Ischemic stricture of the small intestine associated with acute pancreatitis.
A 37-yr-old man underwent an open drainage operation for severe acute pancreatitis and received respiratory ventilation support for 4 mo because of respiratory failure based on disseminated intravascular coagulation (DIC) and septic shock. Under intensive care, he sometimes had bloody diarrhea for about 6 wk. Colonoscopic findings suggested that the bleeding had derived from the small intestine. The patient then gradually recovered from acute pancreatitis and was discharged from the hospital. Thereafter, he suffered relapses of ileus and his symptoms progressively worsened. The patient underwent a second operation about 2 yr after the onset of acute pancreatitis. At celiotomy, multiple stenoses of the distal ileum measuring about 60 cm in length were found and the segment was resected. The resected specimen demonstrated six separate circumferential strictures and shallow ulcerations. Histologically, multiple ulcerations were restricted to the mucosa and were accompanied by marked submucosal edema and fibrosis. The mucosa between the ulcers revealed chronic regenerative changes: intimal thickening of small mesenteric arteries causing luminal narrowing and organized thrombosis in small mesenteric veins. Therefore, these were considered to be a series of segmental ischemic lesions. Note that delayed ischemic stricture of the small intestine may occur as a chronic complication of acute pancreatitis.


Reliability, validity, and responsiveness of the Japanese version of the Patient-Specific Functional Scale in patients with neck pain.
The aims of this study were to translate and culturally adapt the Patient-Specific Functional Scale (PSFS) and validate the Japanese version of the PSFS (PSFS-J) in outpatients with neck pain. The PSFS was translated and adapted into Japanese in accordance with the published guidelines. A total of 103 outpatients with neck pain were recruited for this study. Psychometric evaluation included test-retest reliability, convergent validity by comparing the PSFS-J to the Neck Disability Index (NDI), patient's global impression of change (PGIC), and responsiveness (unpaired t test, minimal detectable change). The intraclass correlation coefficient for test-retest reliability was 0.98 (95% confidence interval = 0.95-0.99). The Pearson correlation coefficient with the NDI was -0.35. The Spearman correlation coefficient showed a strong relationship between the change score in the PSFS-J and PGIC (-0.70). The analysis of responsiveness was calculated with the unpaired t test showing a significant difference between the stable and improved patients (P < 0.01). The minimal detectable change was calculated as 0.64. The Japanese version of the PSFS is a valid, reliable, and responsive instrument to assess Japanese outpatients with neck pain.


Genome-wide DNA methylation profiling of gastric cardia cancer.
Aberrant DNA methylation has been found in various cancer types including gastric cancer, yet the genome-wide DNA methylation profile of gastric cardia cancer (GCC) remains unclear. Therefore, we aimed to profile the DNA methylation pattern of GCC and identify promising diagnostic epigenetic biomarkers. We investigated the genome-wide DNA methylation pattern in eight pairs of GCC and adjacent normal tissues using Illumina 850K microarrays. Subsequently, bisulfite-pyrosequencing and quantitative real-time PCR were performed on eight pairs of GCC-adjacent normal tissues for validation. Finally, we performed immunohistochemistry to examine ADHFE1 expression on 126 pairs of GCC-adjacent normal samples. DNA methylome analysis showed global hypomethylation and local hypermethylation of promoter cytosine-phosphate-guanine (CpG) islands (CGIs) in GCC tissues compared with gastric cardia normal mucosa (P < 2.2 × 10-16 ). Differential methylation analysis identified a total of 91 723 differentially-methylated probes (DMPs), and the candidate gene with the largest average DNA methylation difference mapped to ADHFE1 (mean Δβ = 0.53). Subsequently, three DMPs in the ADHFE1 promoter were validated by pyrosequencing. Notably, the mean methylation level of the three candidate DMPs (ADHFE1_cg08090772, ADHFE1_cg19283840, and ADHFE1_cg20295442) was negatively associated with ADHFE1 mRNA expression level (Spearman rho = -0.64, P = 0.01). Moreover, both mRNA (P = 0.0213) and protein (P < 0.0001) expression of ADHFE1 were significantly decreased in GCCs compared with the adjacent normal tissues. Our results reveal DNA methylation aberrations in GCC and that ADHFE1 gene DNA methylation contributes to the risk of GCC, thus providing novel mechanistic insights into gastric cardia cancer carcinogenesis.


Fibroblasts from the growing margin of keloid scars produce higher levels of collagen I and III compared with intralesional and extralesional sites: clinical implications for lesional site-directed therapy.
Overproduction of collagen and its abnormal assembly are hallmarks of keloid scars. Type I/III collagen ratios are altered in keloids compared with normal skin. Fibroblasts from different sites in keloid tissue, perilesional compared with intralesional and extralesional sites, show differential apoptosis and contraction. Additionally, early vs. later cell culture passages display differential collagen expression. We therefore hypothesize that keloid fibroblasts from the growing margin of the keloid express higher levels of collagen type I and III, and that collagen production is altered by extended cell culture passage. (i) To measure collagen I and III at mRNA and protein levels quantitatively in keloid fibroblasts, growth media and tissue sections; and (ii) to perform tissue staining for collagen I and III expression in different lesional sites. Keloid fibroblast cultures from intralesional, perilesional and extralesional sites (n = 8 separate keloid cases, yielding 64 biopsy samples) were established from passage 0 to passage 3. Collagen I and III mRNA was quantified using quantitative reverse transcription-polymerase chain reaction. We also measured the protein levels quantitatively by developing a highly specific and sensitive capture sandwich enzyme-linked immunosorbent assay. A novel in-cell Western blotting was carried out in addition to haematoxylin and eosin and Herovici staining on keloid tissue sections for collagen I and III. Collagen types I and III were significantly higher (P < 0·03) in fibroblasts from the growing margin (perilesional site) compared with extralesional and intralesional keloid biopsy sites. As the passage number increased, the amount of collagen I significantly (P < 0·05) decreased and the collagen I/III ratio also decreased. Our data show that cells from the growing margin of keloid scars have a higher production of collagen I and III compared with other lesional sites. Additionally, temporal extension of cell passage affects collagen production. Clinically these findings may influence selection and interpretation of extended cell passage and provide future direction for lesional site-specific therapy in keloid scars.


Proliferative potential after DNA damage and non-homologous end joining are affected by loss of securin.
The faithful repair of DNA damage, especially chromosomal double-strand breaks (DSBs), is crucial for genomic integrity. We have previously shown that securin interacts with the Ku70/80 heterodimer of the DSB non-homologous DNA end-joining (NHEJ) repair machinery. Here we demonstrate that securin deficiency compromises cell survival and proliferation, but only after genotoxic stress. Securin(-/-) cells show a significant increase in gross chromosomal rearrangements and chromatid breaks after DNA damage, and also reveal an altered pattern of end resection in an NHEJ assay in comparison with securin(+/+) cells. These data suggest that securin has a key role in the maintenance of genomic stability after DNA damage, thereby providing a previously unknown mechanism for regulating tumour progression.


QSAR and molecular graphics analysis of N2-phenylguanines as inhibitors of herpes simplex virus thymidine kinases.
A quantitative structure-activity relationship study of N2-(substituted)-phenylguanines (PHG) as inhibitors of herpes simplex virus thymidine kinase (HSV TK) was performed. The activity of a set of PHG derivatives were analyzed against the thymidine kinase of herpes simplex virus types 1 (HSV1 TK) and 2 (HSV2 TK). Classic and calculated physicochemical parameters were included in the analysis. The results showed that there is an important difference in the activity of the meta substituted PHG derivatives against HSV1 TK and HSV2 TK. The activity of the meta derivatives against HSV2 TK is influenced by a steric effect, which is not observed against HSV1 TK. The superposition of the three-dimensional structures of the active sites of HSV1 TK (crystal structure) and HSV2 TK (homology model) revealed that the amino acid Ile97 is located near the meta position in the HSV1 TK active site, whereas the amino acid Leu97 is located near the meta position in the HSV2 TK active site. This single difference in the active sites of both enzymes can explain the source of the steric effect and serves as an indication that our previously proposed binding mode for the PHG derivatives is plausible. However, another observed mutation in the active site region, Ala168 by Ser168, suggests that an alternative binding mode, similar to that of ganciclovir, could be possible.


Tracing of two-neuron pathways in the olfactory system by the aid of transneuronal degeneration: projections to the amygdaloid body and hippocampal formation.
Following an olfactory bulb lesion in guinea pig (2 to 3 days), neuronal degeneration occurs in several olfactory-bulb-related areas, primarily in the piriform cortex. The degenerating neurons, which are argyrophilic, are also found in the posterolateral cortical amygdaloid nucleus and the ventrolateral entorhinal cortex. It is suggested that the neurons degenerate because of a transneuronal effect due to a sudden loss of afferent input from the olfactory bulb, although a retrograde effect acting in concert with transneuronal factors cannot be excluded. Terminal degeneration can be identified in several areas outside the olfactory bulb projection area, and is interpreted as degeneration in the axons of the degenerating cortical neurons. Such terminal degeneration, which is best seen 3 to 4 days postoperatively, has been identified in part of the basolateral amygdaloid complex, in the basomedial amygdaloid nucleus, and in the temporal parts of the fascia dentata of the hippocampal formation. Terminal degeneration has also been observed in the deep layers of the anterior olfactory nucleus, the olfactory tubercle, the nucleus of the lateral olfactory tract, and the anterior amygdaloid area. All these projections, apparently, represent the second link in two-neuron pathways, where mitral or tufted cells in the olfactory bulb make up the first neuron. This interpretation was confirmed in control experiments in which areas of argyrophilic neurons coincided with the location of retrogradely labeled neurons following injection of fluorescent substances into several of the above-mentioned areas of terminal degeneration.


What does it mean to be musical?
Music can be seen as a model system for understanding gene × environment interactions and how these can influence neurocognitive development. The concept of musicality, however, is underspecified and not well understood. Here, I propose a framework for defining musicality to provide a foundation for studying the contributions of biological and environmental factors.


Trans fatty acids in the Portuguese food market.
Consistent evidence exist on the harmful health effects of industrial trans fatty acids (TFA). In order to have accurate data on TFA intake and implement adequate measures to reduce their intake, each country should have updated estimates of TFA content in the diet. The objective of the present study was to provide data on the TFA content in food commercialized in the Portuguese market. The results on the TFA content of 268 samples acquired between October and December 2013 are reported. Samples were categorized as margarines and shortenings (n = 16), spreadable chocolate fats (n = 6), fried potatoes and chips (n = 25), industrial bakery (n = 4), breakfast cereals (n = 3), pastry products (n = 120), seasonings (n = 5), instant soups (n = 5), instant desserts (n = 6), chocolate snacks (n = 4), microwave popcorn (n = 4), cookies, biscuits and wafers (n = 53), and fast-food (n = 13), with butter (n = 4) included for comparison purposes. TFA were quantified by gas chromatography. Total TFA content in the fat ranged from 0.06% to 30.2% (average 1.9%), with the highest average values in the "biscuits, wafers and cookies" group (3.4% TFA), followed by the pastry group (2.0%). Fifty samples (19%) had TFA superior to 2% in the fat. These findings highlight there is still much need for improvement in terms of the TFA content in Portuguese foods, particularly in traditional pastry.


An inducement to exercise after flexor tendon repair.
A simple gadget is described which provides the encouragement necessary for children to exercise in dynamic traction following flexor tendon repair in the hand. Its use has made possible the incorporation of dynamic splinting into the aftercare of very young patients.


Hypothalamic unit responses to alimentary perfusions in the anesthetised rat.
Single unit discharges in the ventromedial hypothalamic nucleus (VMH) and lateral hypothalamic area (LH) were extracellularly recorded in urethane anesthetised female rats, while various solutions were perfused through the stomach or duodenum via implanted polythene tubes. Perfusates, which were maintained at 38 degrees C, were 0.9% (w/v) NaCl, 2.5% NaCl, 5.25% glucose, 30% glucose, 5.0% casein hydrolysate, and liquid food. Only units which did not respond to somatosensory stimuli were tested. One hundred and twenty six units were recorded for periods of up to 3 hr, occasionally longer, in 57 animals. Of these, 74 were recorded during gastric perfusions and 52 during duodenal perfusions. Distension of the stomach elicited changes in firing rate in 16 LH and 8 VMH units. Both increases and decreases in firing rate in response to gastric distension were observed in both the LH and VMH. There was no evidence that nutrient or osmotic properties of the perfusates exerted any modifying influence on hypothalamic unit discharges. Distention of the duodenum by the perfusions elicited changes in firing rate in 12 LH and 6 VMH units. In this case all LH units decreased firing and all VMH units increased firing during distension of the lumen. In addition 2 VMH units appeared to increase their firing rate in association with glucose perfusions. The results are discussed in terms of the role of gastrointestinal feedback to the hypothalamus in food intake regulation.


[Klaforan in the treatment of newly diagnosed gonorrhea in men].
Two injections of klaforan, 1 g per injection, with a 12 hrs interval is an effective method for the therapy of male patients with fresh gonorrheal urethritis.


Distressing and positive experiences and important aspects of care for adolescents treated for cancer. Adolescent and nurse perceptions.
Distressing and positive experiences for adolescents with cancer with regard to being told the diagnosis, receiving chemotherapy and being admitted to the ward, and important aspects of care for adolescents with cancer was investigated. Data were gathered through semi-structured interviews with 23 adolescents and 21 nurses, and analysed by content analysis. The findings indicate that cancer during adolescence is connected with a range of negative experiences such as fears of alienation, fears of altered appearance, fears of dying, and various physical concerns. Positive experiences include positive relations to staff and being well cared for. Important care for adolescents treated for cancer consists mainly of meeting nice, friendly, supportive, and competent staff, who provide them with age-appropriate information. The findings indicate that adolescents with cancer experience a range of negative and positive experiences related to disease and treatment and that good care for adolescents with cancer is a broad, complex, and multidimensional phenomenon.


[Theoretical discussion on stress and its projection to pathology].
The stress is presented in the perspective of an automatic response related to hereditary behavior, where the threat played the role of a a basic stressor. Thus only offensive or disagreeable agents are accepted as stressors, a point of theoretical important implications. The demonstration that only the inescapable chronic stressor produces immunodepression enriched the transformation of a pathogenic factor into a pathological event by means of the repeated stress reaction.


[Effect of adenosine on hemodynamic changes during the development of neurogenic myocardial lesions].
The influence of adenosine on hemodynamic changes induced by electrostimulation of reflexogenic zone of aorta was studied in this article. It was shown that 3-hour electrostimulation increased the total peripheral resistance and decreased cardiac output and aortic pressure. Intravenous infusion of adenosine during electrostimulation led to the normalization of main indices of hemodynamics.


Designing observation charts to optimize the detection of patient deterioriation: reliance on the subjective preferences of healthcare professionals is not enough.
Observation charts are critical to detecting patient deterioration. Research suggests their design has a dramatic impact on user performance in terms of failure rates for detecting abnormal vital signs and how quickly users can interpret recorded observations. In this study, we examined the design preferences of professional chart users to assess their alignment with objective performance data. In addition, we tested the assumptions of prior knowledge that chart designers appear to have made about chart users. We conducted an online survey of health professionals (n=347). Participants answered questions about their observation chart design preferences in general, and were randomly assigned to evaluate one of nine specific charts. Chart users' preferences for design features were not always consistent with objective performance data. While some views concurred with empirical findings (e.g., participants preferred to plot observations on a graph with graded colouring, where the colours corresponded with degrees of abnormality), others did not (e.g., participants preferred plotting blood pressure and pulse together on the same chart area, which the objective data suggest is problematic). Additionally, a substantial proportion of respondents were unfamiliar with some of the assumed knowledge required to interpret many charts (e.g., particular abbreviations). It is dangerous to rely solely on subjective opinions - even those of experienced health professionals - when developing patient observation charts, as optimal design may be counterintuitive and some preferences may merely reflect familiarity. Objective performance data is also required. In addition, the level of assumed knowledge required to use a chart should be minimized.


Is aging a barrier to reprogramming? Lessons from induced pluripotent stem cells.
The discovery of induced pluripotent stem cells (iPSCs) has the potential to revolutionize the field of regenerative medicine. In the past few years, iPSCs have been the subject of intensive research towards their application in disease modeling and drug screening. In the future, these cells may be applied in cell therapy to replace or regenerate tissues by autologous transplantation. However, two major hurdles need to be resolved in order to reach the later goal: the low reprogramming efficiency and the safety risks, such as the integration of foreign DNA into the genome of the cells and the tumor formation potential arising from transplantation of residual undifferentiated cells. Recently, aging emerged as one of the barriers that accounts, at least in part, for the low reprogramming efficiency of bona fide iPSCs. Here, we review the molecular pathways linking aging and reprogramming along with the unanswered questions in the field. We discuss whether reprogramming rejuvenates the molecular and cellular features associated with age, and present the recent advances with iPSC-based models, contributing to our understanding of physiological and premature aging.


Modulation of cardiac renin-angiotensin system, redox status and inflammatory profile by different volumes of aerobic exercise training in obese rats.
Overactivation of the classical arm of the renin-angiotensin (Ang) system (RAS) occurs during inflammation, oxidative stress and obesity-induced cardiomyopathy. The activation of the protective arm of RAS may act to counterbalance the deleterious effects of the classical RAS. Although aerobic exercise training (AET) shifts the balance of the RAS towards the protective arm, little is known about the molecular adaptations to different volumes of AET. The aim of this study was to evaluate the impact of AET volume on the modulation of RAS, as well as on cardiac biomarkers of oxidative stress and inflammation, in a diet-induced obesity model. Male Wistar rats were fed either control (CON) or high fat (HF) diet for 32 weeks. At week 20, HF group was subdivided into sedentary, low (LEV, 150 min/week) or high (HEV, 300 min/week) exercise volume. After 12 weeks of exercise, body mass gain, systolic blood pressure and heart rate were evaluated, as well as RAS, oxidative stress and inflammation in the heart. Body mass gain, systolic blood pressure and heart rate were higher in HF group when compared with SC group. Both trained groups restored systolic blood pressure and heart rate, but only HEV reduced body mass gain. Regarding the cardiac RAS, the HF group exhibited favoring of the classical arm and both trained groups shifted the balance towards the counterregulatory protective arm. The HF group had higher B1R expression and lower B2R expression than the control group, and B2R expression was reverted in both trained groups. The HF group also presented oxidative stress. The LEV and HEV groups improved the cardiac redox status by reducing Nox 2 and nitrotyrosine expression, but only the LEV group was able to increase the antioxidant defense by increasing Nrf2 signaling. While the HF group presented higher TNF-α, IL-6 and NFκB expression, and lower IL-10 expression, than the SC group, both training protocols improved the inflammatory profile. Although both trained groups improved the deleterious changes related to obesity cardiomyopathy, it is clear that the molecular mechanisms differ between them. Our results suggest that different exercise volumes might reach different molecular targets, and this could be a relevant factor when using exercise to manage obesity.


Costs of implementing pharmaceutical care in community pharmacies.
To estimate the costs and benefits to community pharmacies of converting a traditional practice into one based on pharmaceutical care. Community-based ambulatory care pharmacies. Community pharmacy. Pharmaceutical care. Costs incurred and revenues received. Twenty-five community pharmacies that had made the transition from traditional practice to one based on pharmaceutical care returned a survey providing data on the costs and revenues associated with the transition. Mean total cost of making the conversion for the 25 pharmacies was $36,207. The largest cost component associated with the transition was personnel, which had a mean cost of $16,512 per pharmacy. Mean revenues received for pharmaceutical care by these 25 pharmacies was $3,687, mainly for disease management services. Pharmacies that spent more on the conversions, and used brochures and physician detailing as well as consultants and franschises, tended to be more successful in generating revenues from pharmaceutical care. Most pharmacies that have made the conversion to pharmaceutical care have not experienced an increase in profits as a result of that conversion. More effort needs to be directed toward improving the flow of revenues obtained from providing pharmaceutical care.


The dextran acceptor reaction of dextransucrase from Streptococcus mutans K1-R.
Soluble dextransucrase activity(ies) was eluted with a solution of clinical dextran from the insoluble dextran--cell complex produced by Streptococcus mutans K1-R grown in the presence of sucrose. Studies of the dextran acceptor-reaction of the soluble enzyme-preparation indicate that it is highly specific for dextran of high molecular weight. Increased dextran synthesis in the presence of dextran acceptor and the apparent inhibition of this stimulation by higher concentrations of dextran result from product modification rather than a direct effect on the level of enzyme activity. The results demonstrate that the potentially water-insoluble structure synthesized by dextransucrase on exogenous, soluble dextran acts as a more-efficient acceptor than the soluble dextran. The role of the acceptor reaction in the biosynthesis of complex dextrans is discussed.


Cross-talk among epidermal growth factor, Ap(5)A, and nucleotide receptors causing enhanced ATP Ca(2+) signaling involves extracellular kinase activation in cerebellar astrocytes.
In previous papers, we reported that ATP calcium responses in cerebellar astrocytes were strongly potentiated by preincubation with nanomolar concentrations of the diadenosine pentaphosphate Ap(5)A. However, the intracellular signaling pathway mediating this effect was not defined. We also showed that stimulation of astrocytes with the dinucleotide led to the activation of extracellular regulated kinases (ERKs). Here, we examined whether ERKs are involved in the potentiating mechanism and intracellular mechanism leading to their activation. Epidermal growth factor (EGF) exactly reproduced the potentiation displayed by the dinucleotide. Moreover, the potentiation of ATP responses by Ap(5)A and EGF was completely abolished by the MAP kinase (MEK) inhibitor U-0126, indicating that ERK activation is a required step for the potentiation event. Our data also indicated that ERK activation and the potentiation of ATP calcium responses were sensitive to the src-like kinase inhibitor herbimycin A, p21(ras) farnesyltransferase inhibitor peptide, and some PKC inhibitors. Taken together, our findings reveal that Ap(5)A triggers the potentiation of ATP calcium responses through an intracellular mechanism that is insensitive to pertussis toxin and that this potentiation requires src protein-mediated ERK activation and the participation of an atypical protein kinase C isoform activated downstream from ERK.


Inhibition of the Fenton reaction by nitrogen monoxide.
The toxicity of iron is believed to originate from the Fenton reaction which produces the hydroxyl radical and/or oxoiron2+. The effect of nitrogen monoxide on the kinetics of the reaction of iron(II) bound to citrate, ethylenediamine-N,N'-diacetate (edda), ethylenediamine-N,N,N',N'-tetraacetate (edta), (N-hydroxyethyl)amine-N,N',N'-triacetate (hedta), and nitrilotriacetate (nta) with hydrogen peroxide was studied by stopped-flow spectrophotometry. Nitrogen monoxide inhibits the Fenton reaction to a large extent. For instance, hydrogen peroxide oxidizes iron(II) citrate with a rate constant of 5.8x10(3) M(-1) s(-1), but in the presence of nitrogen monoxide, the rate constant is 2.9x10(2) M(-1) s(-1) . Similar to hydrogen peroxide, the reaction of tert-butyl hydroperoxide with iron(II) complexes is also efficiently inhibited by nitrogen monoxide. Generally, nitrogen monoxide binds rapidly to a coordination site of iron(II) occupied by water. The rate of oxidation is influenced by the rate of dissociation of the nitrogen monoxide from iron(II).


Antioxidants of therapeutic relevance in COPD from the neotropical blueberry Anthopterus wardii.
Four flavone C-glycosides, isoorientin (1), orientin (2), vitexin (3), and isovitexin (4), were isolated from the neotropical blueberry of Anthopterus wardii, a so-called "superfruit", using antioxidant activity-guided fractionation. A dose-response relationship of compounds 1-4 was determined for their anti-inflammatory activity against interleukin-8 (IL-8) and for the inhibition of matrix metalloproteinase-1 (MMP-1) expression, an inflammatory marker for chronic obstructive pulmonary disease. The four flavone C-glycosides exhibited inhibitory activity against IL-8 production and MMP-1 expression, with compounds 1, 3, and 4 having the most potent inhibitory activities in both assays at 100 μg/ml. The structures of compounds 1-4 were determined by spectroscopic methods. These flavone C-glycosides are reported for the first time in the Anthopterus genus.


Rotations of macromolecules affect nonspecific biological responses to magnetic fields.
We have previously proposed that there are at least two initial molecular transduction mechanisms needed to explain specific and nonspecific biological effects of weak magnetic fields. For the specific effect associated with animal magnetic navigation, the radical pair mechanism is the leading hypothesis; it associates the specialised magnetic sense with the radical pairs located in the eye retina. In contrast to the magnetic sense, nonspecific effects occur through the interaction of magnetic fields with magnetic moments dispersed over the organism. However, it is unlikely that the radical pair mechanism can explain such nonspecific phenomena. In order to explain these, we further develop our physical model for the case of magnetic moments residing in rotating molecules. It is shown that, in some conditions, the precession of the magnetic moments that reside on rotating molecules can be slowed relative to the immediate biophysical structures. In terms of quantum mechanics this corresponds to the mixing of the quantum levels of magnetic moments. Hence this mechanism is called the Level Mixing Mechanism, or the LMM. The results obtained are magnetic field-dependences that are in good agreement with known experiments where biological effects arise in response to the reversal of the magnetic field vector.


TRIAD1 Is a Novel Transcriptional Target of p53 and Regulates Nutlin-3a-Induced Cell Death.
Nutlin-3a is a non-genotoxic, p53-activating, MDM2 inhibitor being investigated as an anticancer agent. Although Nutlin-3a selectively antagonizes the ubiquitin E3 ligase activity of MDM2, its efficacy is not entirely regulated by MDM2 levels in cancer cells. Here, we report that the cytotoxic effects of Nutlin-3a are regulated by TRIAD1 via a positive feedback loop with p53. We found that Nutlin-3a enhanced TRIAD1 transcription in a p53-dependent manner. Using in silico analysis and promoter luciferase assays, we demonstrated that p53-mediated transcription of TRIAD1 is mediated by a p53 consensus sequence in the TRIAD1 promoter region. Silencing TRIAD1 expression in wild-type p53 (p53WT ) cancer cells suppressed Nutlin-3a-mediated p53 activation and p53 target gene expression. These effects were enhanced in TRIAD1-overexpressing p53WT cancer cells, but not in p53-deficient cancer cells. Furthermore, TRIAD1 knockdown significantly reduced the growth inhibitory and cytotoxic effects of Nutlin-3a in p53WT cancer cells, as demonstrated by cell viability assays, cell cycle analysis, clonogenic growth, and soft-agar colony forming assays. Together, these data indicate that TRIAD1 regulates Nutlin-3a-mediated p53 activation and the cytotoxic activity of Nutlin-3a. J. Cell. Biochem. 118: 1733-1740, 2017. © 2016 Wiley Periodicals, Inc.


Optical imaging of shock waves produced by a high-energy electromagnetic transducer.
An electromagnetic acoustic transducer (EMAT) and acoustic lens have been constructed to provide reproducible and well characterized acoustic shock waves in water. The peak pressure amplitude variation for the unfocused and focused shock waves was found to be within +/- 5%. The focal region has been characterized both optically and by conventional piezoelectric pressure measurements. Optical investigations centre around ruby laser illuminated Schlieren and focused shadow imaging. The temporal resolution of the optical technique was determined by the ruby laser pulse length of 20 ns, giving a spatial resolution of 30 microns for a shock front in water.


Anomalous d-like surface resonances on Mo(110) analyzed by time-of-flight momentum microscopy.
The electronic surface states on Mo(110) have been investigated using time-of-flight momentum microscopy with synchrotron radiation (hν=35 eV). This novel angle-resolved photoemission approach yields a simultaneous acquisition of the E-vs-k spectral function in the full surface Brillouin zone and several eV energy interval. (kx,ky,EB)-maps with 3.4 Å(-1) diameter reveal a rich structure of d-like surface resonances in the spin-orbit induced partial band gap. Calculations using the one-step model in its density matrix formulation predict an anomalous state with Dirac-like signature and Rashba spin texture crossing the bandgap at Γ¯ and EB=1.2 eV. The experiment shows that the linear dispersion persists away from the Γ¯-point in an extended energy- and k∥-range. Analogously to a similar state previously found on W(110) the dispersion is linear along H¯-Γ¯-H¯ and almost zero along N¯-Γ¯-N¯. The similarity is surprising since the spin-orbit interaction is 5 times smaller in Mo. A second point with unusual topology is found midway between Γ¯ and N¯. Band symmetries are probed by linear dichroism.


Patient-reported Outcomes Associated With Preoperative Opioid Use in Revision Total Hip Arthroplasty: A Propensity Score-Matched Cohort Study.
Opioid use is a public health crisis in the United States and an area of increased focus within the arthroplasty literature. The aim of this study was to investigate the effect of preoperative opioid use on patient-reported outcome measures (PROMs) before and after revision total hip arthroplasty (THA). A total of 381 consecutive revision THA patients with both preoperative and postoperative PROMs were identified. Because of differences in baseline characteristics, 104 opioid users were matched to 208 nonusers using nearest-neighbor propensity score matching. Propensity score-matched opioid users had significantly lower preoperative PROMs than the nonuser for hip disability and osteoarthritis outcome score physical function (53.2 versus 60.1, P < 0.01) and patient-reported outcomes measurement information system (PROMIS) short form (SF) Physical (38.5 versus 43.2, P < 0.01). Postoperatively, opioid users demonstrated significantly lower scores across all PROMs: hip disability and osteoarthritis outcome score physical function (58.1 versus 70.0, P < 0.001), PROMIS SF Physical (40.3 versus 48.4, P < 0.001), and PROMIS SF Mental (43.7 versus 53.2, P < 0.001). Propensity score-matched opioid users demonstrated an increased hospital stay (P = 0.04). Revision THA patients who use opioids preoperatively have notably lower preoperative and postoperative outcome scores compared with propensity score-matched nonusers. As opioid use has the potential to be a modifiable factor, it would be important to counsel patients on the benefit of minimizing or eliminating opioid use preoperatively to optimize outcome after revision THA.


Adolescent ego development: relationship to family cohesion and adaptability.
Adolescence has been a focus of research for several decades. Recently, a portion of this body of research has addressed the relationship between adolescent development and family functioning. The intent of much of this research has been the attempt to determine how family dynamics influence the developmental processes of adolescents. Adolescents' perceptions of family cohesion and adaptability, as well as their levels of satisfaction with those perceptions, have been correlated with ego development within a sample of middle adolescents. Adaptability and cohesion were found to be significantly related to ego development, but interactions among the two variables, as well as with family structure were important.


Development and Assessment of Acyclovir Gel Plaster Containing Sponge Spicules.
Acyclovir is an acyclic purine nucleoside analog that is highly effective in inhibiting the herpes simplex virus. However, topical acyclovir has poor efficacy because of its low skin permeability. This study aimed to develop an acyclovir gel plaster containing sponge spicules (AGP-SS) to achieve synergistic improvements in skin absorption and deposition of acyclovir. The process of preparing the gel plaster was optimized by orthogonal experiments, while the composition of the formulation was optimized using the Plackett-Burman and Box-Behnken experimental designs. The selected formula was tested for physical properties, in vitro release, stability, ex vivo permeation, skin irritation, and pharmacokinetics. The optimized formulation exhibited good physical characteristics. In vitro release and ex vivo permeation studies showed that acyclovir release from AGP-SS was dominated by diffusion with significantly higher skin permeation (20.00 ± 1.07 μg/cm2) than that of the controls (p < 0.05). Dermatopharmacokinetic analyses revealed that the maximum concentration (78.74 ± 11.12 μg/g), area under the curve (1091.81 ± 29.05 μg/g/h) and relative bioavailability (197.12) of AGP-SS were higher than those of the controls. Therefore, gel plaster containing sponge spicules show potential for development as transdermal delivery systems to achieve higher skin absorption and deposition of acyclovir, especially in deep skin layers.


Clinical neuropathology of brain tumors.
Brain tumor typing is a major task in the daily practice of clinical neuropathologists. For more than 100 years, brain tumors have been classified on the basis of a histogenetic concept, with the definition of more than 120 brain tumor entities over time. In the past decades, biomedical research on brain tumors has led to the identification of clinically meaningful diagnostic, prognostic, and predictive molecular markers. Taking this progress into account, the 2016 update of the World Health Organization classification of tumors of the central nervous system has incorporated for the first time molecular markers for definition of brain tumor entities. This development has resulted in integrated diagnostics on the basis of histologic and molecular characteristics. This chapter summarizes essential features of brain tumors in the light of integrated diagnostics. To provide a comprehensive view on the individual tumor entities, we included crucial epidemiologic, clinical, and neuroradiologic aspects as well. In addition we illustrate neuroimaging and histologic characteristics of the various tumor types. In this way we aim to provide concise up-to-date insight into the nature and classification of brain tumors.


New pharmacological approaches to atrial fibrillation.
Atrial fibrillation (AF) is the most common cardiac arrhythmia facing physicians, afflicting 13% of men and 11% of women over 85 years of age. Epidemiological studies estimate that there are ≥ 11 million AF sufferers in the seven major economies and that its prevalence will increase two- to threefold over the next 50 years. Current strategies for treating AF involve either sinus rhythm (SR) maintenance or heart rate control, combined with anticoagulation therapy. Although SR control is the preferred and most effective treatment of AF, none of the SR control drugs currently available are able to maintain rhythm without significant side effects. In this article we discuss some of the recent advancements in developing new antiarrhythmic drugs for AF.


A nationwide survey of the severity, comorbidity, and mortality of hospitalized patients with asthma in Taiwan.
To clarify the epidemiology of asthma admission in a nationwide survey, we analyze the characteristics of hospitalized patients in Taiwan. Data regarding asthma-associated hospitalizations were obtained from the National Health Insurance Research Database of Taiwan from January 2001 to December 2002. Patient characteristics in terms of severity, mortality, and cost were stratified by age, gender, and presence of comorbidities. A total of 59,983 hospitalizations with International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 493.xx and asthma-related treatment were included in the current analysis. When stratified by age, the number and duration of hospitalizations were distributed in J-shape distribution, with the nadir located in the range of 8-18 years of age. The severity of asthma was found to increase with age (p < 0.001) and was more severe in men compared with women (p < 0.001). The severity of in-hospital patients was significantly greater in subjects with underlying respiratory disease compared to patients with other comorbidities, such as cardiovascular disease and infectious disease. The mortality rates of all hospitalized asthma patients and pediatric hospitalized asthma patients were 0.77% and 0.02%, respectively. The risk factor for mortality of asthma was older age and male gender in multiple regression. The severity of asthma increased after 18 years of age. Increased comorbidities in elderly patients might contribute to asthma severity. The mortality rate was low in pediatric patients and significantly increased in males and the elderly. The above findings suggest that additional effort is required in the treatment of elderly and male asthmatic patients.


High-Risk Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma Among Non-Indigenous and Indigenous Populations: A Systematic Review.
To estimate the prevalence of oral high-risk human papillomavirus (hr-HPV) infection and the proportion of hr-HPV-related oropharyngeal squamous cell carcinoma (OPSCC) among Indigenous and non-Indigenous populations. Electronic database searches of PubMed, PubMed Central, Embase, MEDLINE, Scope, and Google Scholar were conducted for articles published from January 2000 until November 2019. Studies were included with a minimum of 100 cases assessing hr-HPV infection in either population samples or oropharyngeal cancer tumor series. The objective was to conduct meta-analyses to calculate the pooled prevalence of oral hr-HPV infection by adjusting for age group or sex in primary studies, the incidence of OPSCC, and the proportion of hr-HPV-related OPSCC in Indigenous people and non-Indigenous/general populations. We identified 47 eligible studies from 157 articles for meta-analyses. The pooled prevalence of oral hr-HPV infection was 7.494% (95% CI, 5.699%-9.289%) in a general population, with a higher prevalence among men (10.651%) than women (5.176%). The pooled incidence rate was 13.395 (95% CI, 9.315-17.475) and 7.206 (95% CI, 4.961-9.450) per 100,000 person-years in Indigenous and non-Indigenous populations, respectively. The overall pooled proportion of hr-HPV-related OPSCC was 50.812% (95 CI, 41.656%-59.969%). The highest proportion was in North America (60.221%), while the lowest proportion was in the Asia-Pacific (34.246%). Our findings suggest that in the general population, the prevalence of oral hr-HPV infection is lower among females and those in younger age groups. The incidence of OPSCC was higher among Indigenous than non-Indigenous populations, with the proportion being highest in North America.


A review of the applications of data mining and machine learning for the prediction of biomedical properties of nanoparticles.
This article presents a comprehensive review of applications of data mining and machine learning for the prediction of biomedical properties of nanoparticles of medical interest. The papers reviewed here present the results of research using these techniques to predict the biological fate and properties of a variety of nanoparticles relevant to their biomedical applications. These include the influence of particle physicochemical properties on cellular uptake, cytotoxicity, molecular loading, and molecular release in addition to manufacturing properties like nanoparticle size, and polydispersity. Overall, the results are encouraging and suggest that as more systematic data from nanoparticles becomes available, machine learning and data mining would become a powerful aid in the design of nanoparticles for biomedical applications. There is however the challenge of great heterogeneity in nanoparticles, which will make these discoveries more challenging than for traditional small molecule drug design.


The cytotoxic and genotoxic potential of surface water and wastewater effluents as determined by bioluminescence, umu-assays and selected biomarkers.
Two bacterial tests employing Photobacterieum phosphoreum (Microtox bioluminescence test) and Salmonella typhimurium TA 1535 pSK1002 (umu-assay) were evaluated to estimate the cytotoxic and genotoxic potential of water samples from the selected rivers in Germany as well as the primary and secondary effluents of some sewage treatment plants. Rainbow trout (Onchorynchus mykiss) were exposed to different concentrations (20-40%) of secondary effluent in the model online aquatic monitoring plant WaBoLu-Aquatox. The toxic potential of water samples from the exposure tanks was determined in two prokaryotic test systems and the biomarkers acethylcholinesterase (AChE) activity in muscle tissue and DNA unwinding assay in liver tissue of fish. Samples from the tested rivers showed no inhibition of the bioluminescence of P. phosphoreum or growth of umu-bacteria. Only primary effluent samples from the treatment plants at the Saale River inhibited the light emission or the growth of test bacteria by more than 20%. The induction ratio of umu-bacteria was in most of the river samples less than the threshold for genotoxicity (IR < 1.5). Only some samples from the Saale River, especially at sites downstream of secondary effluents caused genotoxic responses in the umu-assay. Samples of primary effluents contained the greatest genotoxic potential up to GEUI = 6 which was not detectable in samples of secondary effluents. A concentration range 20-40% secondary effluent inhibited AChE activity in muscle tissue and significantly increased DNA fragmentation in liver tissue of rainbow trout. In contrast, no cytotoxic or genotoxic responses in the umu-assay were caused by water samples. Both bacterial methods can be successfully used to analyse the cytotoxic and genotoxic response of industrial and domestic wastewater and to estimate the effectiveness of sewage treatment units. However, because of their low sensitivity and high susceptibility, they are not reliable as a single test for the detection of cytotoxicity and genotoxicity in surface water. The application of prokaryotic tests systems with biomarkers such as AChE activity and DNA fragmentation in different tissues of test organisms seems to be a useful combination for the assessment of cytotoxic and genotoxic potential in surface water and secondary effluent.


Relation between alkaline phosphatase in gingigval crevicular fluid of implant teeth and the curing result.
To discover the relation between alkaline phosphatase (ALP) in gingival crevicular fluid (GCF) of implant teeth and the curing results. We measured the ALP level in GCF among 56 cases of implant teeth which included 2 failed cases, 5 cases with bad oral hygiene and gingivitis, and compared it with that in the normal group composed of 10 persons. The ALP levels in normal group and success implant group showed no difference. The ALP levels in normal group and success with gingivitis group showed obvious difference. The ALP levels of the 2 failed cases are the highest of all. The ALP level in GCF is an important index in evaluating the curing result of the implant teeth.


Assessment of background ozone concentrations in China and implications for using region-specific volatile organic compounds emission abatement to mitigate air pollution.
Mitigation of ambient ozone (O3) pollution is a great challenge because it depends heavily on the background O3 which has been poorly evaluated in many regions, including in China. By establishing the relationship between O3 and air temperature near the surface, the mean background O3 mixing ratios in the clean and polluted seasons were determined to be 35-40 and 50-55 ppbv in China during 2013-2019, respectively. Simulations using the chemical transport model (i.e., the Weather Research and Forecasting coupled with Chemistry model, WRF/Chem) suggested that biogenic volatile organic compounds (VOC) emissions were the primary contributor to the increase in the background O3 in the polluted season (BOP) compared to the background O3 in the clean season (BOC), ranging from 8 ppbv to 16 ppbv. More importantly, the BOP continuously increased at a rate of 0.6-8.0 ppbv yr-1 during 2013-2019, while the non-BOP stopped increasing after 2017. Consequently, an additional 2%-16% reduction in anthropogenic VOC emissions is required to reverse the current O3 back to that measured in the period from 2013 to 2017. The results of this study emphasize the importance of the relative contribution of the background O3 to the observed total O3 concentration in the design of anthropogenic precursor emission control strategies for the attainment of O3 standards.


Mepacrine pigmentation in systemic lupus erythematosus. New data from an ultrastructural, biochemical and analytical electron microscopic investigation.
A case of mepacrine pigmentation occurring in a patient with systemic lupus erythematosus has been investigated by fluorescent light microscopy, gas--liquid chromatography and analytical electron microscopy. There is strong evidence for the presence of mepacrine itself within the typical granules, which have been shown by electron microscopy to be membrane bound and intracellular. Analytical electron microscopy also showed that the granules contain large quantities of iron and smaller quantities of sulphur.


Assessing Outpatients' Knowledge, Attitude, and Practice Toward Managing Diabetes in Saudi Arabia.
When it comes to non-communicable diseases like diabetes, inadequate knowledge, attitude, and practice are often linked to poor health outcomes. This study aims to assess the patients' knowledge, attitude, and practice (KAP) of diabetes in the outpatient department of a university teaching hospital in Saudi Arabia. In this cross-sectional study, diabetes type 2 patients attending outpatient departments at a university teaching hospital, Riyadh, were assessed regarding their knowledge, attitude, and practice toward diabetes using a validated KAP scale. Descriptive and inferential analysis was done to determine the factors associated with KAP score using SPSS version 26.0 software (SPSS Inc., Chicago, IL, U.S.). Males made up 69.7% of the sample (n = 165), while 56.9% were between the ages of 41 and 75. The level of knowledge and practice had "good" in 37.6%, and 47.9%, respectively, but level of attitude had "positive" in 30.9% of patients. The association between knowledge tier and gender (p0.014) and insurance status (p0.008), respectively, was shown to be significant. However, the attitude tier was only significantly associated with gender (P = .003). The practice tier also showed a significant age association (P = .049). As regards, the mean scores for diabetes-related knowledge were higher only among insured participants (P = .03) than for other participants' sociodemographic factors. Meanwhile, the mean attitude scores were also higher among males (P = .006) than for other sociodemographic characteristics. A comparison of the participants' sociodemographic characteristics found no statistically significant variations in practice scores. Unfortunately, this study found that outpatient diabetes patients had insufficient knowledge, practice, and a negative attitude toward diabetes type 2. This imposes a great burden on healthcare workers and hence the healthcare system to improve patient scores via diabetes education programs or pharmacist-led patient counseling initiatives.


Structure and activity of an anti-epidermal growth factor receptor antibody without galactose-α-1,3-galactose residues.
Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, which has been considered as one of the key targets for cancer therapy. However, currently approved therapeutic anti-EGFR antibody may cause the hypersensitivity reaction induced by galactose-α-1,3-galactose (α-Gal) structure, which is inevitable in insect cell expression system. In this study, the Chinese hamster ovary cell line was used to produce a monoclonal antibody containing simplified glycosylation patterns (code: AB01). And cetuximab was used as a control. The two antibodies were highly similar in molecular weight, secondary structure, binding affinity and endocytosis behavior, whereas the glycotypes are extremely distinct. The flow cytometry assay suggested that AB01 induced cell cycle arrest in G1, thus inhibit cell proliferation. Moreover, both cetuximab and AB01 showed similar sensitivity for all tested cell lines in this research. In conclusion, AB01 could be a potential anti-EGFR drug candidate for cancer therapy.


[Damage analysis illustrated by two cases of broken ceramic inserts. Recommendations for avoiding breakages caused by handling].
Due to modular design today's total hip endoprostheses provide the choice of different bearing surfaces. Particle-induced osteolysis is the major reason for implant failure. Therefore, minimization of wear rates is the essential factor for the improvement of long-term function of the implants. The bearing couple ceramic-on-ceramic offers a linear wear rate of about 0.005 mm/year. That is an essential prerequisite for successful treatment of young and active patients. Ceramic femoral heads and taper fixation became standard. After some problems in the 1970s, manufacturers achieved all kinds of improvements. Surgeons learned how to handle ceramic femoral heads correctly. Nowadays ceramic heads are reliable implants. Ceramic inserts have been used since the mid-1990s. Some acetabular systems with ceramic inserts are used in clinical studies, some are approved. Complications with ceramic inserts are rare, e.g., fracturing or chipping off. Mostly those problems are due to mishandling. In this study some clinical failures are analyzed. Recommendations how to improve the handling of ceramic inserts are proposed and discussed.


Determination of isoelectric points and relative charge variants of 23 therapeutic monoclonal antibodies.
Despite the popularity of therapeutic monoclonal antibodies (mAbs), data relative to their ionic physico-chemical properties are very scarce in the literature. In this work, isoelectric points (pIs) of 23 Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved mAbs were determined by imaged capillary isoelectric focusing (icIEF), and ranged from 6.1 to 9.4. The obtained values were in good agreement with those calculated by both Vector NTI and MassLynx softwares. icIEF can therefore be considered as a reference technique for such a determination. The relative percentages of acidic and basic variants determined by cation exchange chromatography (CEX) using both salt- and pH-gradients were comprised between 15% and 30% for most mAbs and were in good agreement with each other, whereas generic icIEF seems to overestimate the amount of acidic charge variants in mAb products. To our knowledge, this is the first study focusing on the ionic properties of a wide range of FDA and EMA approved reference mAbs, using both generic chromatographic and electrophoretic methodologies. To illustrate the interest of the study for mAb developability purposes, ionic properties of a clinical mAb candidate (dalotuzumab) were also investigated.


[Questionnaire on auditory perception disorders: psychometric correlates in preschool children].
A standardized questionnaire on central auditory processing disorders ["Anamnesebogen zur Erfassung auditiver Verarbeitungs- und Wahrnehmungsstörungen (AVWS)"] was developed by the German Society of Phoniatrics and Pediatric Audiology and standardized for school-age children. This study was designed to elucidate the validity of this questionnaire in preschool children. The responses, which were given by the parents of 84 preschool children with respect to auditory discrimination and auditory memory, were correlated with the results of the Heidelberg screening test for preschool children (HVS), and their accuracy of prediction was determined. Similar to the results of other studies in school-age children, weak but significant correlations were found between the questionnaire results regarding auditory discrimination and auditory memory and the respective results of the HVS subtests. With a few exceptions, the questionnaire's accuracy of prediction was low. For preschool children, the questionnaire provides a reasonable method to get specific information about a child's history in a standardized and economic way. However, it is not valid as a screening or diagnostic tool.


Structure of bacteriophage T4 lysozyme refined at 1.7 A resolution.
The structure of the lysozyme from bacteriophage T4 has been refined at 1.7 A resolution to a crystallographic residual of 19.3%. The final model has bond lengths and bond angles that differ from "ideal" values by 0.019 A and 2.7 degrees, respectively. The crystals are grown from electron-dense phosphate solutions and the use of an appropriate solvent continuum substantially improved the agreement between the observed and calculated structure factors at low resolution. Apart from changes in the conformations of some side-chains, the refinement confirms the structure of the molecule as initially derived from a 2.4 A resolution electron density map. There are 118 well-ordered solvent molecules that are associated with the T4 lysozyme molecule in the crystal. Four of these are more-or-less buried. There is a clustering of water molecules within the active site cleft but, other than this, the solvent molecules are dispersed around the surface of the molecule and do not aggregate into ice-like structures or pentagonal or hexagonal clusters. The apparent motion of T4 lysozyme in the crystal can be interpreted in terms of significant interdomain motion corresponding to an opening and closing of the active site cleft. For the amino-terminal domain the motion can be described equally well (correlation coefficients approx. 0.87) as quasi-rigid-body motion either about a point or about an axis of rotation. The motion in the crystals of the carboxy-terminal domain is best described as rotation about an axis (correlation coefficient 0.80) although in this case the apparent motion seems to be influenced in part by crystal contacts and may be of questionable relevance to dynamics in solution.


Tissue interactions and measurement of ablation rates with ultraviolet and visible lasers in canine and human arteries.
Ablation rates measured as the depth of tissue excavation per unit time were determined in human and canine aortas subjected to radiation with ultraviolet (UV) excimer (ArF 193 nm, KrF 248 nm, XeF 351 nm) and visible lasers [continuous wave (cw) and 50-ms chopped argon ion, 478 nm-514 nm; pulsed double-frequency Nd:YAG, 532 nm]. For UV and pulsed double-frequency Nd:YAG lasers ablation rates were constant in time and depended linearly on average laser power, but for cw and chopped argon lasers ablation rates varied with irradiation time and were nonlinearly dependent on laser power. In human aortas, atherosclerosis without gross calcification had no influence on ablation rates. Charring and tissue disruption were observed with cw and chopped argon ion, whereas excimer and pulsed Nd:YAG lasers produced only minimal injury to surrounding tissue. We conclude that the determination of ablation rates is useful for the selection of laser wavelengths and power densities applicable to angioplasty and that UV and pulsed visible laser permit a better control of ablation compared to continuous wave lasers.


A zero waste vision for industrial networks in Europe.
'ZeroWIN' (Towards Zero Waste in Industrial Networks--www.zerowin.eu) is a five year project running 2009-2014, funded by the EC under the 7th Framework Programme. Project ZeroWIN envisions industrial networks that have eliminated the wasteful consumption of resources. Zero waste is a unifying concept for a range of measures aimed at eliminating waste and challenging old ways of thinking. Aiming for zero waste will mean viewing waste as a potential resource with value to be realised, rather than as a problem to be dealt with. The ZeroWIN project will investigate and demonstrate how existing approaches and tools can be improved and combined to best effect in an industrial network, and how innovative technologies can contribute to achieving the zero waste vision.


High molecular mass radioimmunoconjugates are promising for intraperitoneal α-emitter immunotherapy due to prolonged retention in the peritoneum.
Therapeutic efficacy of intraperitoneal radioimmunotherapy is dependent on the time of retention of the radioimmunoconjugates within the peritoneal cavity. Therefore, the aim of this study was to investigate intraperitoneal retention of Fab, IgG and IgM radioimmunoconjugates. Female Balb/c mice were injected with 213Bi- or 111In-labeled IgM, IgG and recombinant Fab conjugates intraperitoneally or intravenously. At different time points after injection, whole body distribution of radionuclides was imaged using a gamma camera. Distribution of radionuclides in selected organs was determined via γ-counting after sacrifice. Biological half-lives of the conjugates were calculated from whole body activities. After i.p. injection 213Bi-Fab rapidly accumulated in the kidneys indicative of glomerular filtration and reabsorption. Accumulation of 213Bi-IgG in the kidneys was significantly lower. 213Bi-IgM showed a striking accumulation in the liver 180 min after i.p. injection. 111In-IgG persisted in the circulation up to 72 h both after i.p. and i.v. injection. 111In-IgM showed a continuous accumulation in the liver. Moreover, 111In-IgM was significantly higher 24 h after i.v. injection than i.p. injection both in liver and spleen. These differences could be confirmed via scintigraphy. After injection of 111In-IgG differences in scintigraphic images between i.v. and i.p. were clearly visible only at 3 h. Biological half lives were 24 h, 45 h and 165 h for 111In-IgM, 111In-Fab and 111In-IgG, respectively. Retention of radioimmunoconjugates in the peritoneal cavity positively correlates with the molecular mass of the antibody. Therefore, IgM radioimmunoconjugates should be preferably used in radioimmunotherapy of free floating tumor cells and small tumor cell clusters in the ascites of the peritoneal cavity.


Characterization of the microbial community composition and the distribution of Fe-metabolizing bacteria in a creek contaminated by acid mine drainage.
A small watershed heavily contaminated by long-term acid mine drainage (AMD) from an upstream abandoned coal mine was selected to study the microbial community developed in such extreme system. The watershed consists of AMD-contaminated creek, adjacent contaminated soils, and a small cascade aeration unit constructed downstream, which provide an excellent contaminated site to study the microbial response in diverse extreme AMD-polluted environments. The results showed that the innate microbial communities were dominated by acidophilic bacteria, especially acidophilic Fe-metabolizing bacteria, suggesting that Fe and pH are the primary environmental factors in governing the indigenous microbial communities. The distribution of Fe-metabolizing bacteria showed distinct site-specific patterns. A pronounced shift from diverse communities in the upstream to Proteobacteria-dominated communities in the downstream was observed in the ecosystem. This location-specific trend was more apparent at genus level. In the upstream samples (sampling sites just below the coal mining adit), a number of Fe(II)-oxidizing bacteria such as Alicyclobacillus spp., Metallibacterium spp., and Acidithrix spp. were dominant, while Halomonas spp. were the major Fe(II)-oxidizing bacteria observed in downstream samples. Additionally, Acidiphilium, an Fe(III)-reducing bacterium, was enriched in the upstream samples, while Shewanella spp. were the dominant Fe(III)-reducing bacteria in downstream samples. Further investigation using linear discriminant analysis (LDA) effect size (LEfSe), principal coordinate analysis (PCoA), and unweighted pair group method with arithmetic mean (UPGMA) clustering confirmed the difference of microbial communities between upstream and downstream samples. Canonical correspondence analysis (CCA) and Spearman's rank correlation indicate that total organic carbon (TOC) content is the primary environmental parameter in structuring the indigenous microbial communities, suggesting that the microbial communities are shaped by three major environmental parameters (i.e., Fe, pH, and TOC). These findings were beneficial to a better understanding of natural attenuation of AMD.


Anaesthetic and other treatments of shell shock: World War I and beyond.
Post-traumatic stress disorder (PTSD) is an important health risk factor for military personnel deployed in modern warfare. In World War I this condition (then known as shell shock or 'neurasthenia') was such a problem that 'forward psychiatry' was begun by French doctors in 1915. Some British doctors tried general anaesthesia as a treatment (ether and chloroform), while others preferred application of electricity. Four British 'forward psychiatric units' were set up in 1917. Hospitals for shell shocked soldiers were also established in Britain, including (for officers) Craiglockhart War Hospital in Edinburgh; patients diagnosed to have more serious psychiatric conditions were transferred to the Royal Edinburgh Asylum. Towards the end of 1918 anaesthetic and electrical treatments of shell shock were gradually displaced by modified Freudian methods psychodynamic intervention. The efficacy of 'forward psychiatry' was controversial. In 1922 the War Office produced a report on shell shock with recommendations for prevention of war neurosis. However, when World War II broke out in 1939, this seemed to have been ignored. The term 'combat fatigue' was introduced as breakdown rates became alarming, and then the value of pre-selection was recognised. At the Maudsley Hospital in London in 1940 barbiturate abreaction was advocated for quick relief from severe anxiety and hysteria, using i.v. anaesthetics: Somnifaine, paraldehyde, Sodium Amytal. 'Pentothal narcosis' and 'narco-analysis' were adopted by British and American military psychiatrists. However, by 1945 medical thinking gradually settled on the same approaches that had seemed to be effective in 1918. The term PTSD was introduced in 1980. In the UK the National Institute for Health and Clinical Excellence (NICE) guidelines for management (2005) recommend trauma-focussed Cognitive Behavioural Therapy and consideration of antidepressants.


Prevalence of psychiatric disorders in a mandatory screening program for infection with human immunodeficiency virus: a pilot study.
Ninety-five randomly selected human immunodeficiency virus (HIV)-seropositive Air Force personnel were psychiatrically examined during a routine medical evaluation. Of the 95, 95% did not have acquired immunodeficiency syndrome and were largely asymptomatic; 61.1% had clinical axis I diagnoses, which included simple phobia, adjustment disorders, hypoactive sexual desire disorder, alcohol use disorder, major depression, and organic mental disorders; 30.5% had personality disorders. Significantly higher frequencies (p less than 0.05) of simple phobia and hypoactive sexual desire disorder were noted with knowledge of HIV seropositivity. Disorders that occurred more commonly than in age-matched Epidemiologic Catchment Area (ECA) participants included: simple phobia, antisocial personality disorder, alcohol abuse, and organic mental disorders. The high prevalence of major psychiatric illness in this sample supports the notion that screening for psychiatric illness, and counseling where indicated, should be integral to HIV screening programs.


Caffeine prevents antihyperalgesic effect of gabapentin in an animal model of CRPS-I: evidence for the involvement of spinal adenosine A1 receptor.
This study was designed to determine whether 3 weeks of gabapentin treatment is effective in alleviating neuropathic pain-like behavior in animal models of complex regional pain syndrome type-I and partial sciatic nerve ligation (PSNL). We investigated the contribution of adenosine subtypes to the antihyperalgesic effect of gabapentin by examining the effect of caffeine, a non-selective adenosine A1 and A2 receptor antagonist or 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), a selective adenosine A1 subtype receptor antagonist on this effect. Neuropathic pain was produced by unilateral prolonged hind paw ischemia and reperfusion (I/R) or PSNL procedures which resulted in stimulus-evoked mechanical hyperalgesia. After procedures, animals received gabapentin (10, 30, or 100 mg/kg intraperitoneal, respectively), caffeine (10 mg/kg intraperitoneal or 150 nmol intrathecally) or DPCPX (3 µg intrathecally) alone or in combination. Mice were tested for tactile mechanical hyperalgesia at 1, 2, and 3 weeks following procedures. Gabapentin produced dose-related inhibition of mechanical hyperalgesia over a 3-week period, and this effect was blocked by concomitant caffeine or DPCPX administration 1 week after injuries. The results of this study demonstrated that the mechanism through which gabapentin produces its effect may involve the activation of adenosine A1 subtype receptor.


Coding and noncoding genomic regions of Entamoeba histolytica have significantly different rates of sequence polymorphisms: implications for epidemiological studies.
To evaluate genetic variability among Entamoeba histolytica strains, we sequenced 9,077 bp from each of 14 isolates. The polymorphism rates from coding and noncoding regions were significantly different (0.07% and 0.37%, respectively), indicating that these regions are subject to different selection pressures. Additionally, single nucleotide polymorphisms (SNPs) potentially associated with specific clinical outcomes were identified.


Chromosomal abnormalities and sister-chromatid exchange in bone marrow cells of mice and Chinese hamsters after inhalation and intraperitoneal administration: I. Diepoxybutane.
Diepoxybutane (DEB), a direct-acting animal carcinogen, was found to increase the frequency of structural chromosomal abnormalities (CA) and sister-chromatid exchange (SCE) in bone marrow cells of mice and Chinese hamsters, when inhaled from an aerosol during a 2-h head-only exposure or administered as a single intraperitoneal injection. For the purpose of comparing the genotoxicity in the 2 species, both after inhalation and intraperitoneal administration, the systemic DEB dose obtained by inhalation was determined on the basis of blood concentrations and inhalation duration after the investigation of the blood kinetics. The bone marrow cells of male and female NMRI mice were found to be more sensitive than those of Chinese hamsters to the genotoxic activity of DEB.


Oral Cnm-positive Streptococcus Mutans Expressing Collagen Binding Activity is a Risk Factor for Cerebral Microbleeds and Cognitive Impairment.
Cerebral microbleeds (CMBs) are an important risk factor for stroke and dementia. We have shown that the collagen binding surface Cnm protein expressed on cnm-positive Streptococcus mutans is involved in the development of CMBs. However, whether the collagen binding activity of cnm-positive S. mutans is related to the nature of the CMBs or to cognitive impairment is unclear. Two-hundred seventy nine community residents (70.0 years) were examined for the presence or absence of cnm-positive S. mutans in the saliva by PCR and collagen binding activity, CMBs, and cognitive function were evaluated. Cnm-positive S. mutans was detected more often among subjects with CMBs (p < 0.01) than those without. The risk of CMBs was significantly higher (odds ratio = 14.3) in the group with S. mutans expressing collagen binding activity, as compared to the group without that finding. Deep CMBs were more frequent (67%) and cognitive function was lower among subjects with cnm-positive S. mutans expressing collagen binding activity. This work supports the role of oral health in stroke and dementia and proposes a molecular mechanism for the interaction.


Anomalous origin of the right coronary artery from the main pulmonary artery: incidental finding in a case of dilated cardiomyopathy.
We have described a 25-year-old man with an idiopathic dilated biventricular cardiomyopathy and end-stage glomerulonephritis due to IgA nephropathy, who was found incidentally at angiographic examination to have an anomalous right coronary artery arising from the main pulmonary artery.


Brain slices from glutaminase-deficient mice metabolize less glutamine: a cellular metabolomic study with carbon 13 NMR.
In the brain, glutaminase is considered to have a key role in the provision of glutamate, a major excitatory neurotransmitter. Brain slices obtained from wild-type (control) and glutaminase-deficient (GLS1+/-) mice were incubated without glucose and with 5 or 1 mmol/L [3-(13)C]glutamine as substrate. At the end of the incubation, substrate removal and product formation were measured by both enzymatic and carbon 13 nuclear magnetic resonance ((13)C-NMR) techniques. Slices from GLS1+/- mice consumed less [3-(13)C]glutamine and accumulated less [3-(13)C]glutamate. They also produced less (13)CO(2) but accumulated amounts of (13)C-aspartate and (13)C-gamma-aminobutyric acid (GABA) that were similar to those found with brain slices from control mice. The newly formed glutamine observed in slices from control mice remained unchanged in slices from GLS1+/- mice. As expected, flux through glutaminase in slices from GLS1+/- mice was found diminished. Fluxes through all enzymes of the tricarboxylic acid cycle were also reduced in brain slices from GLS1+/- mice except through malate dehydrogenase with 5 mmol/L [3-(13)C]glutamine. The latter diminutions are consistent with the decreases in the production of (13)CO(2) also observed in the slices from these mice. It is concluded that the genetic approach used in this study confirms the key role of glutaminase for the provision of glutamate.


Summary of inaugural meeting of the Skin Care in Organ Recipients Group, UK, held at the Royal Society of Medicine, 7 October 2004.
This summarizes a meeting held in London at the Royal Society of Medicine, which was brought together by Prof. Fenella Wojnarowska, Professor of Dermatology at Churchill Hospital, Oxford and cofounder of Skin Care in Organ Recipients, UK (SCOR.UK).


Double dislocation of the interphalangeal joints in the finger. Case report and review of publications.
A 66-year-old woman presented with a painful swollen finger and was shown radiographically to have dorsal dislocation of both interphalangeal joints, which responded to immobilisation and physiotherapy. Unlike single dislocations of finger joints double dislocations are rare, only 52 cases have been reported between 1874 and 1992 to our knowledge.


Treatment of irreducible atlantoaxial dislocation by bony deformity osteotomy, remodeling, releasing, and plate fixating through transoral approach.
Investigate a novel method for treating irreducible atlantoaxial dislocation (IAAD) or with basilar invagination (BI) by bony deformity osteotomy, remodeling, releasing, and plate fixating through transoral approach. From March 2015 to December 2019, 213 consecutive patients diagnosed as IAAD/BI were treated with transoral bony deformity remodeling and releasing combined with plate fixation. The main clinical symptoms include neck pain, headache, numbness of the limbs, weakness, unstable walking, inflexible hand-held objects, and sphincter dysfunction. The bony factors that impact reduction were divided into as follows: type A1 (sloping of upper facet joint in C2), type A2 (osteophyte in lateral mass joints between C1 and C2), type A3 (ball-and-socket deformity of lateral mass joint), type A4 (vertical interlocking between lateral mass joints of C1-C2), type A5 (regional bone fusion in lateral mass joints), type B1 (bony factor hindering reduction between the atlas-dens gap), type B2 (uncinate odontoid deformity), and type B3 (hypertrophic odontoid deformity). All of them were treated with bony deformity osteotomy, remodeling, and releasing techs. The operation time was 144 [Formula: see text] 25 min with blood loss of 102 [Formula: see text] 35 ml. The average pre-operative ADI improved from 7.5 [Formula: see text] 3.2 mm pre-surgery to 2.5 [Formula: see text] 1.5 mm post-surgery (p < 0.05). The average VDI improved from 12.3 [Formula: see text] 4.8 mm pre-surgery to 3.3 [Formula: see text] 2.1 mm post-surgery (p < 0.05). The average pre-operative CMA improved from 115 [Formula: see text] 25° pre-surgery to 158 [Formula: see text] 21° post-surgery (p < 0.05); the pre-operative CAA changed from 101 [Formula: see text] 28° pre-surgery to 141 [Formula: see text] 10° post-surgery. After the operation, the clinic symptoms improved, and the JOA score improved from 9.3 [Formula: see text] 2.8 pre-operatively to 13.8 [Formula: see text] 2.5 in the sixth months of follow-up. In addition to soft tissue factors, bony obstruction was another important factor impeding atlantoaxial reduction. Transoral bony deformity osteotomy, remodeling, releasing combined with plate fixating was effective in treating IAAD/BI with bony obstruction factors.


Aging, the brain and human prion disease.
Human prion diseases (PrD) preferentially manifest in the elderly. Their neuropathology may coexist with tau immunoreactive neuropil threads, neurofibrillary tangles, and beta-amyloid senile plaques, most likely representing an age-related change rather than a pathogenic link with Alzheimer's disease. Cerebrovascular disease with brain infarction, another malady preferring the elderly, is useful to prove the origin of PrD-associated prion protein deposition exclusively from neurons.


The short-term effect and safety of duloxetine in osteoarthritis: A systematic review and meta-analysis.
Previous clinical trials indicated that duloxetine may be effective in the treatment of osteoarthritis (OA) pain. This meta-analysis is conducted to evaluate short term analgesic effect and safety of duloxetine in the treatment of OA. Electronic databases were searched in February 2019, including PUBMED, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science. All eligible studies should be randomized controlled trials (RCTs) comparing duloxetine treatment group to placebo about OA pain relief and safety outcomes. Five RCTs with 2059 patients were involved in this systematic review and meta-analysis. Compared to placebo, duloxetine treatment showed significant better result, with higher reduction pain intensity (mean difference [MD] = -0.77, P < .00001), higher rates of both 30% and 50% reduction in pain severity (risk ratio [RR] = 1.42, P < .00001; RR = 1.62, P < .00001), lower mean Patient Global Improvement-Inventory (PGI-I) score (MD = -0.48, P < .00001). The results of the Western Ontario and McMaster Universities (WOMAC) score change from baseline to endpoint also favored duloxetine treatment group in all four categories, including total (MD = -5.43, P < .00001), pain (MD = -1.63, P = .001), physical function (MD = -4.22, P < .00001), and stiffness score (MD = -0.58, P < .00001). There were higher rates of treatment-emergent adverse events (TEAEs) (RR = 1.32, P < .00001) and discontinuation (RR = 1.88, P < .00001) in duloxetine group. However, there was no significant difference in the incidence of severe adverse events (SAEs) between these 2 groups (RR = 0.84, P = .68). Duloxetine was an effective and safe choice to improve pain and functional outcome in OA patients. However, further studies are still needed to find out the optimal dosage for OA and examine its long-term efficacy and safety. CRD42019128862.


Usefulness of high-dose anticoagulants in preventing left ventricular thrombus in acute myocardial infarction.
Fifty-three patients with a suspected first anterior wall acute myocardial infarction (AMI) were randomized to intervention with intravenous heparin followed by oral warfarin (26 patients) or matching placebo (27 patients). The regimen was started within 12 hours after the onset of AMI. Anticoagulation was maintained at a therapeutic level (for heparin, activated partial thromboplastin time 70 to 140 seconds; for warfarin, thrombotest 5 to 10%) for 10 days, and no bleeding episodes occurred. The baseline characteristics of the 2 study groups were well matched. In 7 patients in the placebo group and in none in the anticoagulant group, left ventricular thrombus developed during the study, as detected by serial 2-dimensional echocardiography. Early intervention with high-dose anticoagulant drugs may prevent the development of left ventricular thrombus in anterior wall AMI.


Paradiscogaster flindersi and P. oxleyi n. sp. (Digenea: Faustulidae): overlapping host and geographical distributions in corallivore chaetodontid fishes in the tropical Indo-west Pacific.
A total of 2,868 individuals of 47 species of chaetodontids were examined for faustulids at seven major localities in the Tropical Indo-West Pacific (TIWP). Combined morphological and molecular analyses allowed us to describe Paradiscogaster oxleyi n. sp. from three localities in the TIWP and in three host species, Chaetodon lunulatus Quoy & Gaimard (type-host), C. ornatissimus Cuvier and C. meyeri Bloch & Schneider. Molecular analysis of the ITS2 region of rDNA from two host species and three localities supports the morphology-based conclusion that P. oxleyi n. sp. is the same species at the three localities. Paradiscogaster flindersi Bray, Cribb & Barker, 1994 is reported from three new localities in the TIWP and is now known from 13 chaetodontid species. Sequences from samples consistent with P. flindersi differed from those from P. oxleyi n. sp. in 11-12 base pairs. The host ranges of the two species overlap broadly. Neither species was found in French Polynesia but both were found at Swain Reefs on the Great Barrier Reef. Only one of the two species was found at each of the five other sites. Both species occur almost exclusively in specialist corallivores allowing the inference that the metacercariae occur in corals. Finally, a key to the species of Paradiscogaster is provided.


The Drosophila gene CG9918 codes for a pyrokinin-1 receptor.
The database from the Drosophila Genome Project contains a gene, CG9918, annotated to code for a G protein-coupled receptor. We cloned the cDNA of this gene and functionally expressed it in Chinese hamster ovary cells. We tested a library of about 25 Drosophila and other insect neuropeptides, and seven insect biogenic amines on the expressed receptor and found that it was activated by low concentrations of the Drosophila neuropeptide, pyrokinin-1 (TGPSASSGLWFGPRLamide; EC50, 5 x 10(-8) M). The receptor was also activated by other Drosophila neuropeptides, terminating with the sequence PRLamide (Hug-gamma, ecdysis-triggering-hormone-1, pyrokinin-2), but in these cases about six to eight times higher concentrations were needed. The receptor was not activated by Drosophila neuropeptides, containing a C-terminal PRIamide sequence (such as ecdysis-triggering-hormone-2), or PRVamide (such as capa-1 and -2), or other neuropeptides and biogenic amines not related to the pyrokinins. This paper is the first conclusive report that CG9918 is a Drosophila pyrokinin-1 receptor gene.


An enzyme-linked immunoassay for lipoprotein lipase.
Polyclonal antibodies against bovine milk lipoprotein lipase (LPL) were used to generate an enzyme-linked immunosorbent assay (ELISA) for rat LPL. The antibodies to LPL were affinity purified on bovine LPL columns and were shown to be specific for LPL by immunoprecipitation and enzyme inhibition. The solid-phase ELISA was sensitive from 1.0 to 20 ng/ml of LPL and paralleled enzyme activity. Denatured rat LPL showed the same LPL mass as undenatured samples, allowing LPL mass to be quantitated effectively in a variety of rat tissue extracts.


Triple negative breast cancer: microRNA expression profile and novel discriminators according to BRCA1 status.
Triple-negative breast cancer (TNBC) represents 15% of breast carcinomas. More than 80% of women with a breast cancer associated with a breast cancer type 1 (BRCA1) mutation develop a TNBC. microRNAs (miRNAs) play critical roles in diverse biological processes and are aberrantly expressed in several human neoplasms including breast cancer, where they function as actors of tumor onset, behavior, and progression. However, an extensive microRNA profile has not yet been determined for TNBC. Taqman low-density arrays (TLDAs) were used to screen the expression level of 667 miRNAs in TNBC versus normal breast tissues. Our TLDA results revealed 20 differentially expressed miRNAs among which 14 (10 upregulated and four downregulated) were confirmed by an individual quantitative real-time polymerase chain reaction. Interestingly, a novel link between BRCA1 status and miRNA expression level was identified through miR-96 and miR-10b that were very important discriminators between TNBC with mutated BRCA1 and TNBC with wild type BRCA1. This study promises discoveries of new pathological pathways at work in this dreadful disease and clearly warrants validation in large prospective studies with the aim of identifying novel biomarkers for diagnosis and targets for clinical interventions.


Evolution of the quantum Hall bulk spectrum into chiral edge states.
One of the most intriguing and fundamental properties of topological systems is the correspondence between the conducting edge states and the gapped bulk spectrum. Here, we use a GaAs cleaved edge quantum wire to perform momentum-resolved spectroscopy of the quantum Hall edge states in a tunnel-coupled 2D electron gas. This reveals the momentum and position of the edge states with unprecedented precision and shows the evolution from very low magnetic fields all the way to high fields where depopulation occurs. We present consistent analytical and numerical models, inferring the edge states from the well-known bulk spectrum, finding excellent agreement with the experiment-thus providing direct evidence for the bulk to edge correspondence. In addition, we observe various features beyond the single-particle picture, such as Fermi level pinning, exchange-enhanced spin splitting and signatures of edge-state reconstruction.


Sucrose octaacetate tasting in a heterogeneous population of CFW mice.
Three experiments investigated the genetic underpinnings of the sucrose octaacetate (SOA) avoidance-indifference dimorphism that exists among outbred CFW mice. In the first experiment, results from 687 subjects across three generations of segregation were consistent with predictions from a single-autosomal, two-allele model, with dominance for the avoidance (Taster) phenotype. In the second experiment, heterogeneous CFW Tasters and Nontasters were mated with SWR/J (Taster) and C57BL/6J (Nontaster) inbred mice. The SWR and CFW mice are both derived from Swiss mice, and the results were consistent with the possibility that the Taster animals share an allele which is identical by descent. The second and third experiments also investigated sensitivity to SOA across an extended range of concentrations. Nontaster CFWs avoided SOA at the near-saturation 10(-3) M concentration but did not avoid any weaker concentrations. Taster CFWs avoided all concentrations down to approximately 10(-6) M SOA.


Long-term ursodeoxycholate improves circulating redox changes in primary biliary cirrhotic patients.
Cholestasis is associated with systemic and hepatic oxidative and nitrosative stress; in this scenario, the conjugated hydrophilic bile salt ursodeoxycholate (UDCA) might play a protective role. Circulating oxidative and nitrosative stress markers were assessed in patients with primary biliary cirrhosis (PBC) before and during UDCA (15-20mg/kg/day) therapy. In patients with stage I-II PBC, UDCA improved ALT and alkaline phosphatase levels and near normalized serum thioredoxin (1.97 ± 0.37 vs 2.41 ± 0.39 nmol/L), nitrotyrosine (15 ± 4 vs 22 ± 7 nmol/L), nitrosothiols (144 ± 28 vs 205 ± 84 nmol/L) and K-18 levels (162 ± 21 vs 228 ± 33 U/L). Conversely, less marked changes were noted in patients with stages III-IV who showed lower thioredoxin (1.01 ± 0.31 nmol/L), higher nitrosothiols (605 ± 64 nmol/L), nitrotyrosine (62 ± 13 nmol/L) and K-18 levels (521 ± 57 U/L). Overall, thioredoxin was inversely related with nitrotyrosine (r=-0.838, P<0.001) and K-18 (r=-0.838, P<0.001) levels. Nitrosothiols and K-18 were linearly and significantly related with nitrotyrosine (r=0.862, P<0.001; r=0.894, P<0.001, respectively). Oxidative and nitrosative changes in patients with PBC are effectively counteracted by UDCA. The protective effect of UDCA, however, are limited to early disease stages and progressively diminishes with ongoing cholestasis.


The variant Arg110Gln of human IL-13 is associated with an immunologically hyper-reactive form of onchocerciasis (sowda).
Onchocerca volvulus infection usually results in a predominantly immunopermissive reaction called generalized onchocerciasis and characterized by high microfilarial burden and immunological tolerance to the worms. Rarely, however, infection leads to the sowda form of the disease displaying low microfilarial numbers, i.e. microfilarial control, and a T helper 2 (Th2)-type immune response including high immunoglobulin (Ig)E levels, and interleukin (IL)-13 being one of the key cytokines. The aim of this study was to investigate a possible association of a variant of the IL-13 gene, which confers an IgE-independent risk for asthma and atopy, with the immunologically hyper-reactive sowda form of onchocerciasis. Genotyping for the IL-13 variant Arg110Gln revealed a highly significant association of Arg110Gln with the sowda form (relative risk of 2.98, n = 19 patients), whereas the frequency of the variant was significantly lower in patients with generalized onchocerciasis (n = 92 individuals). Sowda patients had higher IgE levels than those with generalized onchocerciasis. Logistic regression analysis revealed that IgE and IL-13 are independent variables, each increasing the relative risk for sowda. Arg110Gln has been suggested to lead to enhanced IL-13 signaling and thus may be involved in shifting the immune reaction towards the hyper-reactivity characteristic for the sowda form, thereby promoting defense mechanisms.


Recent advances in obstetric anesthesia.
The low-dose technique of combined spinal/epidural analgesia is to be welcomed in obstetrics. Its merits include rapid onset of analgesia, with the flexibility of an epidural technique, and high maternal satisfaction. It is a safe and effective technique. Pulse oximetry should be employed when using intrathecal opioids. Commercially available combined-needle devices may make this technique more attractive to users. The role of spinal anesthesia for emergency cesarean section in severe preeclampsia has been reevaluated recently. We consider it a feasible option for those severely preeclamptic women requiring urgent cesarean section who do not have an epidural catheter in place. The choice of anesthetic technique for this patient population should be made on clinical judgment and not on anticipated hemodynamic changes. Spinal anaesthesia for cesarean section is associated with hypotension; however, certain interventions may reduce the incidence and severity of the hypotension. An increase in cardiac output appears to be key in attenuating the hypotensive response to spinal anesthesia. Colloids have exhibited most success in this regard. At our institution, we do not delay spinal anesthesia for urgent cesarean section in order to administer a predetermined volume of fluid; in such cases, we simultaneously administer a fluid preload and spinal anesthesia. Recent studies regarding the use of cell savers for blood conservation in obstetrics are based on small numbers of patients. These studies show great promise, particularly with the modern emphasis on avoiding blood transfusion, which can be massive in this usually young patient population.


Clinicopathological profile and management of thyroid carcinoma: a Sub-Saharan country experience.
In Sudan, there is limited knowledge on the epidemiology, clinical characteristics and pathological patterns of thyroid cancer. To address this shortcoming, we studied the clinical, pathological and treatment patterns of thyroid cancer at the National Cancer Institute ‒ University of Gezira (NCI-UG), Sudan. We performed a retrospective health facility-based study of patients with thyroid cancer who were treated at NCI-UG from January 2009 to December 2017. A total of 139 patients with thyroid cancer were identified during the study period. Tumors were more common among women (69%). Goiter was the main presenting symptom (85%). The most common type of thyroid cancer was follicular carcinoma (41%), followed by papillary carcinoma (24%), then anaplastic carcinoma (20%). The mean age of the women was 56.3 years (SD ± 14.7), compared to 52.5 years (SD ± 16.6) for the men. The frequencies of stage I, II, III, and IV were 17%, 22%, 16%, and 45%, respectively. Different types of thyroidectomies were performed in 79% of the cases, lobectomy in 4%, and no surgery in 17%. Only 28% of the cases received radioactive iodine. Palliative chemotherapy and radiotherapy were prescribed to 17% and 37% of the cases, respectively. Thyroid cancer is more prevalent among women and most patients present at later stages. The dominance of follicular type suggests that the majority of this population is iodine-deficient.


Network Pharmacology Analysis, Molecular Docking, and In Vitro Verification Reveal the Action Mechanism of Prunella vulgaris L. in Treating Breast Cancer.
Prunella vulgaris L. is effective in the treatment of breast cancer (BRCA); however, the underlying mechanism is still unclear. The aim of this study was to elucidate the mechanism of treatment of BRCA by P. vulgaris using network pharmacology and molecular docking technology, and to verify the experimental results using human BRCA MDA-MB-231 cells. Active components and action targets of P. vulgaris were determined using the TCMSP™, SwissTarget Prediction™, and TargetNet™ databases. GeneCards™ and OMIM™ provided BRCA targets. After obtaining common targets, a protein-protein interaction (PPI) network was constructed using the STRING™ database, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted using the Xiantao™ academic database. Cytoscape™ was used to construct "single drug-disease-component-target" and "single drug-disease-component-target-pathway" networks. The Human Protein Atlas™ was used to determine protein expression levels in BRCA cell lines. AutoDock tools™ were used to carry out molecular docking for the first 10 targets of quercetin and the PPI network. Finally, the abovementioned results were verified using cell experiments. We obtained 11 active components, 198 targets, and 179 common targets, including DUOX2, MET, TOP2A, and ERBB3. The results of KEGG pathway analysis screened 188 related signaling pathways and indicated the potential key role of PI3K-Akt and MAPK signaling pathways in the antibreast cancer process of P. vulgaris. The results of molecular docking showed that the first 10 targets of quercetin interacted well with the protein network. Cell experiments showed that quercetin effectively inhibited the proliferation of MDA-MB-231 cells by regulating apoptosis and cell cycle, which may be partly related to the MAPK signaling pathway. Synergistic effects of multiple components, targets, and pathways on the anti-BRCA activity of P. vulgaris could provide a theoretical basis for further study on its complex anti-BRCA mechanism.


Amorphous nickel hydroxide shell tailors local chemical environment on platinum surface for alkaline hydrogen evolution reaction.
In analogy to natural enzymes, an elaborated design of catalytic systems with a specifically tailored local chemical environment could substantially improve reaction kinetics, effectively combat catalyst poisoning effect and boost catalyst lifetime under unfavourable reaction conditions. Here we report a unique design of 'Ni(OH)2-clothed Pt-tetrapods' with an amorphous Ni(OH)2 shell as a water dissociation catalyst and a proton conductive encapsulation layer to isolate the Pt core from bulk alkaline electrolyte while ensuring efficient proton supply to the active Pt sites. This design creates a favourable local chemical environment to result in acidic-like hydrogen evolution reaction kinetics with a lowest Tafel slope of 27 mV per decade and a record-high specific activity and mass activity in alkaline electrolyte. The proton conductive Ni(OH)2 shell can also effectively reject impurity ions and retard the Oswald ripening, endowing a high tolerance to solution impurities and exceptional long-term durability that is difficult to achieve in the naked Pt catalysts. The markedly improved hydrogen evolution reaction activity and durability in an alkaline medium promise an attractive catalyst material for alkaline water electrolysers and renewable chemical fuel generation.