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Research on the prevalence, course, and correlates of behavior problems in preschool children was examined. Prospective epidemiological studies and follow-up studies of clinical/high risk samples indicate that serious externalizing problems identified early often persist. Negative, inconsistent parental behavior and high levels of family adversity are associated with the emergence of problems in early childhood and predict their persistence to school age. Studies are examined from a developmental perspective and integrated with research on optimal parent-child relationships. The severity of initial problems and family context are related to different developmental outcomes.

In this paper, a ternary-emission fluorescence imprinted polymer was one-pot synthesized by sol-gel method after mixing luminescence metal organic framework, green CdTe and near infrared red CdTe for visual detection of chloramphenicol in food. The ternary-emission fluorescence imprinted sensor showed wider linear range within concentration of 10 pM-0.5 nM and 0.5 nM-4.5 nM, with rapid response time of 3 min and the lower detection limit of 3.8 pM toward chloramphenicol. Meanwhile, NH₂-UiO-66 improved the fluorescence sensitivity and response speed, the near-infrared CdTe enhanced the anti-interference ability of the imprinted sensor. Compared with the traditional single-emission and dual-emission fluorescence imprinted sensors, the ternary-emission imprinted sensor provided richer color changes from yellowish green to apricot to orange-salmon to amaranth to purple to final blue. It was applied to detect trace chloramphenicol in food with the recoveries of 98.2-101.2 %, which provided a new way for rapid visual detection of chloramphenicol.

Specific receptors for dexamethasone (11beta, 17alpha, 21-trihydroxy-9alpha-fluoro-16alpha-methyl-1,4-pregnadiene-3,20-dione) in the cytoplasm of the liver from AH 130 (solid type) tumor-bearing rats markedly increased in the advanced stage of tumor growth. The cytoplasmic receptors of the livers of normal and tumor-bearing rats differed in their affinities for dexamethasone, and their apparent equilibrium (dissociation) constants (K) for dexamethasone were 4.0 and 2.6 X 10(-9) M, respectively. The rates of dissociation of dexamethasone-receptor complexes and the heat denaturations of the receptors in the livers of normal and tumor-bearing rats were similar. The glucocorticoid receptors of tumor-bearing rat liver had slightly higher affinities than did those of normal liver for all the steroids tested. Only a trace amount of receptors for dexamethasone could be detected in the cytoplasm of AH 130 ascites cells.

Twenty Thai medicinal plant extracts were evaluated for anti-herpes simplex virus type 1 (HSV-1) activity. Eleven of them inhibited plaque formation of HSV-1 more than 50% at 100microg/ml in a plaque reduction assay. Aglaia odorata, Moringa oleifera, and Ventilago denticulata among the 11 were also effective against thymidine kinase-deficient HSV-1 and phosphonoacetate-resistant HSV-1 strains. These therapeutic efficacies were characterized using a cutaneous HSV-1 infection in mice. The extract of M. oleifera at a dose of 750mg/kg per day significantly delayed the development of skin lesions, prolonged the mean survival times and reduced the mortality of HSV-1 infected mice as compared with 2% DMSO in distilled water (P<0.05). The extracts of A. odorata and V. denticulata were also significantly effective in limiting the development of skin lesions (P<0.05). There were no significant difference between acyclovir and these three plant extracts in the delay of the development of skin lesions and no significant difference between acyclovir and M. oleifera in mean survival times. Toxicity of these plant extracts were not observed in treated mice. Thus, these three plant extracts may be possible candidates of anti-HSV-1 agents.

Pantothenate kinase (PanK) is a regulatory enzyme that controls coenzyme A (CoA) biosynthesis. The association of PanK with neurodegeneration and diabetes suggests that chemical modifiers of PanK activity may be useful therapeutics. We performed a high throughput screen of >520000 compounds from the St. Jude compound library and identified new potent PanK inhibitors and activators with chemically tractable scaffolds. The HTS identified PanK inhibitors exemplified by the detailed characterization of a tricyclic compound (7) and a preliminary SAR. Biophysical studies reveal that the PanK inhibitor acts by binding to the ATP-enzyme complex.

To show that human muscle may adapt to tendon transfer, adaptation of flexor carpi ulnaris (FCU) function was studied by measuring active and passive length-force characteristics at initial operation and at reoperation in a case of extension deformity secondary to FCU tendon transfer. At reoperation, FCU was 20 mm shorter; active force decreased approximately 10%, indicating atrophy; and passive force increased, reflecting increased stiffness. FCU fiber length was unchanged. The presented case shows that human forearm muscle may adapt to a transferred function.

The sterilization of the male by vasectomy receives increasing acceptance in this country as part of family planning in general. Current laws and bylaws are lacking. The present procedures, indications and methods for vasectomy for fertility are described and discussed. This type of vasectomy differs in some points from vasectomy for other therapeutic indications. Noticeable complications, especially immunologic complications were not observed and were not detectable by immunologic testing of 23 men. Since all attempts to achieve a temporary occlusion of the vas have failed, vasectomy for the control of fertility is irreversible, in the majority of the cases. It is therefore advisable to deposit semen in sperm banks in these cases. The success rate of re-anastomosis of the vas to the vas or the vas to the epididimus varies between 10 and 30%.

This paper constitutes an introduction to the forthcoming series of publications summing up the present store of knowledge on the incidence and ecology of avian haematozoa in Central Europe. The paper contains bibliography dealing with the incidence of these parasites in the region studied. The problem of the incidence of blood parasites in domestic birds is discussed in detail. The incidence of blood parasites in wild birds is only briefly outlined as it is to be treated in detail in forthcoming papers.

Poly(amidoamine) dendrimers (PAMAM) are well-defined, highly branched, nanoscale macromolecules with numerous active amine groups on the surface. PAMAM dendrimer can enhance the solubility of hydrophobic drugs, and with numerous reactive groups on the surface PAMAM dendrimer can be engineered with various functional groups for specific targeting ability. However, in physiological conditions, these amine groups are toxic to cells and limit the application of PAMAM. In the recent years, polyethylene glycol (PEG) conjugation has been the most widely used approach to reduce the toxicity of the active group on dendrimer surface. PEG molecules are known to be inert, non-immunogenic, and non-antigenic with a significant water solubility. PEGylated PAMAM-mediated delivery could not only overcome the limitations of dendrimer such as drug leakage, immunogenicity, hemolytic toxicity, systemic cytotoxicity but they also have the ability to enhance the solubilization of hydrophobic drugs and facilitates the potential for DNA transfection, siRNA delivery and tumor targeting. This review focuses on the recent developments on the application and influence of PEGylation on various biopharmaceutical properties of PAMAM dendrimers.

The aim of this study was to analyse the main problems which involve renal function in major vascular surgery and can lead to postoperative acute renal failure. The factors responsible for renal damage in this surgical branch are at first analysed, then followed by the physiological changes which characterize the renal injury, the techniques employed to detect and monitor them and finally the therapeutic tools available to prevent acute renal failure. The most significant data of personal experience on the use of nifedipine and low-dose dopamine during abdominal aortic surgery are then presented. It is concluded that: a) an ischemic attack is the main cause of acute renal failure in mayor vascular surgery; b) prevention of ischemic renal damage is far superior to treatment; c) the optimal management of the cardiovascular function by means of the invasive hemodynamic monitoring, is the main tool to protect the kidneys and prevent acute renal failure; d) the pharmacological protection by diuretics and low-dose dopamine is of minor importance and anyway subordinate to the maintenance of adequate hemodynamics, as well as for calcium antagonist whose employment however seems to protect the kidneys better against an ischemic attack.

Vascular cytokines, total nitrite, and cyclophilin-A (CyP-A) may be related to the pathogenesis of untreated hypertension. Forty males with normotensive and untreated essential hypertension were recruited in this cytokines survey. Body mass index (BMI), hyperlipidemia, and plasma CyP-A were increased in the hypertensive group (p < 0.05). However, only BMI (p = 0.022) and plasma CyP-A (p = 0.020) were found to be significant contributors to hypertension by multiple regression analysis. CyP-A was also positively correlated with systolic blood pressure (p = 0.029) and diastolic blood pressure (p = 0.047). These findings indicated that plasma CyP-A is a critical molecular biomarker in the early pathogenesis of essential hypertension.

Recent proteome analyses have provided a comprehensive overview of various posttranslational modifications (PTMs); however, PTMs involving protein citrullination remain unclear. We performed a proteomic analysis of citrullinated proteins, and we identified more than 100 PAD4 (peptidyl arginine deiminase 4)&#160;substrates. Approximately one-fifth of the PAD4 substrates contained an RG/RGG motif, and PAD4 competitively inhibited the methylation of the RGG motif in FET proteins (FUS, EWS, and TAF15) and hnRNPA1, which are causative genes for ALS (amyotrophic lateral sclerosis). PAD4-mediated citrullination significantly inhibited the aggregation of FET proteins, a frequently observed feature in neurodegenerative diseases. FUS protein levels in arsenic-induced stress granules were significantly increased in Padi4^-/- mouse embryonic fibroblasts (MEFs). Moreover, rs2240335 was associated with low expression of PADI4 in the brain and a high risk of ALS (p&#160;= 0.0381 and odds ratio of 1.072). Our findings suggest that PAD4-mediated RGG citrullination plays a key role in protein solubility and ALS pathogenesis.

<i>Background and objectives:</i> Non-steroidal anti-inflammatory drugs (NSAIDs) have been among the major causes of small intestinal injury in clinical practice. As such, the current study investigated the protective effect of 5-aminosalicylic acid (5-ASA) against an NSAID-induced small intestinal injury. <i>Materials and Methods</i>: IEC-6 cells were treated with various concentrations of indomethacin with or without 5-ASA in a serum-free medium, after which an 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Dromide (MTT) assay, a cell apoptosis assay, a caspase-3 activity assay, a reactive oxygen species (ROS) content and Superoxide dismutase 2 (SOD2) activity measurement, a Western blotting for occludin and zonula occludens-1 (ZO-1) and a wound healing assay were conducted. <i>Results:</i> 5-ASA ameliorated indomethacin-induced cell apoptosis and an increase in the intracellular ROS content while augmenting the indomethacin-induced suppression of SOD2 activity in IEC-6 cells. Moreover, 5-ASA reversed the indomethacin-induced attenuation of occludin and ZO-1 expression and promoted faster wound healing effects in IEC-6 cells following an indomethacin-induced injury. <i>Conclusion:</i> Our results suggested that 5-ASA protects small intestinal cells against an NSAID-induced small intestinal injury by scavenging free radicals. Therefore, 5-ASA could be a potential treatment for an NSAID-induced small intestinal injury.

Three groups of ovariectomized rats were treated for 6 days: 1) estradiol benzoate (100 micrograms/kg) (SC) and fed ad lib; 2) vehicle-injected controls fed the same amount of food as eaten by estradiol-treated rats; 3) vehicle-injected, free-feeding controls. Specific binding of insulin to liver and hypothalamus slices was measured by quantitative film autoradiography. Estradiol-treated rats lost weight (p < 0.001) and had elevated plasma insulin (p < 0.01). Liver insulin binding in rats with estradiol treatment was greater (p < 0.01) than in rats without estradiol, but was less (p < 0.05) than in controls fed the same food levels as consumed by the estradiol-treated rats. Therefore, with equal food intake, estradiol decreased liver insulin binding. Insulin binding in the dorsomedial, ventromedial, and arcuate nuclei of the hypothalamus was unchanged by food intake or estradiol, however. Thus, altered insulin binding in the arcuate, ventromedial, or dorsomedial nuclei of the hypothalamus is probably not involved in the effects of insulin or estradiol on food intake.

Reactive oxygen and nitrogen species such as superoxide (O(2)(-)) and nitric oxide (NO) are produced under diverse conditions and provoke distinct signaling reactions. The formation of NO has been shown to induce apoptosis and/or necrosis in mesangial cells and to protect other cells such as hepatocytes. Often, NO and O(2)(-) are simultaneously generated, which results in their diffusion-controlled interaction and, thus, redirects the signaling properties of either NO or O(2)(-). This has been proven for mesangial cells, where O(2)(-) formation attenuates NO-initiated apoptosis. As the mechanisms involved remained unclear, we studied the potential impact of the glutathione redox system and compared the results obtained with mesangial cells with those obtained with Hep G2 hepatocytes. In contrast to mesangial cells, Hep G2 cells appeared resistant to NO donors but displayed massive cell destruction following NO/O(2)(-) cogeneration. As a result, we noticed a greater increase in GSSG levels in Hep G2 cells than in mesangial cells. GSH depletion reversed the cell protection in mesangial cells and enhanced the cell damage in Hep G2 cells. NO/O(2)(-)-mediated mesangial protection is associated with an increased glutathione reductase activity and an increase in GSH. In conclusion, NO/O(2)(-) sensitivity is cell type specific and is determined by the glutathione redox system.

Both VEGF (vascular endothelial growth factor)-A and Orf-virus-encoded VEGF-E bind and activate VEGFR (VEGF receptor)-2; however, only VEGF-A binds VEGFR-1. To understand the biological differences between VEGF-A and VEGF-E in vivo, we established transgenic mouse models. K14 (keratin-14)-promoter-driven VEGF-E transgenic mice showed a significant increase in mature blood vessels. However, K14-VEGF-A transgenic mice exhibited severe inflammation and oedema with increased angiogenesis, as well as lymphangiogenesis and lymph vessel dilatation. K14-VEGF-A transgenic mice deficient in VEGFR-1 signalling (K14-VEGF-A-tg/VEGFR-1 TK(-/-) mice) showed decreases in oedema and inflammation with less recruitment of macrophage-lineage cells, suggesting an involvement of VEGFR-1 in these adverse effects. VEGFE might be more useful than VEGFA for pro-angiogenic therapy.

Accurate diagnosis of patent foramen ovale (PFO) and grading of right-to-left shunt severity by the standard method of transthoracic or transesophageal echocardiography (TEE) with bubble injection is often challenging. We proposed the novel Maximum Intensity T-Projection (MIP) Imaging method as a complementary or alternative approach for simplified diagnosis and grading of PFO. MIP Imaging represents the superimposition of all frames of an echocardiographic video onto one image. Thus, all bubbles passing from right to left atrium are represented in this single image. Diagnosis and quantification of PFO by MIP Images were compared to those obtained by standard echocardiographic methods, using the same echocardiography video loops. We applied the MIP Imaging approach to 122 echo examinations (75% of them TEE studies), performed to rule out PFOs. The average time needed to manually analyze video loops taken during bubble injection was 102 ± 52 s vs. less than 1 s using the MIP Imaging method. There was good concordance between the conventional echo method and MIP Imaging in the diagnosis and quantification of PFOs. MIP Imaging for diagnosis and quantification of PFOs was much less time consuming than the classical method and at least as accurate as the classical method. Thus MIP Imaging may be used initially as an adjunct method for PFO diagnosis and quantification and may eventually replace the classical method.

An 8-year-old boy, known with a Diamond-Blackfan anaemia, was admitted to the hospital because of frequent vomiting since 3 days and loin pain. In previous years, he had been admitted several times for the same complaints but no cause had been identified. Ultrasound examination of the abdomen performed at admittance showed dilatation of the left renal pelvis. A renal scintigraphy was discussed with the mother, and she refused the injection of furosemide, because her son was allegedly allergic to furosemide: previous furosemide treatments during blood transfusions for his anaemia had always resulted in stomach-ache and vomiting, which may be attributed, however, to an acute dilatation of the renal pelvis due to the diuretic effect of furosemide. Scintigraphy without furosemide showed a significant obstruction and asymmetric renal function, so a pyeloplasty was performed after which he has been symptom-free. In patients with cyclic vomiting, an intermittent uretero-pelvic junction obstruction should be considered and can only be ruled out when ultrasound during the complaints and renal scintigraphy under adequate hydration and after furosemide are normal.

The completeness of a 'first consultation' human immunodeficiency virus (HIV) clinical history before and after the introduction of an HIV proforma was audited by a retrospective case notes review. Twenty key variables considered essential to every history were assessed. There was a significant improvement in the documentation of 14 of the 18 items for men and 14 of the 20 items for women post-proforma with no deterioration in documentation of any of the variables. Our study supports the introduction of a structured 'first consultation' notes proforma for use during consultations with both newly diagnosed HIV-positive patients and those transferring their care from other centres.

The precise modification of redox species on the inner and outer surfaces of hollow nanostructures is relevant in catalysis, surface science, and nanotechnology, but has proven difficult to achieve. Herein, we develop a facile approach to specifically fabricate Pt and Co3 O4 nanoparticles (NPs) onto the interior and exterior surface of hollow carbon nitride spheres (HCNS), respectively, to promote the surface redox functions of the polymer semiconductors. The photocatalytic water splitting activities of HCNS with spatially separated oxidation and reduction centers at their nanodomains were enhanced. The origin of the enhanced activity was attributed to the spatially separated reactive sites for the evolution of H2 and O2 and also to the unidirectional migration of the electron and hole on the Janus surfaces, thereby preventing the unwanted reverse reaction of water splitting and decreasing charge recombination.

Acute experiments on sexually mature mongrel male rats showed that microinjection of dopamine into the area of paraventricular nucleus of the hypothalamus and the anterior lobe of the hypophysis failed to influence the secretion from the hypophysis of the thyrotropic hormone (TTH), the content of which was determined radioimmunologically. Dophamine injections in the mediobasal hypothalamus decreased the TTH content in the blood of euthyroid rats. In animals given thyroxin preliminarily, an increase in the TTH level occurred in the blood serum in response to dophamine administration into the mediobasal hypothalamus. A conclusion was drawn that dophamine of the mediobasal hypothalamus took part in the TTH secretion from the anterior lobe of the hypophysis. The normalizing action of the given mediator is expressed under conditions of the changed functional activity of the hypophysis-thyroid gland system.

The metabolism of leukotriene (LT) A4, B4, C4, D4, and E4 was studied using both bioassay and reversed phase high performance liquid chromatography (RP-HPLC) methods. The incubation of 20,000 g supernatants of homogenates of human adult lung with LTA4 and LTC4 for various periods of time produced substances of higher biologic activity than the controls (without incubation) when measured on strips of guinea pig lung parenchyma and ileum. RP-HPLC analyses of the incubation media revealed the formation of LTB4, LTC4, LTD4, and LTE4 from LTA4 and the formation of LTD4 and LTE4 from LTC4. LTD4 was converted to LTE4 whereas LTB4 and LTE4 were not catabolized to an appreciable extent during a 2-h incubation period. Supernatants (20,000 g) of human fetal lung homogenates also contain the enzymatic activities to transform LTC4 into LTD4 and LTE4; however, LTA4 was mainly converted to LTB4 and to products of the nonenzymatic hydrolysis of LTA4 such as the delta 6-trans-LTB4, delta 6 -trans-12-epi-LTB4 and the 5,6-dihyroxyeicosatetraenoic acids; much smaller quantities of the peptidoleukotrienes were formed than in adult lung homogenates.

Infection rates with cytomegalovirus among children in three day care centers were compared to that found in a group of children cared for in the home who were from a similar socioeconomic background. Rates of viral excretion for Day Care Centers 1, 2 and 3 were 41% (28 of 68), 26% (15 of 58) and 55% (34 of 62), respectively, with a combined rate of infection for all children in day care of 41% (77 of 188). In contrast 15% (10 of 66) of children in home care were seropositive to cytomegalovirus, and only 2 of 25 (8%) were shedding virus (P less than 0.001). Although the median age of the group in home care was slightly lower, the two groups of children were similar in sex, race, breast-feeding and parental ages and educational background. The only other notable difference between the children in day care and those in home care was the environment in which they received care for almost 40 hours every week. Rates of infection varied also among the age groups within each center, with the highest rate within each center occurring in children 25 to 36 months old. Day care for young children is likely to be associated with high rates of infection with cytomegalovirus. The mechanisms of transmission that are responsible for these higher than expected rates of infection remain to be defined.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a global problem in part because of the emergence of variants of concern that evade neutralization by antibodies elicited by prior infection or vaccination. Here we report on human neutralizing antibody and memory responses to the Gamma variant in a cohort of hospitalized individuals. Plasma from infected individuals potently neutralized viruses pseudotyped with Gamma SARS-CoV-2 spike protein, but neutralizing activity against Wuhan-Hu-1-1, Beta, Delta, or Omicron was significantly lower. Monoclonal antibodies from memory B cells also neutralized Gamma and Beta pseudoviruses more effectively than Wuhan-Hu-1. 69% and 34% of Gamma-neutralizing antibodies failed to neutralize Delta or Wuhan-Hu-1. Although Class 1 and 2 antibodies dominate the response to Wuhan-Hu-1 or Beta, 54% of antibodies elicited by Gamma infection recognized Class 3 epitopes. The results have implications for variant-specific vaccines and infections, suggesting that exposure to variants generally provides more limited protection to other variants.

Nuclei in a fluid subjected to a continuous wave circularly polarized light beam are predicted to experience a static magnetic field proportional to E(+/-) x E(+/-), where E(+/-) is the electric vector of the right or left circularly polarized wave and the dot denotes a time derivative. The field strongly depends on the local electronic structure and is present in all atoms. For an intensity of 10 watts per square centimeter propagating in the direction of the field of a magnetic resonance spectrometer, the general theory presented here predicts shifts of +/- 4 x 10(-8) hertz for protons and +/- 10(-5) hertz for fluorine-19. Larger shifts are predicted if the laser frequency is near an optical absorption.

Salicylic acid (SA)-induced resistance to Cucumber mosaic virus (CMV) in tobacco (Nicotiana tabacum) results from inhibition of systemic virus movement and is induced via a signal transduction pathway that also can be triggered by antimycin A, an inducer of the mitochondrial enzyme alternative oxidase (AOX). In Arabidopsis thaliana, inhibition of CMV systemic movement also is induced by SA and antimycin A. These results indicate that the mechanisms underlying induced resistance to CMV in tobacco and A. thaliana are very similar. In contrast to the situation in tobacco and A. thaliana, in squash (Cucurbita pepo), SA-induced resistance to CMV results from inhibited virus accumulation in directly inoculated tissue, most likely through inhibition of cell-to-cell movement. Furthermore, neither of the AOX inducers antimycin A or KCN induced resistance to CMV in squash. Additionally, AOX inhibitors that compromise SA-induced resistance to CMV in tobacco did not inhibit SA-induced resistance to the virus in squash. The results show that different host species may use significantly different approaches to resist infection by the same virus. These findings also imply that caution is required when attempting to apply findings on plant-virus interactions from model systems to a wider range of host species.

Malignant mesenchymoma within the right ulnar nerve of an 8 year old boy is described. The patient did not have stigmata of von Recklinghausen's neurofibromatosis. The growing and painful tumour was excised five and a half detection, and recurred five months later. Mingling of the nerve sheath sarcoma and rhabdomyosarcoma was noted within the same mass which was separated from the adjacent striated muscles. It is suggested that this mesenchymoma arose from mesenchymal cells or cells of mesenchymal type comprising the peripheral nerve sheath which is derived from ectomesenchyme of the neural crest.

In the context of the recent recalls of contaminated pet food and lead-painted toys in the United States, we examine patterns of risk perceptions and decisions when facing consumer product-caused quality risks. Two approaches were used to explore risk perceptions of the product recalls. In the first approach, we elicited judged probabilities and found that people appear to have greatly overestimated the actual risks for both product scenarios. In the second approach, we applied the psychometric paradigm to examine risk perception dimensions concerning these two specific products through factor analysis. There was a similar risk perception pattern for both products: they are seen as unknown risks and are relatively not dread risks. This pattern was also similar to what prior research found for lead paint. Further, we studied people's potential actions to deal with the recalls of these two products. Several factors were found to be significant predictors of respondents' cautious actions for both product scenarios. Policy considerations regarding product quality risks are discussed. For example, risk communicators could reframe information messages to prompt people to consider total risks packed together from different causes, even when the risk message has been initiated due to a specific recall event.

A 67-year-old man, who was previously diagnosed with vasospastic angina and treated with standard therapy, was admitted to our hospital because of recurrent chest pain refractory to sublingual nitroglycerin. Admission electrocardiography revealed ST segment elevation in II, III and aV(F), and his symptoms were relieved by intravenous bolus administration of nicorandil. He was diagnosed to have active variant angina, and remained symptomatic even after treatment with calcium antagonists and nitrates at optimal doses. Intravenous bolus administration of nicorandil was consistently effective to relieve his symptoms. Anginal attack was finally prevented by massive oral nicorandil in addition to conventional treatment.

Despite the common use of diagnostic pretransplant deceased donor kidney biopsy, there is no consensus on the prognostic significance of the pathologic findings. In order to assist clinicians with interpretation we analyzed 371 pretransplant biopsies and correlated the findings with graft failure. Glomerular pathology was assessed with percent glomerulosclerosis (GS), glomerular size and periglomerular fibrosis (PGF); vascular pathology with arterial wall-to-lumen ratio (WLR) and arteriolar hyalinosis and interstitial pathology with measurement of cumulative fibrosis and presence of scar. Using two-thirds of the study population as a model-development cohort, we found that biopsy features independently associated with an increased risk of graft failure were GS > or =15%, interlobular arterial WLR > or =0.5 and the presence of PGF, arteriolar hyalinosis or scar. The Maryland Aggregate Pathology Index (MAPI), was developed from these parameters and validated on the remaining one-third of the population. Five-year actuarial graft survival was 90% for kidneys with MAPI scores between 0 and 7, 63% for scores from 8 to 11 and 53% for scores from 12 to 15 (p < 0.001). We conclude MAPI may help transplant physicians estimate graft survival from the preimplantation biopsy findings, in clinical situations similar to this study population (cold ischemia over 24 h, GS < 25%).

Captive adult common marmosets (Callithrix jacchus) produce whistle-like "phee" calls in two contexts; in the home cage environment, phee calls may function as part of territorial marking behavior, and when animals are separated from social companions, phee calls may serve to reunite the group. Isolation phee calls tend to have more syllables than calls produced in the home cage by the same animals, and as a result, are longer in duration. The durations of isolation call syllables are shorter than in home cage calls, and isolation calls have lower start and end frequencies, higher peak frequencies, and increased frequency range compared to phee calls produced by the same animals in their home cages. The modifications made to the general structure of the phee call by isolated animals result in more information that may indicate context or location of an isolated caller. When the vocalizations were analyzed by sex, between-sex differences in call structure appeared consistently in both contexts. Males tended to exhibit higher call frequencies and greater variability between syllables than females. Published 1993 Wiley-Liss, Inc.

In most cases, vascularization is the first requirement to achieve tissue regeneration. The delivery from implants of angiogenic factors, like VEGF, has been widely investigated for establishing a vascular network within the developing tissue. In this report, we investigated if encapsulation of VEGF in nanoparticles could enhance angiogenesis in vivo as compared to free VEGF when incorporated into two different types of 3D matrices: Matrigel™ hydrogels and PLGA scaffolds. Negatively charged nanoparticles encapsulating VEGF were obtained with a high efficiency by complex formation with dextran sulfate and coacervation by chitosan. After 2weeks, encapsulation reduced VEGF release from hydrogels from 30% to 1% and increased VEGF release from scaffolds from 20% to 30% in comparison with free VEGF. VEGF encapsulation consistently improved angiogenesis in vivo with both type of 3D matrices: up to 7.5- to 3.5-times more endothelial and red blood cells were observed, respectively, into hydrogels and scaffolds. Hence, encapsulation in nanoparticles enhanced VEGF efficiency by protection and controlled release from 3D implants. Encapsulation and incorporation of VEGF into 3D implants that, in addition to sustaining cell infiltration and organization, will stimulate blood vessel are a promising approach for tissue regeneration engineering.

Cephaloridin (ceporin of "Pliva", Yugoslavia) was used in the treatment of patients after allotransplantation of the kidney from a cadaver during the early postoperative period with a purpose of prevention (5 patients) and therapy of complications, such as pneumonia (7 patients), sepsis (3 patients), pyelonephritis of the transplanted kidney (4 patients). The drug levels in the blood serum and urine were determined 1, 2, 4, 6, 8 and 24 hours after the administration. The drug was used with regard for the transplant function estimated by the data of the glomerular filtration and concentration of the nitrous residues in the blood. The antibiotic dose depended on the transplant function. The study provided some recommendations as for the ceporin use in therapy of such population of patients.

Epidemiologic studies have reported that moderate alcohol consumption is inversely associated with the risk of renal cancer. However, there is no information available on the associations in renal cancer subsites. From 1992 through to 2010, 477,325 men and women in the European Prospective Investigation into Cancer and Nutrition cohort were followed for incident renal cancers (n = 931). Baseline and lifetime alcohol consumption was assessed by country-specific, validated dietary questionnaires. Information on past alcohol consumption was collected by lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazard models. In multivariate analysis, total alcohol consumption at baseline was inversely associated with renal cancer; the HR and 95% CI for the increasing categories of total alcohol consumption at recruitment versus the light drinkers category were 0.78 (0.62-0.99), 0.82 (0.64-1.04), 0.70 (0.55-0.90), 0.91 (0.63-1.30), respectively, (ptrend  = 0.001). A similar relationship was observed for average lifetime alcohol consumption and for all renal cancer subsites combined or for renal parenchyma subsite. The trend was not observed in hypertensive individuals and not significant in smokers. In conclusion, moderate alcohol consumption was associated with a decreased risk of renal cancer.

This is the first multisite, prospective study of behavioral and mental health disorders of youth in residential treatment centers (RTC) and therapeutic foster care (TFC), and the first study to compare the two. This study addressed two questions in a sample of 22 agencies in 13 states: (1) how prevalent were emotional and behavioral disorders in the youth admitted to RTCs and TFC?, and (2) were the youth in RTCs significantly more likely to be disturbed than youth served in TFCs? Data were drawn from the Time 1 phase of the longitudinal national "Odyssey Project" developed by the Child Welfare League of America (1995). Measures included an extensive child and family characteristics form (CFC) and the Child Behavior Checklist (CBCL). The results revealed extremely high levels of behavioral and mental health disorders in the sample as a whole, well above the norms for a non-child welfare population. The prevalence of disorder in the RTC population was substantially greater than in the TFC population.

The Global Invasive Species Database, GISD, comprises 27 species of the most significant invasive alien insects in the world (through November, 2005), 6 of which are originally native to China, 11 are established in China, and 10 have a potential invasion threat to China. This paper discusses these species in terms of distribution, harmfulness and dispersal ways, and finds that: (i) Information regarding invasive insects in the GISD remains inadequate. Such harmful invasive species as Opogona sacchari (Bojer), Oracella acuta (Lobdell), and Dendroctonus valens LeConte are not included. (ii) Ten species of invasive insects, particularly Lasius neglectus Van Loon and Linepithema humile (Mayr) which become established in areas near China, have the potential to become established in China. (iii) Special attention should be paid to species from Asia and the Americas because of their greater likelihood of becoming established in China. Finally, some management strategies including legislation, quarantine, early warning, prevention and control are suggested.

Development of the genitourinary tract requires spatiotemporal expression of a myriad of genes involved in various cascades and signaling events. To date, researchers have put great efforts into defining the etiology of these malformations. However, many aspects remain unsolved. This paper reviews the most recent progress in identifying causally related genes and novel loci assumed to harbor genes involved in the formation of urogenital malformations. These investigations have been considerately accelerated by the implementation of molecular karyotyping using array techniques and next generation sequencing strategies.

Astrocytic glycogen works as an essential energy reserve for surrounding neurons and is reported to accumulate excessively during cerebral ischemia/reperfusion (I/R) injury. Our previous study found that accumulated glycogen mobilization exhibits a neuroprotective effect against I/R damage. In addition, ischemia could transform astrocytes into A1-like (toxic) and A2-like (protective) subtypes. However, the underlying mechanism behind accumulated glycogen mobilization-mediated neuroprotection in cerebral reperfusion injury and its relationship with the astrocytic A1/A2 paradigm is unknown.

Proteins in the eye lens have negligible turnover and therefore progressively accumulate chemical modifications during aging. Carbonyls and oxidative stresses, which are intricately linked to one another, predominantly drive such modifications. Oxidative stress leads to the loss of glutathione (GSH) and ascorbate degradation; this in turn leads to the formation of highly reactive dicarbonyl compounds that react with proteins to form advanced glycation end products (AGEs). The formation of AGEs leads to the crosslinking and aggregation of proteins contributing to lens aging and cataract formation. To inhibit AGE formation, we developed a disulfide compound linking GSH diester and mercaptoethylguanidine, and we named it carboxitin. Bovine lens organ cultured with carboxitin showed higher levels of GSH and mercaptoethylguanidine in the lens nucleus. Carboxitin inhibited erythrulose-mediated mouse lens protein crosslinking, AGE formation and the formation of 3-deoxythreosone, a major ascorbate-derived AGE precursor in the human lens. Carboxitin inhibited the glycation-mediated increase in stiffness in organ-cultured mouse lenses measured using compressive mechanical strain. Delivery of carboxitin into the lens increases GSH levels, traps dicarbonyl compounds and inhibits AGE formation. These properties of carboxitin could be exploited to develop a therapy against the formation of AGEs and the increase in stiffness that causes presbyopia in aging lenses.

Addition of a CAMAC modular data handling system to a small computer used for gamma-camera work has allowed the acquisition and processing of a broad variety of nuclear medicine data. Significant contributions have been made ranging from clinical renal evaluation to radiopharmaceutical development. Digital rectilinear scanning and computer acquisition of physiological signals such as the electrocardiogram are other applications. The system provides an inexpensive means of matching present-day nuclear computers to the diversity of data.

Bile acids are implicated as aetiological factors in many types of gastrointestinal tract cancer including cholangiocarcinoma (CCA). Alterations in bile acid concentrations may affect the pathogenesis of these different types of cancer. Our aim was to determine the bile acid profile in gallbladder bile from patients who underwent liver resection. Thirty-seven patients with cholangiocarcinoma, 5 with hepatocellular carcinoma, and 7 with benign biliary diseases were studied. High pressure liquid chromatography was used to analyze conjugated and unconjugated bile acids. CCA patients with low (≤ 2 mg/dl) and high (>2 mg/dl) levels of total serum bilirubin had significantly higher total bile acid and conjugated bile acid concentrations than the benign biliary disease group. Markedly elevated levels of cholic and chenodeoxycholic acid were found in CCA cases with high levels of total serum bilirubin. Concentrations of total bile acids and primary bile acid were correlated with serum cholesterol, bilirubin and ALP in CCA. Notably, correlation of the carcinoembryonic antigen, a tumor marker, was found with level of total bile acids and chenodeoxycholic acid. These findings suggest a different pattern of bile acid concentration in cancer patients compared to patients with benign biliary diseases. Thus, accumulation of certain bile acids may be involved in carcinogenesis.

In this paper we argue that for the (probabilistic) interpretation of generic sentences of the form "<i>G</i>s are <i>f</i>," three types of alternatives play a role: (i) alternative features of <i>f</i>, (ii) alternative groups, or kinds, of <i>G</i>, and (iii) alternative causal background factors. In the first part of this paper we argue for the relevance of these alternatives. In the second part, we describe the results of some experiments that empirically tested in particular the second use of alternatives.

Seven wild-caught ball pythons (Python regius), including six gravid females and one male, were obtained from Africa and were housed in a government animal facility in Research Triangle Park, North Carolina. Upon arrival, the snakes were found to be infested with ticks (Aponomma latus), which were manually removed. Four weeks following arrival, vesicular skin lesions began to appear on the snakes. Despite treatment of all affected female snakes with amikacin (5 mg/kg i.m., every 3 days) and cefotaxime (25 mg/kg i.m., every 3 days), the condition progressed and five of the female snakes died 7 wk after arrival. The remaining male and one female improved after an increase in environmental temperature, with ecdysis followed by healing. Physiologic stress, ectoparasites, and shipping may have predisposed the snakes to sepsis.

We examined 111 patients with acute type- or lymphoma type-adult T-cell leukemia (ATL) and compared them with 106 patients with non-Hodgkin's lymphoma (NHL). In addition to skin involvement and hypercalcemia which are already known to be frequent in ATL, ATL patients showed an higher incidence of hepatic involvement. There was more frequent palpable hepatomegaly, higher total bilirubin, GOT, GPT, lactate dehydrogenase (LDH), and alkaline phosphatase values in ATL than in NHL patients (p < 0.0001). Among 36 autopsied liver samples, invasion of ATL cells was confirmed in 22 cases. ATL patients with impaired hepatic function showed shorter survival times than patients without hepatic dysfunction. Moreover, ATL patients showed a worse performance status (PS), a higher incidence of lytic bone lesions, lower total protein (TP) and serum albumin levels than NHL patients. This invasive characters of ATL cells and consequent impaired general condition seemed to be factors affecting the poor prognosis recorded in ATL.

Ticks are blood-feeding parasites and vectors of serious human and animal diseases. Ixodes ricinus is a common tick in Europe, transmitting tick-borne encephalitis, Lyme borreliosis, anaplasmosis, or babesiosis. Immunization of hosts with recombinant tick proteins has, in theory, the potential to interfere with tick feeding and block transmission of pathogens from the tick to the host. However, the efficacy of tick antigens has, to date, not been fully sufficient to achieve this. We have focused on 11 in silico identified genes encoding proteins potentially involved in tick iron and heme metabolism. Quantitative real-time PCR (qRT-PCR) expression profiling was carried out to preferentially target proteins that are up-regulated during the blood meal. RNA interference (RNAi) was then used to score the relative importance of these genes in tick physiology. Finally, we performed vaccination screens to test the suitability of these proteins as vaccine candidates. These newly identified tick antigens have the potential to improve the available anti-tick vaccines.

During pregnancy, the demand for folic acid increases since the fetus requires this nutrient for its rapid growth and cell proliferation. The placenta concentrates folic acid into the fetal circulation; as a result the fetal levels are 2 to 4 times higher than the maternal level. Animal and in vitro studies have suggested that alcohol may impair transport of folic acid across the placenta by decreasing expression of transport proteins. We aim to determine if folate transfer to the fetus is altered in human pregnancies with chronic alcohol consumption.

Uric acid is a waste metabolite produced from the breakdown of purines, and elevated serum uric acid levels are associated with higher risk of hypertension, cardiovascular disease, and mortality and progression of chronic kidney disease (CKD). Treatment of hyperuricemia in patients with preexisting CKD has not been shown to improve kidney outcomes, but the associations of uric acid-lowering therapies with the development of new-onset kidney disease in patients with estimated glomerular filtration rate (eGFR) within reference range and no albuminuria is unclear.

Taxometric research methods were developed by Paul Meehl and colleagues to distinguish between categorical and dimensional models of latent variables. We have conducted a comprehensive review of published taxometric research that included 177 articles, 311 distinct findings and a combined sample of 533 377 participants. Multilevel logistic regression analyses have examined the methodological and substantive variables associated with taxonic (categorical) findings. Although 38.9% of findings were taxonic, these findings were much less frequent in more recent and methodologically stronger studies, and in those reporting comparative fit indices based on simulated comparison data. When these and other possible confounds were statistically controlled, the true prevalence of taxonic findings was estimated at 14%. The domains of normal personality, mood disorders, anxiety disorders, eating disorders, externalizing disorders, and personality disorders (PDs) other than schizotypal yielded little persuasive evidence of taxa. Promising but still not definitive evidence of psychological taxa was confined to the domains of schizotypy, substance use disorders and autism. This review indicates that most latent variables of interest to psychiatrists and personality and clinical psychologists are dimensional, and that many influential taxonic findings of early taxometric research are likely to be spurious.

The skins of many plants and animals have intricate microscale surface features that give rise to properties such as directed water repellency and adhesion, camouflage, and resistance to fouling. However, engineered mimicry of these designs has been restrained by the limited capabilities of top-down fabrication processes. Here we demonstrate a new technique for scalable manufacturing of freeform microstructures via strain-engineered growth of aligned carbon nanotubes (CNTs). Offset patterning of the CNT growth catalyst is used to locally modulate the CNT growth rate. This causes the CNTs to collectively bend during growth, with exceptional uniformity over large areas. The final shape of the curved CNT microstructures can be designed via finite element modeling, and compound catalyst shapes produce microstructures with multidirectional curvature and unusual self-organized patterns. Conformal coating of the CNTs enables tuning of the mechanical properties independently from the microstructure geometry, representing a versatile principle for design and manufacturing of complex microstructured surfaces.

Survivors of critical illness often undergo an extended recovery trajectory. Reduced functional ability is one of several adverse outcomes of prolonged bed rest and mechanical ventilation during critical illness. Skeletal muscle weakness is known to be one of the major phenomena that account for reduced functional ability. Although skeletal muscle weakness is evident after prolonged mechanical ventilation (PMV), few studies have tested the benefits of various types of mobility interventions in this population. The purpose of this article is to review the published research on improving mobility outcomes in patients undergoing PMV. For this review, published studies were retrieved from MEDLINE, PubMed, CINAHL, and the Cochrane Database of Systematic Reviews from January 1990 to July 2007. A total of 10 relevant articles were selected that examined the effect of whole body physical therapy, electrical stimulation (ES), arm exercise, and inspiratory muscle training (IMT). Overall, there is support for the ability of mobility interventions to improve outcomes in patients on PMV but limited evidence of how to best accomplish this goal. Generating more data from multicenter studies and randomized controlled trials is recommended.

This paper surveys the data-driven dose prediction methods investigated for knowledge-based planning (KBP) in the last decade. These methods were classified into two major categories-traditional KBP methods and deep-learning (DL) methods-according to their techniques of utilizing previous knowledge. Traditional KBP methods include studies that require geometric or anatomical features to either find the best-matched case(s) from a repository of prior treatment plans or to build dose prediction models. DL methods include studies that train neural networks to make dose predictions. A comprehensive review of each category is presented, highlighting key features, methods, and their advancements over the years. We separated the cited works according to the framework and cancer site in each category. Finally, we briefly discuss the performance of both traditional KBP methods and DL methods, then discuss future trends of both data-driven KBP methods to dose prediction.

Lactate racemase (LarA), a new nickel enzyme discovered recently, catalyzes the racemization between d- and l-lactates with a novel nickel pincer cofactor (Ni-PTTMN) derived from nicotinic acid. In this study, by using DFT and a 200-atom active-site model, LarA is revealed to employ a modified proton-coupled hydride-transfer mechanism in which a hydride is transferred to a cofactor pyridine carbon from the substrate &#945;-carbon along with proton transfer from the substrate hydroxy group to a histidine, and then moved back from the opposite side. Tyr294 and Lys298 provide significant acceleration effects by orientating substrates and stabilizing the negative charge developing at the substrate hydroxy oxygen. The barrier was determined to be 12.0&#8197;kcal&#8201;mol^-1 , which reveals enhanced racemase activity relative to the LarA reaction using NAD⁺ -like cofactors. Compared with NAD⁺ , Ni-PTTMN has a stronger hydride-addition reactivity in moderate and high environmental polarity and may fit perfectly the moderately polar active site of LarA.

Extracellular signal-regulated kinase 8 (ERK8), proposed as a novel potential therapeutic target for cancer, has been implicated in cell transformation, apoptosis, the protection of genomic integrity, and autophagy. To facilitate ERK8 research, a highly specific anti-ERK8 antibody is needed. In this article, we use the Immune Epitope Database and Analysis Resource online tool to predict B-cell epitopes of human ERK8 protein, and choose a 28 aa-peptide sequence to generate the GST-ERK8(28aa) fusion protein as the antigen for developing polyclonal antibody against ERK8. The specificity and sensitivity of anti-ERK8 antibody were robustly validated by immunoblotting, immunocytochemical and immunohistochemical analyses; and we found that both the endogenous and ectopically-expressed human ERK8 proteins can be recognized by our anti-ERK8 antibody. This suggested that our characterized anti-ERK8 antibody will be a valuable tool for the elucidation of the distribution of ERK8 at cellular and histological levels. Finally, our tissue array analysis also demonstrated that the ERK8 protein was localized in both the nucleus and cytoplasm of human lung cancers.

Adipose-derived stem cells (ASCs) have been found adapted to a specific niche with low oxygen tension (hypoxia) in the body. As an important component of this niche, oxygen tension has been known to play a critical role in the maintenance of stem cell characteristics. However, the effect of O2 tension on their functional properties has not been well determined. In this study, we investigated the effects of O2 tension on ASCs stemness, differentiation and proliferation ability. Human ASCs were cultured under normoxia (21% O2) and hypoxia (2% O2). We found that hypoxia increased ASC stemness marker expression and proliferation rate without altering their morphology and surface markers. Low oxygen tension further enhances the chondrogenic differentiation ability, but reduces both adipogenic and osteogenic differentiation potential. These results might be correlated with the increased expression of HIF-1α under hypoxia. Taken together, we suggest that growing ASCs under 2% O2 tension may be important in expanding ASCs effectively while maintaining their functional properties for clinical therapy, particularly for the treatment of cartilage defects.

A series of 4-dimethylamine flavonoid derivatives 5a-5r were designed, synthesized and evaluated as potential multi-functional anti-Alzheimer agents. The results showed that most of the synthesized compounds exhibited high acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity at the micromolar range (IC50, 1.83-33.20 μM for AChE and 0.82-11.45 μM for BChE). A Lineweaver-Burk plot indicated a mixed-type inhibition for compound 5j with AChE, and molecular modeling study showed that 5j targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, the derivatives showed potent self-induced Aβ aggregation inhibitory activity at 20 μM with percentage from 25% to 48%. In addition, some compounds (5j-5q) showed potent oxygen radical absorbance capacity (ORAC) ranging from 1.5- to 2.6-fold of the Trolox value. These compounds should be further investigated as multi-potent agents for the treatment of Alzheimer's disease.

This study investigated the relationship between visuo-spatial representation, mental rotation (MR) and functional anatomy examination results. A total of 184 students completed the Group Embedded Figures Test (GEFT), Mental Rotation Test (MRT) and Gordon Test of Visual Imagery Control. The time spent on personal assignment was also considered. Men were found to score better than women on both GEFT and MRT, but the gender effect was limited to the interaction with MRT ability in the anatomy learning process. Significant correlations were found between visuo-spatial, MR abilities, and anatomy examination results. Data resulting from the best students' analyzes underscore the effect of high MR ability which may be considered reliable predictor of success in learning anatomy. The use of specific tests during learning sessions may facilitate the acquisition of anatomical knowledge.

Plant seeds accumulate large amounts of storage reserves comprising biodegradable organic matter. Humans rely on seed storage reserves for food and as industrial materials. Gene expression profiles are powerful tools for investigating metabolic regulation in plant cells. Therefore, detailed, accurate gene expression profiles during seed development are required for crop breeding. Acquiring highly purified RNA is essential for producing these profiles. Efficient methods are needed to isolate highly purified RNA from seeds. Here, we describe a method for isolating RNA from seeds containing large amounts of oils, proteins, and polyphenols, which have inhibitory effects on high-purity RNA isolation. Our method enables highly purified RNA to be obtained from seeds without the use of phenol, chloroform, or additional processes for RNA purification. This method is applicable to Arabidopsis, rapeseed, and soybean seeds. Our method will be useful for monitoring the expression patterns of low level transcripts in developing and mature seeds.

The first revision of the guideline 'Influenza and influenza vaccination' from the Dutch College of General Practitioners contains the new indications for influenza vaccination. The most important revisions are: the minimum age has been lowered from 65 to 60 years, the indication for furunculosis patients and their families has been removed, and vaccination is recommended to healthcare professionals who have regular and intensive contact with patients. The purpose of vaccinating healthcare professionals against influenza is to reduce the transmission of the influenza virus to patients at very high risk of complications from influenza and reduce sick leave among healthcare professionals. The use of antiviral agents should only be considered for patients with a very high risk of complications from influenza.

Given the recent emergence of chikungunya in the Americas, the accuracy of forecasting and prediction of chikungunya transmission potential in the U.S. requires urgent assessment. The La Reunion-associated sub-lineage of chikungunya (with a valine substitution in the envelope protein) was shown to increase viral fitness in the secondary vector, Ae. albopictus. Subsequently, a majority of experimental and modeling efforts focused on this combination of a sub-lineage of the East-Central-South African genotype (ECSA-V)-Ae. albopictus, despite the Asian genotype being the etiologic agent of recent chikungunya outbreaks world-wide. We explore a collection of data to investigate relative transmission efficiencies of the three major genotypes/sub-lineages of chikungunya and found difference in the extrinsic incubation periods to be largely overstated. However, there is strong evidence supporting the role of Ae. albopictus in the expansion of chikungunya that our R0 calculations cannot attribute to fitness increases in one vector over another. This suggests other ecological factors associated with the Ae. albopictus-ECSA-V cycle may drive transmission intensity differences. With the apparent bias in literature, however, we are less prepared to evaluate transmission where Ae. aegypti plays a significant role. Holistic investigations of CHIKV transmission cycle(s) will allow for more complete assessment of transmission risk in areas affected by either or both competent vectors.

Nitrate aqueous solutions, Mg(NO(3))(2), Ca(NO(3))(2), Sr(NO(3))(2), and Pb(NO(3))(2), are investigated using Raman spectroscopy and free energy profiles from molecular dynamics (MD) simulations. Analysis of the in-plane deformation, symmetric stretch, and asymmetric stretch vibrational modes of the nitrate ions reveal perturbation caused by the metal cations and hydrating water molecules. Results show that Pb(2+) has a strong tendency to form contact ion pairs with nitrate relative to Sr(2+), Ca(2+), and Mg(2+), and contact ion pair formation decreases with decreasing cation size and increasing cation charge density: Pb(2+) > Sr(2+) > Ca(2+) > Mg(2+). In the case of Mg(2+), the Mg(2+)-OH(2) intermolecular modes indicate strong hydration by water molecules and no contact ion pairing with nitrate. Free energy profiles provide evidence for the experimentally observed trend and clarification between solvent-separated, solvent-shared, and contact ion pairs, particularly for Mg(2+) relative to other cations.

Withania somnifera, popularly known as Indian ginseng, is one of the most important medicinal plants. The plant is well studied in terms of its pharmaceutical activities and genes involved in biosynthetic pathways. However, not much is known about the regulatory mechanism of genes responsible for the production of secondary metabolites. The idea was to identify miRNA transcriptome responsible for the regulation of withanolide biosynthesis, specifically of root and leaf tissues individually. The transcriptome data of in vitro culture of root and leaf tissues of the plant was considered for miRNA identification. A total of 24 and 39 miRNA families were identified in root and leaf tissues, respectively. Out of these, 15 and 27 miRNA families have shown their involvement in different biological functions in root and leaf tissues, respectively. We report here, specific miRNAs and their corresponding target genes for corresponding root and leaf tissues. The target genes have also been analyzed for their role in withanolide metabolism. Endogenous root-miR5140, root-miR159, leaf-miR477, and leaf-miR530 were reported for regulation of withanolide biosynthesis.

The use of tapered, fluted, modular, distally fixing stems has increased in femoral revision surgery. The goal of this retrospective study was to assess mid-term to long-term outcomes of this implant. Seventy-one hips in 70 patients with a mean age of 69 years were followed for an average of 10 years. Preoperative HHS averaged 50 and improved to 87 postoperatively. Seventy-nine percent hips had Paprosky type 3A or more bone-loss. All stems osseointegrated distally (100%). Two hips subsided >5mm but achieved secondary stability. Sixty-eight percent hips had evidence of bony reconstitution and 21% demonstrated diaphyseal stress-shielding. One stem fractured near its modular junction and was revised with a mechanical failure rate of 1.4%. Distal fixation and clinical improvement were reproducibly achieved with this stem design.

A methodology is described for analysing the Cambridge Structural Database (CSD) in terms of molecular conformations. Molecular species that have more than a single occurrence across the complete CSD are identified, either as the sole crystal component or co-crystallized with other components. Cluster analysis, based on a root-mean-square fit of coordinates and chemical connectivity, is performed to identify conformational variance for each molecule. Results are analysed in terms of the number of discrete conformations observed versus the number of crystal environments and number of acyclic torsion angles in the molecule. Special subsets of environments are also analysed, namely polymorphs, co-crystals and solvates. In general, conformational diversity increases with an increasing number of different crystal environments and with an increasing number of flexible torsion angles. Overall, molecules with one or more acyclic flexible torsion angle are observed to exist in more than one conformation in ca 40% of cases. There is evidence that solvated molecules exhibit more conformational flexibility on average, compared with polymorphs and co-crystals.

Brain activity relating to recognition of action varies among subjects. These differences have been hypothesised to originate from genetic and environmental factors although the extent of their effect remains unclear. Effects of these factors on brain activity during action recognition were evaluated by comparing magnetoencephalography (MEG) signals in twins. MEG signals of 20 pairs of elderly monozygotic twins and 11 pairs of elderly dizygotic twins were recorded while they observed finger movements and copied them. Beamformer and group statistical analyses were performed to evaluate spatiotemporal differences in cortical activities. Significant event-related desynchronisation (ERD) of the β band (13-25 Hz) at the left inferior parietal lobule (IPL) was observed for both action observation and execution. Moreover, β-band ERD at the left IPL during action observation was significantly better correlated among monozygotic twins compared to unrelated pairs (Z-test, p = 0.027). β-band ERD heritability at the left IPL was 67% in an ACE model. These results demonstrate that β-band ERD at the IPL, which is commonly observed during action recognition and execution, is affected by genetic rather than environmental factors. The effect of genetic factors on the cortical activity of action recognition may depend on anatomical location and frequency characteristics.

Solutions to the radiation diffusion equation predict the absorbed energy ("wall loss") within an inertial confinement fusion (ICF) hohlraum. Comparing supersonic versus subsonic solutions suggests that a high metallic foam as hohlraum wall material will reduce hydrodynamic losses, and hence, net absorbed energy by . We derive an analytic expression for the optimal density (for any given drive temperature and pulse-length) that will achieve this reduction factor and which agrees well with numerical simulations. This approach can increase the coupling efficiency of indirectly driven ICF capsules.

Ants are the hosts of many microorganisms, including pathogens that are incidentally brought inside the nest by foragers. This is particularly true for scavenging species, which collect hazardous food such as dead insects. Foragers limit sanitary risks by not retrieving highly infectious prey releasing entomopathogenic fungal spores. This study investigates whether similar prophylactic strategies are also developed for food associated with weak or delayed risks of fungal contamination. We compared, in <i>Myrmica rubra</i> ant colonies, the retrieval dynamics of dead flies that were (1) conidia-free, (2) covered with a low amount of <i>Metarhizium brunneum</i> entomopathogenic conidia or (3) recently fungus-killed but not yet sporulating. Foragers mostly avoided fungus-killed prey and delayed the retrieval of conidia-covered flies. A second sanitary filter occurred inside the nest through a careful inspection of the retrieved prey. Ultimately, ants mostly consumed conidia-free and conidia-covered flies, but they relocated and discarded all fungus-killed prey outside of the nest. Our study confirms that, as a host of generalist entomopathogenic fungi, <i>Myrmica rubra</i> ants have developed a prophylactic avoidance and a differential management of prey depending on their infectious potential. We discuss the functional value as well as the possible cues underlying pathogen avoidance and prey discrimination in ants.

PI3Ks are important lipid kinases that produce phosphoinositides phosphorylated in position 3 of the inositol ring. There are three classes of PI3Ks: class I PI3Ks produce PIP3 at plasma membrane level. Although D. melanogaster and C. elegans have only one form of class I PI3K, vertebrates have four class I PI3Ks called isoforms despite being encoded by four different genes. Hence, duplication of these genes coincides with the acquisition of coordinated multi-organ development. Of the class I PI3Ks, PI3Kα and PI3Kβ, encoded by PIK3CA and PIK3CB, are ubiquitously expressed. They present similar putative protein domains and share PI(4,5)P2 lipid substrate specificity. Fifteen years after publication of their first isoform-selective pharmacological inhibitors and genetically engineered mouse models (GEMMs) that mimic their complete and specific pharmacological inhibition, we review the knowledge gathered in relation to the redundant and selective roles of PI3Kα and PI3Kβ. Recent data suggest that, further to their redundancy, they cooperate for the integration of organ-specific and context-specific signal cues, to orchestrate organ development, physiology, and disease. This knowledge reinforces the importance of isoform-selective inhibitors in clinical settings.

The association of Helicobacter pylori in the stomach, trachea and lungs with the incidence of SIDS, gastric ulcers and cancer may have a counterpart in animals. In field studies of white muscle disease (WMD) and hepatic necrosis in selenium-deficient pigs dying suddenly, veterinarians identified gastric ulcers in 40% of inspected piglets. The lesion was also commonly observed by researchers in experimentally produced vitamin E-selenium deficiency and other researchers suspected that gastric ulcers in swine may be associated with vitamin E-selenium deficiency. Mice preferentially concentrated (75)selenium in peritoneal exudative cells (PEC) when (75)selenium as selenium selenate was administered by stomach tube to selenium-deficient mice. Selenium concentrated in PECs as glutathione peroxidase (GSHP(x)). GSHP(x)-deficient leucocytes in peritoneal exudate failed to kill yeast cells. GSHP(x) deficiency has also been associated with decreased microbicidal activity of leucocytes in patients with chronic granulomatosis. The selenium-deficient swine were usually growing rapidly in crowded conditions, and, apart from WMD and hepatic necrosis, edema was prominent in the spiral colon, subcutaneous tissues, lungs and submucosa of the stomach. The elevated immunological response in the spleen and lungs of SIDS victims suggests an initial defective microbicidal propensity of the peritoneal exudative cells.

Considerable research effort in the past several decades has focused on the impact of psychological stress, and stress hormones, on cancer <i>progression</i>. Numerous studies have reported that stress hormone treatment or <i>in vivo</i> stress exposure can enhance the growth of tumor cell lines <i>in vitro</i>, as well as tumors in animal models, and have begun to explore molecular mechanisms. Comparatively little research has focused on the impact of psychological stress and stress hormones on cancer <i>initiation</i>, in part due to inherent methodological challenges, but also because potential underlying biological mechanisms have remained obscure. In this review, we present a testable theoretical model of pathways by which stress may result in cellular transformation and tumorigenesis. This model supports our overarching hypothesis that psychological stress, acting through increased levels of catecholamines and/or cortisol, can increase DNA damage and/or reduce repair mechanisms, resulting in increased risk of DNA mutations leading to carcinogenesis. A better understanding of molecular pathways by which psychological stress can increase the risk of cancer initiation would open new avenues of translational research, bringing together psychologists, neuroscientists, and molecular biologists, potentially resulting in the development of novel approaches for cancer risk reduction at the population level.

While the family's primacy in the patient's adaptation to chronic illness increasingly is being recognized by health professionals and social scientists, the reverse side of the coin, that is, the impact of chronicity on the family, has received little attention. A life-span development perspective is used to enrich the more traditional frameworks employed to study family development and also as a unifying framework from which to view the impact of illness on individual family members and the family as a unit. A review of selected literature reveals a profile of families most at risk for serious disruption in situations involving chronic illness. Propositions suggesting interventions directed at patients and families experiencing chronicity are derived.

Children require a large amount of time, effort, and resources to raise. Physical help, financial contributions, medical care, and other types of assistance from kin and social network members allow couples to space births closer together while maintaining or increasing child survival. We examine the impact of kin availability on couples' reproductive success in the early twentieth-century United States with a panel data set of over 3.1 million couples linked between the 1900 and 1910 U.S. censuses. Our results indicate that kin proximity outside the household was positively associated with fertility, child survival, and net reproduction, and suggest that declining kin availability was an important contributing factor to the fertility transition in the United States. We also find important differences between maternal and paternal kin inside the household-including higher fertility among women residing with their mother-in-law than among those residing with their mother-that support hypotheses related to the contrasting motivations and concerns of parents and parents-in-law.

The yellow-pigmented, Gram-stain-negative, rod-shaped bacterium KJ1R5(T) was isolated from the root of a pepper plant grown in a field in Kwangju, Korea. Strain KJ1R5(T) was characterized by physiological, biochemical, and molecular genetic analyses. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain KJ1R5(T) was most closely related to members of the genus Chryseobacterium, and that the strain exhibited the highest similarities with type strains of Chryseobacterium vrystaatense (97.0 %) and Chryseobacterium rhizosphaerae (97.1 %). DNA-DNA hybridization reassociation values between strain KJ1R5(T) and type strains of C. vrystaatense KACC 11675(T) and C. rhizosphaerae KACC 14918(T) were 46.9 and 38.4 %, respectively. The DNA G+C content of KJ1R5(T) is 40.2 mol%. The predominant respiratory quinone of KJ1R5(T) was menaquinone MK-6; major cellular fatty acids were iso-C15 : 0, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), iso-C17 : 1ω9c, and iso-C17 : 0 3-OH. On the basis of these phenotypic and genotypic characteristics, the strain significantly differed from representative strains belonging to the genus Chryseobacterium. Thus, we propose that strain KJ1R5(T) represents a novel species of the genus Chryseobacterium, named Chryseobacterium kwangjuense sp. nov. The type strain is KJ1R5(T) (= KACC 13029(T) = JCM 15904(T)).

Computed tomography and magnetic resonance imaging are routinely used during follow-up of radiofrequency ablation (RFA) of renal masses. Widespread acceptance of needle ablation is limited by the need to rely on radiographic criteria to confirm effective ablation. In this report, we correlated the long-term radiographic appearance of RFA with the histologic findings in three delayed nephrectomy specimens. This should enhance our understanding of the histopathologic features of successful RFA and highlight potential shortcomings of modern imaging after ablation.

Recent evidence has documented that a combination of single-modality evidence-based care principles into a multimodal effort to enhance postoperative recovery (the fast track methodology) has led to enhanced recovery with reduced medical morbidity, need for hospitalisation and convalescence. Nevertheless, general implementation of fast track surgery has been relatively slow despite concomitant economic benefits. Further improvement in postoperative outcome may be obtained by developments within each care principle with a specific focus on minimally invasive surgery, effective multimodal, non-opioid analgesia and pharmacological stress reduction.

Transmissible spongiform encephalopathies (TSEs), also called prion diseases, are fatal, infectious, genetic or sporadic neurodegenerative disorders of humans and animals. In humans, TSEs are represented by Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome, Fatal Familial Insomnia and Kuru. In animals, the most prominent prion diseases are scrapie of sheep and goats, bovine spongiform encephalopathy (BSE) of cattle and chronic wasting disease (CWD) of deer and elk. A critical event in prion diseases is the accumulation in the central nervous system (CNS) of the abnormally folded PrP(Sc) protein that is the protease-resistant isoform of a normal cellular protein encoded by the host and called PrP(C). PrP(Sc) (also known as rPrP(Sc) or PrP27-30) represents the main marker of prion diseases and is routinely used in the reference method for the diagnosis of prion diseases. Most of the therapeutic strategies developed so far aimed at identifying compounds that diminish the levels of PrP(Sc), with variable success when tested in vivo. In this review, we present an alternative approach in which small molecules that induce PrP(Sc) oligomers are identified. By using virtual and cellular screenings, we found several thienyl pyrimidine compounds that trigger PrP(Sc) oligomerization and trap prion infectivity.

Positional asphyxia is a specific type of suffocation that results from the body being forced and fixed in a particular position causing death by suffocation. The body exhibits obvious general characteristics of death by suffocation. We report a case of custody death that may have been caused by positional asphyxia. The mute criminal suspect died in a detention room after arrest. The suspect was found unconscious and died following placement in a hanging position for 8 h. We reviewed the case with respect to the autopsy findings, pathological changes, and specific scene where the death occurred as well as the circumstantial correlation of the investigation.

The objective of the present study was to examine whether prostaglandin H synthase (PGHS) can be regulated by pathways independent of de novo synthesis of PGHS. Incubation of bovine aortic endothelial cells (BAEC) for as short as 5 min with NaF (40 mM) resulted in a 60% increase in PGHS activity. PGHS activity induced by NaF was unaffected by either 10 microM cycloheximide or 1 microM actinomycin D. Aspirin (25 microM) completely inhibited resting PGHS activity, and NaF did not induce further stimulation. NS-398 (500 nM), a specific PGHS-2 inhibitor, was ineffective. Basic fibroblast growth factor (bFGF) induced a significant increase in PGHS activity within 30 min and was insensitive to cycloheximide. The levels of PGHS-1 and PGHS-2 proteins, as measured by Western blots, were not affected by NaF or bFGF. The tyrosine kinase inhibitor genistein attenuated PGHS activity that was induced by NaF and bFGF, whereas the tyrosine phosphatase inhibitor, sodium orthovanadate, augmented these responses. The G protein activators 5'-guanylyl imidodiphosphate and guanosine 5'-O-(3-thiotriphosphate) inhibited both resting and NaF-induced PGHS activities. These results suggest-that, in BAEC, PGHS-1 activity can be regulated by tyrosine kinase and/or G proteins, independently of de novo protein synthesis.

The pathogenicity of a Streptococcus ictaluri isolate in channel catfish Ictalurus punctatus at the fry (0.5 g), fingerling (15 g), and juvenile (55 g) stages was determined by experimental bath immersion and injection experiments. Channel catfish were exposed in 1-L immersion baths containing 10(8), 10(9), 10(10), 10(11) or 10(12) colony-forming units (cfu) of S. ictaluri. Fish were also injected intraperitoneally with 0.1 mL of bacterial solution for final doses of 10(4), 10(5), 10(6), 10(7), or 10(8) cfu of S. ictaluri per fish. Streptococcus ictaluri caused mortality in fry, fingerling, and juvenile channel catfish within 21 d postinfection. When mortalities were calculated based on size and challenge route, the cumulative percent mortalities were 11% for fry and 0% for fingerlings by the bath immersion route and 14% for fingerlings and 6% for juveniles by the injection route. Isolation of S. ictaluri from moribund and dead catfish was confirmed by the newly established BIOLOG profile (MicroLog3 system). The results indicate that channel catfish were only susceptible to high concentrations of S. ictaluri and that juvenile channel catfish were less susceptible, possibly explaining why little mortality has been attributed to S. ictaluri infection in catfish aquaculture.

Novel techniques have been developed to image cells at cellular and subcellular levels. They allow images to be analyzed with ultra-high resolution, in 2D and/or 3D. Several of these tools have been tested on cytology specimens demonstrating emerging applications that are likely to change the field of cytopathology. This review covers several of these advanced imaging methods. The use of optical coherence tomography to perform optical biopsies during endoscopic ultrasound procedures or visualize cells within effusion samples is discussed. The potential for quantitative phase microscopy to accurately screen Pap test slides or resolve indeterminate diagnoses in urine cytology is reviewed. The article also examines the application of 3D cytology using LuCED for lung cancer detection in sputum samples and the feasibility of imaging flow and mass cytometry to measure multiple biomarkers at the single cell level. Although these novel technologies have great potential, further research is necessary to validate their routine use in cytopathology practice.

1. The pharmacokinetics of rolipram were studied in rat, rabbit, rhesus monkey and cynomolgus monkey using 14C- or 3H-labelled rolipram and a radioimmunoassay for measurement of unchanged drug. 2. Rolipram was rapidly and completely absorbed after oral doses of up to 50 mg/kg. Bioavailability was 0.1% in rhesus monkey, 3.7% in cynomolgus monkey, 3.6% in rabbit, 35% in rat, and 75% in man. 3. Rolipram was able to pass the blood-brain barrier achieving concentrations in brain twice those in plasma. 4. Plasma levels of the unchanged drug declined with a similar half-life of 1-3 h in all species investigated. In the rat, there were indications for a different clearance of the two rolipram enantiomers. 5. Labelled rolipram was excreted rapidly and completely. The main route of elimination was via the urine.

The interactions between N-methyl-D-aspartate (NMDA), (+/-)2-amino-5-phosphonovalerate (2AP5) and (+/-)cis-2.3-piperidine dicarboxylate (cis-PDA) were examined quantitatively in the neonatal rat spinal cord in vitro. NMDA and cis-PDA evoked concentration-dependent motoneuronal depolarizations. The maximal cis-PDA-evoked response was approximately 60% of that evoked by NMDA. When applied in combination with fixed concentrations of cis-PDA, NMDA evoked concentration-dependent depolarizations superimposed upon the basal cis-PDA-evoked depolarizations, the dose-response curve for which intercepted the control dose-response curve and was subsequently moved to the right compared with the control curve. 2AP5 shifted the NMDA dose-response curves to the right and Schild regression analysis gave a pKB of 5.0 with a slope of 1.00. 2AP5 also moved the cis-PDA dose-response-curve (apparent KB 3.1 X 10(-5) M) to the right and abolished the cis-PDA component of the NMDA + cis-DPA dose-response curve. These results are consistent with the predictions of drug-receptor theory for the interactions of a full agonist (NMDA), competitive antagonist (2AP5) and partial agonist (cis-PDA) and represent further evidence for a population of excitatory amino acid receptors for which NMDA is a selective agonist.

Over the past 11 years (1974 to 1985) ten patients with perianal Paget's disease were treated. The average age was 64 years and half were male. Two patients were diagnosed as an incidental finding after hemorrhoidectomy and the remainder presented with a symptomatic perianal rash (itching and moisture) that averaged two years in duration. Physical examination in these patients demonstrated characteristic lesions (seven with erythematous or ulcerated, whitish gray lesions and one with a papillary lesion). Three patients presented with invasive carcinomas and, despite aggressive therapy, all developed metastatic disease. Two patients had local excisions with minimal margins and developed associated invasive cancers at four and ten years after diagnosis. The remaining five patients were treated by wide local excision and skin grafts. At present all are free of disease. The characteristic appearance of this lesion and its failure to respond quickly to conventional therapy should lead the clinician to obtain a biopsy which readily establishes the diagnosis. Experience confirms that wide local excision is adequate therapy, but adequate initial evaluation and close follow-up are necessary to identify other malignancies that may develop.

Since more solid evidence has emerged supporting the effectiveness of loco-regional treatment (LRT), clinicians consider LRT a treatment option for selected de novo stage IV breast cancer (BC) patients. This is the first report on long-term quality of life (QoL) in a cohort of patients who were randomized to receive either LRT and then systemic treatment (ST) or ST alone in the protocol MF07-01. We aimed to evaluate QoL in patients living at least 3 years since randomization using scores from the SF-12 health survey.

This article outlines the origins and theory of the Alexander Technique and how it is learnt. Recent research is listed and a description given of main presenting symptoms and medical problems of pupils coming for lessons. The paper also describes how the Alexander Technique is used by women in pregnancy and childbirth and explains why it is beneficial. The final section describes Parkinson's research results, mainly from a preliminary study designed some years ago to test a methodology for a randomized controlled trial.

The flow field velocity is an important parameter for completely characterizing the topologies of unsteady coherent flow structures. Synthetic aperture (SA)-based particle image velocimetry (SAPIV) has been used for three-dimensional flow measurements, owing to its wide range of acceptable tracer particle intensities and ability to view partially occluded fields. However, SAPIV typically suffers from poor reconstruction quality for nonuniformly illuminated particle volumes. In this paper, we propose a hybrid remapping particle field reconstruction method for SAPIV in a nonuniformly illuminated fluid flow. Both additive and minimum line-of-sight remapping are used to reconstruct the in-focus particles from the refocused image stacks. The structural similarity between the images projected by the reconstructed particle field and the images captured by the cameras are used to determine the reconstruction quality. This method was verified by both synthetic simulation and an experimental implementation. The performance of the proposed technique was compared with existing methods. The proposed method has the best reconstruction quality and computational speed among the considered methods.

In the present study, we aimed to investigate the effects of continuous glucose monitoring (CGM) on blood glucose levels, body weight, blood pressure, and hypoglycaemia in patients with type 2 diabetes mellitus using a meta-analysis of randomized controlled trials (RCTs). A literature search was performed using MEDLINE, Cochrane Controlled Trials Registry, and ClinicalTrials.gov. RCTs using CGM in patients with type 2 diabetes mellitus were then selected. Statistical analysis included calculation of the standardized mean difference (SMD) or risk ratio and 95% confidence intervals (CIs) using a random effects model. After literature search, seven RCTs (669 patients) satisfied the eligibility criteria established herein and were included into the meta-analysis. Compared with the self-monitoring blood glucose group, the CGM group exhibited significantly lower HbA1c levels (SMD, -0.35; 95% CI, -0.59--0.10; <i>P</i> = 0.006) and shorter time spent with hypoglycaemia (SMD, -0.42; 95% CI, -0.70--0.13; <i>P</i> = 0.004). Conversely, no differences in body weight and blood pressure were observed between the groups. CGM in patients with type 2 diabetes mellitus could reduce HbA1c levels and time spent with hypoglycaemia. However, because few RCTs were included in this present study and heterogeneity was also noted, care should be taken when interpreting the results.

Human papillomavirus (HPV)-independent vulvar squamous cell carcinomas (VSCC) and its precursors frequently harbour <i>TP53</i> mutations. Recently, six p53 immunohistochemical (IHC) patterns have been defined, which have shown strong correlation with <i>TP53</i> mutation status. However, few studies have applied this new six-pattern framework and none of them exhaustively compared p53 IHC positivity and patterns between invasive VSCC and adjacent skin lesion. We performed p53 IHC in a series of 779 HPV-independent VSCC with adjacent skin and evaluated the IHC slides following the newly described classification. Some 74.1% invasive VSCC showed abnormal p53 IHC staining. A skin lesion was identified in 450 cases (57.8%), including 254 intraepithelial precursors and 196 inflammatory/reactive lesions. Two hundred and ten of 450 (47%) VSCC with associated skin lesions showed an abnormal p53 IHC stain, with an identical staining pattern between the VSCC and the adjacent skin lesion in 80% of the cases. A total of 144/450 (32%) VSCC showed wild-type p53 IHC both in the invasive VSCC and adjacent skin lesion. Finally, 96/450 (21%) VSCC showed p53 IHC abnormal staining in the invasive VSCC but a wild-type p53 staining in the skin lesion. Most of the discordant cases (70/96; 73%) showed adjacent inflammatory lesions. In conclusion, the p53 IHC staining and pattern are usually identical in the VSCC and the intraepithelial precursor.

White-footed mice (Peromyscus leucopus) serve as the principal reservoir for Borrelia burgdorferi and have been shown to remain infected for life. Complex infections with multiple genetic variants of B. burgdorferi occur in mice through multiple exposures to infected ticks or through exposure to ticks infected with multiple variants of B. burgdorferi. Using a combination of cloning and single strand conformation polymorphism (SSCP), B. burgdorferi ospC variation was assessed in serial samples collected from individual P. leucopus during a single transmission season. In individuals with ospC variation, at least seven ospC variants were recognized at each time point. One to four of these variants predominated at each time point; however, the predominant variants seldom remained consistent in an individual mouse throughout the entire sampling period. These results confirmed that mice in southern Maryland were persistently infected with multiple variants of B. burgdorferi throughout the transmission season. However, the presence of multiple ospC variants and the fluctuations in the frequency of these variants indicates that either new ospC variants are regularly introduced to this mouse population and predominate while the existing infections are cleared, or that the variation detected in the genetic profile at different time points reflects a complex mixture of B. burgdorferi populations whose relative frequencies may continually change.

Our investigations embraced the group of patients with vulval cancer before surgical treatment (n = 10). We measured in serum of blood the level of the total human chorionic gonadotrophin hCG, beta subunit of human Chorionic Gonadotrophin, CA 125 and CA 19-9 antigen. We ascertained significant elevation the beta subunit of hCG level in the group of women with neoplasms in comparison with control group (n = 96) and significant positive correlation between beta subunit level and degree of cancer cells maturity (r = 0.66, p < 0.05). We also ascertained strong positive correlation among beta subunit of hCG and CA 19-9 antigen level in the serum of the patients with vulval cancer (r = 0.55 and p < 0.05).

Human Vγ2Vδ2 (also termed Vγ9Vδ2) T cells play important roles in microbial and tumor immunity by monitoring foreign- and self-prenyl pyrophosphate metabolites in isoprenoid biosynthesis. Accumulation of isoprenoid metabolites after bisphosphonate treatment allows Vγ2Vδ2 T cells to recognize and kill tumors independently of their MHC expression or burden of non-synonymous mutations. Clinical trials with more than 400 patients show that adoptive immunotherapy with Vγ2Vδ2 T cells has few side effects but has resulted in only a few partial and complete remissions. Here, we have tested Vγ2Vδ2 T cells for expression of inhibitory receptors and determined whether adding PD-1 checkpoint blockade to adoptively transferred Vγ2Vδ2 T cells enhances immunity to human PC-3 prostate tumors in an NSG mouse model. We find that Vγ2Vδ2 T cells express PD-1, CTLA-4, LAG-3, and TIM-3 inhibitory receptors during the 14-day ex vivo expansion period, and PD-1, LAG-3, and TIM-3 upon subsequent stimulation by pamidronate-treated tumor cells. Expression of PD-L1 on PC-3 prostate cancer cells was increased by co-culture with activated Vγ2Vδ2 T cells. Importantly, anti-PD-1 mAb treatment enhanced Vγ2Vδ2 T cell immunity to PC-3 tumors in immunodeficient NSG mice, reducing tumor volume nearly to zero after 5 weeks. These results demonstrate that PD-1 checkpoint blockade can enhance the effectiveness of adoptive immunotherapy with human γδ T cells in treating prostate tumors in a preclinical model.

In the form of a letter, the writer communicates to Freud her appreciation for the incomparable richness and complexity of the psychoanalytic enterprise in its century-long evolution from classical, Freudian origins to new developments in theory and technique. At the same time, concern is expressed about the continuity and survival of psychoanalysis in a cultural milieu that has absorbed its once radical ideas about sexuality and unconscious motivation while resisting its viability as a method of treatment.

Although many cancer survivors could benefit from supportive care, they often do not utilize such services. Previous studies have shown that patient-reported outcomes (PROs) could be a solution to meet cancer survivors' needs, for example through an eHealth application that monitors quality of life and provides personalized advice and supportive care options. In order to develop an effective application that can successfully be implemented in current health care, it is important to include health care professionals in the development process.

We retrospectively studied 14 patients with proximal and diaphyseal tumours and disappearing bone (Gorham's) disease of the humerus treated with wide resection and reconstruction using an allograft-resurfacing composite (ARC). There were ten women and four men, with a mean age of 35 years (8 to 69). At a mean follow-up of 25 months (10 to 89), two patients had a fracture of the allograft. In one of these it was revised with a similar ARC and in the other with an intercalary prosthesis. A further patient had an infection and a fracture of the allograft that was revised with a megaprosthesis. In all patients with an ARC, healing of the ARC-host bone interface was observed. One patient had failure of the locking mechanism of the total elbow replacement. The mean post-operative Musculoskeletal Tumor Society score for the upper extremity was 77% (46.7% to 86.7%), which represents good and excellent results; one patient had a poor result (46.7%). In the short term ARC effectively relieves pain and restores shoulder function in patients with wide resection of the proximal humerus. Fracture and infection remain significant complications.

Intracanalicular vestibular schwannomas (IVS) account for 8% of all vestibular schwannomas and their detection is still increasing due to high availability of magnetic resonance (MRI). Radiosurgery is one of several commonly acceptable methods of IVS treatment, but some risk may still exist with that treatment. The aim of this study is to analyze the clinical outcomes in tumor control and hearing preservation after radiosurgery of IVS. The retrospective analysis included 14 scientific papers available in the PubMed database. Assessment of tumor volume was performed based on gadolinium-enhanced T1-weighted scans. Hearing preservation was assessed using the Gardner-Robertson classification (GR class). Statistical analysis was performed using IBM SPSS Statistics 27. It was revealed that tumor growth control in IVS treated with radiosurgery was higher than in the wait-and-see strategy. The hearing preservation was similar in patients after wait and see and the surgical group. Radiosurgery was associated with low risk of facial nerve dysfunction.

UVA irradiation (320-400 nm) comprises about 95 percent of incident midday solar ultraviolet irradiation. It penetrates skin much deeper than UVB irradiation. The absorption of UVA irradiation in endogenous chromophores frequently leads to the generation of reactive oxygen species such as singlet oxygen ((1)O(2)). (1)O(2) is an important biochemical intermediate in multiple biological processes. Beside other procedures, the direct detection of (1)O(2) by its luminescence is a powerful tool that helps to understand the generation of (1)O(2) during UVA exposure in solution, in vitro and in vivo. This article describes the endogenous photosensitizers, their ability to generate (1)O(2) under UVA irradiation, and the detection technology to visualize the action of (1)O(2).

The role of calcium in the mechanism of thrombin activation of bone marrow-derived mast cells (BMMC) was explored by measuring the changes in the uptake of 45Ca2+ into quiescent BMMC and into cells stimulated by thrombin or by IgE-antigen. The results indicate that activation of BMMC by either thrombin or IgE-antigen is Ca2+-dependent. One million BMMC, activated by 0.05-5 U thrombin, accumulated 45Ca2+ in a concentration-dependent manner, which levelled off at around 1 U thrombin. Extracellular 45Ca2+ uptake of thrombin-stimulated cells is saturable within 90 seconds and corresponds to the kinetics of histamine release, whereas that of IgE-antigen exposed cells continues unabated for over 5 min. The pattern of 45Ca2+ uptake of IgE-sensitized BMMC exposed to thrombin suggests that the pro-stimulatory locus of thrombin action on the surface membrane is distinct from that of IgE.

This paper investigates the significance of the magnitude or the phase in the short term Fourier spectrum for speech intelligibility as a function of the time-window length. For a wide range of window lengths (1/16-2048 ms), two hybrid signals were obtained by a cross-wise combination of the magnitude and phase spectra of speech and white noise. Speech intelligibility data showed the significance of the phase spectrum for longer windows (>256 ms) and for very short windows (<4 ms), and that of the magnitude spectrum for medium-range window lengths. The hybrid signals used in the intelligibility test were analyzed in terms of the preservation of the original narrow-band speech envelopes. Correlations between the narrow-band envelopes of the original speech and the hybrid signals show a similar pattern as a function of window length. This result illustrates the importance of the preservation of narrow-band envelopes for speech intelligibility. The observed significance of the phase spectrum in recovering the narrow-band envelopes for the long term windows and for the very short term windows is discussed.

Significant amounts of non-point source runoff enter the Santa Monica Bay from the Ballona Creek Watershed during wet weather flow. The primary objective of this study was to determine the concentrations of hazardous metal pollutants associated with the aqueous and suspended solid phases during wet weather flow. A calculation of the mass of the pollutants for each storm was conducted. Other objectives of this study were to evaluate during a storm event the relationships between (1) soluble and sorbed metals, (2) storm flow and pollutant loading, including a determination if a first flush was present, and (3) total mass loading of pollutants and relative pollution loading from three watershed sub-basins. This study focused on the urbanized watershed of Ballona Creek, which is approximately 330 km2 (127 miles2) in size and developed primarily with residential and light commercial industries. In the 1997-98 rain season, an El Niño year, two storm events were monitored by the collection of hourly grab samples. An initial storm monitored Ballona creek, while a second storm also monitored Ballona Creek along with two smaller sub-watersheds, Centinela Channel and Sepulveda Channel. The results indicated the suspended solids phase primarily transported the mass for five of the six hazardous metals studied: cadmium, chromium, copper, lead, and nickel. Arsenic was found primarily in the aqueous phase.

Recent advances in health information technologies (HIT) in systemic lupus erythematosus have included electronic databases and registries, computerised clinical charts for patient monitoring, computerised diagnostic tools, computerised prediction rules and, more recently, disease-specific applications for mobile devices for physicians, health care professionals, and patients. Traditionally, HIT development has been oriented primarily to physicians and public administrators. However, more recent development of patient-centered Apps could improve communication and empower patients in the daily management of their disease. Economic advantages could also result from the use of HIT, including these Apps by collecting real life data that could be used in both economic analyses and to improve patient care.

The intracerebral microinjection technique was used to localize sites in the brain where morphine facilitated the self-stimulation rate at hypothalamic electrode sites. Bilateral injections of morphine (2 x 1 microgram) into the ventral tegmental area and substantia nigra produced the strongest enhancement at the shortest latencies. At these sites, bilateral injections of 200 ng of morphine also produced a significant enhancement whereas a dose of 50 ng was below threshold for the rate increasing effect. The enhancement by morphine was effectively antagonized by naloxone (5 mg/kg). When injected bilaterally into the same area, D-Ala2-Met5-enkephalinamide (2 x 1 microgram) also induced a strong enhancement of self-stimulation lasting for 70 minutes. A possible dopaminergic substrate for the opiate induced behavioral stimulation is discussed.