concentrations as low as 10-9 mol/L.


Comparison of uterine artery Doppler measurements at 6 weeks of pregnancy after IVF between pregnancies that resulted in miscarriage and ongoing pregnancies.
To compare uterine artery pulsatility index (UTPI) at 6 weeks of pregnancy following in vitro fertilization (IVF) and embryo transfer (ET) between clinical pregnancies that resulted in a miscarriage and those that were ongoing beyond 12 weeks. A prospective observational study was conducted in an IVF unit at Prince of Wales Hospital, Hong Kong, between December 1, 2017 and December 31, 2019. UTPI was measured at 6 weeks of pregnancy among women who conceived following IVF/ET. Among 153 participants, 22 (14.4%) had a miscarriage whereas 131 (85.6%) had an ongoing pregnancy beyond 12 weeks. Median UTPI in pregnancies that ended in a miscarriage was significantly lower than those that progressed beyond 12 weeks (2.1, IQR 1.9-2.4 vs 2.50, IQR 2.2-2.9, respectively; P<0.001). The likelihood of the pregnancy ending in a miscarriage when the UTPI was above the 75th percentile (>2.9), between the 25th-75th percentiles (2.2-2.9), and below the 25th percentile (<2.2) was 0%, 13.2%, and 27.7%, respectively (P=0.001). IVF pregnancies that resulted in a miscarriage were associated with reduced resistance to uterine artery blood flow at 6 weeks of pregnancy.


Follow-Up Functional Class and 6-Minute Walk Distance Identify Long-Term Survival in Pulmonary Arterial Hypertension.
Guidelines recommend specific treatment goals for pulmonary arterial hypertension (PAH) patients: functional class I or II, 6-min walk distance (6MWD) ≥ 380 to 440 m, normal natriuretic peptide levels, and normal right-sided invasive hemodynamics. Only observational registry data support this recommendation. Our aim was to test these goals in a large group 1 PAH cohort against long-term survival. We analyzed the PHIRST and TRIUMPH populations (n = 563, age 53.5 ± 14.7 years, female sex 79%). The predictor variables were the treatment goals measured at the end of the placebo-controlled phase (16 and 12 weeks, respectively). The primary outcome was all-cause mortality at the end of follow-up during the open-label extension phase. There were 73 deaths during median follow of 1072 days (range 27 to 2177). Patients who achieved a functional class I or II had better survival. Both a 6MWD ≥ 380 m and ≥ 440 m were associated with lower mortality, but survival was better in patients able to walk ≥ 440 m. The best long-term survival was achieved with functional class I or II and 6MWD ≥ 440 m. In a subset of the population, cardiac index > 2.5 L/min/m2 was weakly associated with better survival. WHO functional class I or II, 6MWD ≥ 440 m and CI > 2.5 L/min/m2 measured 12-16 weeks after the introduction of PAH-targeted therapy are associated with better long-term survival in PAH. Best survival is observed by reaching both the functional class and the 6MWD goals.


Complex sparse Bayesian learning for guided wave dispersion curve estimation in plate-like structures.
This paper proposes a new dispersion curve estimation method that employs the complex sparse Bayesian learning (CSBL). It is well accepted that guided wave packets are distorted because of the differences in propagation velocities at different frequencies; thus, the preceding velocity-frequency curve estimation is beneficial for wave packet recovery, feature recognition and defect localization. Conventional dispersion curve estimation methods, such as two-dimensional Fourier transform and multiple signal classification, are suitable for array signal and are restricted by the transducer aperture, leading to a small application scope. According to the frequency-response model of the guided wave, for each frequency, the responses obtained by the transducers can be sparsely represented based on an overcomplete dictionary matrix constructed using multiple discretized wavenumbers and known distances. A CSBL algorithm was developed to infer the posterior probability density function of the weight vector in the sparse representation. The non-zero elements in the sparse weight vector mean that the corresponding dictionary atoms indicated wavenumbers are contained in the frequency response, and the velocity-frequency curve can be finally derived from the wavenumber-frequency curve. The proposed CSBL method has a satisfactory capability to solve this sparse representation of the complex frequency response because a hierarchical form of the Laplace prior is employed to achieve a high degree of sparsity of the weight vector. This method effectively incorporates the real and imaginary parts of the complex frequency response by employing the same hyperparameter to integrate the known information. This method requires only a few randomly placed transducers; thus, it has a wide range of applications. The effectiveness of the proposed approach was validated using multiple guided-wave signals obtained through numerical simulations and an experimental study on a plate structure.


Atomically Dispersed Iron Active Sites Promoting Reversible Redox Kinetics and Suppressing Shuttle Effect in Aluminum-Sulfur Batteries.
Rechargeable aluminum-sulfur (Al-S) batteries have been considered as a highly potential energy storage system owing to the high theoretical capacity, good safety, abundant natural reserves, and low cost of Al and S. However, the research progress of Al-S batteries is limited by the slow kinetics and shuttle effect of soluble polysulfides intermediates. Herein, an interconnected free-standing interlayer of iron single atoms supported on porous nitrogen-doped carbon nanofibers (FeSAs-NCF) on the separator is developed and used as both catalyst and chemical barrier for Al-S batteries. The atomically dispersed iron active sites (Fe-N4) are clearly identified by aberration-corrected high-angle annular dark-field scanning transmission electron microscopy and X-ray absorption near-edge structure. The Al-S battery with the FeSAs-NCF shows an improved specific capacity of 780 mAh g-1 and enhanced cycle stability. As evidenced by experimental and theoretical results, the atomically dispersed iron active centers on the separator can chemically adsorb the polysulfides and accelerate reaction kinetics to inhibit the shuttle effect and promote the reversible conversion between aluminum polysulfides, thus improving the electrochemical performance of the Al-S battery. This work provides a new way that can not only promote the conversion of aluminum sulfides but also suppress the shuttle effect in Al-S batteries.


When is "brainstem death" brain death? The case for ancillary testing in primary infratentorial brain lesion.
The widely accepted concept of brain death (BD) comprises the demonstration of irreversible coma in combination with the loss of brainstem reflexes and irreversible apnea. In some countries the combined clinical finding of coma, apnea, and loss of all tested brainstem reflexes ("brainstem death") is sufficient for diagnosing BD irrespective of the primary location of brain lesion. The present article aims to substantiate the need for ancillary testing in patients with primary infratentorial brain lesions. Anatomically, the "brainstem-death" syndrome can theoretically occur without relevant lesion of the mesopontine tegmental reticular formation (MPT-RF). Thus, a brainstem lesion may cause an apneic total locked-in syndrome, a rare syndrome with preserved capability for consciousness, mimicking "brainstem death". Findings in animals and humans have shown that alpha- or alpha/theta- EEG patterns in case of isolated brainstem lesion indicate intactness of relevant parts of the MPT-RF. In such patients the presence of irreversible coma has to be doubted, and the potential capacity for some degree of consciousness cannot be excluded as long as the EEG activity persists. Consequently the demonstration of either ancillary finding, electro-cortical inactivity or, preferably, cerebral circulatory arrest, is mandatory for diagnosing BD in patients with a primary infratentorial brain lesion.


Detection of fetal trisomy and single gene disease by massively parallel sequencing of extracellular vesicle DNA in maternal plasma: a proof-of-concept validation.
During human pregnancy, placental trophectoderm cells release extracellular vesicles (EVs) into maternal circulation. Trophoblasts also give rise to cell-free DNA (cfDNA) in maternal blood, and has been used for noninvasive prenatal screening for chromosomal aneuploidy. We intended to prove the existence of DNA in the EVs (evDNA) of maternal blood, and compared evDNA with plasma cfDNA in terms of genome distribution, fragment length, and the possibility of detecting genetic diseases. Maternal blood from 20 euploid pregnancies, 9 T21 pregnancies, 3 T18 pregnancies, 1 T13 pregnancy, and 2 pregnancies with FGFR3 mutations were obtained. EVs were separated from maternal plasma, and confirmed by transmission electronic microscopy (TEM), western blotting, and flow cytometry (FACS). evDNA was extracted and its fetal origin was confirmed by quantitative PCR (qPCR). Pair-end (PE) whole genome sequencing was performed to characterize evDNA, and the results were compared with that of cfDNA. The fetal risk of aneuploidy and monogenic diseases was analyzed using the evDNA sequencing data. EVs separated from maternal plasma were confirmed with morphology by TEM, and protein markers of CD9, CD63, CD81 as well as the placental specific protein placental alkaline phosphatase (PLAP) were confirmed by western blotting or flow cytometry. EvDNA could be successfully extracted for qPCR and sequencing from the plasma EVs. Sequencing data showed that evDNA span on all 23 pairs of chromosomes and mitochondria, sharing a similar distribution pattern and higher GC content comparing with cfDNA. EvDNA showed shorter fragments yet lower fetal fraction than cfDNA. EvDNA could be used to correctly determine fetal gender, trisomies, and de novo FGFR3 mutations. We proved that fetal DNA could be detected in EVs separated from maternal plasma. EvDNA shared some similar features to plasma cfDNA, and could potentially be used to detect genetic diseases in fetus.


Impaired Th2 development and increased mortality during Schistosoma mansoni infection in the absence of CD40/CD154 interaction.
The role of CD40/CD154 interaction during infection has primarily focused on pathogens that drive inflammatory Th1 responses. In this study, we show that CD40/CD154 interaction is a fundamental requirement for Th2 response development to the parasitic helminth Schistosoma mansoni. Compared with infected wild-type mice, greatly reduced levels of Th2-associated cytokines were measured both in vitro and in vivo, and no IgE or IgG1 was detected in infected CD154(-/-) mice. In the absence of an overt Th2 response, no exaggerated Th1 response was mounted by CD154(-/-) mice. Infected CD154(-/-) mice suffered severe morbidity and mortality, even though parasitemias in wild-type and CD154(-/-) mice did not differ significantly. These data indicate that CD40/CD154 interaction is required to allow development of a Th2-dominated immune response to S. mansoni and support the view that failure to develop such a response can have fatal consequences.


The hydrophobic-staple motif and a role for loop-residues in alpha-helix stability and protein folding.
A recurrent local structural motif is described at the amino terminus of alpha-helices, that consists of a specific hydrophobic interaction between a residue located before the N-cap, with a residue within the helix (i,i+5 interaction). NMR and CD analysis of designed peptides demonstrate its presence in aqueous solution, its contribution to alpha-helix stability and its role in defining the alpha-helix N terminus limit. Comparison between the N-terminal structures of the peptide and those in proteins with the same fingerprint sequence, shows striking similarities. The change in the polypeptide chain direction produced by the motif suggests an important role in protein folding for residues located in polypeptide segments between secondary structure elements.


Schizophrenia patients with a metabolically abnormal obese phenotype have milder negative symptoms.
Schizophrenia patients with a metabolically abnormal obese (MAO) phenotype have been shown poor cardiovascular outcomes, but the characteristics of their current psychiatric symptoms have not been characterized. This study mainly explored the psychiatric symptoms of schizophrenia patients with the MAO phenotype. A total of 329 patients with schizophrenia and 175 sex- and age-matched people without schizophrenia from Anhui Province in China were enrolled. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate the mental symptoms of the schizophrenia patients. The MAO phenotype was defined as meeting 1-4 metabolic syndrome criteria (excluding waist circumference) and having a body mass index (BMI) ≥ 28 kg/m2. And, metabolically healthy normal-weight (MHNW) phenotype was defined as meeting 0 criteria for metabolic syndrome and 18.5 ≤ BMI < 24 kg/m2. Overall, 15.8% of the schizophrenia patients and 9.1% of the control group were consistent with the MAO phenotype, and the prevalence of MAO in the schizophrenia group was higher than that in the control group. Among the patients with schizophrenia, the MAO group had lower negative factor, cognitive factor and total PANSS scores than the MHNW group. However, when confounding factors were controlled, only the negative factor remained lower significantly. We found that schizophrenia patients with the MAO phenotype had reduced negative symptoms, which may indicate an internal mechanism linking metabolic disorders and negative symptoms. This study was registered in the China Clinical Trial Registration Center (No. chiCTR 1,800,017,044 ).


Immunochemical Detection of Modified Cytosine Species in Lampbrush Chromatin.
The lampbrush chromosomes found in the giant nucleus or germinal vesicle (GV) of amphibian oocytes provide unique opportunities for discrete closed and open chromatin structural domains to be directly observable by simple light microscopy. Moreover, the method described here for preparing spreads of lampbrush chromatin for immunostaining enables a straightforward approach to establishing the distributions of modified nucleotides within and between structurally and functionally distinctive chromatin domains.


Climatic, physical, and biogeochemical changes drive rapid oxygen loss and recovery in a marine ecosystem.
Dissolved oxygen (DO) concentrations shape the biogeochemistry and ecological structure of aquatic ecosystems; as a result, understanding how and why DO varies in space and time is of fundamental importance. Using high-resolution, in situ DO time-series collected over the course of a year in a novel marine ecosystem (Jellyfish Lake, Palau), we show that DO declined throughout the marine lake and subsequently recovered in the upper water column. These shifts were accompanied by variations in water temperature and were correlated to changes in wind, precipitation, and especially sea surface height that occurred during the 2015-2016 El Niño-Southern Oscillation event. Multiple approaches used to calculate rates of community respiration, net community production, and gross primary production from DO changes showed that DO consumption and production did not accelerate nor collapse; instead, their variance increased during lake deoxygenation and recovery, and then stabilized. Spatial and temporal variations in rates were significantly related to climatic variability and changes in DO, and causality testing indicated that these relationships were both correlative and causative. Our data indicate that climatic, physical, and biogeochemical properties and processes collectively regulated DO, producing linked feedbacks that drove DO decline and recovery.


Fast-HMQC using Ernst angle pulses: An efficient tool for screening of ligand binding to target proteins.
The application of Ernst angle pulses in multidimensional NMR spectroscopy is theoretically and experimentally investigated. Theory shows that only for a few pulse sequences employed at high repetition rate, a remarkable gain in sensitivity is possible using Ernst angle pulses. As an example, a new variant of the heteronuclear multiple quantum coherence (HMQC) experiment, the fast-((1)H,(15)N)-HMQC, is described. This sequence allows, with a 1 mM protein sample in H(2)O, the acquisition of a highly resolved two-dimensional ((1)H,(15)N) correlated spectrum within 37 s. The high efficiency of the fast-HMQC to detect ligand binding to a target protein is demonstrated.


Prediction performance and reliability evaluation of three ginsenosides in Panax ginseng using hyperspectral imaging combined with a novel ensemble chemometric model.
Panax ginseng C. A. Meyer (PG) is a health-promoting food, and its ginsenosides (Rb1, Rg1, Re) content, as the quality indicator, is affected by the planting modes (garden or forest ginsengs) and years. Effective prediction of this content remains to be investigated. In this study, hyperspectral (HSI) combined with ensemble model (CGRU-GPR) including the convolutional neural network (CNN), gate recurrent unit (GRU), and Gaussian process regression (GPR) realized a comprehensive evaluation of the prediction performance and predictive uncertainty. With effective wavelengths, the proposed CGRU-GPR model improved operation efficiency and obtained satisfactory prediction results with relative percent deviation (RPD) values all higher than 2.70 in three ginsenosides. Meanwhile, the interval prediction with a high prediction interval coverage probability (PICP) of 0.97 - 1.0 and a low mean width percentage (MWP) of 0.7 - 1.66 indicated a low prediction uncertainty. This study provides a rapid and reliable method for predicting ginsenosides contents in PG.


Immunogenic properties of a trimeric gp41-based immunogen containing an exposed membrane-proximal external region.
The membrane-proximal external region (MPER) of HIV-1 gp41 is an attractive target for vaccine development. Thus, better understanding of its immunogenic properties in various structural contexts is important. We previously described the crystal structure of a trimeric protein complex named gp41-HR1-54Q, which consists of the heptad repeat regions 1 and 2 and the MPER. The protein was efficiently recognized by broadly neutralizing antibodies. Here, we describe its immunogenic properties in rabbits. The protein was highly immunogenic, especially the C-terminal end of the MPER containing 4E10 and 10E8 epitopes ((671)NWFDITNWLWYIK(683)). Although antibodies exhibited strong competition activity against 4E10 and 10E8, neutralizing activity was not detected. Detailed mapping analyses indicated that amino acid residues critical for recognition resided on faces of the alpha helix that are either opposite of or perpendicular to the epitopes recognized by 4E10 and 10E8. These results provide critical information for designing the next generation of MPER-based immunogens.


Influence of perinatal low-dose acetylsalicylic acid therapy on fetal hemodynamics evaluated by determining the acceleration-time/ejection-time ratio in the ductus arteriosus.
Acceleration-time/ejection-time ratio (At/Et ratio) of Doppler waveform is an established hemodynamic parameters that reflect proximal stenosis. Using this parameter, we evaluated whether perinatal low-dose acetylsalicylic acid (ASA) therapy could alter hemodynamics in the ductus arteriosus. Pulse Doppler measurements of the fetal ductus arteriosus were performed longitudinally from 20 to 37 gestational weeks in 106 healthy pregnant women (controls) and 65 pregnant women taking daily low-dose ASA (80 or 100 mg/day) because of a history of recurrent pregnancy loss. The At/Et ratio, pulsatility index (PI), and peak systolic velocity were evaluated and statistically analyzed. The At/Et ratio significantly increased with gestational age in both the ASA group (r = 0.54) and the control group (r = 0.35), while the PI did not. Median peak systolic velocities also increased with gestational age in both the ASA group (r = 0.39) and the control group (r = 0.31). No significant differences in At/Et ratio, PI, or peak systolic velocity were observed between the ASA group and the control group. Administration of low-dose ASA during pregnancy did not appear to alter hemodynamics in the fetal ductus arteriosus.


Infant mortality in American Indians and Alaska Natives 1995-1999 and 2000-2004.
(1) To determine the infant mortality rate (IMR) in American Indians/Alaska Natives (AI/AN) and whites between 1995-1999 and 2000-2004. (2) To compare the leading causes of infant mortality in AI/AN and whites. (3) To examine differences in neonatal vs. postneonatal causes of death in whites and AI/AN. Using the 1995-99 and 2000-04 Centers for Disease Control and Prevention's National Center for Health Statistics national linked birth/infant death data, we examined neonatal and post-neonatal IMR among AI/AN and whites. AI/AN experienced significantly greater overall IMR in 1995-1999 and 2000-2004 than whites. While the reduction in the IMR between these time periods was statistically significant for whites, the reduction among AI/AN was not. We found that AI/AN had an IMR 1.5 times as high as that of whites. While the overall IMR has decreased in AI/AN, disparities in postneonatal IMR persist between AI/AN and Whites.


Awareness of temperature and pain sensation.
Evoked potentials (EPs) to radiant or contact heat pain stimuli reflect the synchronization of brain activity to noxious inputs. However, we do not know how they relate to conscious awareness (AW) of a sensation. In healthy volunteers, we determined the time of AW for thermal noxious and non-noxious sensory inputs and examined its correlation to parametric measures of vertex EPs. Subjects had to report the position of the hand of a Libet's clock at the moment they perceived either a laser or a thermode stimulus. AW was determined after subtracting the position of the clock hand at the moment of stimulus delivery from the one reported by the subject, in ms. Subjects estimated AW in all single trials, including those in which no EPs could be identified. Mean AW was estimated earlier than the corresponding EP latency for both types and intensities of stimuli. There was a weak but significant negative correlation of AW to EPs amplitude, which was higher than the correlation of AW to EPs latency. Our results indicate that the timing of AW is influenced by the subjective relevance of sensory inputs. This feature could be used for the analysis of cognitive aspects of pain processing. This article presents a way to measure the subjective awareness of the sensation induced by a noxious heat stimulus, either radiant or contact, in healthy human subjects. This method could be used for the analysis of cognitive aspects of pain processing.


Cocaine self-administration in rats: threshold procedures.
Cocaine self-administration provides a methodology allowing researchers to study changes in distinct aspects of drug-taking behavior that model behaviors observed in drug addicts. Traditionally, self-administration schedules were designed to independently study changes in drug-taking behaviors (e.g., rate of responding, reinforcing efficacy, etc.). The threshold self-administration procedure was developed to measure two distinct dependent measures within the same experimental session that are important in the study of drug addiction: the maximal price an animal expends to self-administer cocaine and an animal's preferred level of cocaine consumption when available at a low behavioral cost.


Ligand-independent activation of platelet-derived growth factor receptor β promotes vitreous-induced contraction of retinal pigment epithelial cells.
Epiretinal membranes in patients with proliferative vitreoretinopathy (PVR) consist of extracellular matrix and a number of cell types including retinal pigment epithelial (RPE) cells and fibroblasts, whose contraction causes retinal detachment. In RPE cells depletion of platelet-derived growth factor (PDGF) receptor (PDGFR)β suppresses vitreous-induced Akt activation, whereas in fibroblasts Akt activation through indirect activation of PDGFRα by growth factors outside the PDGF family (non-PDGFs) plays an essential role in experimental PVR. Whether non-PDGFs in the vitreous, however, were also able to activate PDGFRβ in RPE cells remained elusive. The CRISPR/Cas9 technology was utilized to edit a genomic PDGFRB locus in RPE cells derived from an epiretinal membrane (RPEM) from a patient with PVR, and a retroviral vector was used to express a truncated PDGFRβ short of a PDGF-binding domain in the RPEM cells lacking PDGFRβ. Western blot was employed to analyze expression of PDGFRβ and α-smooth muscle actin, and signaling events (p-PDGFRβ and p-Akt). Cellular assays (proliferation, migration and contraction) were also applied in this study. Expression of a truncated PDGFRβ lacking a PDGF-binding domain in the RPEM cells whose PDGFRB gene has been silent using the CRISPR/Cas9 technology restores vitreous-induced Akt activation as well as cell proliferation, epithelial-mesenchymal transition, migration and contraction. In addition, we show that scavenging reactive oxygen species (ROS) with N-acetyl-cysteine and inhibiting Src family kinases (SFKs) with their specific inhibitor SU6656 blunt the vitreous-induced activation of the truncated PDGFRβ and Akt as well as the cellular events related to the PVR pathogenesis. These discoveries suggest that in RPE cells PDGFRβ can be activated indirectly by non-PDGFs in the vitreous via an intracellular pathway of ROS/SFKs to facilitate the development of PVR, thereby providing novel opportunities for PVR therapeutics. The data shown here will improve our understanding of the mechanism by which PDGFRβ can be activated by non-PDGFs in the vitreous via an intracellular route of ROS/SFKs and provide a conceptual foundation for preventing PVR by inhibiting PDGFRβ transactivation (ligand-independent activation).


Detection of extracellular matrix molecules synthesized in vitro by monkey and human retinal pigment epithelium: influence of donor age and multiple passages.
The retinal pigment epithelium of various species, including man, can synthesize extracellular matrix components in vitro. We studied extracellular matrix molecule production by human, rhesus and cynomolgus monkey pigment epithelium in vitro, using a panel of specific antibodies to collagen types I-V, fibronectin, laminin, the basement membrane heparan sulfate proteoglycan, human alpha elastin, glial fibrillary acidic protein (GFAP), and Factor VIII in a modified indirect immunofluorescence reaction. Results were similar between human and both monkey species in early passage cultures with respect to the positive detection of collagen types I, III, IV, V laminin, basement membrane proteoglycan, and fibronectin. The fluorescence was strongest in the center of confluent monolayers and was absent in border or isolated cells. Collagen type II, elastin, GFAP, or Factor VIII were not detected. Based on these findings, human and monkey pigment epithelium in vitro should be useful for the study of the synthesis, deposition and supramolecular interactions of a variety of extracellular matrix molecules.


Poplar rotation coppice at a trace element-contaminated phytomanagement site: A 10-year study revealing biomass production, element export and impact on extractable elements.
Growing lignocellulosic crops on marginal lands could compose a substantial proportion of future energy resources. The potential of poplar was explored, by devising a field trial of two hectares in 2007 in a metal-contaminated site to quantify the genotypic variation in the growth traits of 14 poplar genotypes grown in short-rotation coppice and to assess element transfer and export by individual genotypes. Our data led us to conclusions about the genotypic variations in poplar growth on a moderately contaminated site, with the Vesten genotype being the most productive. This genotype also accumulated the least amounts of trace elements, whereas the Trichobel genotype accumulated up to 170 mg Zn kg-1 DW in the branches, with large variation being exhibited among the genotypes for trace element (TE) accumulation. Soil element depletion occurred for a range of TEs, whereas the soil content of major nutrients and the pH remained unchanged or slightly increased after 10 years of poplar growth. The higher TE content of bark tissues compared with the wood and the higher proportion of bark in branches compared with the wood led us to recommend that only stem wood be harvested, instead of the whole tree, which will enable a reduction in the risks encountered with TE-enriched biomass in the valorization process.


Spatial variation profiling of four phytochemical constituents in Gentiana straminea (Gentianaceae).
Gentiana straminea is the famous Tibetan folk medicine thought to cure various diseases. Historically, the Qinghai-Tibetan region has been considered as the geo-authentic production area of "Mahua Jiao," where large quantities of the medicine are grown. However, there is still little known about the phytochemical constituent spatial variation of this species. In order to find the differences between the main phytochemical constituents of G. straminea and to provide comprehensive information for quality evaluation, four main bioactive compounds (loganic acid, swertiamarin, gentiopicroside and sweroside) were analysed in 26 populations grown in areas with elevations ranging from 2320 to 4720 m across the Qinghai-Tibetan Plateau. The results showed that the four phytochemical constitutes' concentrations varied greatly in the spatial profiling of the Qinghai-Tibetan region. Throughout the range of distribution of this species, no altitudinal, latitudinal or longitudinal trends have proven to be significant in any of the four constitutes' concentrations or their summation. Furthermore, hierarchical clustering analysis and statistical tests showed that four populations (Liu0609-18, Liu0609-15, Liu2006-13-9 and Liu0609-22) had total constitute contents that were higher than other populations. The spatial profiling of the four phytochemical constituents suggests that the geo-authentic producing area of this species exists at a few regions within the Qinghai province, which could be attributed to specific environmental or genetic factors.


2-Methoxyestradiol at low dose induces differentiation of myeloma cells.
Previous studies showed that 2-methoxyestradiol (2ME2) could suppress the proliferation of myeloma cells and induce their apoptosis. In the present study, we found that treatments with low-concentration of 2ME2 resulted in some maturing morphological changes of myeloma cells. Flow cytometric analysis showed that the expression of CD49e on the myeloma cells surface was significantly increased by 2ME2. Moreover, 2ME2 increased the secretion of light chain protein remarkably. Furthermore, the expressions of transcription factor XBP-1 mRNA and protein were also up-regulated. These results demonstrated that 2ME2 at low-concentration could induce differentiation of the myeloma cells, which would provide a new, safe strategy for myeloma therapy.


Assays to Demonstrate the Roles of Arenaviral Nucleoproteins (NPs) in Viral RNA Synthesis and in Suppressing Type I Interferon.
Arenaviruses, such as Lassa virus (LASV) and Pichindé virus (PICV), are enveloped viruses with a bi-segmented ambisense RNA genome. The large (L) genomic segment encodes the Z matrix protein and the L RNA-dependent RNA polymerase, whereas the small (S) genomic segment encodes the nucleoprotein (NP) and the glycoprotein (GPC). The NP encapsidates viral genome, is required for viral transcription and replication, and acts as a type I interferon (IFN) antagonist. This article describes assays to demonstrate that NP contains 3'-5' exoribonuclease (RNase) activity to degrade modeled RNA of the pathogen-associated molecular pattern type and suppresses the IFNβ promoter-driven luciferase reporter gene. The minigenomic (MG) assay is used to assess the role of NP in replicating and transcribing a viral promoter-driven luciferase reporter gene. These powerful assays demonstrate the versatility of NP in mediating viral replication as well as in modulating host innate immune responses.


Differentiating a chronic hyperplastic mass from pancreatic cancer: a challenge remaining in multidetector CT of the pancreas.
A multitude of clinical symptoms originate from pancreatic inflammatory or neoplastic processes due to their highly complex composition, function, and anatomic relationships to adjacent organs as well as the heterogeneous patterns of vascular perfusion and neural innervation of the pancreatic gland which complicate an early and precise diagnosis. Whereas early assessment of inflammatory or neoplastic pancreatic processes is a prerequisite for a successful curative approach, the classical radiologic signs of chronic pancreatitis and pancreatic carcinoma show significant similarities. This article provides an overview of the pathogenesis and imaging findings in chronic pancreatitis and pancreatic cancer, including some new approaches for visualizing the subtle but distinct differences between these two entities.


Laparoscopic versus transverse Incision right colectomy for colon carcinoma.
We investigated whether laparoscopic right colectomy has short-term and ⁄ or oncological advantages compared with transverse incision right colectomy. Patients who underwent an elective laparoscopic right colectomy or an open right colectomy through a transverse incision at the VU University Medical Center or Zaans Medical Center from 2005 to 2009 were prospectively followed. Patient groups were comparable in terms of gender, body mass index and American Society of Anesthesiology classification. Patients in the transverse incision group were older (68 years vs 75 years, P = 0.07) and blood loss was greater during this procedure (60 ml vs 130 ml, P = 0.001), which cost less than the laparoscopic procedure (€6.033 vs €7.221, P = 0.03). Hospital stay for the laparoscopic group was shorter (8 days vs 9 days, P = 0.04), but laparoscopic procedures took longer (155 min vs 77 min, P < 0.001) and 8% of patients in the laparoscopic group were converted to a median laparotomy. Postoperative complications were comparable for both groups (28% vs 32%, P = 0.74), and in both groups a radical resection rate of 96% (P = 0.94) was achieved. At a median follow up of 20 months the incidence of incisional hernia was similar in both groups and no patient required additional surgery as a result. Overall survival at 60 months was 70% for the laparoscopic group and 67% for the transverse incision group (P = 0.84). There a re few clinically relevant differences between a laparoscopic right colectomy and a transverse incision right colectomy. Transverse incision right colectomy is cheaper. The study may be the first to compare these two techniques, but it is a nonrandomized trial and therefore has its limitations.


Evidence for early right ventricular and septal mechanical activation (interventricular dyssynchrony) in pulmonary hypertension.
This study sought to characterize mechanical activation in pulmonary arterial hypertension (PAH) using 2-dimensional echocardiography with tissue Doppler imaging. Whether pathologic alterations of the right ventricle in PAH affect interventricular dyssynchrony due to changes in mechanical activation of the septum and the right ventricle is unclear. We studied 20 patients with PAH (14 women, mean age 55 +/- 16 years) and 20 healthy controls (15 women, mean age 41 +/- 11 years) that underwent tissue Doppler imaging between July 2006 and May 2007. PAH was associated with accelerated right ventricular (RV) (p <0.0001) and septal (p = 0.022) activation times, but no differences were found in lateral wall activation times between groups (p = 0.35). Measures of ventricular dyssynchrony indicated that patients with PAH had significantly lower RV-lateral wall delays (patients 3.2 +/- 66.2 ms vs controls 56.7 +/- 52.0 ms, p = 0.007), reflecting a faster activation of the right ventricle relative to the lateral wall than controls. In conclusion, PAH is associated with interventricular dyssynchrony manifested by accelerated RV free wall and septal activation times. Whether such dyssynchrony should serve as a therapeutic target remains to be determined.


Understanding the psychosocial issues of African American couples surviving prostate cancer.
African Americans are disproportionately affected by prostate cancer, yet less is known about the most salient psychosocial dimensions of quality of life. The purpose of this study was to explore the perceptions of African American prostate cancer survivors and their spouses of psychosocial issues related to quality of life. Twelve African American couples were recruited from a National Cancer Institute Comprehensive Cancer Center registry and a state-based non-profit organization to participate in individual interviews. The study was theoretically based on Ferrell's Quality of Life Conceptual Model. Common themes emerged regarding the psychosocial needs of African American couples. These themes were categorized into behavioral, social, psychological, and spiritual domains. Divergent perspectives were identified between male prostate cancer survivors and their female spouses. This study delineated unmet needs and areas for future in-depth investigations into psychosocial issues. The differing perspectives between patients and their spouses highlight the need for couple-centered interventions.


Real-time programmable metasurface for terahertz multifunctional wave front engineering.
Terahertz (THz) technologies have become a focus of research in recent years due to their prominent role in envisioned future communication and sensing systems. One of the key challenges facing the field is the need for tools to enable agile engineering of THz wave fronts. Here, we describe a reconfigurable metasurface based on GaN technology with an array-of-subarrays architecture. This subwavelength-spaced array, under the control of a 1-bit digital coding sequence, can switch between an enormous range of possible configurations, providing facile access to nearly arbitrary wave front control for signals near 0.34 THz. We demonstrate wide-angle beam scanning with 1° of angular precision over 70 GHz of bandwidth, as well as the generation of multi-beam and diffuse wave fronts, with a switching speed up to 100 MHz. This device, offering the ability to rapidly reconfigure a propagating wave front for beam-forming or diffusively scattered wide-angle coverage of a scene, will open new realms of possibilities in sensing, imaging, and networking.


Comparison of Oxford Cognitive Screen and Montreal Cognitive Assessment feasibility in the stroke unit setting. A pilot study.
: Cognitive status evaluation is not routine in the acute stroke setting and there is no consensus on which neuropsychological tool is more feasible and informative. The aim of this pilot study was to compare the feasibility and acceptability of two brief cognitive tests, the Montreal Cognitive Assessment (MoCA) and the Oxford Cognitive Screen (OCS), in acute stroke, with a focus on patients' experience, administration time, and the cognitive data obtained. : Patients with a diagnosis of ischemic or hemorrhagic stroke or of transient ischemic attack admitted to two stroke units were included. The sample consisted of 34 participants (mean age ±SD 71.1 ± 16.1 years, 25 males). Within five days of onset, patients were evaluated by means of the MoCA and OCS by a trained neuropsychologist. Both tests were feasible in the stroke unit setting and had a high level of acceptability by patients. MoCA test was fully completed by 25 patients, OCS by 21 patients. The OCS administration time was longer than that of the MoCA. However, OCS was perceived less demanding than MoCA by patients. Twenty patients completed both the MoCA and the OCS entirely, and only 2 of them did not show any impairment in both tests. Seventeen patients showed at least an impaired domain on the OCS and 15 patients presented with a MoCA global score below cut-off for cognitive impairment. Our preliminary study did not show a superiority of the OCS over the widely used MoCA, and suggests the need for further validation in larger samples of stroke patients, exploring tests accuracy in detecting cognitive post-stroke impairment.


Engineered mesenchymal stromal cell therapy during human lung ex vivo lung perfusion is compromised by acidic lung microenvironment.
Ex vivo lung perfusion (EVLP) is an excellent platform to apply novel therapeutics, such as gene and cell therapies, before lung transplantation. We investigated the concept of human donor lung engineering during EVLP by combining gene and cell therapies. Premodified cryopreserved mesenchymal stromal cells with augmented anti-inflammatory interleukin-10 production (MSCIL-10) were administered during EVLP to human lungs that had various degrees of underlying lung injury. Cryopreserved MSCIL-10 had excellent viability, and they immediately and efficiently elevated perfusate and lung tissue IL-10 levels during EVLP. However, MSCIL-10 function was compromised by the poor metabolic conditions present in the most damaged lungs. Similarly, exposing cultured MSCIL-10 to poor metabolic, and especially acidic, conditions decreased their IL-10 production. In conclusion, we found that "off-the-shelf" MSCIL-10 therapy of human lungs during EVLP is safe and feasible, and results in rapid IL-10 elevation, and that the acidic target-tissue microenvironment may compromise the efficacy of cell-based therapies.


Microarrays of near-field optical probes with adjustable dimensions.
We present the fabrication and the characterization of high-density microarrays comprising thousands of near-field optical probes. Two types of microarrays have been prepared by adapting the SNOM methodology: arrays of uncoated fiber nanotips (i.e. apertureless probes) and arrays of apertures with adjustable subwavelength dimensions. Such arrays were fabricated by retaining the coherent structure of monomode optical fiber bundles and therefore keeping their imaging properties. The size of the apertures in a microarray was tuned at the nanometer scale by modifying the fabrication parameters. Far-field characterization of these near-field probe arrays shows completely different behavior depending both on their architecture and on their characteristic size. The angular distribution of the far-field intensity transmitted through the aperture arrays is used to determine the optical size of such diffracting apertures. Aperture radii ranging from 95 to 250 nm were found in good agreement with SEM data. Furthermore, each nanoaperture of the array is optically independent in the far-field regime. Eventually, this study demonstrates potential applications of these imaging arrays as parallel near-field optical probes in both configurations (apertureless and with apertures).


Oxidized proteins in plasma of patients with heart failure: role in endothelial damage.
Oxidative stress is increased in the failing heart, and this might contribute to the pathogenesis of myocardial remodelling and heart failure (HF). To identify the oxidized proteins in plasma of chronic HF patients and to evaluate their possible role in endothelial damage. Plasma levels of oxidized proteins were measured by immunoassay and by analysis in albumin and immunoglobulin depleted plasma using a proteomic approach, in 40 HF patients and in 20 age-matched normal subjects. Analysis of the effects of proteins oxidized in vitro on human endothelial cell (EC) viability was also performed. Plasma levels of oxidized proteins were significantly higher in HF patients than in controls (p<0.01). We identified two proteins, alpha-1-antitrypsin and fibrinogen, which underwent oxidation. Oxidation of alpha-1-antitrypsin resulted in loss of its protease inhibitor activity, thus leading to EC death in the presence of elastase. Fibrinogen, when oxidized, became otherwise cytotoxic and induced apoptosis in EC. This study shows that plasma levels of oxidized proteins are increased in HF, and permitted the identification of two proteins, namely alpha-1-antitrypsin and fibrinogen, which underwent oxidation. In vitro results highlighted the potential role of oxidized proteins in the EC damage that occurs in HF.


Synthesis and evaluation of platelet aggregation inhibitory activity of some 3-phenyl-pyrroloquinazolinones.
A series of 3-phenyl-2,7-dihydro-1H-pyrrolo[3,2-f]quinazolin-1-one derivatives (3-PPyQZ) was synthesized starting from 5-amino-indoles, via condensation with N-ethoxycarbonylthiobenzamides followed by thermal cyclization. On the basis of their structural analogy with reported anti-thrombin pyrroloquinazolines, the derivatives were first tested for their capacity to inhibit platelet aggregation. Some of them had in vitro inhibitory effects on collagen and thrombin-induced aggregation in the micromolar range, and much higher inhibition than that shown by some phenyl-pyrroloquinolinones. Experiments to determine the mechanism of action of the most potent inhibitor (compound 18) indicated that it acts in at least two sites: one preceding the agonist-induced increase of cytosolic [Ca(2+)], and one following this step of the platelet activation cascade. The compound also inhibited thrombin-evoked protein-Tyr-phosphorylation. Although it is premature to draw definitive conclusions, the present results indicate that 3-PPyQZ structure, with the quite potent inhibitor of platelet aggregation compound 18, might constitute a starting point for the synthesis of potential anti-thrombosis agents.


Isolated perfused rabbit colon crypts: stimulation of Cl- secretion by forskolin.
The aim of this study was to characterize ion conductances and carrier mechanisms of isolated in vitro perfused rabbit colonic crypts. Crypts were isolated from rabbit colon mucosa and mounted on a pipette system which allowed controlled perfusion of the lumen. In non-stimulated conditions basolateral membrane voltage (Vbl) was -65 +/- 1 mV (n = 240). Bath Ba2+ (1 mmol/l) and verapamil (0.1 mmol/l) depolarized Vbl by 21 +/- 2 mV (n = 7) and 31 +/- 1 (n = 4), respectively. Lowering of bath Cl- concentration hyperpolarized Vbl from -69 +/- 3 to -75 +/- 3 mV (n = 9). Lowering of luminal Cl- concentration did not change Vbl. Basolateral application of loop diuretics (furosemide, piretanide, bumetanide) had no influence on Vbl in non-stimulated crypts. Forskolin (10(-6) mol/l) in the bath depolarized Vbl by 29 +/- 2 mV (n = 54) and decreased luminal membrane resistance. In one-third of the experiments a spontaneous partial repolarization of Vbl was seen in the presence of forskolin. During forskolin-induced depolarization basolateral application of loop diuretics hyperpolarized Vbl significantly and concentration dependently with a potency sequence of bumetanide > piretanide > or = furosemide. Lowering bath Cl- concentration hyperpolarized Vbl. Lowering of luminal Cl- concentration from 120 to 32 mmol/l during forskolin-induced depolarization led to a further depolarization of Vbl by 7 +/- 2 mV (n = 10). We conclude that Vbl of rabbit colonic crypt cells is dominated by a K+ conductance. Stimulation of the cells by forskolin opens a luminal Cl- conductance. Basolateral uptake of Cl- occurs via a basolateral Na+:2Cl-:K+ cotransport system.


Predicting murder rates of police and civilians by each other.
For 1960-1992, while divorce rates predicted the general homicide rates, neither divorce nor unemployment rates predicted the rates with which police killed civilians or civilians killed police.


Epidemiological, methodological, and statistical characteristics of network meta-analysis in anaesthesia: a systematic review.
Network meta-analyses (NMAs) combine direct and indirect estimates to provide mixed (or network) estimates of effect sizes. The scientific rigour of the conduct and reporting of anaesthesia NMAs is unknown. This review assessed the epidemiological, methodological, and statistical characteristics of anaesthesia NMAs. We searched four databases for anaesthesia NMAs and developed a 64-item checklist to evaluate NMAs. For 29 binary items, we defined compliance as 'the ratio of NMAs that was awarded a 'yes' for that item, divided by the total number of NMAs. The compliance of such binary items was reclassified as very low (≤25%), low (26-50%), fair (51-75%), and high (>75%). We amalgamated findings from 29 key items to provide specific recommendations (post hoc). We compared the compliance of NMAs in anaesthesia across 26 items, with that of cancer NMAs and Cochrane NMAs, and analysed improvement over time (post hoc). Among 62 included NMAs, compliance was low (26-50%) for protocol registration, use of PRISMA-NMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses for NMA), publication bias assessment, evidence appraisal, reporting of Bayesian methodology and consistency evaluation. Compliance was very low (≤25%) for bias assessment, biostatistician involvement, search specialist, and use of predefined important differences. Anaesthesia NMAs need improvement in their conduct and reporting. Anaesthesia journals should mandate the registration of protocols and reporting of NMAs using PRISMA-NMA. Authors should carefully assess publication bias, and use updated bias assessment tools, and evidence appraisal methods designed for NMAs. PROSPERO CRD42021227608.


Occupational risk factors for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among healthcare personnel: A 6-month prospective analysis of the COVID-19 Prevention in Emory Healthcare Personnel (COPE) Study.
To determine the incidence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among healthcare personnel (HCP) and to assess occupational risks for SARS-CoV-2 infection. Prospective cohort of healthcare personnel (HCP) followed for 6 months from May through December 2020. Large academic healthcare system including 4 hospitals and affiliated clinics in Atlanta, Georgia. HCP, including those with and without direct patient-care activities, working during the coronavirus disease 2019 (COVID-19) pandemic. Incident SARS-CoV-2 infections were determined through serologic testing for SARS-CoV-2 IgG at enrollment, at 3 months, and at 6 months. HCP completed monthly surveys regarding occupational activities. Multivariable logistic regression was used to identify occupational factors that increased the risk of SARS-CoV-2 infection. Of the 304 evaluable HCP that were seronegative at enrollment, 26 (9%) seroconverted for SARS-CoV-2 IgG by 6 months. Overall, 219 participants (73%) self-identified as White race, 119 (40%) were nurses, and 121 (40%) worked on inpatient medical-surgical floors. In a multivariable analysis, HCP who identified as Black race were more likely to seroconvert than HCP who identified as White (odds ratio, 4.5; 95% confidence interval, 1.3-14.2). Increased risk for SARS-CoV-2 infection was not identified for any occupational activity, including spending >50% of a typical shift at a patient's bedside, working in a COVID-19 unit, or performing or being present for aerosol-generating procedures (AGPs). In our study cohort of HCP working in an academic healthcare system, <10% had evidence of SARS-CoV-2 infection over 6 months. No specific occupational activities were identified as increasing risk for SARS-CoV-2 infection.


The mechanisms of 6-hydroxydopamine-induced astrocyte death.
Treatment with 6-hydroxydopamine significantly reduced the viability of cultured rat primary astrocytes, rat astrocytoma cell line C6, and human astrocytoma cell line U251. 6-Hydroxydopamine-treated astrocytes exhibited altered nuclear morphology, DNA fragmentation, and reduced intracellular esterase activity, which indicated apoptotic cell death. Astrocytes were protected by neutralization of 6-hydroxydopamine autooxidation products H(2)O(2), O(2)(*-), and (*)OH, but not by cell-derived or chemically generated anti-apoptotic free radical nitric oxide. Finally, 6-hydroxydopamine activated extracellular signal-regulated kinase in astrocytes and selective inhibitor of extracellular signal-regulated kinase activation partially prevented astrocyte death. Taken together, these data indicate that 6-hydroxydopamine-triggered oxidative stress induces extracellular signal-regulated kinase-dependent apoptotic death of astrocytes.