[Synchronization of proliferating cells in the liver, gastric glands and duodenum].
Multiple injections (5-6 times) of hydroxyurea to hepatectomized rats lead to synchronization of 78% of proliferating cells in the regenerating liver. The amount of DNA-synthesizing cells of the foveolar epithelium of the pyloric glands of the gastric mucosa increases 2.7-fold, the proliferation in slowly renewing Brunner glands of the duodenum is dramatically activated.


Environmental heterogeneity can tip the population genetics of range expansions.
The population genetics of most range expansions is thought to be shaped by the competition between Darwinian selection and random genetic drift at the range margins. Here, we show that the evolutionary dynamics during range expansions is highly sensitive to additional fluctuations induced by environmental heterogeneities. Tracking mutant clones with a tunable fitness effect in bacterial colonies grown on randomly patterned surfaces we found that environmental heterogeneity can dramatically reduce the efficacy of selection. Time-lapse microscopy and computer simulations suggest that this effect arises generically from a local 'pinning' of the expansion front, whereby stretches of the front are slowed down on a length scale that depends on the structure of the environmental heterogeneity. This pinning focuses the range expansion into a small number of 'lucky' individuals with access to expansion paths, altering the neutral evolutionary dynamics and increasing the importance of chance relative to selection.


Application of biological study for met expression to cancer therapy.
Metastasization is an undesirable process in cancer development and may represent the most critical factor in deciding patient prognosis. Organ specificity of the metastasis process suggests the importance of the paracrine factors: one of the most potent paracrine regulators of tumor cell migration is hepatocyte growth factor/scatter factor (HGF/SF). Because the liver-specific growth factor is HGF, its receptor c-Met expression might play a critical role in metastasization to the liver. Activation of HGF/c-Met signaling has been shown to promote cancer cell invasiveness and trigger metastasis though direct involvement of the angiogenic pathway. Given the importance of aberrant HGF/c-Met signaling, several different therapeutic strategies aimed at inhibiting the pathway have been developed and are currently being evaluated in clinical trials. Among these agents, NK4 and AM102 were introduced as HGF inhibitors, and PHA-665752 and Su11274 as c-Met inhibitors and are under study in clinical trials. Further, clinical experience-based study to apply the accumulation of biological knowledge concerning HGF/c-Met to the surgical field is presented.


A Geographic Assessment of the Global Scope for Rewilding with Wild-Living Horses (Equus ferus).
Megafaunas worldwide have been decimated during the late Quaternary. Many extirpated species were keystone species, and their loss likely has had large effects on ecosystems. Therefore, it is increasingly considered how megafaunas can be restored. The horse (Equus ferus) is highly relevant in this context as it was once extremely widespread and, despite severe range contraction, survives in the form of domestic, feral, and originally wild horses. Further, it is a functionally important species, notably due to its ability to graze coarse, abrasive grasses. Here, we used species distribution modelling to link locations of wild-living E. ferus populations to climate to estimate climatically suitable areas for wild-living E. ferus. These models were combined with habitat information and past and present distributions of equid species to identify areas suitable for rewilding with E. ferus. Mean temperature in the coldest quarter, precipitation in the coldest quarter, and precipitation in the driest quarter emerged as the best climatic predictors. The distribution models estimated the climate to be suitable in large parts of the Americas, Eurasia, Africa, and Australia and, combined with habitat mapping, revealed large areas to be suitable for rewilding with horses within its former range, including up to 1.5 million ha within five major rewilding areas in Europe. The widespread occurrence of suitable climates and habitats within E. ferus' former range together with its important functions cause it to be a key candidate for rewilding in large parts of the world. Successful re-establishment of wild-living horse populations will require handling the complexity of human-horse relations, for example, potential conflicts with ranchers and other agriculturalists or with other conservation aims, perception as a non-native invasive species in some regions, and coverage by legislation for domestic animals.


Effects of acute exercise, exercise training, and diabetes on the expression of lymphangiogenic growth factors and lymphatic vessels in skeletal muscle.
Blood and lymphatic vessels together form the circulatory system, allowing the passage of fluids and molecules within the body. Recently we showed that lymphatic capillaries are also found in the capillary bed of skeletal muscle. Exercise is known to induce angiogenesis in skeletal muscle, but it is not known whether exercise has effects on lymphangiogenesis or lymphangiogenic growth factors. We studied lymphatic vessel density and expression of the main lymphangiogenic growth factors VEGF-C and VEGF-D and their receptor VEGFR-3 in response to acute running exercise and endurance exercise training in the skeletal muscle of healthy and diabetic mice. VEGF-C mRNA expression increased after the acute exercise bout (P < 0.05) in healthy muscles, but there was no change in diabetic muscles. VEGF-C levels were not changed either in healthy or in diabetic muscle after the exercise training. Neither acute exercise nor exercise training had an effect on the mRNA expression of VEGF-D or VEGFR-3 in healthy or diabetic muscles. Lymphatic vessel density was similar in sedentary and trained mice and was >10-fold smaller than blood capillary density. Diabetes increased the mRNA expression of VEGF-D (P < 0.01). Increased immunohistochemical staining of VEGF-D was found in degenerative muscle fibers in the diabetic mice. In conclusion, the results suggest that acute exercise or exercise training does not significantly affect lymphangiogenesis in skeletal muscle. Diabetes increased the expression of VEGF-D in skeletal muscle, and this increase may be related to muscle fiber damage.


Influence of noninvasive positive pressure ventilation on inspiratory muscles.
Intermittent positive pressure ventilation reduces inspiratory muscle electromyographic activity among patients with restrictive ventilatory failure. It has therefore been suggested that the reduction of energy expenditure at night could result in improved inspiratory muscle function during the day. Reported successes with nocturnal ventilation have not included measurements of inspiratory muscle endurance. We therefore electively ventilated six (five female, one male) patients (mean +/- SD) aged 36 +/- 13 years in whom respiratory failure (room air PaCO2, 60 +/- 13 mm Hg; PaO2, 44 +/- 11 mm Hg; SaO2, 75 +/- 12 percent) was consequent on restrictive ventilatory disease (vital capacity, 25 +/- 7 percent predicted; FEV1/FVC, 81 +/- 12 percent; total lung capacity, 40 +/- 5 percent predicted; MIPRV -42 +/- 10 cm H2O; MEP, 81 +/- 28 cm H2O). Positive pressure ventilation was administered with a customized closely fitting nasal mask attached to a volume-cycled pressure-limited ventilator. Full respiratory polysomnographic measurements as well as arterial blood gases, pulmonary function, distance walked in six minutes, and inspiratory muscle endurance were measured at baseline and after 3 and 14 months of ventilation. Ventilation improved saturation (baseline on O2; SWS 87 +/- 10, REM 79 +/- 14, ventilator on R/A; SWS 90 +/- 6, REM 89 +/- 5 percent) and transcutaneous Pco2 (baseline on O2; SWS 85 +/- 26, REM 94 +/- 39, ventilator on R/A; SWS 53 +/- 9, REM 58 +/- 9 mm Hg). During ventilation, the quantity and distribution of sleep was similar to that observed prior to ventilation. Daytime gas exchange improved as did the six-minute walking test (initial test = 429 +/- 120 m, three months after ventilation = 567 +/- 121 m), both of these improvements being sustained at 14 months. Inspiratory muscle endurance measured using a pressure threshold load (mean mouth pressure = 45 percent MIPRV) improved from 7.1 +/- 3.4 minutes at baseline to 14.8 +/- 7.6 minutes at 3 months, an improvement sustained at 14 months. There was no change in measured lung volumes or respiratory muscle strength. We conclude that the improvement in nocturnal gas exchange, daytime functioning, and arterial blood gases resulting from nocturnal positive pressure ventilation is associated with an increase in inspiratory muscle endurance sustained at 14 months.


CLN1 and its repression by Xbp1 are important for efficient sporulation in budding yeast.
Xbp1, a transcriptional repressor of Saccharomyces cerevisiae with homology to Swi4 and Mbp1, is induced by stress and starvation during the mitotic cycle. It is also induced late in the meiotic cycle. Using RNA differential display, we find that genes encoding three cyclins (CLN1, CLN3, and CLB2), CYS3, and SMF2 are downregulated when Xbp1 is overexpressed and that Xbp1 can bind to sequences in their promoters. During meiosis, XBP1 is highly induced and its mRNA appears at the same time as DIT1 mRNA, but its expression remains high for up to 24 h. As such, it represents a new class of meiosis-specific genes. Xbp1-deficient cells are capable of forming viable gametes, although ascus formation is delayed by several hours. Furthermore, Xbp1 target genes are normally repressed late in meiosis, and loss of XBP1 results in their derepression. Interestingly, we find that a deletion of CLN1 also reduces the efficiency of sporulation and delays the meiotic program but that sporulation in a Deltacln1 Deltaxbp1 strain is not further delayed. Thus, CLN1 may be Xbp1's primary target in meiotic cells. We hypothesize that CLN1 plays a role early in the meiotic program but must be repressed, by Xbp1, at later stages to promote efficient sporulation.


Beaked whales and state-dependent decision-making: how does body condition affect the trade-off between foraging and predator avoidance?
Body condition is central to how animals balance foraging with predator avoidance-a trade-off that fundamentally affects animal fitness. Animals in poor condition may accept greater predation risk to satisfy current foraging 'needs', while those in good condition may be more risk averse to protect future 'assets'. These state-dependent behavioural predictions can help interpret responses to human activities, but are little explored in marine animals. This study investigates the influence of body condition on how beaked whales trade-off foraging and predator avoidance. Body density (indicating lipid-energy stores) was estimated for 15 foraging northern bottlenose whales tagged near Jan Mayen, Norway. Composite indices of foraging (diving and echolocation clicks) and anti-predation (long ascents, non-foraging dives and silent periods reducing predator eavesdropping) were negatively related. Experimental sonar exposures led to decreased foraging and increased risk aversion, confirming a foraging/perceived safety trade-off. However, lower lipid stores were not related to a decrease in predator avoidance versus foraging, i.e. worse condition animals did not prioritize foraging. Individual differences (personalities) or reproductive context could offer alternative explanations for the observed state-behaviour relationships. This study provides evidence of foraging/predator-avoidance trade-offs in a marine top predator and demonstrates that animals in worse condition might not always take more risks.


Intracellular heme coordinately modulates globin chain synthesis, transferrin receptor number, and ferritin content in differentiating Friend erythroleukemia cells.
The effect of succinylacetone (SA), a highly specific inhibitor of ALA-dehydratase and heme synthesis, on hemoglobin (Hb) production, transferrin receptor (TfR), and ferritin expression was analyzed in differentiating Friend leukemia cells (FLC). This compound exerted a pronounced inhibitory effect not only on heme and Hb synthesis, but also on all the remaining above-mentioned parameters. In particular, SA induced: (1) a reduction of the level of alpha-globin mRNA; (2) a decreased number of exposed TfR molecules, without modification of their affinity for the ligand; (3) a reduced level of TfR RNA, without significant change of TfR gene transcription rate; and (4) a lower ferritin content. The addition of exogenous hemin to differentiating FLC exerted opposite effects, and particularly induced an increase of both the number of TfRs and ferritin content. These findings suggest that in erythroid cells optimal heme synthesis is required to coordinately sustain globin chains synthesis and TfR/ferritin production; thus, the intracellular heme level may represent a key regulatory factor in the Hb synthesis pathway.


[Assessment of fatty acids content in margarines available on Polish market in the years 1996-2000].
Fatty acids content in margarines from Polish market in the years 1996-2000 was investigated. 56 samples of low fat, 40 normal fat and 78 stick were examined derived from different producers. Considerable differences in amount of particular groups of fatty acids were observed during investigation period i.e. saturated, monounsaturated, polyunsaturated and trans isomers in the same type of margarines. The low fat soft type of margarines showed the most desirable from nutritional point of view fatty acids content--such as low level of saturated acids as well as absence of trans isomers.


Characterization of the antihypertensive activity of SK&F 86466, a selective alpha-2 antagonist, in the rat.
The effects of SK&F 86466 (6-chloro-N-methyl-2,3,4,5-tetrahydro-1-H-3-benzazepine), a potent and selective alpha-2 adrenoceptor antagonist, on blood pressure and heart rate were examined in normotensive and hypertensive rats. SK&F 86466 was approximately 10-fold more potent in lowering blood pressure in deoxycorticosterone acetate (DOCA)-salt hypertensive than in normotensive rats, when administered by i.v. infusion. A dose-related antihypertensive effect was observed in conscious DOCA-salt rats after p.o. doses of SK&F 86466 (2-15 mg/kg), with a duration of over 6 hr after the highest dose. Oral administration of SK&F 86466 was associated with tachycardia, which reached maximal levels within 15 min after dosing, followed by an interval of bradycardia. The duration of antihypertensive activity observed with SK&F 86466 was at least 6 hr, compared to less than 90 min with phentolamine, at doses which produced equal peak reductions in blood pressure in conscious DOCA-salt rats. In contrast, heart rate was still significantly elevated by phentolamine 90 min postdosing, whereas the transient tachycardia induced by SK&F 86466 had dissipated within 30 min. SK&F 86466 was also an effective antihypertensive agent in the spontaneously hypertensive rat, although lower antihypertensive efficacy was observed than in the DOCA-salt model. SK&F 86466 was even less effective in the two-kidney one-clip Goldblatt model in which hypertension is maintained by the renin-angiotensin system rather than by the sympathetic nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of Vanadium on the Structural and Optical Properties of Borate Glasses Containing Er3+ and Silver Nanoparticles.
The erbium-vanadium co-doped borate glasses, embedded with silver nanoparticles (Ag NPs), were prepared to improve their optical properties for potential optical fiber and glass laser application. The borate glasses with composition (59.5-x) B2O3-20Na2O-20CaO-xV2O5-Er2O3-0.5AgCl (x = 0-2.5 mol%) were successfully prepared by conventional melt-quenching method. The structural properties of glass samples were investigated by XRD, TEM and by Fourier transform infrared (FTIR) spectroscopy while optical properties were carried out by UV-Vis spectroscopy by measuring optical absorption and the emission properties were investigated by photoluminescence spectroscopy. The XRD patterns confirmed the amorphous nature of the prepared glass samples whilst the FTIR confirmed the presence of VO4, VO5, BO3 and BO4 vibrations. UV-Vis-NIR absorption spectra reveal eight bands which were located at 450, 490, 519, 540, 660, 780, 980, and 1550 nm corresponding to transition of 4F5/2, 4F7/2, 2H11/2, 4S3/2, 4F9/2, 4I9/2, 4I11/2, and 4I13/2, respectively. The optical band gap (Eopt), Urbach energy and refractive index were observed to decrease, increase and increase, respectively, to the addition of vanadium. Under 800 nm excitation, three emission bands were observed at 516, 580 and 673 nm, which are represented by 2H11/2-4I15/2, 4S3/2-4I15/2 and 4F15/2-4I15/2, respectively. The excellent features of achieved results suggest that our findings may provide useful information toward the development of functional glasses.


Reactivity of cuprous stellacyanin as a quinone and semiquinone reductase.
The reactivity of cuprous stellacyanin as a quinone and semiquinone reductase has been examined. Rate constants (25.0 degrees C) measured for the oxidation of stellacyanin by 1,4-benzoquinone and benzosemiquinone are 2.3 X 10(4) M-1 s-1 (delta H not equal to = 4.4 kcal/mol, delta S not equal to = -24 eu) and 5.1 X 10(6) M-1 s-1, respectively [pH 7.0, I = 0.1 M (phosphate)]. The agreement of these rate constants with those calculated on the basis of relative Marcus theory is discussed. Stellacyanin is more effective than laccase in quenching benzosemiquinone, suggesting that the physiological role of this metalloprotein is to regulate the concentration of free radicals generated through the laccase-catalyzed oxidation of phenols.


Serum levels of mac-2 binding protein are associated with diabetic microangiopathy and macroangiopathy in people with type 2 diabetes.
Non-alcoholic fatty liver disease is reportedly associated with type 2 diabetes and progressive liver fibrosis, as evaluated by transient elastography, and has been linked with micro- and macroangiopathy in people with type 2 diabetes. The purpose of this cross-sectional study was to investigate the association between serum mac-2 binding protein glycosylation isomer (M2BPGi) levels and diabetic complications in people with type 2 diabetes. Serum M2BPGi levels were measured in terms of cut-off index (C.O.I.) units. Urinary albumin excretion (UAE) was calculated and nephropathy was graded as normoalbuminuria, microalbuminuria, or macroalbuminuria. Retinopathy was divided into three groups: no-diabetic retinopathy (NoDR), non-proliferative-diabetic retinopathy (NPDR), or proliferative-diabetic retinopathy (PDR) . The mean age for the 363 studied subjects (212 males) was 66.4±10.6 years, the median serum M2BPGi level was 0.77 (0.57-1.04) C.O.I., and the median UAE was 22 (9-82.1) mg/g creatinine. M2BPGi levels in microalbuminuria (0.83 (0.61 to 1.18) C.O.I.) and macroalbuminuria (0.88 (0.67 to 1.22) C.O.I.) cases were higher than those in normoalbuminuria cases (0.71 (0.54 to 0.92) C.O.I.). M2BPGi levels in NPDR (0.93 (0.68 to 1.28) C.O.I.) and PDR (0.95 (0.71 to 1.31) C.O.I.) cases were higher than in cases with NoDR (0.73 (0.56 to 0.99) C.O.I.). Furthermore, M2BPGi levels in subjects with a history of cardiovascular diseases were higher than in those with no such history (0.82 (0.65 to 1.22) vs 0.76 (0.55 to 1.03) C.O.I., p=0.019). The logarithm of (M2BPGi+1) was associated with the logarithm of UAE values after adjusting for covariates (standardized β=0.107, p=0.031). This study reveals a close association between serum M2BPGi levels and diabetic microangiopathy and macroangiopathy in people with type 2 diabetes. The results also show that liver fibrosis, evaluated by M2BPGi, is independently associated with an increased risk of albuminuria.


Effect of d-myo-Inositol 1,4,5-Trisphosphate on the Electrical Properties of the Red Beet Vacuole Membrane.
The effect of channel opening in the tonoplast by d-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] has been examined on red beet (Beta vulgaris) vacuoles. Patch-clamp measurements of the vacuolar potential and current were performed on vacuoles isolated in 0.1 micromolar free Ca(2+) medium. With vacuoles clamped at +30 millivolts, the Ins(1,4,5)P(3) induced changes in current were depending on the Ca(2+) buffer strength in the external medium. The spontaneous depolarization of vacuoles in which H(+)-pumps were activated by 5 millimolar MgATP was increased from +6 to +18 millivolts by 1 micromolar Ins(1,4,5)P(3). We have interpreted our data by assuming that even with 2 millimolar EGTA to buffer Ca(2+) at 0.1 micromolar in the external medium, Ins(1,4,5)P(3) released enough Ca(2+) from the vacuole to produce an accumulation of this ion near the tonoplast. Apart from their dependency with free Ca(2+) in the cytoplasm, the electrical properties of the tonoplast could be depending on the Ins(1,4,5)P(3) and Ca(2+) buffer values in the cytoplasm.


Fine-needle aspiration cytology of submandibular gland lesions.
The usefulness of fine-needle aspiration cytology (FNAC) in the diagnosis and treatment of submandibular gland lesions is not well known. The 210 FNACs taken from submandibular gland lesions at Turku University Central Hospital between 1984 and 1991 were reviewed. Of these FNACs, 78 samples from primary lesions were confirmed histologically. Within this subset 10 FNACs were taken from benign neoplasms, all of which were correctly classified (sensitivity 100 per cent; specificity 88 per cent). Only four of the 14 FNACs from malignant lesions were cytologically considered malignant (sensitivity 29 per cent). On the other hand, four FNACs raised a false suspicion of malignancy (specificity 6 per cent). Out of 54 FNACs from non-neoplastic lesions 43 were correct (sensitivity 80 per cent; specificity 63 per cent). There were 104 patients (123 FNACs), who had not been operated on: the follow-up of these patients shows that in this subset of FNACs there were no false malignant but probably one false benign finding (1 per cent). We conclude that FNAC can offer valuable information about the type of the submandibular gland lesion, but the decision of operative and other treatment should not be based solely on the result of FNAC.


Abnormal Static and Dynamic Local-Neural Activity in COPD and Its Relationship With Pulmonary Function and Cognitive Impairments.
Patients with chronic obstructive pulmonary disease (COPD) are characterized by attenuated pulmonary function and are frequently reported with cognitive impairments, especially memory impairments. The mechanism underlying the memory impairments still remains unclear. We applied resting-state functional magnetic resonance imaging (RS-fMRI) to compare the brain local activities with static and dynamic amplitude of low-frequency fluctuations (sALFF, dALFF) among patients with COPD (n = 32) and healthy controls (HC, n = 30). Compared with HC, COPD patients exhibited decreased sALFF in the right basal ganglia and increased dALFF in the bilateral parahippocampal/hippocampal gyrus. The reduced the left basal ganglia was associated with lower oxygen partial pressure. Besides, the increased dALFF in the left hippocampal/parahippocampal cortex was associated with poor semantic-memory performance and the increased dALFF in the left hippocampal/parahippocampal cortex was associated the forced vital capacity. The present study revealed the abnormal static and dynamic local-neural activities in the basal ganglia and parahippocampal/hippocampal cortex in COPD patient and its relationship with poor lung function and semantic-memory impairments.


Multispecialty clinic practice.
A multispecialty clinic practice is a common practice arrangement for colorectal surgeons. A practice of this type has a variety of features, both positive and negative. This article explores the location, practice patterns, lifestyles, compensation, and academic opportunities associated with a multispecialty clinic practice. This information can assist younger surgeons in choosing a practice opportunity and guide experienced surgeons' career progression.


[Carbohydrate antigens in carcinoma invasion and metastasis].
Human colorectal carcinomas with increased metastatic potential and with poor prognosis are characterized by high content of sialyl-Lewis X carbohydrate antigen as detected by monoclonal antibody (mAb) FH6. The levels of these carbohydrate antigens apparently increase during colorectal carcinoma progression from nonmetastatic to metastatic tumors and inversely correlate with post operative survival of colon carcinoma patients. Cell lines have been selected for high and low levels of cell surface sialyl-Lewis X antigen using mAb FH6. The high expresser cells adhere strongly to cytokine-activated endothelial cells apparently through E-selectin. The high expresser cells are also adhesive to sections of human livers, although involvement of selectins in this process is unknown. Increased expression of sialyl-Lewis X antigens on the surface of these high expresser variant cells is apparently due to increased alpha 1,3-fucosyltransferase, a biosynthetic enzyme presumable responsible for the final step of the production of sialyl-Lewis X antigens. Human fucosyltransferase VI cDNA has been stably transfected into the low expresser variant cells. alpha 1,3-Fucosyltransferase activity, cell surface sialyl-Lewis X carbohydrate antigen, and adhesion to activated endothelial cells have been showed to increase in these transfectant cells. Furthermore, these cells show dramatic increase in their liver metastatic potential when it is tested by the intrasplenic injection into nude mice. We propose that carbohydrate antigens with unique peripheral epitopes serve as unique molecular phenotypes that determine colorectal cancer metastasis.


Capillary isoelectric focusing coupled with dynamic imaging detection: A one-dimensional separation for two-dimensional protein characterization.
Here, we devised a novel approach for two-dimensional (2D) protein characterization using a single one-dimensional separation followed by a second characterization in the same instrument. The approach combines capillary isoelectric focusing (CIEF), which separates proteins according to pI, with dynamic imaging detection, which permits monitoring of protein diffusion in real time and thereby allows estimation of molecular weight from diffusion coefficient. Compared with classical 2D gel electrophoresis, the approach provided several significant advantages including speed and ease in operation and automation, while yielding comparable accuracy. The approach was applicable for protein samples of low to moderate complexity.


Caregiving outcomes for older mothers of adults with mental retardation: a test of the two-factor model of psychological well-being.
A two-factor model of caregiving appraisal and psychological well-being, based on previous findings with caregiving spouses (M.P. Lawton, M. Moss, M.H. Kleban, A. Glicksman, & M. Rovine, 1991), was tested with 225 older mothers who provided care at home to an offspring with mental retardation. The effects of objective caregiving stressors, caregiver resources, and subjective appraisals (caregiving satisfaction and burden) on the positive and negative dimensions of psychological well-being were examined. LISREL 8 analyses revealed that the model differed in two key ways for caregiving mothers: (a) Positive psychological well-being appeared to diminish subjective burden, and (b) both objective stressors and resources were unrelated to subjective burden. These findings suggest the need for future research into how caregiving dynamics are influenced by the specific nature of the relationship between the caregiver and the recipient.


The first anniversary: stress, well-being, and optimism in older widows.
The first anniversary for older widows (n = 47) has been explored during Months 11, 12, and 13. Concurrent correlations show that optimism inversely correlates with psychological (intrusion and avoidance) stress as measured with the Impact of Event Scale (r = -.52 to -.66, p < .005) and positively correlates with well-being (physical: r = .36 to .46, p < .025; psychosocial: r = .58 to .72, p < .005; spiritual: r = .50 to .69, p < .005). Lagged correlation patterns suggest that higher levels of optimism at a given time are associated with higher life satisfaction and spiritual well-being at later times. Psychological stress is higher at Month 12 when compared to Month 13, t(43) = 2.54, p = .01, but not when compared to Month 11, t(43) = 1.49, p > .10. There are no significant differences in physiologic stress (salivary cortisol) or well-being during the first anniversary of spousal bereavement.


Peptide analogues compete with the binding of alpha-factor to its receptor in Saccharomyces cerevisiae.
alpha-Factor, a secreted tridecapeptide pheromone, is required for mating between the a- and alpha-haploid mating types of Saccharomyces cerevisiae. An analogue of alpha-factor, [DHP8,DHP11,Nle12] tridecapeptide (where DHP represents 3,4-dehydro-L-proline and Nle represents norleucine), was catalytically reduced in the presence of 3H gas to produce a radiolabeled pheromone with high specific activity, purity, and biological activity. Association and dissociation kinetics indicated values of 4.9 x 10(4) M-1 s-1 for k1 and 1.1 x 10(-3) s-1 for k-1. Saturation binding studies gave an equilibrium dissociation constant equal to 2.3 x 10(-8) M, which approximated the kinetically derived KD of 2.2 x 10(-8) M. These values compare favorably to the previously determined KD of 6 x 10(-9) M (Jenness, D.D., Burkholder, A.C., and Hartwell, L.H. (1986) Mol. Cell. Biol. 6, 318-320). Scatchard analysis and dissociation in the presence of excess unlabeled ligand indicated interaction with a homogeneous population of noninteracting binding sites (13,000 sites/cell). A number of alpha-factor analogues, previously investigated for their structure-function relationships (Naider, F., and Becker, J.M. (1986) CRC Crit. Rev. Biochem. 21, 225-249), were used to compete with [3H]alpha-factor binding. Four tridecapeptides having conservative amino acid replacements bound strongly to the receptor. In contrast, [Phe3]alpha-factor and 10 des-Trp1-alpha-factor analogues bound to the receptor 1-3 orders of magnitude less effectively than did alpha-factor itself. The binding constants for all active pheromones correlated with biological activity. However, des-Trp1[Phe3]alpha-factor and des-Trp1-[Ala3]alpha-factor, which were not biologically active, still competed with alpha-factor binding, indicating that these analogues fail to induce a secondary signal necessary for biological response to the pheromone. One analogue, des-Trp1-[Cha3,L-Ala9]alpha-factor (where Cha represents cyclohexylalanine), was not biologically active and did not demonstrate binding to the receptor, whereas des-Trp1-[Cha3,D-Ala9]alpha-factor was active and bound to the receptor. This finding suggests that a type II beta-turn is necessary for binding of alpha-factor to its receptor and for subsequent biological activity.


[Clinical and pharmacological aspects of pancreatic enzyme substitution therapy].
The adequate therapy of pancreatic enzyme replacement in patients with exocrine pancreatic insufficiency is still a difficult clinical problem especially in patients following pancreatectomys, with chronic alcoholic pancreatitis or cystic fibrosis. The substitution of lipase to eliminate steatorrhoea is the most important aim but due to its acid lability even the most serious problem in pancreatic enzyme replacement therapy. Various different medications are meanwhile available: conventional preparations from porcine pancreatin or fungal enzymes as rizolipase, enteric-coated tablets or even enteric-coated microspheres or adjunctive therapy with H2-receptor antagonists. While dosage requirements vary widely and therefore have to be tried out individually, the choice of the adequate preparation should be influenced by the realization of the physiological and pathophysiological characteristics of the individual patient and the pharmaceutical characteristics of the different supplements. The advantages and disadvantages of the various medications for enzyme replacement therapy in patients with exocrine pancreatic insufficiency are reviewed in this article.


Grape breeding is a key link in the development of the grapes and wine-making industry.
The article considers the legislative and regulatory acts that specify the tasks in the implementation of breeding processes. The results of the creation, variety testing, patenting and introduction of grape varieties and clones into the State Register of the Russian Federation for 2010-2020 are presented. The article analyzes the relationship between the indicators of industrial development with the production volumes of planting material, the use of domestic varieties that are included in the State Register of the Russian Federation. The characteristic of ampelographic collections - the genetic resources of grapes - is given. A comparative analysis of many years' worth of data on the assessment of the adaptive potential of domestic varieties and introduced varieties is presented. The article describes domestic varieties, from which premium wines are produced, which not only competes with European varieties, but also surpasses the organoleptic properties and biochemical parameters of grape must and wine material. The main problems hindering the wide demand for domestic varieties on the market, including a substantial amount of imported European varietal planting material, are described. The necessity of accelerating breeding processes is actualized, modern methods are identified, including those of generative and genomic selection, transgenic technologies, cellular, mutational, and clone selection, and priority areas in breeding are presented. The numerical and qualitative analyses of the composition of breeding scientists is given, the trends of increasing the number and qualitative composition of breeders, the influx of young people, the growing need for training qualified personnel are noted. The number of bachelor's, master's and post-graduate students specializing in viticulture in general and in selection in particular as well as the number of defended dissertation studies on grape breeding has been found to be insufficient. The main scientific and practical problems in the organization and implementation of breeding processes in ensuring the development of the industry are updated, including a low share of domestic varieties in the produced planting material and planting, the lack of a systemically implemented varietal and technological policy, the imperfection of the legal system for the protection of intellectual property, a low availability of instrumentation and analytical equipment for the implementation of breeding by modern methods.


Subcutaneous fat necrosis of the newborn presenting as a large plaque with lobulated cystic areas.
Subcutaneous fat necrosis of the newborn (SFN) usually occurs in the first few weeks of life in full-term infants and presents as indurated, distinct nodules with a predilection for the cheeks, shoulders, back, buttocks, and proximal extremities. Most cases are related to some form of fetal distress, including obstetric trauma. Some cases are associated with hypercalcemia. We report a case of SFN with an unusual clinical presentation, complicated by hypercalcemia.


Step-Economical Photoassisted Diversity-Oriented Synthesis: Sustaining Cascade Photoreactions in Oxalyl Anilides to Access Complex Polyheterocyclic Molecular Architectures.
Atom- and step-economy in photoassisted diversity-oriented synthesis (DOS) is achieved with a versatile oxalyl linker offering rapid access to complex alkaloid mimics in very few experimentally simple steps: (i) it allows for fast tethering of the photoactive core to the unsaturated pendants, especially important in the case of (hetero)aromatic amines-essentially a one-pot reaction with no isolation of intermediates; (ii) the α-dicarbonyl tether acts as a chromophore enhancer, extending the conjugation chain and facilitating the "harvest" of the lower energy photons for the primary and secondary photoreactions; (iii) it enhances the quantum yield of intersystem crossing (ISC), i.e., it is capable of sensitizing secondary photochemical processes in the cascade; and (iv) the tether forms an additional heterocyclic moiety, imidazolidine-4,5-dione, a known pharmacophore. The overall photoassisted cascade is an efficient complexity-building process as quantified by computed step-normalized complexity indices, leading to extended polyheterocyclic molecular architectures comparable in complexity to natural products such as paclitaxel while requiring only 2-4 simple synthetic steps from readily available chemical feedstock.


Estimating Complex Measurement and Growth Models Using the R Package PLmixed.
Measurement models, such as factor analysis and item response theory models, are commonly implemented within educational, psychological, and behavioral science research to mitigate the negative effects of measurement error. These models can be formulated as an extension of generalized linear mixed models within a unifying framework that encompasses various kinds of multilevel models and longitudinal models, such as partially nonlinear latent growth models. We introduce the R package PLmixed, which implements profile maximum likelihood estimation to estimate complex measurement and growth models that can be formulated within the general modeling framework using the existing R package lme4 and function optim. We demonstrate the use of PLmixed through two examples before concluding with a brief overview of other possible models.


Metaraminol-induced reversal of acute myocardial ischaemia associated with hypotension and refractory to intravenous nitroglycerin.
In seven patients, acute myocardial ischaemia associated with ST segment elevation (5.7 +/- 1.6 mm, mean +/- SEM) and arterial hypotension (systolic blood pressure 57 +/- 9 mmHg), was reversed within 9 min (mean time to reversal 274 +/- 45 s) by the intravenous administration of metaraminol (1.9 +/- 0.2 mg). This myocardial ischaemia was refractory to nitroglycerin and, in every patient, the increases in blood pressure induced by metaraminol (to a mean systolic blood pressure of 191 +/- 22 mmHg) preceded reversal of the ECG changes. It is suggested that, in some patients, transmural myocardial ischaemia of recent onset associated with hypotension can be reversed by transiently increasing blood pressure with metaraminol.


Immune reconstitution cryptococcosis after initiation of successful highly active antiretroviral therapy.
Five of 10 patients who commenced successful highly active antiretroviral therapy (HAART) for infection with human immunodeficiency virus type 1 (HIV-1) concurrent with or soon after a diagnosis of cryptococcal infection experienced clinical events characterized by sterile inflammation. Two patients developed aseptic meningitis with elevated intracranial pressure, 1 developed intrathoracic lyphadenopathy with hypercalcemia, 1 developed cavitary pneumonia at the site of a cryptococcal nodule, and 1 developed a supraclavicular abscess. These events occurred 2-11 months after initiation of HAART. For 3 patients, biopsy demonstrated findings atypical for acquired immunodeficiency syndrome-associated cryptococcosis. Results of fungal cultures were negative for all 5 patients, and cryptococcal antigen levels had declined markedly in 4 patients. The timing and clinical features of and biopsy findings for these cases of cryptococcosis suggest the existence of a paradoxical reaction to Cryptococcus infection that occurs in the context of HIV immune restoration.


Nonverbal interactional behavior in the families of persons with schizophrenic and bipolar disorders.
Whereas verbal interactional behaviors have been repeatedly found to distinguish the families of persons with and without major psychiatric disorders, there has been comparatively little examination of the discriminative value of nonverbal interactional behaviors. We developed the Nonverbal Interactional Coding System to measure "affiliative" and "distancing" nonverbal behaviors in 18 schizophrenic and 18 bipolar patients and their parents during 10-minute interactions conducted during a posthospital period. Bipolar patients and their parents displayed affiliative nonverbal behaviors ("illustrator gestures" or "prosocial behaviors") for longer durations than schizophrenic patients and their parents. In contrast, parents of schizophrenic patients displayed distancing nonverbal behaviors (looking away) for longer durations than those of bipolar patients. The nonverbal interactional data added to the statistical strength of patients' and parents' verbal interactional data in distinguishing between these diagnostic groups. Nonverbal interactional behaviors are important variables to consider in interventions aimed at improving the communication skills of families coping with psychiatric disorders.


[Wound healing following laser cordectomy for early glottic carcinoma].
To study the wound healing following CO2 laser microsurgery for early glottic cancer, and to evaluate the treatment outcomes and cost-effectiveness of microsurgery, open surgery and radiotherapy for early glottic cancer. Thirty-six patients with early glottic carcinoma (T1-T2) treated by transoral CO2 laser microsurgery from January 2011 to June 2014 were observed, and 112 patients undergoing open approach and 27 receiving radiotherapy from January 2008 to June 2014 in our hospital were used as control. The wound healing process, the hospital stay, the cost, the oncologic and functional results were evaluated. The mean time of laryngeal mucous membrane stabilization in morphology was 93 days, less than 120 days in 91% cases. The average score of VHI-10 was 5.9, which was better in the cases with T1 than the cases with T2, and was worse in cases with the anterior commissure involvement. Transoral CO2 laser microsurgery offered a similar oncologic result, shorter hospital stay and lower cost compared with open surgery or radiotherapy. The transoral laser surgery could be a better choice for early glottic carcinoma because of good oncologic and functional results and less cost.


[Pathological Study of Pure Autonomic Failure].
Pure autonomic failure (PAF) is a subtype of Lewy body disease whose main target is the peripheral autonomic nervous system. The differential diagnosis includes multiple system atrophy and small fiber neuropathy like amyloidosis. Low uptake of 123I- metaiodebenzyl guanidine (MIBG) cardiac scintigraphy is of diagnosis use. Biopsy of skins affected with decreased sweating could prove Lewy pathology in the peripheral autonomic nerves. Among more than 10,000 autopsy cases in BBAR (Brain Bank for Aging Research), representing an aging cohort in Tokyo metropolitan suburban area, only two cases had clinical diagnosis of PAF. Orthostatic hypotension without parkinsonism is common clinical features. Both presented with diffuse Lewy body pathology involving the peripheral autonomic nervous system, brain stem, limbic system and neocortex with mild loss of pigmented neurons in substantia nigra. Other senile changes like Alzheimer pathology, argyrophlic grains and TDP43 (TAR DNA- binding protein of 43kDa) proteinopathy were mild. Neuropathological features fulfilled morphological criteria of dementia with Lewy bodies (DLB) pure neocortical form, suggesting dementia as one of the late clinical complications. About one third of autopsy cases registered to BBAR contained Lewy pathology in the body, among whom, 5% had Lewy pathology only in the peripheral autonomic nervous system. These cases may be the earliest stage of PAF.


Familial risks of glomerulonephritis - a nationwide family study in Sweden.
Familial risks of glomerulonephritis (acute, chronic and unspecified glomerulonephritis) have not been studied. This study aims to determine the familial risks of glomerulonephritis. Individuals born from1932 onwards diagnosed with glomerulonephritis (acute [n = 7011], chronic [n = 10,242] and unspecified glomerulonephritis [n = 5762]) were included. The familial risk (Standardized incidence ratio = SIR) was calculated for individuals whose parents/full-siblings were diagnosed with glomerulonephritis compared to those whose parents/full-siblings were not. The procedure was repeated for spouses. Familial concordant risk (same disease in proband and exposed relative) and discordant risk (different disease in proband and exposed relative) of glomerulonephritis were determined. Familial concordant risks (parents/full-sibling history) were: SIR = 3.57 (95% confidence interval, 2.77-4.53) for acute glomerulonephritis, SIR = 3.84 (3.37-4.36) for chronic glomerulonephritis and SIR = 3.75 (2.85-4.83) for unspecified glomerulonephritis. High familial risks were observed if two or more relatives were affected; the SIR was 209.83 (150.51-284.87) in individuals with at least one affected parent as well as one full-sibling. The spouse risk was only moderately increased (SIR = 1.53, 1.33-1.75). Family history of glomerulonephritis is a strong predictor for glomerulonephritis, and is a potentially useful tool in clinical risk assessment. Our data emphasize the contribution of familial factors to the glomerulonephritis burden in the community. Key Messages The familial risks (full-sibling/parent history) of glomerulonephritis (acute, chronic and unspecified glomerulonephritis) have not been determined previously. The familial risks of glomerulonephritis were increased among individuals with family history of acute, chronic or unspecified glomerulonephritis. The familial risks of glomerulonephritis were slightly increased among spouses indicating a modest non-genetic contribution. Very high familial risks were observed in multiplex families, i.e. with one or more affected first-degree relatives.


An increased cell cycle gene network determines MEK and Akt inhibitor double resistance in triple-negative breast cancer.
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with poor clinical prognosis and limited targeted treatment strategies. Kinase inhibitor screening of a panel of 20 TNBC cell lines uncovered three critical TNBC subgroups: 1) sensitive to only MEK inhibitors; 2) sensitive to only Akt inhibitors; 3) resistant to both MEK/Akt inhibitors. Using genomic, transcriptomic and proteomic datasets of these TNBC cell lines we unravelled molecular features associated with the MEK and Akt drug resistance. MEK inhibitor-resistant TNBC cell lines were discriminated from Akt inhibitor-resistant lines by the presence of PIK3CA/PIK3R1/PTEN mutations, high p-Akt and low p-MEK levels, yet these features could not distinguish double-resistant cells. Gene set enrichment analyses of transcriptomic and proteomic data of the MEK and Akt inhibitor response groups revealed a set of cell cycle-related genes associated with the double-resistant phenotype; these genes were overexpressed in a subset of breast cancer patients. CDK inhibitors targeting the cell cycle programme could overcome the Akt and MEK inhibitor double-resistance. In conclusion, we uncovered molecular features and alternative treatment strategies for TNBC that are double-resistant to Akt and MEK inhibitors.


Rod-signal interneurons in the rabbit retina: 1. Rod bipolar cells.
The cellular morphology and topographic distribution of the rod bipolar cells in the rabbit retina have been investigated by selective labelling with protein kinase C-immunohistochemistry (Negishi et al., Neurosci, Lett. 94:247-252, 1988) and by Lucifer Yellow injection of microscopically identified cells in a superfused retinal preparation. The distribution of the rod bipolar cells parallels that of their input neurons, the rod photoreceptors, in that the rod bipolars reach maximum densities of 5,000-7,000 cells/mm2 on the inferior and superior flanks of the visual streak, dropping to slightly lower densities at the peak visual streak. The centre-to-periphery density gradient of the rod bipolars is about 2.5:1, and the density ratio of rods to rod bipolars shows little variation across the retina, ranging from 43:1 in superior retina to 58:1 in inferior retina. The dendritic field area of the rod bipolar cells increases from 600 microns2 on the visual streak to 1,200 microns2 in the far-superior retina, with each point on the retina overlapped by 2.5-3.5 dendritic fields. The axonal field area of the rod bipolar cells increases from about 100 microns2 at the peak visual streak to about 250 microns2 at the retina edge, and the axonal field coverage ranges from 0.55 in the visual streak to about 0.8 in peripheral retina. Although there appear to be gaps in the local array of rod bipolar somata, these areas are covered by the axonal arbours of neighbouring rod bipolar cells.


Intestinal Dominance by Serratia marcescens and Serratia ureilytica among Neonates in the Setting of an Outbreak.
(1) Background: We determined the relevance of intestinal dominance by Serratia spp. during a neonatal outbreak over 13 weeks. (2) Methods: Rectal swabs (n = 110) were obtained from 42 neonates. Serratia spp. was cultured from swabs obtained from 13 neonates (Group 1), while the other 29 neonates were culture-negative (Group 2). Total DNA was extracted from rectal swabs, and quantitative PCRs (qPCRs) using Serratia- and 16SrRNA-gene-specific primers were performed. relative intestinal loads (RLs) were determined using ΔΔCt. Clonality was investigated by random amplified polymorphic DNA analysis and whole-genome sequencing. (3) Results: The outbreak was caused by Serratia marcescens during the first eight weeks and Serratia ureilytica during the remaining five weeks. Serratia spp. were detected by qPCR in all Group 1 neonates and eleven Group 2 neonates. RLs of Serratia spp. were higher in Group 1 as compared to Group 2 (6.31% vs. 0.09%, p < 0.05) and in the first swab compared to the last (26.9% vs. 4.37%, p < 0.05). Nine neonates had extraintestinal detection of Serratia spp.; eight of them were infected. RLs of the patients with extraintestinal spread were higher than the rest (2.79% vs. 0.29%, p < 0.05). (4) Conclusions: Intestinal dominance by Serratia spp. plays a role in outbreaks and extraintestinal spread.


Nanomechanical Insights into Versatile Polydopamine Wet Adhesive Interacting with Liquid-Infused and Solid Slippery Surfaces.
Mussel-inspired polydopamine (PDA) can be readily deposited on almost all kinds of substrates and possesses versatile wet adhesion. Meanwhile, slippery surfaces have attracted much attention for their self-cleaning capabilities. It remains unclear how the versatile PDA adhesive would interact with slippery surfaces. In this work, both liquid-infused poly(tetrafluoroethylene) (PTFE) (LI-PTFE) and solid slippery surfaces (i.e., self-assembly of small thiol-terminated organosilane, polysiloxane covalently attached to substrates) were fabricated to investigate their capability to prevent PDA deposition. It was found that PDA particles could be easily deposited on a PTFE membrane and the two types of solid slippery surfaces, which resulted in the alternation of their surface wettability and slippery behavior of water droplets. Adhesion was detected between a PDA-coated silica colloidal probe and the PTFE membrane or solid slippery surfaces through quantitative force measurements using an atomic force microscope (AFM), mainly due to van der Waals (vdW) and hydrophobic interactions, which led to the PDA deposition phenomenon. In contrast, LI-PTFE with a thin liquid lubricant film could effectively prevent PDA deposition, with negligible changes in surface morphology, wettability, and slippery characteristics. Although PDA particles could be loosely attached to the lubricant/water interface for LI-PTFE based on the capillary adhesion measured by AFM, they could be readily removed by gentle rinsing with water, as demonstrated by the ultralow friction over LI-PTFE as compared to PTFE using lateral force microscopy (LFM). Our results indicate that LI-PTFE possesses excellent antifouling and self-cleaning properties even when interacting with the versatile PDA wet adhesives. This work provides new insights into the deposition of PDA on slippery surfaces and their interaction mechanism at the nanoscale, with useful implications for the design and development of novel slippery surfaces.


Idiopathic eruptive macular pigmentation with papillomatosis (IEMPP): A controversial entity.
A 19-year-old man with a 6-month history of progressive development of hyperpigmented, velvety plaques on the face and body. A diagnosis of idiopathic eruptive macular pigmentation with papillomatosis (IEMPP) was determined. This entity is discussed.


[A case of thyroid crisis in acute tonsillitis treatment].
We report a case of fatal thyroid crisis induced by acute tonsillitis. A 33-year-old woman with untreated hyperthyroidism developed thyroid crisis during acute tonsillitis treatment. The four days passing from crisis onset to treatment initiation unduly compromised her condition, resulting in death. Such cases point up the need for prompt thyroid crisis diagnosis and treatment, the difference between a proactive life-sustaining response and a negative mortal result.


On the composition fluctuations of reverse micelles.
The polydispersity of the reverse micelles is determined mainly by the fluctuations of their composition. The composition of the reverse micelle is a two-dimensional random variable whose components are the numbers of water (i) and surfactant (j) molecules. In this study the fluctuations of the composition of the reverse micelles are considered in the Gaussian approximation. It is shown that the standard deviation of the quantity w=i/j may be calculated from the dependence of the water vapor pressure above the microemulsion on the molar ratio W=[water]/[surfactant]. The estimation based on the literature data for microemulsion system sodium bis(2-ethylhexyl)sulfosuccinate/water/isooctane at 37°C in the range W=0-18 has shown that the relative standard deviation of the quantity w is about 10%. It is shown that the value of the composition fluctuations is related to the dependence of average composition on the concentration of reverse micelles at constant parameter W.


Theoretical evaluation of zirconia and hafnia as gate oxides for si microelectronics.
Parameters determining the performance of the crystalline oxides zirconia (ZrO2) and hafnia (HfO2) as gate insulators in nanometric Si electronics are estimated via ab initio calculations of the energetics, dielectric properties, and band alignment of bulk and thin-film oxides on Si (001). With their large dielectric constants, stable and low-formation-energy interfaces, large valence offsets, and reasonable (though not optimal) conduction offsets (electron injection barriers), zirconia and hafnia appear to have considerable potential as gate oxides for Si electronics.


Meta-analysis of the use of rescue antiemetics following PONV prophylactic failure with 5-HT3 antagonist/dexamethasone versus single-agent therapies.
To assess the use of rescue antiemetic medication following 5-HT3 receptor antagonist (5-HT3RA) plus dexamethasone therapy versus monotherapy with a 5-HT3RA for prophylaxis of postoperative nausea and vomiting (PONV). Reports of randomized, controlled trials were identified via a MEDLINE search (1966-September 2005) using the key terms ondansetron, dolasetron, tropisetron, granisetron, 5-HT3, PONV, vomiting, emesis, and nausea. Randomized, controlled trials of adult populations that had treatment arms comparing 5-HT3RA/dexamethasone combination therapy with 5-HT3RA or dexamethasone monotherapies versus placebo or 5-HT3RA versus dexamethasone or placebo were selected for analysis. Another criterion was that a proportion of patients required rescue medication 48 hours or less following surgery. Odds ratios (ORs) with 95% confidence interval were calculated to determine incidence rates for use of rescue medications within early (0-6 h), late (6-24 h), and overall (0-24 or 48 h) postoperative periods. Overall effect sizes were calculated by pooling ORs within fixed and random effects models. Prophylaxis with 5-HT3RA/dexamethasone was associated with lower use of rescue antiemetics than 5-HT3RA (OR(pooled) = 0.48; 95% CI 0.29 to 0.77) or dexamethasone (OR(pooled) = 0.26; 95% CI 0.12-0.57) monotherapy during the overall postoperative period. Insufficient data were available to assess rescue use during early or late postoperative periods. It appears that patients at high risk of PONV who are treated prophylactically with combination 5-HT3RA/dexamethasone therapy are overall less likely to require rescue medication than if treated with 5-HT3RAs or dexamethasone alone. Additional large prospective studies are needed to determine the optimal regimen and timing of administration of prophylactic antiemetic therapy for different surgical populations.


Primary reconstruction of traumatic bony defects using allografts.
We retrospectively reviewed 207 patients suffering from traumatic bone defect who had been treated at our institution between 1973 and 1993. Three types of traumatic bone defects were identified: I, minor; II, major cortical; III, major articular. Each type was further subdivided into: A, open injury; B, closed injury. The proposed treatment modality of each type was included within each classification. Types II and III posed the greatest difficulties in management. However, massive bone allografts can be successfully used in these situations, even in the early phases of treatment, but only given specific prerequisites.


Estrogen-growth factor interactions and their contributions to neurological disorders.
Estrogen has diverse and powerful effects in the brain, including actions on neurons, glia, and the vasculature. It is not surprising, therefore, that there are many changes in the female brain as serum estradiol levels rise and fall during the normal ovarian cycle. At times of life when estradiol levels change dramatically, such as puberty, postpartum, or menopause, there also are dramatic changes in the central nervous system. Changes that occur because of fluctuations in serum estrogen levels are potentially relevant to neurological disorders because symptoms often vary with the time of the ovarian cycle. Moreover, neurological disorders (eg, seizures and migraine) often increase in frequency in women when estradiol levels change. In this review, the contribution of 2 growth factors targeted by estrogen, the neurotrophin brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), will be discussed. Estrogen-sensitive response elements are present on the genes for both BDNF and VEGF, and they are potent modulators of neuronal, glial, and vascular function, making them logical candidates to mediate the multitude of effects of estrogen. In addition, BDNF induces neuropeptide Y, which has diverse actions that are relevant to estrogen action and to the same neurological disorders.


Gene expression profiling of morphologic subtypes of pancreatic ductal adenocarcinoma using surgical and EUS-FNB specimens.
Various classifications of pancreatic ductal adenocarcinoma (PDAC) based on RNA profiling resulted in two main subtypes. Kalimuthu and coworkers proposed a morphology-based classification that concurred with these subtypes. Immune therapy approaches in PDAC were so far disappointing. Morphologic PDAC subtypes may differ regarding key immune-oncology pathways. We aimed to examine the reproducibility and prognostic value of Kalimuthu's morphologic classification, and to evaluate differences between subtypes regarding gene expression related to tumor biology and immune-oncology. PDAC specimens from 196 patients were included, 108 consecutive chemotherapy-naïve surgical specimens and 88 endoscopic ultrasound-guided fine needle biopsies (EUS-FNBs). The specimens were evaluated as per Kalimuthu by two pancreatic pathologists, resulting in Group A and Group B tumors. Digital mRNA expression profiling was performed, on the surgical specimens using the NanoString IO360 panel of 770 key tumor biology related and 30 custom-genes, and on the EUS-FNBs using a targeted panel of 123 genes. Morphologic subtyping reached substantial interobserver agreement between the two pathologists. In the surgical and EUS-FNB cohorts, 44.4% and 38.6% were Group A tumors, which were associated with improved survival. Group A showed higher expression of immune-related genes and cytokine/chemokine/interleukin signaling and Group B of genes related to cancer cell proliferation and cell cycle regulation. Hierarchical clustering based on significant differences in gene expression levels between Groups A and B revealed clusters with prognostic value. Morphologic subtyping according to Kalimuthu is reproducible and holds prognostic value, in surgical as well as EUS-FNB specimens. As upregulation of immune-related genes was found in Group A, future studies should evaluate the potential of immune therapy approaches with special emphasis on this subtype of PDAC.


Self-assembled ZnS nanowire arrays: synthesis, in situ Cu doping and field emission.
Well-aligned single-crystalline ZnS nanowire arrays have been grown on highly conductive Cu substrates through controlling the morphology evolution of self-patterned ZnS nanoparticles. The ZnS nanowires have sharp tips with an average size of approximately 30 nm and a length of approximately 3 microm. Field emission measurements demonstrated that the aligned ZnS nanowires grown on Cu substrates are excellent field emitters having a turn-on field as low as 2.92 V microm(-1) and a field-enhancement factor as high as 3400. The use of highly conductive metal substrate may promote the commercial applications of ZnS-based emitters in flat panel displays and other optoelectronic devices.


The first experience with non-operative treatment of hypersplenism in children with portal hypertension.
The register of Latvian children with portal hypertension (PH) includes 34 patients from 2 to 16 years old. In 26 children the PH is caused by a prehepatic obstruction. The most widespread symptoms of PH are variceal bleeding and hypersplenism. The traditional management of hypersplenism has been splenectomy. We have used partial splenic embolization (PSE) as an alternative to splenectomy. From 1998 to 2000 we carried out PSE in 8 patients with PH. A percutaneous femoral artery approach to the splenic artery was used to deliver microspheres with a diameter of 0.3 mm into the spleen, minimizing blood circulation to the organ by 60 - 70 %. In 7 patients symptoms of hypersplenism disappeared and blood tests returned to normal status. In one patient we carried out PSE twice. In one case PSE was not successful and the patient underwent partial resection. Abdominal pain and subfebrility were observed on average 2 weeks after PSE. In 7 patients the 4 - 20 months follow-up period demonstrated the efficiency of the non-operative hypersplenism management method. We conclude that PSE is the method of choice to treat hypersplenism.


Detection of bacteriocins produced by Lactobacillus plantarum strains isolated from different foods.
Bacterial strains (106 in toto) isolated from different foods and identified as Lactobacillus plantarum were screened for antagonistic activities against other bacteria under conditions which eliminated the effects of organic acids and hydrogen peroxide. Five isolates were shown to be bacteriocin producers, and the bacteriocins, on the basis of their host range inhibition and cross inhibition were all different. The bacteriocins were preliminarily characterized by temperature stability, sensitivity to proteolytic, lipolytic and glycolytic enzymes and precipitation with ammonium sulphate.


Median raphe cyst of the penis with ciliated cells.
Cystic lesions occurring on the ventral surface of the penis have been classified as median raphe cysts of the penis. They are lined by pseudostratified, columnar or stratified squamous cell epithelium, mimicking the epithelial lining of the male urethra. Ciliated cysts of the human skin are unusual. Cystic lesions containing ciliated cells have been noted to occur in the chest, neck, or head, and bronchogenic origin has been the most accepted explanation for its origin. Other reports show the presence of ciliated cysts on the lower extremities, and the mechanism of formation is still a debated question. A case of median raphe cyst of the penis containing ciliated epithelium is presented. The existing literature about these cutaneous lesions is reviewed, including the possible mechanisms believed to be involved in its origin.


A three-dimensional atlas of human tongue muscles.
The human tongue is one of the most important yet least understood structures of the body. One reason for the relative lack of research on the human tongue is its complex anatomy. This is a real barrier to investigators as there are few anatomical resources in the literature that show this complex anatomy clearly. As a result, the diagnosis and treatment of tongue disorders lags behind that for other structures of the head and neck. This report intended to fill this gap by displaying the tongue's anatomy in multiple ways. The primary material used in this study was serial axial images of the male and female human tongue from the Visible Human (VH) Project of the National Library of Medicine. In addition, thick serial coronal sections of three human tongues were rendered translucent. The VH axial images were computer reconstructed into serial coronal sections and each tongue muscle was outlined. These outlines were used to construct a three-dimensional (3D) computer model of the tongue that allows each muscle to be seen in its in vivo anatomical position. The thick coronal sections supplement the 3D model by showing details of the complex interweaving of tongue muscles throughout the tongue. The graphics are perhaps the clearest guide to date to aid clinical or basic science investigators in identifying each tongue muscle in any part of the human tongue.


Stability behaviour of antiretroviral drugs and their combinations. 8: Characterization and in-silico toxicity prediction of degradation products of efavirenz.
Efavirenz (EFV), an antiretroviral drug, was evaluated for its degradation behaviour in solution state. A total of twelve degradation products were detected on high performance liquid chromatography (HPLC) analyses. Initially, comprehensive mass fragmentation pattern of the drug was established by direct injection and collection of high resolution mass spectrometry (HRMS) and multi-stage tandem mass spectrometry (MSn) data. Subsequently, LC-HRMS studies were carried on the stability samples containing the degradation products. Eleven degradation products were isolated and subjected to 1D and 2D nuclear magnetic resonance (NMR) studies for their structural confirmation. The collated information was utilized for the characterization of all the degradation products and hence in outlining the comprehensive degradation pathway of the drug. In-silico toxicity of the degradation products was evaluated by TOPKAT analyses.


The impact of thiopurines on the risk of surgical recurrence in patients with Crohn's disease after first intestinal surgery.
Smoking and a lack of immunosuppressive (IS) therapy are considered risk factors for intestinal surgery in Crohn's disease (CD). Good evidence for the latter is lacking. The objective of this study was to evaluate the impact of thiopurine treatment on surgical recurrence in patients after first intestinal resection for CD and its possible interaction with smoking. Data on 326 patients after first intestinal resection were retrieved retrospectively, and subjects were grouped according to their postoperative exposure to thiopurines. Treatment with either azathioprine (AZA) or 6-mercaptopurine (6-MP) was recorded on 161 patients (49%). Smoking status was assessed by directly contacting the patients. Surgical recurrence occurred in 151/326 (46.3%) patients after a median time of 71 (range 3-265) months. Cox regression revealed a significant reduction of re-operation rate in patients treated with AZA/6-MP for > or = 36 months as compared with patients treated for 3-35 months, for less than 3 months, and to those without postoperative treatment with AZA/6-MP (P=0.004). Cox regression analysis revealed treatment with thiopurines for > or = 36 months (hazard ratio (HR) 0.41; 95% confidence interval (CI) 0.23-0.76, P=0.004) and smoking (HR 1.6; 95% CI 1.14-2.4, P=0.008) as independent predictors for surgical recurrence. Furthermore, longer duration of disease tended to be protective (HR 0.99; 95% CI 0.99-1.0, P=0.067). Long-term maintenance treatment with AZA/6-MP reduces the risk of surgical recurrence in patients with CD. We also identified smoking as a risk factor for surgical recurrence.


Brain structural changes and their correlation with vascular disease in type 2 diabetes mellitus patients: a voxel-based morphometric study.
Voxel-based morphometry has been used in the study of alterations in brain structure in type 1 diabetes mellitus patients. These changes are associated with clinical indices. The age at onset, pathogenesis, and treatment of type 1 diabetes mellitus are different from those for type 2 diabetes mellitus. Thus, type 1 and type 2 diabetes mellitus may have different impacts on brain structure. Only a few studies of the alterations in brain structure in type 2 diabetes mellitus patients using voxel-based morphometry have been conducted, with inconsistent results. We detected subtle changes in the brain structure of 23 cases of type 2 diabetes mellitus, and demonstrated that there was no significant difference between the total volume of gray and white matter of the brain of type 2 diabetes mellitus patients and that in controls. Regional atrophy of gray matter mainly occurred in the right temporal and left occipital cortex, while regional atrophy of white matter involved the right temporal lobe and the right cerebellar hemisphere. The ankle-brachial index in patients with type 2 diabetes mellitus strongly correlated with the volume of brain regions in the default mode network. The ankle-brachial index, followed by the level of glycosylated hemoglobin, most strongly correlated with the volume of gray matter in the right temporal lobe. These data suggest that voxel-based morphometry could detect small structural changes in patients with type 2 diabetes mellitus. Early macrovascular atherosclerosis may play a crucial role in subtle brain atrophy in type 2 diabetes mellitus patients, with chronic hyperglycemia playing a lesser role.


Unusual DQA-DR haplotypes in rheumatoid vasculitis.
DQA and DQB variants and HLA haplotypes were defined in Caucasian subjects with rheumatoid arthritis (RA), in a rheumatoid subset characterized clinically by extra-articular features of major vasculitis, and in controls. DQ variants were defined using a panel of sequence specific oligonucleotide probes. In RA subjects without extra-articular features the frequency of DQB*0301 was significantly increased but this was secondary to the main association with DR4. In rheumatoid vasculitis by contrast, DQB*0302 rather than DQB*0301 was increased in frequency, in addition to an increase of C4A null alleles. Family studies showed that DR4 negative haplotypes had an increased frequency of unusual DR-DQA combinations as compared to other rheumatoid subsets. These findings are in keeping with the concept that genes within the MHC other than DR4 have a disease-modifying role in rheumatoid subsets. HLA haplotypes were defined in a family where the proband has RA and Felty's syndrome and an affected sister has rheumatoid vasculitis. These siblings share a DR4 bearing haplotype typing for DQB*0301, and the sister with rheumatoid vasculitis has a DR4 negative haplotype carrying a C4A null allele and an unusual DR-DQA combination.


Neuronal differentiation of human mesenchymal stromal cells increases their resistance to Aβ42 aggregate toxicity.
Cell therapy is a promising approach for the treatment of neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. However, the presence of toxic aggregates in tissue raises the question of whether grafted stem cells are susceptible to amyloid toxicity before they differentiate into mature neurons. To address this question, we investigated the relative vulnerability of human mesenchymal stromal cells and their neuronally differentiated counterparts to Aβ(42) oligomers and whether susceptibility correlates with membrane GM1 content, a key player in oligomer toxicity. We found that our cell model was highly susceptible to aggregate toxicity, whereas neuronal differentiation induced resistance to amyloid species. This data correlated well with the content of membrane GM1, levels of which decreased considerably in differentiated cells. These findings extend our knowledge of stem cell vulnerability to amyloid species, which remains a controversial issue, and confirm that amyloid-GM1 interactions play an important role in cell impairment.


Multinational comparison of diagnostic clues for uterine cervical lesions among cytotechnologists in Asian countries.
Vaccination has been underway in several countries for sexually inactive young girls or women against HPV 16 and 18 to prevent them from infection of these HPV types and concurrent cancer development. However, uterine cervical cancers may remain uncontrolled among some Asian countries, where other types of HPV infection are more frequent. A sensitive cancer screening system would remain important for detection of the earlier stage cervical cancers in Asian countries. In this study, 130 cytotechnologists (CTs) in Asian countries (Taiwan 80, Japan 18, Korea 15, Thailand 11, Singapore 3, Bhutan 2, and Mongolia 1) participated in the vote. Selected 10 cervical Pap smears that would be adequate to identify the diagnostic clues especially for atypical squamous cells (ASC) with two or three representative pictures for each case were displayed on the website. The percentages of consistent diagnosis voted by certified CTs with ≥5 years of experience were compared among 10 cervical cases or among Asian countries enrolled. As results, low consistency for ASC cases and high consistency for squamous intraepithelial lesion (SIL) were observed. Examining specimens for the diagnostic clues of ASC in TBS is crucial to maintain the high sensitivity and positive predictive value of SIL in Asian countries.


Physical activity counseling intervention to promote weight loss in overweight rural women.
To identify key behavioral factors that contribute to physical activity and weight management in overweight, rural women and determine the degree to which social support, stage of behavior change, and self-efficacy for physical activity and depressive symptoms are linked to physical activity, body weight, and body mass index (BMI). Twenty-five overweight or obese rural women completed self-report scales and height and weight measurements; BMI was calculated. Self-report scales included the International Physical Activity Questionnaire (physical activity level), Social Support for Exercise and Social Support Questionnaire (social support), Stage of Exercise Adoption (stage of behavior change), Self-efficacy for Exercise (self-efficacy), and the Patient Health Questionnaire (depressive symptoms). Higher levels of physical activity were associated with greater self-efficacy and the self-esteem domain of social support. Rural women reported more depressive symptoms over the year. Women did not significantly increase physical activity and gained weight during the 1-year study. Rural women have limited resources available to increase physical activity to facilitate weight loss. Routine screening and treatment for depression in rural women may need to be initiated concurrently with interventions to promote health behavior changes.


Establishment of monoclonal antibodies against human nerve growth factor.
We have generated and characterized a monoclonal antibody to human nerve growth factor (hNGF). The monoclonal antibody NGFA-133 neutralizes hNGF activity, as assayed by neurite-outgrowth of nerve cells from chick embryonal dorsal root ganglion. Using this antibody, we have developed a sensitive and specific two-site enzyme immunoassay (EIA) system for hNGF. The assay is based on a sandwiching of the antigen between NGFA-133 coated on a microtiter plate and the same monoclonal antibody (NGFA-133) conjugated with horseradish peroxidase (HRP). The two-site EIA was sensitive enough to detect 920 fg/well of hNGF and did not cross-react either human neurotrophin-3 (hNT-3) or sodium dodecyl sulfate (SDS) denatured hNGF.


Impact of commercial feed dilution with copra meal or cassava leaf meal and enzyme supplementation on broiler performance.
A preliminary study investigated the impact of commercial feed dilution with copra meal (CM) or cassava leaf meal (CLM) and enzyme supplementation on broiler performance. Commercial feed alone (control) or diluted with CM and CLM at a concentration of 100 and 200 g/kg in the starter and finisher diets, respectively, was fed without and with Challenzyme 300A at a concentration of 300 g/tonne in 2 × 2 factorial arrangements with a control. Two hundred, 7-day-old male, Cobb 500 broiler chicks were randomly assigned to 5 diets containing 4 replicates of 10 birds each. There were no interaction or main effects (P > 0.05) on feed intake during either the starter or finisher phase. In the starter phase, feed-to-gain ratio (F:G) increased (P < 0.05) in the group fed with CM without enzyme. Enzyme supplementation restored F:G similar to the control. Diet dilution with CM or CLM had no effect (P > 0.05) on weight gain (WG) in the starter phase. Diluting the feed with CM or CLM without enzyme suppressed (P < 0.05) WG and F:G in the finisher phase, but enzyme supplementation restored the lost performances. There were no interaction or main effects (P > 0.05) on the carcass traits. Enzyme supplementation reduced (P < 0.05) feed cost per kilogram of carcass. Heavier ceca were observed in the group fed with dilution diets (P < 0.05). Enzyme supplementation reduced cecum weight in the group fed with CM (P < 0.05). The heaviest (P < 0.05) abdominal fat was recorded in the group fed with enzyme-supplemented CM diet, and the lightest (P < 0.05) abdominal fat was recorded in the group fed with CLM with enzyme. In the main effects, lighter (P < 0.05) liver, gizzard, and proventriculus were recorded in the group fed with control diet than in the group fed with the CLM diets, but the weight of these segments did not differ (P > 0.05) between the control and CM groups and between the fiber sources. The results suggest that dilution of commercial diet with CM or CLM may be a viable option for medium- and small-scale broiler production in the region. There is need for more research in the level of dilution, enzyme source, and concentration.


Are topical retinoids teratogenic?
Retinoic acid is a physiological compound of human blood. Blood levels range from 1000 to 7000 pg/mL (usually 1500-5000 pg/mL). Results of studies on absorption of topical retinoic acid in laboratory animals, although rather conflicting, demonstrate that it induces plasma concentrations which are well below concentrations caused by non-teratogenic oral doses. In humans, minimal percutaneous absorption of tretinoin was observed after topical applications. Neither single dose nor long-term treatment with topical tretinoin affect the endogenous levels of retinoic acid or its metabolites. Topical application of tretinoin at doses used in acne unlikely induces systemic effects. Although some clinical cases of suspected tretinoin-related embryotoxicity have been described, three prospective cohort studies clearly demonstrated the safety of topical tretinoin as an embryotoxic agent.


A three-dimensional, noninterpenetrating metal--organic framework with the moganite topology: a simple (4(2)x6(2)x8(2))(4x6(4)x8)(2) net containing two kinds of topologically nonequivalent points.
Self assembly of Cu(2+) with the multifunctional ligand 2-(4-pyridyl)thiazole-4-carboxylic acid (Pytac) affords the neutral 3D coordination polymer [Cu(3)(Pytac)(6)](H(2)O)(14) (hereafter, SZL-1), which has the rare moganite topology. The mineral moganite has a topology that is closely related to the well-known quartz topology, but the two topologies are differentiated by the number of topologically inequivalent nodes. Whereas only one kind of node is present in quartz, two types of topologically inequivalent nodes are present in moganite. The title compound, which has three vertices in its repeat unit, has two types of topologically inequivalent nodes with the overall vertex symbol (4(2)x6(2)x8(2))(4x6(4)x8)(2) corresponding to the moganite net. Prior to this report, few metal-organic framework materials (MOFs) have been found to contain more than one type of node, and SZL-1 is the first MOF with the moganite topology.


Conflict: an imperative for success.
Conflict in organizations of any type is inevitable. Medical institutions, particularly multispecialty clinics, are no exception. This paper presents an examination of the anatomy of conflict in group practice settings. Several case studies, including the "Hunterdon Experiment," are presented to illustrate the outcome of conflict situations where management was unable to direct its energy to productive ends. Recommendations are made for identifying, considering, and resolving conflicts in a proactive fashion. The conflict management role of the top management of the organization is described, with particular emphasis on the pivotal position of the Medical Director.


Propofol sedation for ERCP procedures: a dilemna? Observations from an anesthesia perspective.
Propofol sedation for endoscopic retrograde cholangiopancreatography (ERCP) procedures is a popular current technique that has generated controversy in the medical field. Worldwide, both anesthetic and nonanesthetic personnel administer this form of sedation. Although the American and Canadian societies of gastroenterologists have endorsed the administration of propofol by nonanesthesia personnel, the US Food and Drug Administration (FDA) has not licensed its use in this manner. There is some evidence for the safe use of propofol by nonanesthetic personnel in patients undergoing endoscopy procedures, but there are few randomized trials addressing the safety and efficacy of propofol in patients undergoing ERCP procedures. A serious possible consequence of propofol sedation in patients is that it may result in rapid and unpredictable progression from deep sedation to general anesthesia, and skilled airway support may be required as a rescue measure. Potential complications following deep propofol sedation include hypoxemia and hypotension. Propofol sedation for ERCP procedures is an area of clinical practice where discussion and mutual cooperation between anesthesia and nonanesthesia personnel may enhance patient safety.


Electrophoresis studies on the contaminating glycosaminoglycans in commercially available hyaluronic acid products.
Hyaluronic acid (HA) samples showing inhibition effect on digestion with testicular hyaluronidase (HAase) were found from 16 commercially available HA products, which were supplied from 11 different manufacturers. Most of these HA samples (six samples) were derived from the rooster comb, and one sample was derived from the human umbilical cord. HA oligosaccharides produced by exhaustive digestion of these HA samples with testicular HAases were monitored by capillary electrophoresis, and we found that a few HA samples gave no oligosaccharide products. Detailed analysis of HA samples by cellulose acetate membrane electrophoresis revealed that the HA samples were not digested with HAase because of the presence of a small amount of dermatan sulfate (DS). Analysis of disaccharide units of these HA samples produced by digestion with chondroitinase ABC supported the observations. And the content of DS in the sample was estimated to be ca. 8%. In contrast, these HA samples were easily digested with bacterial hyaluronate lyases from Streptomyces hyalurolyticus and Streptococcus dysgalactiae and gave endproducts of unsaturated disaccharide or unsaturated tetra- or hexasaccharides. The results suggested that the inhibitory effect of DS on HAase is specific to endo-type hydrolase (i.e. testicular HAase). In addition, pharmaceutical preparations of HA derived from rooster comb were easily digested with testicular HAase. These findings will be useful information for clinical or cosmetic use of HA preparations in terms of their half-life.


Ascitic and solid Ehrlich tumor inhibition by Chenopodium ambrosioides L. treatment.
The leaves of Chenopodium ambrosioides L. [Chenopodiaceae] ('mastruz') have been indicated for the treatment of several diseases, among which the cancer. There are no results focusing the effect of C. ambrosioides treatment on tumor development in vivo. The aim of this study was to investigate the effect of treatment with C. ambrosioides on Ehrlich tumor development. Swiss mice were treated by intraperitoneal route (i.p.) with hydroalcoholic extract from leaves of C. ambrosioides (5 mg/kg) or with PBS (control group) 48 h before or 48 h later the Ehrlich tumor implantation. The tumor cells were implanted on the left footpad (solid tumor) or in the peritoneal cavity (ascitic tumor). To determine the solid tumor growth, footpad was measured each 2 days until the fourteenth day, when the feet were weighed. Ascitic tumor development was evaluated after 8 days of tumor implantation by quantification of the ascitic fluid volume and tumor cell number. The i.p. administration of C. ambrosioides extract before or after the tumor implantation significantly inhibited the solid and ascitic Ehrlich tumor forms. This inhibition was observed in ascitic tumor cell number, in the ascitic volume, in the tumor-bearing foot size and foot weight when compared to control mice. The treatments also increased the survival of tumor-bearing mice. In conclusion, C. ambrosioides has a potent anti-tumoral effect which was evident with a small dose and even when the treatment was given two days after the tumor implantation. This effect is probably related with anti-oxidant properties of C. ambrosioides.


Aggressive angiomyxoma: The first case report in skull.
Aggressive angiomyxoma (AAM) is a rare mesenchymal tumor primarily growing in the soft tissue of the pelvis and perineum in women of reproductive age. It is a benign tumor that still has a probability of being accompanied by localized invasion. Although negative margins of resection are difficult to achieve due to the invasive nature of the tumor and the lack of a well-defined capsule, the first line of treatment for AAM is surgery. The diagnosis of AAM is difficult to make due to a lack of specific manifestations and specific tumor markers. In this study, we reported a case of aggressive angiomyxoma in a 2-year-old girl that rarely develops in the skull with craniocerebral compression. The patient initially had a mass on her head that attracted the attention of her family, and then she began to have episodic headaches. Surgery was performed after hospitalization, and the tumor recurred 1 year after the operation, around the originally affected skull.


Quantitative aspects of adenosine triphosphate-driven proton translocation in spinach chloroplast thylakoids.
After illumination in the presence of dithiothreitol, chloroplast thylakoids catalyze ATP hydrolysis and an exchange between ATP and Pi in the dark. ATP hydrolysis is linked to inward proton translocation. The relationships between ATP hydrolysis, ATP-Pi exchange, and proton translocation during the steady state were examined. The internal proton concentration was found to be proportional to the rate of ATP hydrolysis when these parameters were varied by procedures that do not alter the proton permeability of the thylakoid membranes. A linear relationship between the internal proton concentration and the rate of nonphosphorylating electron flow was previously verified. By determining the constant relating internal proton concentration to both ATP hydrolysis and electron flow, the proton/ATP ratio for the chloroplast ATPase complex was calculated to be 3.4 +/- 0.3. The presence of Pi, which allows ATP-Pi exchange to occur, lowers the internal proton concentration, but does not alter the relationship between the net rate of ATP hydrolysis and internal proton concentration. ATP-Pi exchange shows a dependence on the proton activity gradient very similar to that of ATP synthesis in the light. These results suggest that ATP-Pi exchange resembles photophosphorylation. In agreement with this idea, it is nucleoside diphosphate from the medium that is phosphorylated during exchange. Moreover, the energy-linked incorporation of Pi and ADP into ATP during exchange occurs at a similar rate. Thus, ATP synthesis from medium ADP and Pi takes place at the expense of the pH gradient generated by ATP hydrolysis.


Nuclear-cytoplasmic shuttling is not required for the Epstein-Barr virus EBNA-LP transcriptional coactivation function.
Epstein-Barr virus (EBV) EBNA-LP is a transcriptional coactivator of EBNA2 that works though interaction with the promyelocytic leukemia nuclear-body-associated protein Sp100A. EBNA-LP localizes predominantly in the nucleus through the action of nuclear localization signals in the repeated regions of the protein. EBNA-LP has also been detected in the cytoplasm, and a previous study suggested that some of the EBNA-LP coactivation function is mediated by relocalizing histone deacetylase 4 (HDAC4) from the nucleus to the cytoplasm. Although EBNA-LP can be found in the cytoplasm, it has no obvious nuclear export signal, and there is no direct evidence for active shuttling between these cellular compartments. Whether active shuttling between the nucleus and cytoplasm is required for coactivation remains to be clarified. To address these issues, we tested a variety of EBNA-LP isoforms and mutants for nuclear-cytoplasmic shuttling activity in an interspecies heterokaryon assay and for the ability to associate with HDAC4. EBNA-LP isoforms smaller than 42 kDa shuttle efficiently in the heterokaryon assay via a crm-1-independent mechanism. In addition, no specific EBNA-LP domain that mediates nuclear export could be identified. In contrast, an EBNA-LP 62-kDa isoform does not demonstrate detectable shuttling in the heterokaryon assay yet still coactivates EBNA2 similarly to the smaller EBNA-LP isoforms. All of the EBNA-LP mutants tested, including the coactivation-deficient DeltaCR3 mutant and the nonshuttling 62-kDa isoform, were capable of associating with HDAC4. Taken together, our results suggest that simple diffusion may account for the nuclear export observed with smaller isoforms of EBNA-LP, that nuclear-cytoplasmic shuttling is not required for efficient EBNA-LP coactivation function, and that competence for HDAC4 association is not sufficient to mediate nuclear-cytoplasmic shuttling or EBNA-LP coactivation in the absence of a functional interaction with Sp100A.


When to Censor?
Loss to follow-up is an endemic feature of time-to-event analyses that precludes observation of the event of interest. To our knowledge, in typical cohort studies with encounters occurring at regular or irregular intervals, there is no consensus on how to handle person-time between participants' last study encounter and the point at which they meet a definition of loss to follow-up. We demonstrate, using simulation and an example, that when the event of interest is captured outside of a study encounter (e.g., in a registry), person-time should be censored when the study-defined criterion for loss to follow-up is met (e.g., 1 year after last encounter), rather than at the last study encounter. Conversely, when the event of interest must be measured within the context of a study encounter (e.g., a biomarker value), person-time should be censored at the last study encounter. An inappropriate censoring scheme has the potential to result in substantial bias that may not be easily corrected.


[Usefulness of procalcitonin for the diagnosis of infection in cardiac surgical patients].
To determine the value of procalcitonin (PCT) as an early marker of postoperative infection after cardiac surgery with cardiopulmonary bypass (CPB). A retrospective study was conducted. Patients with systemic inflammatory response syndrome (SIRS) after cardiac surgery with CPB admitted to intensive care unit (ICU) of Peking Union Medical College Hospital from November 2014 to January 2017 were enrolled. The cardiac surgery types and intraoperative conditions, the treatments in ICU, postoperative 28-day mortality and hospital mortality of the patients; the levels of plasma PCT measured at ICU admission, postoperative 1, 3, and 5 days were collected. According to whether patients with postoperative infection or not, they were divided into infection group and non-infection group. Receiver operating characteristic curve (ROC) was used to analyze the predictive value of plasma PCT levels at different time points in patients with infection. Eighty-two patients were included in this study, 25 (30.5%) had microbiological evidence of pneumonia. The levels of plasma PCT were increased with a peak 1 day after cardiac surgery in all patients, then significantly decreased 5 days after operation. Compared with patients without infection, the levels of plasma PCT were significantly increased in patients with infection at immediate and 1, 3, 5 days post operation in ICU [μg/L: 10.0 (6.0, 64.5) vs. 5.0 (1.0, 10.0), 31.0 (10.0, 116.2) vs. 5.0 (1.0, 10.0), 34.7 (10.0, 60.4) vs. 2.9 (0.7, 9.3), 15.8 (7.7, 29.4) vs. 0.7 (0.5, 2.6), all P < 0.01]. The area under the ROC curve (AUC) of the plasma PCT levels at ICU admission, and 1, 3, 5 days thereafter to predict infection for critically ill patients with SIRS after CPB was 0.77, 0.82, 0.86, and 0.91, respectively (all P < 0.01), cut-off values were 6.8, 9.4, 9.2 and 3.9 μg/L, with the sensitivities of 76.0%, 84.0%, 79.2%, and 88.0%, and the specificities of 66.7%, 68.4%, 75.4%, and 78.9%, respectively. In the presence of SIRS, elevated plasma PCT levels correlated with evidence of infection in early stage post operation in the ICU patients after cardiac surgery with use of CPB. The level of plasma PCT exceeded the cut-off value in different time points, suggesting infection, and it is helpful to predict the occurrence of infection early after operation.


Conformations of Organophosphine Oxides.
The conformations of a series of organophosphine oxides, OP(CH3)2R, where R = methyl, ethyl, isopropyl, tert-butyl, vinyl, and phenyl, are predicted using the MP2/cc-pVTZ level of theory. Comparison of potential energy surfaces for rotation about P-C bonds with crystal structure data reveals a strong correlation between predicted location and energetics of minima and histograms of dihedral angle distributions observed in the solid state. In addition, the most stable conformers are those that minimize the extent of steric repulsion between adjacent rotor substituents, and the torsional barriers tend to increase with the steric bulk of the rotating alkyl group. MM3 force field parameters were adjusted to fit the MP2 results, providing a fast and accurate model for predicting organophosphine oxides shapes-an essential part of understanding the chemistry of these compounds. The predictive power of the modified MM3 model was tested against MP2/cc-pVTZ conformations for triethylphosphine oxide, OP(CH2CH3)3, and triphenylphosphine oxide, OP(Ph)3.


Heterogeneous metal alloy engineering: embryonic growth of M13 icosahedra in Ag-based alloy superatomic nanoclusters.
Alloying is an effective tool to comprehend the packing mechanism and adjust the properties of nanomaterials. Herein, two crystal structures of alloy nanoclusters with M13 icosahedron cores, formulated as [Pt2Ag51(S-Adm)28(PPh3)2Cl7](SbF6)2 and [Au3Ag48(S-Adm)28Cl7](SbF6)2, are determined. The preferable site(s) of alloy metals in M13 induces various packing patterns of M13. The Pt2Ag21 and Au3Ag22 kernels are observed in Pt2Ag51 and Au3Ag48, respectively. The electronic structures of these two nanoclusters are evaluated. Overall, this work presents the effect of alloying on the packing patterns of M13 and electronic structures of the metal nanoclusters.


Improved detection of magnetic signals by a MEMS sensor using stochastic resonance.
We introduce the behavior of the electrical output response of a magnetic field sensor based on microelectromechanical systems (MEMS) technology under different levels of controlled magnetic noise. We explored whether a particular level of magnetic noise applied on the vicinity of the MEMS sensor can improve the detection of subthreshold magnetic fields. We examined the increase in the signal-to-noise ratio (SNR) of such detected magnetic fields as a function of the magnetic noise intensity. The data disclosed an inverted U-like graph between the SNR and the applied magnetic noise. This finding shows that the application of an intermediate level of noise in the environment of a MEMS magnetic field sensor improves its detection capability of subthreshold signals via the stochastic resonance phenomenon.


Medicinal chemistry of fluorinated cyclic and acyclic nucleoside phosphonates.
The fluorine atom plays an important role in medicinal chemistry because fluorine substitution has a strong impact on the physical, chemical, and biological properties of bioactive compounds. Such fluorine modifications have also been extensively studied among the pharmaceutically important class of nucleoside phosphonates, nucleotide analogues in which the phosphate group is replaced by the enzymatically and chemically stable phosphonate moiety. The fluorinated nucleoside phosphonates abound with antiviral, antiparasitic, and anticancer properties because they are able to act as inhibitors of important enzymes of nucleoside/nucleotide metabolism. In this paper, we review the biological properties of cyclic and acyclic nucleoside phosphonates modified by the attachment of one or more fluorine atoms to various parts of the molecule, namely to nucleobases, alkylphosphonate groups, cyclic or acyclic linkers, or to prodrug moieties.