The impact of disability on motherhood decisions: New evidence from Spain.
There exists a high proportion of women with disabilities who decide to be mothers although there is a high stigma about their capabilities. The objective is to analyze the impact of disability, among other socioeconomic conditions, on the motherhood decisions. We compared the results of treating disability as exogenous with a bivariate probit model. A cross-sectional analytical study has been analyzed by using data from the Fecundity Survey of 2018. The model estimates the probability of having children having disability, which is a 3.5%. Moreover, motherhood propensity for disabled women is 0.4 percentage points lower than for non-disabled.In this article the authors undertook a significant literature review, then it is included a development of the theoretical and methodology framework for analyzing the effect of disability on the attitudes of women toward the decision of having children. In this context, many disabled women have successfully become mothers but the existent barriers have unmotivated others. The difficulty is basically due to the stigma about their mothering capabilities or associated with physical conditions such as risk of abortion or even a worsening of health. The economic framework under our specification is an extension of the Households Health Production Model where women derive utility from having children and they use their skills, knowledge or time to achieve their objective. In this case, to have children is the outcome and education, health status and other socioeconomic factors are the inputs. Having children is only one of the sources of utility that a woman has, they also derive utility from labor time, consumption or healthcare, among others. Despite several studies used this methodology to analyze motherhood decisions in many Countries in the world, the impact of disability is much less explored.


Specific receptor sites for PAF in iris and ciliary body of the rabbit eye.
The existence of specific binding sites by using tritiated 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine (3H-PAF) was investigated on iris and ciliary body tissue of pigmented rabbit eyes. The binding was saturable, specific, time-dependent and reversible. Scatchard's analysis indicated the presence of two types of binding sites with a Kd1 4.90 +/- 0.47 nM, a Kd2 11.60 +/- 0.33 nM, a Bmax1 3.17 +/- 0.50 pmol/mg protein and a Bmax2 12.45 +/- 2.30 pmol/mg protein for iris tissue, and a Kd1 5.71 +/- 0.09 nM, a K2d 24.40 +/- 0.91 nM, a Bmax1 3.41 +/- 1.00 pmol/mg protein and a Bmax2 16.60 +/- 0.51 pmol/mg protein for ciliary body. The binding was fully displaced by unlabelled PAF in both iris and ciliary body preparations, and partially inhibited by the PAF antagonist BN 52021 in iris tissue.


Involvement of central amygdalar and bed nucleus of the stria terminalis corticotropin-releasing factor in behavioral responses to social defeat.
The authors investigated whether corticotropin-releasing factor (CRF) within the central nucleus of the amygdala (CeA) and bed nucleus of the stria terminalis (BNST) is a critical component of the neural circuitry mediating conditioned defeat. In this model, hamsters that have experienced social defeat subsequently display only submissive-defensive agonistic behavior instead of territorial aggression. Conditioned defeat was significantly reduced following infusion of the CRF receptor antagonist D-Phe CRF((12-41)) into the BNST but not into the CeA. In another experiment, hamsters given unilateral lesions of the CeA and infusions of D-Phe CRF((12-41)) into the contralateral BNST displayed significantly less submissive behavior than did controls. These data suggest that CRF acts within a neural circuit that includes the amygdala and the BNST to modulate agonistic behavior following social defeat.


Single-shot experiments for the acquisition of coherence-transfer functions in real time.
Simple pulse sequences are introduced that make it possible to acquire experimental Hartmann-Hahn transfer functions for arbitrary multiple-pulse sequences in a single shot. With this approach it is possible to study the detailed dependence of coherence-transfer functions on experimental parameters in real time.


A model for glucose-induced wave propagation in pancreatic islets of Langerhans.
A reaction-diffusion type model is constructed, describing the spatio-temporal dynamics of the basic intracellular variables assumed to be involved in the initiation of the insulin secretion process by beta -cells in the pancreatic islets of Langerhans. The model includes equations for the electric membrane potential of the cells, with respective kinetics for ionic currents, for concentrations of both free and stored intracellular calcium, and for the intra- and extracellular concentrations of glucose. An empirical expression connecting the equation for the intracellular glucose concentration to the electrical equation is introduced. The model reproduces the events observed in experiments in vitro upon external glucose application to the islets of Langerhans, such as usual bursting oscillations of the membrane potential and corresponding oscillations of the intracellular calcium concentration. It also allows simulation of electric wave propagation through the islet, initiated by the spatial gradient of glucose concentration within the islet. The gradient emerges due to glucose diffusing into the islets from the external medium, being high at the edges. The latter results show that glucose diffusion presents a means for wave initiation in the islets, which supports our previous assumption (Aslanidi et al., 2001).


Assessing compliance to antihypertensive medications using computer-based pharmacy records.
Systematic approaches for compliance problem detection and intervention are needed if the benefits of prescribed drug therapy in chronic disease management are to be optimized. As with all measures of compliance, computer algorithms based on refill patterns have advantages and disadvantages. They are unobtrusive and easily determined, but they measure the timeliness of prescription refills, not actual drug-taking. Computer-generated algorithms for assessing compliance based on refill patterns should be used by practitioners with caution, because they are not only markers for potential drug taking compliance problems, but also for discrepancies between the medical chart, pharmacy records and verbal advice given to the patient. Because patients may obtain refills before depleting their supply, compliance rates using this methodology are best determined across several refills. In particular, we urge caution in applying them over time periods of less than 60 days. Longer minimum time periods further decrease the likelihood of "false positives" but limit the number of patients for whom a compliance measure can be computed. For the health professional (eg, the pharmacist) responsible for monitoring drug-taking compliance of patients, the message seems clear: when reviewing computer-generated noncompliance "flags," the first task is to fully explore the possibility of discrepancies in drug records before initiating compliance-related interventions.


Dantrolene modulates the influence of steady magnetic fields on hippocampal evoked potentials in vitro.
Direct current-generated magnetic fields (2-3 mT, 20-min exposure) exerted biphasic effects on the population spike recorded from hippocampal slices. The initial decrease in the potential, observed during exposure of the slices to magnetic fields was followed by a recovery/amplification phase, which began after terminating the magnetic field action. During that phase the population spike exceeded the amplitude observed before application of the magnetic fields. The pattern of magnetic fields influence was not affected either by (+)-5-methyl-10,11-dihydro-5H-dibenzo (a,d) cyclohepten-5, 10-imine maleate (MK801), or by D,L,-2amino-5phosphonovalerate (APV), a noncompetitive and competitive NMDA receptor antagonist, respectively. The rising phase of the potential, however, was eliminated by dantrolene, an inhibitor of intracellular Ca(2 +) channels. This suggests that intracellular calcium channels participate in the mechanism of the influence of the direct current magnetic fields on the function of the hippocampal tissue.


Clinical implications of microRNAs in cancer.
MicroRNAs (miRNAs) are endogenously produced non-coding RNAs that serve as micromanagers by negatively regulating gene expression. MiRNAs are implicated in several biological pathways including development of neoplasia. Because altered miRNA expression is implicated in the pathobiology of various cancers, these molecules serve as potential therapeutic targets. Using miRNA mimics to restore levels of aberrantly down-regulated miRNAs or miRNA inhibitors to inactivate over-expressed miRNAs shows promise as the next generation of therapeutic strategies. Manipulation of miRNAs offers an alternative therapeutic approach for chemo- and radiation-resistant tumors. Similarly, miRNA expression patterns can be used for diagnosis and to predict prognosis and efficacy of therapy. We present here an overview of how miRNAs affect cancers, how they may be used as biomarkers, and the clinical implications of miRNAs in cancer.


Respiratory disease as a result of talc inhalation.
Three cases of respiratory disease in workers with occupational exposure to talc containing asbestos fibers are reported. Standard chest roentgenographs, high-resolution computed tomography, respiratory function tests, morphologic study of bronchoalveolar lavage fluid (BAL), light microscopic examination, and mineralogical analysis by transmission electron microscopy (TEM) of BAL was performed. All subjects showed bilateral pleural plaques, and in two subjects the study of BAL revealed lymphocytic alveolitis with an increased T4/T8 ratio. Mineralogical analysis of BAL detected asbestos-fiber concentrations of 510, 2039, and 3392 fibers/mL and many asbestos bodies. In one patient, mineralogical analysis of lung tissue was also performed; a concentration of 3,659,000 fibers/g dry tissue was found. Simultaneously, we performed a mineralogical study of 12 commercial talc samples, including those used by the patients during the last phase of their working lives. TEM revealed asbestos fibers in five samples. Two subjects used two of these talc powders. The study presented here confirms the need to perform all relevant clinical tests together with the study of BAL and mineralogical analysis of the materials to which the patients are or were exposed to determine occupational exposure to fibers, including those associated with talc, which are often misidentified.


Diagnosis Accuracy of Mean Arterial Pressure Variation during a Lung Recruitment Maneuver to Predict Fluid Responsiveness in Thoracic Surgery with One-Lung Ventilation.
Background. Lung recruitment maneuver (LRM) during thoracic surgery can reduce systemic venous return and resulting drop in systemic blood pressure depends on the patient's fluid status. We hypothesized that changes in systemic blood pressure during the transition in LRM from one-lung ventilation (OLV) to two-lung ventilation (TLV) may provide an index to predict fluid responsiveness. Methods. Hemodynamic parameters were measured before LRM (T0); after LRM at the time of the lowest mean arterial blood pressure (MAP) (T1) and at 3 minutes (T2); before fluid administration (T3); and 5 minutes after ending it (T4). If the stroke volume index increased by >25% following 10 mL/kg colloid administration for 30 minutes, then the patients were assigned to responder group. Results. Changes in MAP, central venous pressure (CVP), and stroke volume variation (SVV) between T0 and T1 were significantly larger in responders. Areas under the curve for change in MAP, CVP, and SVV were 0.852, 0.759, and 0.820, respectively; the optimal threshold values for distinguishment of responders were 9.5 mmHg, 0.5 mmHg, and 3.5%, respectively. Conclusions. The change in the MAP associated with LRM at the OLV to TLV conversion appears to be a useful indicator of fluid responsiveness after thoracic surgery. This trial is registered at Clinical Research Information Service with KCT0000774.


Epistaxis in hospitalized patients with COVID-19.
Spontaneous epistaxis in patients with COVID-19 can represent a clinical challenge with respect to both the risk of contamination and the treatment options. We herein present the data of 30 patients with COVID-19 who developed spontaneous epistaxis while hospitalized at Eastern Piedmont Hospital during March and April 2020. All patients received low-molecular-weight heparin during their hospital stay and required supplementary oxygen therapy either by a nasal cannula or continuous positive airway pressure. Both conditions can represent risk factors for developing epistaxis. Prevention of crust formation in patients with rhinitis using a nasal lubricant should be recommended. If any treatment is required, appropriate self-protection is mandatory.


Phospholipase D regulates calcium oscillation frequency and nuclear factor-kappaB activity in histamine- stimulated human endothelial cells.
Histamine stimulates [Ca(2+)](i) oscillations in human aortic endothelial cells (HAEC), the frequency of which regulates the activity of nuclear factor-kappaB (NF-kappaB). This study was performed to determine whether phospholipase D (PLD) is involved in this signaling pathway. At a concentration of 1 microM, which stimulates [Ca(2+)](i) oscillations in this cell type, histamine initiated a twofold increase in [(32)P]phosphatidybutanol (PBt), an index of PLD activity as early as 5 min after stimulation. During established [Ca(2+)](i) oscillations induced by 1 microM histamine, 0.3% n-butanol, which "functionally" redirects phosphatidic acid formed by PLD to PBt, decreased [Ca(2+)](i) oscillation frequency by approximately 50% and produced a similar reduction in NF-kappaB activity. In the presence of the inositol 1,4,5-trisphosphate receptor blocker xestospongin C, which itself decreases the frequency of histamine-stimulated [Ca(2+)](i) oscillations, n-butanol produced a further decrease in oscillation frequency that was not associated with an additional reduction in NF-kappaB activity. This study shows that activation of PLD by histamine regulates [Ca(2+)](i) oscillation frequency and NF-kappaB activity in HAEC.


The Association between Gender and Physical Activity Was Partially Mediated by Social Network Size during COVID-19.
The COVID-19 pandemic has disrupted physical activity, particularly among women. Limited research has explored how social network support may explain gender-based variations in physical activity during COVID-19. The purpose of this study was to examine the mediating role of social networks in the association between gender and physical activity during a pandemic. This cross-sectional survey assessed whether social network characteristics (i.e., in-person social network size, frequency of in-person social network interactions, and online friend network size) mediate the relationship between gender and either past-week or past-year physical activity. Multiple mediation analyses were conducted to determine the indirect effect of gender on physical activity through social networks. Among 205 participants, women (n = 129) were significantly less physically active (β = −73.82; p = 0.02) than men (n = 76) and reported significantly more Facebook friends (β = 0.30; p < 0.001) than men, which was inversely associated with past-week physical activity (β = −64.49; p = 0.03). Additionally, the indirect effect of gender on past-week physical activity through Facebook friends was significant (β = −19.13; 95% CI [−40.45, −2.09]). Findings suggest that social media sites such as Facebook could be used to encourage physical activity among women during a pandemic.


Effects of Naringenin on Experimentally Induced Rheumatoid Arthritis in Wistar Rats.
Naringenin is one of the most important and abundant known flavonoids found in grapefruit and other citrus fruits. This experimental study aimed to assess the clinical effects and immune responses of naringenin in the animal model of rheumatoid arthritis (RA) according to various reports on its anti-inflammatory effects and modulation of the immune system. To this end, 40 Wistar rats in the weight range of 160-180g were randomly assigned to four groups (n=10) including healthy, control, naringenin, and methotrexate orally treated groups. To induce RA disease, a compound of 200 μl of Freund's adjuvant and collagen type II was injected subcutaneously into the rear footpads of rats. The severity of RA clinical signs was assessed based on a standard scoring method. The treatment lasted for three weeks (days7-28 after induction). The obtained data pointed out that the levels of C-reactive protein (CRP), myeloperoxidase, nitric oxide, IL-17, and IFN-γ cytokines significantly increased in the RA rats, while the level of their serum antioxidants significantly reduced, compared to the healthy rats. The inflammation of the paws and the level of CRP decreased similarly in both methotrexate and naringenin-treated groups. In the naringenin-treated group, a further decrease was detected in serum myeloperoxidase, nitric oxide, and the total antioxidant capacity occurred, as compared to the methotrexate-treated rats. Nonetheless, IL-17 and IFN-γ cytokines levels were further decreased in the methotrexate-treated group. Accordingly, it can be concluded that naringenin can be effectively used for the reduction of inflammatory effects and control of RA disease.


[Dysentery and amoebiasis in Poland in 2008].
The number as well as incidence rate of notified as shigellosis, bacillary dysentery cases in XXI century are every year lower. Only 33 cases were notified in the year 2008 (incidence rate 0.09/100 000 population), while the 64 cases were notified in 2007 (incidence rate 0.17/100 000), but 35 (incidence rate 0.09) were notified in 2006 and median in the 2002-2006 years was 75 cases, incidence rate 0.2/100 000 population. Since 2000 no one-death case was notified. Several imported cases were notified as they got infection being abroad, polish citizens on holiday abroad, and foreign children coming for vacations in Poland from countries with higher incidence rate for ex. from Ukraine. Out of 11 imported cases three were due to Shigella sp., eight to S. sonnei. Two persons were found infected by S. boydii 8-11 but no one of S. dysentery. In the period of low frequency of Shigella infections, the external quality assessment control of the quality of bacteriological media, laboratory and prae-laboratory procedures for detection of different Shigella groups and types should be executed. A lower number of amoebic dysentery cases were registered 5 cases in 2008 (incidence rate 0.013/100 000 population), but in 2007: the 19 cases, incidence rate 0.05/100 000, and even more in 2006 the 21 cases, incidence rate 0.055/100 000. The cases were registered in 3 voivodeships; infection was probably imported from underdeveloped countries.


Effect of astigmatism on apparent accommodation in pseudophakic eyes.
To investigate the factors affecting apparent accommodation in pseudophakic eyes from a clinical viewpoint and the effects of corneal and refractive astigmatism on this accommodation from an optical viewpoint. We retrospectively examined 62 eyes of 33 patients who had undergone phacoemulsification with monofocal intraocular lens implantation. We quantitatively assessed the amplitude of apparent accommodation using an accommodometer 3 months after surgery. Multiple regression analysis was used to assess the factors affecting apparent accommodation. We also estimated the accommodation in eyes with corneal astigmatism by optical simulation. The mean amplitude of apparent accommodation was 1.58 = 0.65 D. Explanatory variables relevant to this accommodation were in order of influence, pupil diameter (partial regression coefficient B = 0.293, p = 0.008), and corneal multifocality (B = 0.101, p = 0.03). Other explanatory variables such as age, gender, axial length, corneal astigmatism, and refractive astigmatism showed no significant relationship with this accommodation. The estimated apparent accommodations for a 3.0 mm pupil by optical simulation were 1.25, 1.25, 1.25, 0.75, and 0 D, in eyes with corneal astigmatism of 0, 0.5, 1.0, 1.5, and 2.0 D, respectively. Similar results were obtained for a 4.0 mm pupil. Eyes with smaller pupil diameter and eyes with greater corneal multifocality are more predisposed to have greater apparent accommodation. However, from clinical and optical viewpoints, corneal or refractive astigmatism does not significantly contribute to apparent accommodation after cataract surgery, suggesting that it may be of less significance that the astigmatism is consciously retained in consideration of this accommodation in astigmatic eyes.


High-level Skp2 expression in pancreatic ductal adenocarcinoma: correlation with the extent of lymph node metastasis, higher histological grade, and poorer patient outcome.
Recent studies have shown that overexpression of S-phase kinase-associated protein 2 (Skp2) occurs in many cancers at an advanced stage. We examined the clinicopathologic significance and prognostic implication of Skp2 expression in pancreatic invasive ductal carcinoma. Tissue samples from 46 pancreatic carcinomas were examined immunohistochemically for Skp2. The proportion of constituent tumor cells with Skp2 expression was analyzed and classified as high-level nuclear expression when more than 20% of the cancer cells were positive, or low-level nuclear expression otherwise. High-level Skp2 overexpression was detected in 13 (28.3%) of the 46 tumors. The incidence of high-level Skp2 was correlated with higher histological grade (P = 0.0056), the extent of lymph node metastasis (P = 0.0086), the level of lymphatic permeation (P = 0.0024), and poorer patient outcome (P = 0.0189). Multivariate analysis showed that high-level Skp2 expression was an independent predictor of overall patient survival (P = 0.0140). It is suggested that examination of Skp2 expression might be clinically useful for prognostication in patients with pancreatic carcinoma and that Skp2 protein might be a novel therapeutic molecular target.


Crocetin ameliorates non-alcoholic fatty liver disease by modulating mitochondrial dysfunction in L02 cells and zebrafish model.
Traditional Chinese medicine considers that the etiology and pathogenesis of non-alcoholic fatty liver disease (NAFLD) are related to liver depression and qi stagnation. Saffron and its active ingredient, crocetin (CCT), are used for the treatment of metabolic diseases owing to their "Liver deobstruent" and "Liver tonic" effects. However, the effect of CCT on NAFLD has not been fully elucidated. In the present study, the effect and potential molecular mechanism of CCT were explored in both in vivo and in vitro models of NAFLD. CCT was isolated from saffron and purity and structure characterization were performed using HPLC, MS, 1H-NMR, and 13C-NMR. The effect of CCT on the viability of L02 cells and its maximum tolerable concentration (MTC) in zebrafish were investigated. Free fatty acids (FFA) and thioacetamide (TAA) were used to induce lipid accumulation in L02 cells and steatosis in zebrafish, respectively. The effects of CCT on indexes related to lipid metabolism, oxidative stress, and mitochondrial function in NAFLD models were explored using biochemical assay kits, Western blot analysis, Reverse Transcription-Polymerase Chain Reaction (RT-PCR), histopathology analysis, and determination of mitochondrial membrane potential (ΔΨm). Morphological analysis of mitochondria was performed using transmission electron microscopy (TEM). The levels of triglyceride (TG), total cholesterol (TC), malondialdehyde (MDA), and alanine/aspartate aminotransferases (ALT/AST) activities in FFA treated L02 cells were significantly reduced after CCT treatment. CCT treatment significantly increased ATP concentration, ΔΨm, and activities of superoxide dismutase (SOD), catalase (CAT), and cytochrome c oxidase (COX IV) in FFA treated L02 cells. TEM images showed restoration of mitochondrial morphology. CCT decreased ATP concentration and upregulated expression of B-cell lymphoma-2 (Bcl-2) and COX IV, whereas, CCT downregulated expression of BCL2-Associated X (Bax) and cleaved caspase-3 in TAA treated zebrafish. These findings indicated that mitochondrial dysfunction was alleviated after CCT treatment. Oil Red O staining of L02 cells and zebrafish showed that CCT treatment reversed the accumulation of lipid droplets. In summary, CCT treatment effectively alleviated the symptoms of NAFLD and restored mitochondrial function in L02 cells and zebrafish NAFLD model.


Enhanced tenogenic differentiation and tendon-like tissue formation by tenomodulin overexpression in murine mesenchymal stem cells.
As a highly specific marker of tenocytes, tenomodulin (Tnmd) functions remain largely unexplored. We investigated the effect of Tnmd overexpression on tenogenic differentiation of murine mesenchymal stem cells (mMSCs) via plasmid-mediated overexpression in the C3H10T1/2 cell line. The results showed that overexpressed Tnmd could significantly enhance cell proliferation (p < 0.05) and the gene expressions of tenogenic-related molecules, including Tnmd, Scleraxis (Scx), collagens I, III and VI and decorin (p < 0.05), and significantly inhibit mMSCs differentiation towards the adipogenic, chondrogenic and osteogenic lineages (p < 0.05). Upon in vivo implantation with rat tail collagen gel subcutaneously in nude mice, Tnmd-overexpressed C3H10T1/2 cells formed neotendon-like tissue, which revealed a histological feature of wave-like dense collagen fibres and cells aligned in parallel. By contrast, a disorganized connective tissue structure with randomly distributed cells was observed in the control group. To further confirm this finding, a conditional Tnmd-overexpressing mouse model was established and the derived primary mMSCs could be induced to overexpress Tnmd with > two-fold upregulated gene expression (p < 0.05) by the treatment of doxycycline (Dox). Similarly, conditional overexpression of Tnmd in primary mMSCs also led to faster proliferation (p < 0.05), enhanced gene expression of tenogenic markers (p < 0.05) and the inhibited expressions of adipogenic and osteogenic markers (p < 0.05). The results of enhanced tenogenic differentiation and neotendon formation indicated that Tnmd may serve not only as a tenogenic marker but also as a positive regulator of MSCs tenogenic differentiation, which might be applied to MSCs-mediated tendon regeneration. Copyright © 2016 John Wiley & Sons, Ltd.


Tyrosine kinase activity coupled to the high-affinity nerve growth factor-receptor complex.
Antibodies directed against nerve growth factor (NGF) immunoprecipitate a tyrosine kinase activity from NGF-treated PC12 rat pheochromocytoma cells. Based on several criteria, this activity has been correlated with the high-affinity and not the low-affinity NGF-receptor complex. The in vitro kinase activity and the tyrosine phosphorylation of the high-affinity complex can be blocked by an agent that inhibits NGF (and not epidermal growth factor)-induced tyrosine phosphorylation in PC12 cells, as well as NGF-induced neuronal differentiation of PC12 cells. These observations suggest that the high-affinity NGF-receptor complex is a substrate of tyrosine kinase activity. Phosphorylation reactions by the complex, performed in the absence of added substrate, label a single phosphopeptide of 130-135 kDa. This observation suggests that this phosphopeptide may represent the phosphorylation of the receptor kinase or the phosphorylation of a coimmunoprecipitating substrate, and possible signal-transducing molecule, of the high-affinity NGF-receptor complex.


Effect of bradykinin on respiratory rate in anaesthetized rabbits; role of rapidly adapting receptors.
1. This study was performed in anaesthetized, spontaneously breathing rabbits: (a) to determine the effect of bradykinin administered into the right atrium on the respiratory rate, and (b) to elucidate the potential role of rapidly adapting receptors (RARs) in mediating this effect. The role of RARs was established by graded cooling of the cervical vagi. The respiratory rate was measured from an intrapleural pressure tracing. 2. Dose-response curves relating right atrial injections of bradykinin (0.25, 0.5, 1.0 and 1.5 micrograms/kg) to the respiratory rate were established in the control state (i.e. vagi at 37 degrees C). The respiratory rate increased significantly (P < 0.01, ANOVA) from a control value of 51.3 +/- 6.8 breaths/min by 12 +/- 3, 25 +/- 5, 43 +/- 7 and 58 +/- 11% respectively. At doses of 1.0 and 1.5 micrograms/kg I.V., the increase in rate was preceded by apnoea. 3. The dose-response curves were repeated with bolus injections of bradykinin (0.25, 0.5, 1.0 and 1.5 micrograms/kg) after cooling the cervical vagi to 8-9 degrees C. The increase in respiratory rate was attenuated significantly (P < 0.01 ANOVA). The rate increased from a control value of 27.2 +/- 2.1 breaths/min by 5 +/- 2, 6 +/- 2, 16 +/- 5 and 21 +/- 8% respectively. With vagi cooled, apnoea was increased in duration and occurred at lower doses. On rewarming vagi, the original responses were reestablished. 4. When the study was repeated after bilateral vagotomy, apnoea was abolished but there was a small residual increase in rate. This increase was similar to that seen after cooling the vagi (P > 0.05). 5. RAR (n = 5) activity was recorded from the cervical vagus. Right atrial injections of bradykinin (0.25-1.0 micrograms/kg) stimulated RARs. On cooling the vagi to 8-9 degrees C caudal to the recording site, the increase in activity was blocked. 6. These data support the proposition that bradykinin increases the respiratory rate in rabbits and that this response is, in part, a reflex mediated by RARs. In addition, bradykinin has other secondary effects on respiration: an aponea which is mediated by non-myelinated vagal afferents and a small stimulatory effect on respiration which persists after bilateral vagotomy.


[Pharmacokinetics of breviscapine liposomes following intravenous injection in Beagle dogs].
To prepare the breviscapine liposomes and study the pharmacokinetics of breviscapine liposomes in Beagle dogs. The cross-over design (two periods) was employed. Six Beagle dogs were administrated a single intravenous dosage of 28 mg of breviscapine liposomes and reference preparation, respectively, scutellarin in plasma of 6 dogs at different sampling time was determined by RP-HPLC. The pharmacokinetic parameters were calculated by 3P97 program and compared by statistic analysis. The mean concentration-time curves of breviscapine liposomes and reference preparation were both fitted to two-compartment model with the main pharmacokinetic parameters as follows: T 1/2 alpha were (4.4 +/- 0.7) min and (1.8 +/- 1.3) min respectively; T 1/2 beta were (55 +/- 27) min and (28 +/- 23) min respectively; V(c) were (1 580 +/- 265) mL and (2 460 +/- 2 200) mL respectively; CL(s) were (88 +/- 10) mL x min(-1) and (324 +/- 69) mL x min(-1) respectively; and AUC(0-720) were (363 +/- 42) microg x min x mL(-1) and (102 +/- 19) microg x min x mL(-1) respectively. The T 1/2 alpha, CL(s) and AUC(0-720) of breviscapine liposomes all had significant difference from those of reference preparation, after the data were examined by a one-way analysis of variance (ANOVA). Compared with the reference preparation, breviscapine liposomes had a much more higher concentration in plasma and contained characteristic of sustained-release, which ameliorated the pharmacokinetic properties of scutellarin.


Environmental quality, climate indicators, and COVID-19 pandemic: insights from top 10 most affected states of the USA.
In the current context of the COVID-19 pandemic, researchers are working with health professionals to inform governments on how to formulate health strategies. In this study, we examine the correlation between environmental and climate indicators and COVID-19 outbreak in the top 10 most affected states of the USA. In doing so, PM2.5, temperature, humidity, environmental quality index, and rainfall are included as crucial meteorological and environmental factors. Kendall and Spearman rank correlation coefficients, quantile regression, and log-linear negative binominal analysis are employed as an estimation strategy. The empirical estimates conclude that temperature, humidity, environmental quality index, PM2.5, and rainfall are significant factors related to the COVID-19 pandemic in the top 10 most affected states of the USA. The empirical findings of the current study would serve as key policy input to mitigate the rapid spread of COVID-19 across the USA.


Selectivity in metal-carbon bond protonolysis in p-tolyl- (or methyl)-cycloplatinated(II) complexes: kinetics and mechanism of the uncatalyzed isomerization of the resulting Pt(II) products.
Reaction of each of the known starting complexes [PtR(C^N)(SMe2)], 1, in which R = Me or p-MeC6H4 and C^N is either ppy (deprotonated 2-phenylpyridine) or bhq (deprotonated benzo[h]quinoline), with one equivalent of CF3CO2H, gave the complexes [Pt(C^N)(CF3CO2)(SMe2)], 3 (C^N = ppy, 3a; bhq, 3b). The bis-chelate complexes [Pt(C^N)(P^P)](CF3CO2), 4, were obtained by reaction of complexes 3 with one equivalent of either of the P^P bisphosphine reagents, dppf = 1,1'-bis(diphenylphosphino)ferrocene or dppe = bis(diphenylphosphino)ethane. Complexes 4 were alternatively made by reaction of the complexes [PtMe(κ(1)C-C^N)(P^P)], 2, with one equivalent of CF3CO2H. When the complex 3b was reacted with 0.5 equivalents of dppe, 0.5 equivalents of the related bis-chelate product, 4d, formed along with 0.5 equivalents of the unreacted starting complex 3b. In contrast, when the complex 3b was reacted with 0.5 equivalents of dppf, then the dimeric complex [Pt2(bhq)2(CF3CO2)2(μ-dppf)], 5, formed in pure form. In all the above-mentioned acid reactions, the M-R bond rather than the M-C bond of the cycloplatinated complex is cleaved. When the PPh3 analogues of complexes 1, i.e. the complexes [PtR(C^N)(PPh3)], 6, in which C^N is ppy or tpy = deprotonated 2-p-tolylpyridine, were reacted with one equivalent of CF3CO2H, the course of the reaction reversed and the M-C bonds of the cycloplatinated complexes are cleaved rather than the M-R bonds. The latter reaction gave [PtR(κ(1)N-HC^N)(PPh3)(CF3CO2)], as an equilibrium mixture of two isomers 7 and 8. Crystal structures of the typical complexes show a variety of extensive intermolecular hydrogen bonding involving C-H bonds from the different ligands and electronegative atoms (O or F) from the CF3CO2 moiety. On the basis of data obtained from kinetic studies (using (1)H NMR spectroscopy), a dissociative mechanism is proposed for the case of the 7c/8c isomerization process, involving dissociation of the κ(1)N-Htpy neutral ligand, rather than the alternative route of PPh3 or CF3CO2 ligand dissociation.


Sensing and energy harvesting of fluidic flow by InAs nanowires.
Indium arsenide (InAs) nanowire (NW) field effect transistors (FETs) were incorporated into a microfluidic channel to detect the flow rate change as well as to harvest fluid flow energy for electric power generation. Discrete changes in the electric current through InAs NW FETs were observed upon flow rate changes at steps of 1 mL/h (equivalent to ~3 mm/s change in average linear velocity). The current also showed a sign change upon reversing flow direction. By comparing the response of the device with and without a driving voltage between source-drain electrodes, we conclude that the dominant contribution in the response is the streaming potential tuned conductance of NW. In the absence of source-drain voltage, we further demonstrate that the ionic flow could enable generation of an ~mV electrical potential (or ~nA electrical current) inside the InAs NW per mL/h increase of flow rate, most likely due to the charge dragging effect.


Navigated Iso-C3D-based percutaneous osteoid osteoma resection: a preliminary clinical report.
Minimally invasive osteoid osteoma resection under computer tomography (CT) guidance has yielded good results and has become a viable alternative to open surgical procedures. Limited visualization of the actual drill position under CT guidance can frequently result in inadequate and malpositioned drilling, especially at lesions located in less accessible anatomic regions. With the conventional CT-guided drilling technique, sterility and general operative management poorly correlate with standard operating room conditions, and are at risk of intra- and postoperative complications. The new Iso-C(3D) imaging device provides intraoperative multiplanar reconstructions. Adequate image quality and implementation in navigation systems were described for numerous indications. On the basis of multiplanar reconstructions, minimally invasive navigated techniques under three-dimensional surgical tool control become possible, which is not the case under fluoroscopic or CT-based navigation. We report on our first three cases of navigated Iso-C(3D) osteoid osteoma resection. A minimally invasive resection of the nidus was possible under permanent multiplanar image control. No complications were encountered and all patients reported successful outcomes. Minimally invasive-based navigation offered an effective and reproducible surgical approach. Dependence on CT imaging for proper positioning and complications associated with use away from the operating room environment can be avoided.


Tetralogy of Fallot: perioperative anesthetic management of children and adults.
Tetralogy of Fallot (TOF) is a common congenital heart defect in children. Perioperative considerations include preoperative preparation for surgery, intraoperative anesthetic management, and common postoperative issues in the intensive care unit. Surgical debates have shifted away from 2-stage versus single-stage repairs to debates of how surgery to limit pulmonary insufficiency (PI) may have significant long-term impact as the child grows. There are many adult survivors of TOF repair in infancy who now present with a unique set of problems related to PI and right ventricular dysfunction. These adults provide new insights into congenital heart disease (CHD) and how management strategies early in life may have significant implications much later in life. Patients with complex CHD should have lifelong follow-up, so our knowledge will continue to improve, and the best possible care can be provided for these patients.


Interleukin-4 signals regulating CD23 gene expression in human B cells: protein kinase C-independent signaling pathways.
Signal transduction by IL-4 leading to the activation of CD23(Fc epsilon RII) gene expression using human tonsillar B cells was studied. IL-4 stimulated CD23 mRNA transcription within hours (1-4 hr) which preceded the later induction of cell surface CD23. The induction of CD23 gene transcription by IL-4 was not adversely affected by cycloheximide, suggesting that post-translational modifications are accounted for the gene activation. PKC activators (PMA, diacylglycerol, indolactam) were effective inducers of CD23 gene expression, whereas calcium ionophores were not. PMA and IL-4 also displayed similar induction kinetics for CD23 mRNA. However, the signaling pathways utilized by the two agents appear distinct as shown by (1) cotreatment of IL-4 and PMA caused CD23 gene expression over the maximum level inducible by each agent alone and (2) unlike the PMA-induced CD23 expression, the IL-4-induced expression was not affected by PKC inhibitors. These results strongly suggest that IL-4 signals leading to CD23 gene activation are mediated via a PKC-independent pathway. A possible role of tyrosine kinases in the regulation of CD23 expression is discussed.


The rabbit syndrome: state of the art.
The rabbit syndrome (RS) is a rare movement disorder generally associated with prolonged use of antipsychotics and characterized by inwilling, rhythmic, fast and fine movements of oral and masticatory muscles along the vertical axis of the mouth. The prevalence of RS ranges between 1.5% and 4.4%; middle and elderly ages, the female gender, as well as past brain injuries are considered risk factors for its development. Although a dysbalance of the cholinergic and dopaminergic neurotransmission in the basal ganglia seems to be involved in the pathophysiology of RS, its precise mechanisms need to be clarified as yet. RELATIONSHIPS WITH ANTIPSYCHOTICS: Fifty cases of RS have been published up-to-now: 34 and 10 occurred during treatments with typical and atypical antipsychotics, respectively, while 6 seemed unrelated to these drugs. The differential diagnosis between RS and tardive dyskinesias involving the mouth may be based mainly on the evidence that in these last conditions the movements of the mouth are less regular and slower and involve the tongue. Treatment strategy: The available data suggest that RS responds favourably to anticholinergic drugs and to the change of the antipsychotic.


Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors.
Inhibition of complex I of the mitochondrial respiratory chain (cI) by rotenone and methyl-phenylpyridinium (MPP +) leads to the degeneration of dopaminergic neurons in man and rodents. To formally describe this mechanism of toxicity, an adverse outcome pathway (AOP:3) has been developed that implies that any inhibitor of cI, or possibly of other parts of the respiratory chain, would have the potential to trigger parkinsonian motor deficits. We used here 21 pesticides, all of which are described in the literature as mitochondrial inhibitors, to study the general applicability of AOP:3 or of in vitro assays that are assessing its activation. Five cI, three complex II (cII), and five complex III (cIII) inhibitors were characterized in detail in human dopaminergic neuronal cell cultures. The NeuriTox assay, examining neurite damage in LUHMES cells, was used as in vitro proxy of the adverse outcome (AO), i.e., of dopaminergic neurodegeneration. This test provided data on whether test compounds were unspecific cytotoxicants or specifically neurotoxic, and it yielded potency data with respect to neurite degeneration. The pesticide panel was also examined in assays for the sequential key events (KE) leading to the AO, i.e., mitochondrial respiratory chain inhibition, mitochondrial dysfunction, and disturbed proteostasis. Data from KE assays were compared to the NeuriTox data (AO). The cII-inhibitory pesticides tested here did not appear to trigger the AOP:3 at all. Some of the cI/cIII inhibitors showed a consistent AOP activation response in all assays, while others did not. In general, there was a clear hierarchy of assay sensitivity: changes of gene expression (biomarker of neuronal stress) correlated well with NeuriTox data; mitochondrial failure (measured both by a mitochondrial membrane potential-sensitive dye and a respirometric assay) was about 10-260 times more sensitive than neurite damage (AO); cI/cIII activity was sometimes affected at > 1000 times lower concentrations than the neurites. These data suggest that the use of AOP:3 for hazard assessment has a number of caveats: (i) specific parkinsonian neurodegeneration cannot be easily predicted from assays of mitochondrial dysfunction; (ii) deriving a point-of-departure for risk assessment from early KE assays may overestimate toxicant potency.


Iterative denoising of ghost imaging.
We present a new technique to denoise ghost imaging (GI) in which conventional intensity correlation GI and an iteration process have been combined to give an accurate estimate of the actual noise affecting image quality. The blurring influence of the speckle areas in the beam is reduced in the iteration by setting a threshold. It is shown that with an appropriate choice of threshold value, the quality of the iterative GI reconstructed image is much better than that of differential GI for the same number of measurements. This denoising method thus offers a very effective approach to promote the implementation of GI in real applications.


Disorder of Hydrofluorocarbon Molecules Entrapped in the Water Cages of Structure I Clathrate Hydrate.
Water versus fluorine: Clathrate hydrates encaging hydrofluorocarbons as guests show both isotropic and anisotropic distributions within host water cages, depending on the number of fluorine atoms in the guest molecule; this is caused by changes in intermolecular interactions to host water molecules in the hydrates.


Aircraft detection from VHR images based on circle-frequency filter and multilevel features.
Aircraft automatic detection from very high-resolution (VHR) images plays an important role in a wide variety of applications. This paper proposes a novel detector for aircraft detection from very high-resolution (VHR) remote sensing images. To accurately distinguish aircrafts from background, a circle-frequency filter (CF-filter) is used to extract the candidate locations of aircrafts from a large size image. A multi-level feature model is then employed to represent both local appearance and spatial layout of aircrafts by means of Robust Hue Descriptor and Histogram of Oriented Gradients. The experimental results demonstrate the superior performance of the proposed method.


How does daily performance affect next-day emotional labor? The mediating roles of evening relaxation and next-morning positive affect.
The present study examined the daily relationship between job performance, relaxation, positive affect, and emotional labor. Drawing on the effort-recovery model and broaden-and-build theory, we proposed that job performance on a particular day fosters evening relaxation and next-morning positive affect and that this leads to increased deep acting and decreased surface acting the next day. To test our propositions, we conducted 2 diary studies using the experienced sampling method. In Study 1, 93 flight attendants participated in morning and end-of-workday surveys for 5 workdays. In Study 2, 98 hotel employees responded to morning, end-of-workday, and evening surveys for 5 workdays. In both studies, we found positive relationships between daily job performance, evening relaxation, next-morning positive affect, and next-day deep acting. We further found support for the indirect effect of daily job performance on next-day deep acting through evening relaxation and next-morning positive affect. Although next-morning positive affect had a marginally negative relationship with next-day surface acting in Study 1, this relationship became nonsignificant when next-morning negative affect was included in the model (Study 2). The robustness of these findings was validated in supplementary analyses. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


[Effects of xinfeng capsule on myocardial fibrosis in adjuvant arthritis rats and its mechanism research].
To study effects of Xinfeng Capsule (XFC, a Chinese herbal compound for benefiting qi, invigorating Pi, and dredging col laterals) on myocardial fibrosis in adjuvant arthritis (AA) rats and its mechanism study. Sixty male Wistar rats were randomly divided into the normal control (NC) group (n = 12) and the model control (MC) group (n =48). Except rats in the NC group, Freund's complete adjuvant (0. 1 mL) was intracutaneously injected from the right hind limb to prepare the AA rat model. On the 19th day of inflammation rats in the AA model group were randomly divided into four groups, i.e., the XFC group, the methotrexate (MTX) group, the Tripterygium wilfordii polycoride Tablet (TPT) group, and the MC group, 12 in each group. Rats were sacrificed after 30-day medication. The myocardial ultrastructure was observed under transmission electron microscope. The mRNA and protein expression levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were detected using RT-PCR and Western blot respectively. (1) Results under electron microscope showed obvious hyperplasia of collagen fibers in myocardial cells of AA rats, which indicated the trend of myocardial fibrosis. The myocardial ultrastructural changes could be effectively improved in the MTX group, the TPT group, and the XFC group. The morphology of myocardial cells in the XFC group was contact, with clear nucleus, and little collagen fibers, which was better than the other groups. (2) Compared with the NC group, the mRNA and protein expression levels of MMP-9 in the myocardial tissue of the MC group were obviously up-regulated, while the mRNA and protein expression levels of TIMP-1 were obviously down-regulated (P <0. 01). The mRNA and protein expression levels of MMP-9 decreased, and the mRNA and protein expression levels of TIMP-1 obviously increased in the XFC group, showing statistical difference when compared with the MC group (P < 0. 5, P < 0. 01). XFC could effectively inhibit the myocardial fibrosis of AA rats.lts mechanisms might be correlated with inhibiting the mRNA and protein expression levels of MMP-9, improving the mRNA and protein expression levels of TIMP-1, adjusting the balance of MMP-9/TIMP-1 ,and improving the metabolism of myocardial extracellular matrix.


Incidence of lingual nerve trauma and postinjection complications in conventional mandibular block anesthesia.
Trauma to the lingual nerve is potential risk factor for patients receiving mandibular block anesthesia. This paper describes the results of a patient survey of 9,587 conventional mandibular blocks received by 2,289 adults. The incidence of lingual nerve trauma and postinjection complications is reported along with an associated analysis of the duration of complications, procedures at the time of incident, the side of occurrence (right or left), and gender ratios. In addition, recommendations for patient evaluation, treatment, and follow-up care are discussed.


Respiratory carcinoma cell lines. MUC genes and glycoconjugates.
Lung carcinoma cell lines are being used in many laboratories to study various airway epithelial functions, including mucin gene expression. To identify model systems for investigating regulation of MUC5/5AC gene expression and secretion of MUC5/5AC mucins in airway epithelial cells, we evaluated the expression of several mucin genes in six carcinoma cell lines of respiratory tract origin. RNA was extracted from A549, Calu-3, NCI H292, Calu-6, RPMI 2650, and A-427 cells; MUC1, MUC2, MUC4, MUC5/5AC, and MUC5B messenger RNA (mRNA) expression was determined. By Northern analyses, all cell lines expressed MUC1 mRNA, whereas MUC2 mRNA was not detectable in any of the cell lines. RPMI 2650 cell lines expressed only MUC1 mRNA. NCI-H292 cells expressed MUC4 and low levels of MUC5/5AC mRNA. Calu-3 and A549 cells expressed MUC5/5AC mRNA; A549 cells also expressed MUC5B mRNA. Glycoconjugates secreted by lung carcinoma cells were also examined. By wheat germ lectin analysis, Calu-3, H292, and A549 cells secreted high molecular weight glycoproteins having N-acetylglucosamine and/or sialic acid moieties. Western blot analyses with an anti-MUC5:TR-3A antibody demonstrated that Calu-3 and A549 cells secreted MUC5/5AC mucins. All six carcinoma cell lines secreted large, radiolabeled, sulfated macromolecules; the majority were proteoglycans that were digested by hyaluronidase. However, Calu-3 cells also secreted sulfated high molecular-weight glycoproteins that were immunoprecipitated by anti-MUC5:TR-3A antibody. These studies demonstrated that Calu-3 and A549 cell lines expressed high and moderate amounts of MUC5/5AC mRNA and MUC5/5AC mucins, whereas H292 cells expressed lesser amounts. These cell lines should prove useful for studies of MUC5/5AC gene expression and MUC5/5AC biosynthesis, trafficking, and secretions in airway epithelial cells.


Remissions of diabetes mellitus after weight reduction by jejunoileal bypass.
Limited weight loss following jejunoileal bypass in 24 diabetic persons who were still distinctly overweight five to ten months after a mean weight decrease of 78 lbs. was accompanied by a return of normal fasting glucose and insulin levels, normal insulin responses, and a decrease in glucose intolerance. The glucose disappearance rate had improved in the majority of the subjects, but only three had attained values in the normal range. Concomitants of the undue hyperglycemia and/or obesity included labile and, rarely, sustained hypertension and/or cardiomegaly. The blood pressure returned to normal but heart size did not change. Electrocardiographic abnormalities noted in about one-half of the patients persisted after the operation. Triglyceride and cholesterol levels decreased. No patients had diabetic retinopathy visible on funduscopy. Proteinuria did not change in three patients. Neuropathy consisting of absent ankle reflexes and/or decreased vibration perception noted in one-half of the subjects persisted despite the improvement in carbohydrate metabolism.


Wound closure at the trunk by microvascular free flap transfer.
Defects of the thoracic or abdominal wall can be congenital or caused by trauma or tumour resection. There may be other problems, such as infection and irradiation effects. In most cases those defects can be closed by local cutaneous and fasciocutaneous or by muscle and myocutaneous flaps. In some rare instances, the use of pedicled flaps may be limited. The size of the defect, the impossibility of closing the donor site, an impaired blood supply, or poor quality of local tissues represent such limitations. In these cases microvascular flap transfer has enlarged our choice of alternative methods. Advantages of this method are the one-stage procedure and the wound coverage by well-vascularized tissue. This is especially beneficial in areas of infected or irradiated tissue. On the other hand microvascular flap transfer requires high technical skill and extensive perioperative and postoperative care.


All-Atom Molecular Dynamics Reveals Mechanism of Zinc Complexation with Therapeutic F10.
Advancing the use of therapeutic nucleic acids requires understanding the chemical and structural properties that allow these polymers to promote the death of malignant cells. Here we explore Zn2+ complexation by the fluoropyrimidine polymer F10, which has strong activities in multiple preclinical models of cancer. Delivery of fluoropyrimidine FdUMP in the 10-residue polymer F10 rather than the nucleobase (5-fluorouracil) allows consideration of metal ion binding effects on drug delivery. The differences in metal ion interactions with fluoropyrimidine compared to normal DNA results in conformation changes that affect protein binding, cell uptake, and codelivery of metals such as zinc, and the cytoxicity thereof. Microsecond-time-scale, all-atom simulations of F10 predict that zinc selectively stabilizes the polymer via interactions with backbone phosphate groups and suggest a mechanism of complexation for the zinc-base interactions shown in previous experimental work. The positive zinc ions are attracted to the negatively charged phosphate groups. Once the Zn2+ ions are near F10, they cause the base's N3 nitrogen to deprotonate. Subsequently, magnesium atoms displace zinc from their interactions with phosphate, freeing the zinc ions to interact with the FdU bases by forming weak interactions with the O4 oxygen and the fluorine attached to C5. These interactions of magnesium with phosphate groups and zinc with nucleobases agree with previous experimental results and are seen in MD simulations only when magnesium is introduced after N3 deprotonation, indicating a specific order of metal binding events. Additionally, we predict interactions between zinc and F10's O2 atoms, which were not previously observed. By comparison to 10mers of polyU and polydT, we also predict that the presence of fluorine increases the binding affinity of zinc to F10 relative to analogous strands of RNA and DNA consisting of only native nucleotides.


Measuring agglomerate size distribution and dependence of localized surface plasmon resonance absorbance on gold nanoparticle agglomerate size using analytical ultracentrifugation.
Agglomeration of nanoparticles during measurements in relevant biological and environmental media is a frequent problem in nanomaterial property characterization. The primary problem is typically that any changes to the size distribution can dramatically affect the potential nanotoxicity or other size-determined properties, such as the absorbance signal in a biosensor measurement. Herein we demonstrate analytical ultracentrifugation (AUC) as a powerful method for measuring two critical characteristics of nanoparticle (NP) agglomerates in situ in biological media: the NP agglomerate size distribution, and the localized surface plasmon resonance (LSPR) absorbance spectrum of precise sizes of gold NP agglomerates. To characterize the size distribution, we present a theoretical framework for calculating the hydrodynamic diameter distribution of NP agglomerates from their sedimentation coefficient distribution. We measure sedimentation rates for monomers, dimers, and trimers, as well as for larger agglomerates with up to 600 NPs. The AUC size distributions were found generally to be broader than the size distributions estimated from dynamic light scattering and diffusion-limited colloidal aggregation theory, an alternative bulk measurement method that relies on several assumptions. In addition, the measured sedimentation coefficients can be used in nanotoxicity studies to predict how quickly the agglomerates sediment out of solution under normal gravitational forces, such as in the environment. We also calculate the absorbance spectra for monomer, dimer, trimer, and larger gold NP agglomerates up to 600 NPs, to enable a better understanding of LSPR biosensors. Finally, we validate a new method that uses these spectra to deconvolute the net absorbance spectrum of an unknown bulk sample and approximate the proportions of monomers, dimers, and trimers in a polydisperse sample of small agglomerates, so that every sample does not need to be measured by AUC. These results demonstrate the potential utility of AUC to characterize NP agglomeration and sedimentation for nanotoxicity and biosensor studies, as well as to characterize NP agglomerate size and absorbance to improve LSPR and surface-enhanced Raman spectroscopy based biosensors.


Corrupt captains and convicts.
Australia is unique in that so many of its wine companies were founded by members of the medical profession. The First Fleet, which brought the first convicts and settlers to Australia in 1787, was delayed until wine was provided as a medicine for the long voyage from England. Australia's wine doctors were advocating the use of wine as a medicine 200 years before the French Paradox.


Cholestasis in a neonatal intensive care unit.
A retrospective study of 17 babies admitted to the neonatal intensive care unit of the Royal Maternity Hospital, Belfast, was undertaken to determine the causes and prognosis of conjugated hyperbilirubinaemia (direct fraction greater than 20% of total) over a five year period. Mean gestational age was 29 weeks and mean birth weight was 1,240g with a 2:1 male preponderance. All babies had a complicated clinical course involving prolonged periods of parenteral nutrition and many episodes of sepsis. Liver damage was not found to be a contributory factor to death in any baby who died before the age of one year. Bilirubin levels in the survivors had returned to normal within one year. No permanent pathological cause of cholestasis, such as biliary atresia, was ascribable to any of the cases, indicating that extensive investigation to exclude anatomical causes in this population is unlikely to prove rewarding.


Genetic polymorphisms in non-alcoholic fatty liver disease: interleukin-6-174G/C polymorphism is associated with non-alcoholic steatohepatitis.
Environmental and genetic factors play a role in the pathogenesis and natural history of non-alcoholic fatty liver disease (NAFLD). In 114 subjects with NAFLD we report the prevalence and correlation with clinical parameters of three polymorphisms: interleukin-6 (-174G/C), plasma cell differentiation antigen (K121Q) and microsomal transfer protein (-493G/T). In 59 biopsied patients with NAFLD the polymorphisms were also related to histological features. IL-6 -174C variant was more prevalent (p<0.01) in NAFLD compared to controls. In the NAFLD group, C carriers had higher HOMA-IR and fasting insulin than G carriers (p<0.05). The prevalence of IL-6/C variant was higher (83%) in biopsied than in not biopsied subjects (66%) (p<0.05). In biopsied subjects, C carriers had higher HOMA and fasting insulin (p<0.05) compared than those with G allele. The prevalence of IL-6 -174G/C polymorphism was significantly higher in NASH than in NAFLD (p=0.048). At logistic regression analysis IL-6 -174C was an independent predictor of both NAFLD (OR 4.116, C.I. 1.126-15.048) and NASH (OR 7.035, C.I. 1.167-42.394). Conversely, the distribution of PC-1 and MTP polymorphisms was not significantly different compared to the control group, nor associated with clinical or histological characteristics. Our data suggest that IL-6 -174C genetic polymorphisms, involved in inflammation and insulin resistance, are associated with NASH. These data may contribute to the understanding of the genetic susceptibility to NAFLD.


[Epidemiological analysis for prehypertension and its risk factors in community of Changsha].
To explore the epidemiological features of prehypertension in community of Changsha and its relevant risk factors. A total of 15 000 participants from 5 communities in Changsha were surveyed by randomly stratified cluster sampling. The questionnaire interviews and physical examination were conducted for these people, and their serum biochemical indexes were also collected and analyzed. The prevalence of prehypertension was 34.6%. The prevalence for males was higher than that in females (44.7% vs 21.7%, P<0.01). The prevalence for males was declined in older age, but for females was increased. Central obesity, age, overweight, male, drinking, smoking, high-level total cholesterol, high-level triglyceride, high-level density-lipoprotein cholesterol, low-level density-lipoprotein cholesterol, high-level fasting blood glucose, high-level creatinine, high-level uric acid were the risk factors for prehypertension, while high level of education was a protective factor. The prevalence for prehypertension is 34.6% in community of Changsha, and the prevalence for males is higher than that for females. It is important to strengthen the health publicity and education in community for earlier prevention.


New Trends in Photodynamic Inactivation (PDI) Combating Biofilms in the Food Industry-A Review.
Biofilms cause problems in the food industry due to their persistence and incompetent hygiene processing technologies. Interest in photodynamic inactivation (PDI) for combating biofilms has increased in recent years. This technique can induce microbial cell death, reduce cell attachment, ruin biofilm biomolecules and eradicate structured biofilms without inducing microbial resistance. This review addresses microbial challenges posed by biofilms in food environments and highlights the advantages of PDI in preventing and eradicating microbial biofilm communities. Current findings of the antibiofilm efficiencies of this technique are summarized. Additionally, emphasis is given to its potential mechanisms and factors capable of influencing biofilm communities, as well as promising hurdle strategies.


Web site development: applying aesthetics to promote breast health education and awareness.
This article describes the process of establishing a Web site as part of a collaborative project using visual art to promote breast health education. The need for a more "user-friendly" comprehensive breast health Web site that is aesthetically rewarding was identified after an analysis of current Web sites available through the World Wide Web. Two predetermined sets of criteria, accountability and aesthetics, were used to analyze these sites and to generate ideas for creating a breast health education Web site using visual art. Results of the analyses conducted are included as well as the factors to consider for incorporating into a Web site. The process specified is thorough and can be applied to establish a Web site that is aesthetically rewarding and informative for a variety of educational purposes.


ST-elevation acute myocardial infarction in pregnancy: 2016 update.
Acute myocardial infarction (AMI) during pregnancy or the early postpartum period is rare, but can be devastating for both the mother and the fetus. There have been major advances in the diagnosis and treatment of acute coronary syndromes in the general population, but there is little consensus on the approach to diagnosis and treatment of pregnant women. This article reviews the literature relating to the pathophysiology of AMI in pregnant patients and the challenges in diagnosis and treatment of ST-elevation myocardial infarction (STEMI) in this unique population. From a cardiologist, maternal-fetal medicine specialist, and anesthesiologist's perspective, we provide recommendations for the diagnosis and management of STEMI occurring during pregnancy.


Characterization of O-glycosylated precursors of insulin-like growth factor II by matrix-assisted laser desorption/ionization mass spectrometry.
High molecular weight precursors of insulin-like growth factor II (IGF-II) were isolated from Cohn fraction IV of human plasma by ultrafiltration, affinity chromatography and reversed-phase high-performance liquid chromatography. Molecular weight determination by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) of two high molecular weight IGF-II preparations revealed heterogeneous glycosylation. A combination of enzymatic degradation and MALDI-MS were applied for further structural characterization of the glycosylated precursors of IGF-II. The first step was molecular weight determination of intact high molecular weight IGF-IIs prior to and after treatment with neuraminidase and O-glycosidase. This, together with a comparison of molecular weight information available from the cDNA, revealed that both high molecular weight IGF-II species contain an identical C-terminal extension of 20 residues but different degrees of glycosylation. Second, comparative Endo Glu-C digestion of the preparations prior to and after enzymatic release of carbohydrates and subsequent remeasurement of the molecular weight by MALDI-MS confirmed the primary structure of precursor IGF-II1-87. The O-linked carbohydrates were found to be associated with the C-terminal extension and the heterogeneity was identified as varied sialylated forms of one and two HexNAc-Hex groups.


Anticancer versus antigrowth activities of three analogs of the growth-inhibitory peptide: relevance to physicochemical properties.
A 34-amino acid peptide has been synthesized based on an amino acid sequence from the third domain of native full-length alpha-fetoprotein, which has been shown to have both antigrowth and anticancer activities. This peptide, known as the growth-inhibitory peptide (GIP), has two cysteine residues and demonstrates reduced antigrowth activity after long-term storage, presumably due to disulfide bond formation. The disulfide bridge problem was addressed by replacing the two naturally occurring cysteines with either glycines, alanines, or serines (to produce the G-, A- and S-peptides, respectively). The non-hydrophobic G- and S-peptides were found to exist as dimers, while the more hydrophobic C- and A-peptides formed trimers in solution under certain conditions of pH and peptide concentration. The A-peptide was already known to display anticancer activity; however, the G- and S-serine analogs have not been studied in depth since they had demonstrated low antigrowth activities in rodent uterine assays. Using both in vivo and in vitro assays, the A-, G- and S-peptides were shown to exhibit various degrees of cancer growth suppression. An in vitro culture assay, using MCF-7 breast cancer cells, demonstrated that both the G- and S-peptides showed modest cancer growth suppression, while the A- analog showed strong inhibition at doses ranging from 10(-5) M to 10(-7) M. In contrast, an in vivo ascites tumor study of all four peptides showed them to have notable activity in the suppression of mouse mammary tumor growth. Overall, our data indicated that physicochemical properties, such as hydrophobicity, oligomeric state and secondary structure, contribute to the anticancer activity of both the active C- peptide and its analogs. In addition, the antigrowth rodent uterine assay was not always predictive of the anticancer potential of the peptide forms, suggesting a difference between the mechanism of peptide action in the antigrowth models and that in the anticancer assay. Notably, the antigrowth assay failed to predict the marked anticancer activity of the analogs against a mammary tumor, indicating that the growth bioassay cannot always be relied upon as a screening protocol.


[An Itching Pleasure].
An Itching Pleasure Abstract. A 50-year-old female patient presents in the emergency department with an itchy, acneiform exanthema on the trunk and malaise for two days. Laboratory testing showed no abnormalities. After further questioning, the patient reported frequent use of her new whirlpool. Based on the medical history and the clinic we suspected a pseudomonas folliculitis. A bacterial culture of the pustules showed growth of Pseudomonas aeruginosa, which confirmed the diagnosis. Systemic antibiotics were not necessary in the absence of risk factors for severe progress or immunosuppression. The exanthema healed within a few days without any complications by using external disinfectants.


Auxin-binding Sites of Maize Coleoptiles Are Localized on Membranes of the Endoplasmic Reticulum.
Sites in maize (Zea mays L.) coleoptile homogenates that reversibly bind naphthalene-1-acetic acid with high affinity and may represent receptor sites for auxins are located primarily on cellular membranes that show the enzymic and buoyant density characteristics of membranes of the rough endoplasmic reticulum. The sites remain attached to the endoplasmic reticulum (ER) membranes after the ribosomes have been stripped off them. Binding sites for naphthylphthalamic acid, an inhibitor of auxin transport, are located on membranes different from those that carry the naphthalene-1-acetic-acid (NAA)-binding sites, and which are probably plasma membrane. The two kinds of binding sites can be largely separated by appropriate density gradient centrifugation. The results raise the possibility that primary auxin action occurs at ER membranes and could represent facilitation of the transfer of hydrogen ions and nascent secretory protein into the ER lumen followed by secretory transport of these products to the cell exterior via the Golgi system.


Long-term local hyperthermia in the treatment of advanced breast cancer (case report).
It is difficult to control non-resectable locally advanced primary and recurrent breast cancer by conventional modalities. Recently, hyperthermia (HT) has been recognized as an effective adjuvant to radiotherapy (RT) and chemotherapy (CT) in treatment of various malignancies, including breast cancer. The patient was a 58-year-old female Japanese, with breast cancer, T4N2M0, stage IIIb (papillo-tubular carcinoma). Previous treatment included RT and neoadjuvant CT Local HT was performed with a total number of 87 sessions given over 12 months. The mean time of each session was 40 minutes. Elevation of temperature to a tumoricidal level of 43 degrees C was confirmed. The patient received cyclophosphamide (50 mg p.o./day) and tamoxifen (20 mg p.o./day) during the whole period of HT. Due to the decreased amount of WBC, further CT was not possible, except for one course of CMF performed 3 months after the start of HT. The patient had a decrease in the intensity of pain even after the first 3 sessions. In one month, movement in the right shoulder became possible in an anterio-posterior direction. By 5 months, the healing of ulceration became evident. At present, the patient is in continuous CR for 15 months after HT. The movement in the shoulder joint is markedly improved in all directions. In addition, HT did not cause any notable complications. Long-term HT may be useful in the management of locally advanced breast cancer and these results should encourage further clinical study.


The great contribution: Index Medicus, Index-Catalogue, and IndexCat.
The systematic indexing of medical literature by the Library of the Surgeon-General's Office (now the National Library of Medicine) has been called "America's greatest contribution to medical knowledge." In the 1870s, the library launched two indexes: the Index Medicus and the Index-Catalogue of the Library of the Surgeon-General's Office. Index Medicus is better remembered today as the forerunner of MEDLINE, but Index Medicus began as the junior partner of what the library saw as its major publication, the Index-Catalogue. However, the Index-Catalogue had been largely overlooked by many medical librarians until 2004, when the National Library of Medicine released IndexCat, the online version of Index-Catalogue. Access to this huge amount of material raised new questions: What was the coverage of the Index-Catalogue? How did it compare and overlap with the Index Medicus? Over 1,000 randomly generated Index Medicus citations were cross-referenced in IndexCat. Inclusion, form, content, authority control, and subject headings were evaluated, revealing that the relationship between the two publications was neither simple nor static through time. In addition, the authors found interesting anomalies that shed light on how medical literature was selected and indexed in "America's greatest contribution to medical knowledge."


The combination of stem cell markers CD133 and ABCG2 predicts relapse in stage I non-small cell lung carcinomas.
The aim of the study was to investigate the expression of two cancer stem cell markers CD133 and ATP-binding cassette superfamily G member 2 (ABCG2) in non-small cell lung carcinomas (NSCLC) and evaluate their prognostic values for postoperative relapse. The expression levels of CD133 and ABCG2 in 145 stage I NSCLC tumors were detected by immunohistochemistry. Positive CD133 and ABCG2 expression was defined in 31.7 and 37.9% of the NSCLC tumors, respectively. Both stem markers alone did not correlate with any of the clinicopathological characteristics and were insufficient to predict recurrence after surgery. However, our results showed that the dual expression of CD133 and ABCG2 (CD133+/ABCG2+) status was an independent predictor of postoperative recurrence for patients with stage I NSCLC. Furthermore, CD133+/ABCG2+ NSCLC tumors (33 cases, 22.8%) had a significantly higher microvessel density and higher expression levels of angiogenic factors than the other subgroups. In conclusion, this study suggests that NSCLC patients with the dual expression of CD133 and ABCG2 have a high risk of early relapse and might benefit from anti-angiogenesis therapy.


Sulfatase 2 promotes generation of a spinal cord astrocyte subtype that stands out through the expression of Olig2.
Generation of glial cell diversity in the developing spinal cord is known to depend on spatio-temporal patterning programs. In particular, expression of the transcription factor Olig2 in neural progenitors of the pMN domain is recognized as critical to their fate choice decision to form oligodendrocyte precursor cells (OPCs) instead of astrocyte precursors (APs). However, generating some confusion, lineage-tracing studies of Olig2 progenitors in the spinal cord provided evidence that these progenitors also generate some astrocytes. Here, we addressed the role of the heparan sulfate-editing enzyme Sulf2 in the control of gliogenesis and found an unanticipated function for this enzyme. At initiation of gliogenesis in mouse, Sulf2 is expressed in ventral neural progenitors of the embryonic spinal cord, including in Olig2-expressing cells of the pMN domain. We found that sulf2 deletion, while not affecting OPC production, impairs generation of a previously unknown Olig2-expressing pMN-derived cell subtype that, in contrast to OPCs, does not upregulate Sox10, PDGFRα or Olig1. Instead, these cells activate expression of AP identity genes, including aldh1L1 and fgfr3 and, of note, retain Olig2 expression as they populate the spinal parenchyma at embryonic stages but also as they differentiate into mature astrocytes at postnatal stages. Thus, our study, by revealing the existence of Olig2-expressing APs that segregate early from pMN cells under the influence of Sulf2, supports the existence of a common source of APs and OPCs in the ventral spinal cord and highlights divergent regulatory mechanism for the development of pMN-derived OPCs and APs.


Radial scar and carcinoma of the breast: microscopic findings in 32 cases.
We retrospectively reviewed the microscopic findings in 32 histologically confirmed radial scars in 31 women diagnosed in our unit during 1994-1998. The median age at diagnosis was 53 years (range 47-63 years). Thirty-one (97%) of 32 lesions presented as screen detected mammographic abnormalities (28 stellate lesions, 2 microcalcifications and only 1 architectural distortion). One lesion presented as a palpable breast mass. Stereotactic or ultrasound-guided fine needle aspiration cytology (FNAC) was performed in 28 cases. Cytological analysis of FNAs revealed malignant cells (C5) in 8 (29%) cases, highly suspicious cells (C4) in 3 (11%) cases, atypical benign cells (C3) in 7 (25%) cases and benign epithelial cells (C2) in 10 (35%) cases. All non-palpable lesions were surgically excised following wire localization. Histological examination of the breast specimens (mean weight=16 g) demonstrated, in addition to a radial scar, 6 invasive carcinomas (2 infiltrating ductal, 2 tubular, 1 mixed ductal/lobular and 1 secretory carcinoma) and 4 ductal carcinoma in situ lesions (2 high grade, 1 high grade with micro-invasion and 1 low grade) arising in the radial scar. Of the remaining cases the radial scar was associated with atypical epithelial hyperplasia in 2 cases and regular epithelial hyperplasia in 17 cases (4 florid and 13 mild to moderate). In the 10 cases associated with malignancy, 9 had FNAC and was reported as malignant (C5) in 6 (67%) cases, highly suspicious (C4) in 2 (22%) cases and atypical (C3) in 1 (11%). False positive FNAC (C5) occurred in two patients, one of whom presented with pleomorphic microcalcifications suggestive of ductal carcinoma in situ. This patient was treated with a wire guided segmental mastectomy. All invasive tumours were less than 20 mm in size (T1) and of these 4 were grade I and 2 were grade II. Axillary dissection was performed in 4 patients none of whom had axillary node metastases. Our study demonstrates a significant incidence of malignancy associated with radial scars (31%) suggesting that radial scars may be premalignant lesions. This is supported by detecting various stages of mammary carcinogenesis (atypical epithelial hyperplasia, ductal carcinoma in situ, and early invasive malignancy) in these lesions. Fine needle aspiration cytology seems to be unreliable in the diagnosis of radial scar associated malignancy (67% sensitivity and 91% specificity). Stellate lesions, therefore, should be excised to obtain an histological diagnosis regardless of cytological findings. Further studies examining the biology of radial scars are required.


Deep venous thrombosis of the upper extremity. A review.
Upper extremity deep venous thrombosis (UEDVT) occurs either spontaneously, as a consequence of strenuous upper limb activity (also known as the Paget-Schroetter syndrome) or secondary to an underlying cause. Primary and secondary UEDVT differs in long-term sequelae and mortality. This review will focus on the clinical presentation, risk factors, diagnosis, and treatment strategies of UEDVT. In the period from January to October 2012 an electronic literature search was performed in the PubMed/MEDLINE database, and 27 publications were included. swelling, pain and functional impairment are typical symptoms of UEDVT, although completely asymptomatic cases have been described. However life-threatening, massive pulmonary embolism (PE) can also be a sign of UEDVT. for the primary condition anatomical abnormalities (Thoracic Outlet Syndrome, TOS) may dispose to the condition. Malignancy and therapeutic interventions are major risk factors for the secondary deep vein thrombosis in combination with the patient's characteristics, comorbidities and prior history of deep vein thrombosis. recurrent deep venous thrombosis, pulmonary embolism and Post Thrombotic Syndrome (PTS) are the major complications after UEDVT. PTS is a chronic condition leading to significant functional disability and impaired quality of life. compression ultrasonography is noninvasive and the most frequently used objective test with a high accuracy in experienced hands. Treatment modalities and strategies: the treatment modalities include anticoagulation therapy, catheter-directed thrombolysis, surgical decompression, percutaneous transluminal angioplasty and stenting and they may be combined. However, the optimal treatment and timing of treatment remains controversial. Early diagnosis and treatment is essential to prevent PTS in primary UEDVT; however, there is no consensus on which treatment is the best. Anticoagulation is still considered the treatment of choice for at least 3-6 months, until Randomized Controlled Trials may have demonstrated otherwise.


Runx3 inhibits endothelial progenitor cell differentiation and function via suppression of HIF-1α activity.
Endothelial progenitor cells (EPCs) are bone marrow (BM)‑derived progenitor cells that can differentiate into mature endothelial cells, contributing to vasculogenesis in the blood vessel formation process. Runt‑related transcription factor 3 (RUNX3) belongs to the Runt domain family and is required for the differentiation of specific immune cells and neurons. The tumor suppressive role of RUNX3, via the induction of apoptosis and cell cycle arrest in a variety of cancers, and its deletion or frequent silencing by epigenetic mechanisms have been studied extensively; however, its role in the differentiation of EPCs is yet to be investigated. Therefore, in the present study, adult BM‑derived hematopoietic stem cells (HSCs) were isolated from Runx3 heterozygous (Rx3+/‑) or wild‑type (WT) mice. The differentiation of EPCs from the BM‑derived HSCs of Rx3+/‑ mice was found to be significantly increased compared with those of the WT mice, as determined by the number of small or large colony‑forming units. The migration and tube formation abilities of Rx3+/‑ EPCs were also observed to be significantly increased compared with those of WT EPCs. Furthermore, the number of circulating EPCs, defined as CD34+/vascular endothelial growth factor receptor 2 (VEGFR2)+ cells, was also significantly increased in Rx3+/‑ mice. Hypoxia‑inducible factor (HIF)‑1α was upregulated in Rx3+/‑ EPCs compared with WT EPCs, even under normoxic conditions. Furthermore, in a hindlimb ischemic mouse models, the recovery of blood flow was observed to be highly stimulated in Rx3+/‑ mice compared with WT mice. Also, in a Lewis lung carcinoma cell allograft model, the tumor size in Rx3+/‑ mice was significantly larger than that in WT mice, and the EPC cell population (CD34+/VEGFR2+ cells) recruited to the tumor was greater in the Rx3+/‑ mice compared with the WT mice. In conclusion, the present study revealed that Runx3 inhibits vasculogenesis via the inhibition of EPC differentiation and functions via the suppression of HIF‑1α activity.


Accelerated Development With Increased Bone Mass and Skeletal Response to Loading Suggest Receptor Activity Modifying Protein-3 as a Bone Anabolic Target.
Knockout technologies provide insights into physiological roles of genes. Studies initiated into endocrinology of heteromeric G protein-coupled receptors included deletion of receptor activity modifying protein-3, an accessory protein that alters ligand selectivity of calcitonin and calcitonin-like receptors. Initially, deletion of Ramp3-/- appeared phenotypically silent, but it has emerged that mice have a high bone mass phenotype, and more subtle alterations to angiogenesis, amylin homeostasis, and a small proportion of the effects of adrenomedullin on cardiovascular and lymphatic systems. Here we explore in detail, effects of Ramp3-/- deletion on skeletal growth/development, bone mass and response of bone to mechanical loading mimicking exercise. Mouse pups lacking RAMP3 are healthy and viable, having accelerated development of the skeleton as assessed by degree of mineralisation of specific bones, and by microCT measurements. Specifically, we observed that neonates and young mice have increased bone volume and mineralisation in hindlimbs and vertebrae and increased thickness of bone trabeculae. These changes are associated with increased osteoblast numbers and bone apposition rate in Ramp3-/- mice, and increased cell proliferation in epiphyseal growth plates. Effects persist for some weeks after birth, but differences in gross bone mass between RAMP3 and WT mice lose significance in older animals although architectural differences persist. Responses of bones of 17-week old mice to mechanical loading that mimics effects of vigorous exercise is increased significantly in Ramp3-/- mice by 30% compared with WT control mice. Studies on cultured osteoblasts from Ramp3-/- mice indicate interactions between mRNA expression of RAMPs1 and 3, but not RAMP2 and 3. Our preliminary data shows that Ramp3-/- osteoblasts had increased expression β-catenin, a component of the canonical Wnt signalling pathway known to regulate skeletal homeostasis and mechanosensitivity. Given interactions of RAMPs with both calcitonin and calcitonin-like receptors to alter ligand selectivity, and with other GPCRs to change trafficking or ligand bias, it is not clear whether the bone phenotype of Ramp3-/- mice is due to alterations in signalling mediated by one or more GPCRS. However, as antagonists of RAMP-interacting receptors are growing in availability, there appears the likelihood that manipulation of the RAMP3 signalling system could provide anabolic effects therapeutically.


The clinical value of serial measurement of high-sensitivity cardiac troponin T in acute exacerbations ofchronic obstructive pulmonary disease.
To assess the prevalence and long-term prognostic value of a dynamic (rise/fall) pattern of cardiac troponin T (hs-cTnT) elevation during acute exacerbation of chronic obstructive pulmonary disease (AECOPD) compared with a stable hs-cTnT elevation. Prospective cohort study of unselected patients admitted with AECOPD to the emergency room of a university hospital. Serial hs-cTnT measurements were made during admission. Survival after a median of 1.8 years was recorded. 83 patients with a mean age of 72 years and a mean forced expiratory volume in 1 s (FEV1) of 0.9 L. The mortality rate was 62%. The median hs-cTnT at admission was 27 ng/L (IQR 13.4-51)). 65 patients (78%) had at least one hs-cTnT measurement ≥14 ng/L, and among these the median change in hs-cTnT was 50.7% (IQR 25.2-89.4). Of the patients with serial hs-cTnT measurements, 53 (82%) had a dynamic pattern (ie, ΔTnT ≥20%). In multivariate analysis, stable hs-cTnT elevation was associated with increasing age (OR per 5 years with 95% CI 1.9 (1.01 to 3.7), p=0.045) and low Hb (OR 7.3 (1.1 to 49), p=0.039). Stable hs-cTnT elevation was associated with increased mortality with an HR of 2.4 (95%CI 1.1 to 5.3, p=0.027) in the multivariate Cox regression analysis. Among the patients with at least one hs-cTnT above the 99th centile, 82% had a rise/fall pattern, as requested to make a diagnosis of myocardial infarction. Compared to a dynamic rise/fall pattern of hs-cTnT, a stable and moderately elevated hs-cTnT during AECOPD is associated with poor long-term prognosis.


Oxorhenium(V) complexes of quinoline and isoquinoline carboxylic acids--synthesis, structural characterization and catalytic application in epoxidation reactions.
Six novel oxorhenium(V) complexes incorporating quinoline and isoquinoline carboxylic acid derivatives were prepared in good yields. Relying on the experimental conditions, compounds with two chelate ligands [ReOCl(iqc)2]·MeOH (1), [ReO(OMe)(iqc)2] (2), [ReO(OMe)(mqc)2] (3) and [ReO(OMe)(8-qc)2] (4) and compounds incorporating one bidentate ligand [ReOCl2(iqc)(PPh3)] (5) and [ReOCl2(mqc)(PPh3)] (6) were synthesized (iqcH = isoquinoline-1-carboxylic acid, mqcH = 4-methoxy-2-quinolinecarboxylic acid and 8-qcH = 8-quinolinecarboxylic acid). The reported compounds were characterized by spectroscopic methods and single crystal X-ray diffraction analysis. In compounds 1 and 2, one chelate ligand occupies an axial and an equatorial position, while the other one occupies two equatorial positions, forming a cis-(N,N) isomer. In turn, complexes 3 and 4 show a rare ligand arrangement with two trans-N, trans-O chelate ligands in the equatorial plane and a linear axial [O=Re-OMe] unit. The complexes with one chelate ligand 5 and 6 are cis-(Cl,Cl)-isomers. All compounds were tested as potential catalysts in the epoxidation of cyclooctene with 3 equiv. of tert-butylhydroperoxide. The yield of cyclooctane oxide varies between 16 and 68% (50 °C, 24 h), and the catalytic competency of compounds 1-6 was discussed with regard to the structure of each complex.


Identification and isolation of Lewis blood group antigens from human saliva using monoclonal antibodies.
Solid-phase radioimmunoassay, polyacrylamide gel electrophoresis and thin-layer chromatography were used to compare, identify, and characterize the Lewis antigens from human salivas, using monoclonal antibodies directed to the Lea and Leb determinants. Sialylated Lea glycolipid was detected in saliva from individuals with Le(a+ b+) and Le(a+ b-) phenotypes. Immunoaffinity chromatography of the saliva from individuals with different phenotypes revealed a glycoprotein of molecular weight greater than 200 kD bearing the Lewis antigenic determinants.


Methotrexate and Valproic Acid Affect Early Neurogenesis of Human Amniotic Fluid Stem Cells from Myelomeningocele.
Myelomeningocele (MMC) is a severe type of neural tube defect (NTD), in which the backbone and spinal canal do not close completely during early embryonic development. This condition results in serious morbidity and increased mortality after birth. Folic acid significantly reduces, and conversely, folate antagonist methotrexate (MTX) and valproic acid (VPA) increase the occurrence of NTDs, including MMC. How these pharmacological agents exactly influence the early neurulation process is still largely unclear. Here, we characterized human amniotic fluid-derived stem cells (AFSCs) from prenatally diagnosed MMC and observed an effect of MTX and VPA administration on the early neural differentiation process. We found that MMC-derived AFSCs highly expressed early neural and radial glial genes that were negatively affected by MTX and VPA exposure. In conclusion, we setup a human cell model of MMC to study early neurogenesis and for drug screening purposes. We also proposed the detection of early neural gene expression in AFSCs as an additional MMC diagnostic tool.


A prospective, randomized, three arm, open label study comparing the safety and efficacy of PP110, a novel treatment for hemorrhoids to preparation-H® maximum strength cream in the treatment of grade 2-3 hemorrhoids.
Hemorrhoids are a common disorder that affects the quality of life of millions of people worldwide. The effectiveness of OTC medication is limited and they mainly provide symptomatic relief. In order to treat this ailment, we formulated PP110 Gel and Wipes, as a novel treatment for hemorrhoids. PP110 is based on known active ingredients with a topical film-forming agent designed to provide physical protection and prolonged tissue contact with the active ingredients. PP110 Gel, PP110 Wipes and the comparator Preparation-H® were used on three patient cohorts. Treatment was administered once daily for PP110, and three-four times daily for Preparation-H®, for 14 days. Six different clinical parameters relating to common symptoms of hemorrhoids were monitored. PP110 Gel was significantly better than Preparation-H® in reducing bleeding (Δ = 6 %), providing pain relief (Δ = 10 %) and controlling itching (Δ = 11 %). These three parameters are considered as the most common distressing symptoms for hemorrhoids patients, demonstrating that PP110 is superior to conventional treatment. This study demonstrated the efficacy of the PP110 Gel in treating hemorrhoids and its superiority to conventional treatments. The PP110 film-based formulation provides a slow-release mechanism and as a consequence, a prolonged therapeutic window. PP110 was both more effective in reducing hemorrhoids symptoms and more convenient to use, in that it only required application once per day.


Measured occupational solar UVR exposures of lifeguards in pool settings.
The aim of this study was to measure ultraviolet radiation (UVR) exposures of lifeguards in pool settings and evaluate their personal UVR protective practices. Lifeguards (n = 168) wore UVR sensitive polysulfone (PS) film badges in wrist bracelets on 2 days and completed a survey and diary covering sun protection use. Analyses were used to describe sun exposure and sun protection practices, to compare UVR exposure across locations, and to compare findings with recommended threshold limits for occupational exposure. The measured UVR exposures varied with location, ranging from high median UVR exposures of 6.2 standard erythemal doses (SEDs) to the lowest median of 1.7 SEDs. More than 74% of the lifeguards' PS badges showed UVR above recommended threshold limits for occupational exposure. Thirty-nine percent received more than four times the limit and 65% of cases were sufficient to induce sunburn. The most common protective behaviors were wearing sunglasses and using sunscreen, but sun protection was often inadequate. At-risk individuals were exposed to high levels of UVR in excess of occupational limits and though appropriate types of sun protection were used, it was not used consistently and more than 50% of lifeguards reported being sunburnt at least twice during the previous year.


Modeling tumor cell migration: From microscopic to macroscopic models.
It has been shown experimentally that contact interactions may influence the migration of cancer cells. Previous works have modelized this thanks to stochastic, discrete models (cellular automata) at the cell level. However, for the study of the growth of real-size tumors with several million cells, it is best to use a macroscopic model having the form of a partial differential equation (PDE) for the density of cells. The difficulty is to predict the effect, at the macroscopic scale, of contact interactions that take place at the microscopic scale. To address this, we use a multiscale approach: starting from a very simple, yet experimentally validated, microscopic model of migration with contact interactions, we derive a macroscopic model. We show that a diffusion equation arises, as is often postulated in the field of glioma modeling, but it is nonlinear because of the interactions. We give the explicit dependence of diffusivity on the cell density and on a parameter governing cell-cell interactions. We discuss in detail the conditions of validity of the approximations used in the derivation, and we compare analytic results from our PDE to numerical simulations and to some in vitro experiments. We notice that the family of microscopic models we started from includes as special cases some kinetically constrained models that were introduced for the study of the physics of glasses, supercooled liquids, and jamming systems.


The IL-27 receptor (WSX-1) is an inhibitor of innate and adaptive elements of type 2 immunity.
Although previous studies have investigated the role of IL-27/WSX-1 interactions in the regulation of Th1 responses, little is known about their role in regulating Th2-type responses. Studies presented in this work identify a direct role for IL-27/WSX-1 interactions in the negative regulation of type 2 responses independent of effects on type 1 cytokines. WSX-1-/- mice infected with the gastrointestinal helminth Trichuris muris displayed accelerated expulsion of parasites and the development of exaggerated goblet cell hyperplasia and mastocytosis in the gut due to increased production of Th2 cytokines. Enhanced mast cell activity in the absence of WSX-1 was consistent with the ability of wild-type mast cells to express this receptor. In addition, IL-27 directly suppressed CD4+ T cell proliferation and Th2 cytokine production. Together, these studies identify a novel role for IL-27/WSX-1 in limiting innate and adaptive components of type 2 immunity at mucosal sites.


Normal brain ageing: models and mechanisms.
Normal ageing is associated with a degree of decline in a number of cognitive functions. Apart from the issues raised by the current attempts to expand the lifespan, understanding the mechanisms and the detailed metabolic interactions involved in the process of normal neuronal ageing continues to be a challenge. One model, supported by a significant amount of experimental evidence, views the cellular ageing as a metabolic state characterized by an altered function of the metabolic triad: mitochondria-reactive oxygen species (ROS)-intracellular Ca2+. The perturbation in the relationship between the members of this metabolic triad generate a state of decreased homeostatic reserve, in which the aged neurons could maintain adequate function during normal activity, as demonstrated by the fact that normal ageing is not associated with widespread neuronal loss, but become increasingly vulnerable to the effects of excessive metabolic loads, usually associated with trauma, ischaemia or neurodegenerative processes. This review will concentrate on some of the evidence showing altered mitochondrial function with ageing and also discuss some of the functional consequences that would result from such events, such as alterations in mitochondrial Ca2+ homeostasis, ATP production and generation of ROS.