Reporting endometrial cells in women 40 years and older: assessing the clinical usefulness of Bethesda 2001.
We assessed the usefulness of revised Bethesda System reporting of exfoliated benign endometrial cells (EMs) in postmenopausal women. Cervicovaginal cytology specimens with benign EMs in postmenopausal women and "out-of-phase EMs" in premenopausal women 40 years and older were identified. Cases with histologic follow-up within 12 months were selected. There was tissue follow-up for 130 postmenopausal women: 10 (7.7%) had significant findings (endometrial adenocarcinoma, 6 [2 (33%) in asymptomatic women]; complex atypical endometrial hyperplasia [CAH], 3; leiomyosarcoma, 1); 20 were receiving hormone replacement therapy (HRT; n = 15) or tamoxifen (n = 5); 2 (10%) had significant pathology (endometrial adenocarcinoma, 1; CAH, 1). Eight not taking hormones (7.3%) had significant pathology (adenocarcinoma, 5; CAH, 2; leiomyosarcoma, 1). There were follow-up data for 96 premenopausal women; only 1 (who had vaginal bleeding) had significant pathology (CAH). The difference in incidence of preneoplastic and neoplastic conditions after a cytologic interpretation of "benign EM" between postmenopausal and premenopausal women was significant (P pound .025); There was no difference between postmenopausal women receiving or not receiving HRT (P > .05). Reporting benign EMs for premenopausal women 40 years and older has no clinical significance but does for postmenopausal women, regardless of HRT and symptoms.


Optoacoustic Imaging in Inflammation.
Optoacoustic or photoacoustic imaging (OAI/PAI) is a technology which enables non-invasive visualization of laser-illuminated tissue by the detection of acoustic signals. The combination of "light in" and "sound out" offers unprecedented scalability with a high penetration depth and resolution. The wide range of biomedical applications makes this technology a versatile tool for preclinical and clinical research. Particularly when imaging inflammation, the technology offers advantages over current clinical methods to diagnose, stage, and monitor physiological and pathophysiological processes. This review discusses the clinical perspective of using OAI in the context of imaging inflammation as well as in current and emerging translational applications.


Requirements for integrins during Drosophila development.
The common beta subunit of the PS antigens of Drosophila is homologous with vertebrate integrins and is encoded by the lethal(1)myospheroid gene. We have generated flies mosaic for wild-type and mutant alleles of lethal(1)myospheroid using adult gynandromorphs and radiation-induced somatic crossing over. The defects observed in the gynandromorphs demonstrate widespread requirements for PS integrins during development especially in ventrally derived structures, which also show strong expression of PS beta integrin. Smaller lethal(1)myospheroid clones induced during larval development result in blister and vein defects in the wings and aberrant development of photoreceptor cells, demonstrating roles for PS integrins during development of both wings and eyes. PS integrins are required for the close apposition of the dorsal and ventral wing epithelia and for the proper arrangement of photoreceptor cells. However, many other adhesive and morphogenetic processes proceed normally in the absence of integrins containing the beta subunit encoded by lethal(1)myospheroid.


First Report of Powdery Mildew Caused by Erysiphe heraclei on Chervil in California.
Chervil (Anthriscus cerefolium) is a culinary herb in the Apiaceae family that is grown commercially in California. In 2003 and 2004, shade house plantings of chervil in central coastal California exhibited symptoms and signs of a powdery mildew disease. White, epiphytic mycelia and conidia were present on petioles and leaves. Severely affected leaflets became slightly twisted and bent. Mycelium was amphigenous and effused or in patches. Hyphae measured 5.0 to 7.5 μm in diameter and had lobed appressoria. Conidiophores were straight and had cylindric foot cells measuring 25.0 to 37.5 × 7.5 to 10.0 μm, followed by a longer cell and one to two shorter cells. Conidia formed singly, were cylindric, and measured (37.5-) 40.0 to 50.0 (-52.5) × 15.0 to 17.5 μm. Conidia lacked fibrosin bodies and germinated at the ends with either a very short or a long germ tube forming a lobed appressorium (Polygoni type). No cleistothecia were observed. On the basis of these characteristics, the fungus was identified as Erysiphe heraclei (1). To confirm pathogenicity, severely colonized chervil leaves from a commercial nursery were gently pressed onto leaves of potted chervil plants. Plants were then maintained in a greenhouse (22 to 24°C). After 10 to 12 days, signs of powdery mildew developed on the foliage of inoculated plants, and the pathogen morphology matched that of the originally observed pathogen. Noninoculated control plants did not develop powdery mildew. To investigate the host range of this chervil isolate, parsley (Petroselinum crispum) and celery (Apium graveolens) plants were inoculated in the same way as described. However, after more than 3 weeks, no powdery mildew developed on these two Apiaceae plants. Control chervil plants again developed the disease. To our knowledge, this is the first report of powdery mildew of chervil caused by E. heraclei in California. Disease impact was severe, and in some cases, chervil crops were not harvested. The inability of the chervil isolate to infect two other Apiaceae plants that are listed as hosts of E. heraclei indicates that this pathogen may consist of strains having different host ranges. Reference: (1) U. Braun. Nova Hedwigia 89:1, 1987.


Cyclosporine-associated end-stage nephropathy after cardiac transplantation: incidence and progression.
The salutary immunosuppressive effects of cyclosporine in extending cardiac allograft survival may be curtailed by its nephrotoxic effects. We reviewed our first 9 years of experience with cyclosporine after cardiac transplantation, to evaluate the incidence and progression of cyclosporine-associated end-stage renal failure necessitating chronic hemodialysis. Retrospective computer-based file review and personal interview when possible. The population at risk was comprised of all adult cardiac recipients surviving at least 3 years (n=293). Of these, 19 (6.5%) developed end-stage renal failure requiring chronic hemodialysis. There were 17 men and 2 women (mean age of 45 +/- 11 years). The mean creatinine clearance for the study group decreased by 38% (P<0.001 vs. before transplant) by 6 months after transplantation and by 48% by 3 years postoperatively (P<0.001 vs. before transplant). The mean serum creatinine rose by 80% (P< 0.001 vs. before transplant) by 6 months after transplantation and by 125% by 3 years postoperatively (P<0.001 vs. before transplant). Time elapsed from transplantation to hemodialysis ranged from 3.7 to 9.5 years (mean 6.4 +/- 2). Actuarial 1- year survival after onset of hemodialysis was 75%. Although cyclosporine remains the central immunosuppressive agent for cardiac allograft recipients, its use leads to a greater than one-third decrease in creatinine clearance by 6 months after transplantation and progression to end-stage renal failure, requiring hemodialysis in 6.5% of cardiac transplant recipients. Moreover, these patients are at increased risk of death compared with other cardiac allograft recipients. This data warrants the search of alternative or adjunctive agents that would allow decreased dosing or reduced nephrotoxicity of cyclosporine, while maintaining equivalent survival.


Calcium homeostasis in cisplatin resistant epithelial ovarian cancer.
Intracellular calcium concentration ([Ca2+]i) may have an important role in the development of chemoresistance, which is an essential problem in cancer chemotherapy. Cisplatin (DDP), which modulates the intracellular calcium concentration by different mechanisms, is an antineoplastic agent with high success rate in cancer therapies. We investigated the regulatory role of [Ca2+] in cisplatin resistance in epithelial ovarian cancer cell line, in MDAH-2774, and its chemoresistant subclone MDAH-2774/DDP. The measurement of [Ca2+]i using fluorescence microscope, and flow cytometry revealed that the amount of intracellular calcium decreased in cisplatin resistant cells compared to the amounts in parental cells. mRNA expression profiles of calcium homeostasis-associated major genes (IP3R1/2/3, RYR1/2, SERCA1/2/3, NCX1/2/3, PMCA1/2/3, and PMCA4) decreased in cisplatin resistant cell line in comparison to the expression profiles in parental cells. Owing to the changes in the expression of genes involved in calcium regulation, these results show, drug resistance may be prevented by introducing a new perspective on the use of inhibitors and activators of these genes, and thus of cytostatic treatment strategies, due to changes in the expression of genes involved in calcium regulation.


Coalescent pleural malignant mesothelioma and adenocarcinoma of the lung, involving only minor asbestos exposure.
Coexistence of pulmonary adenocarcinoma and pleural malignant mesothelioma is extremely rare, although both are asbestos-related. Herein is presented a rare case of coalescent lung tumor made up of a malignant mesothelioma and a pulmonary adenocarcinoma in a 62-year-old Japanese man, a high-school teacher with only minor asbestos exposure. Preoperative diagnosis of adenocarcinoma was made on transbronchial biopsy. At surgery, multiple small white nodules were observed on the parietal pleural surface, opposite to the lung tumor. They were confirmed to be malignant mesothelioma on histopathology of paraffin section. The pulmonary tumor mass itself consisted of two distinct portions. The major part contained papillary proliferation of hobnail and columnar cells. Peripherally, neoplastic cells grew in a lepidic fashion and micropapillary growth was also detected. The other component featured tubular structures. The former was positive for adenocarcinoma markers such as CEA, Ber-EP4, PE-10, thyroid transcription factor-1 and Napsin A, and negative for mesothelial markers including calretinin, D2-40, WT-1 and HBME, while the latter was the opposite, resulting in a diagnosis of coalescing malignant mesothelioma and adenocarcinoma. The panel of antibodies used for immunohistochemistry was useful to distinguish the two different components in the one tumor.


Heparin-binding ligands mediate autocrine epidermal growth factor receptor activation In skin organ culture.
Exogenous EGF and TGF-alpha accelerate wound healing, but treatment effects are often modest. Using short-term human skin organ culture, we found that autocrine EGF receptor activation could account for this observation. Amphiregulin and heparin-binding EGF-like growth factor (HB-EGF) transcripts were rapidly and markedly induced, whereas EGF and TGF-alpha mRNAs were undetectable or only slightly increased. Vascular permeability factor and keratin 6 transcripts were also strongly induced, albeit with a >/= 3 h delay relative to HB-EGF and amphiregulin. All four transcripts were upregulated in actual healing skin wounds, HB-EGF and keratin 6 being the most prominent. The highly EGF receptor-specific tyrosine kinase inhibitor PD153035 strongly inhibited induction of all four transcripts in organ culture, as well as release of immunoreactive HB-EGF into the medium. These effects were confirmed using the anti-EGF receptor mAb 225 IgG. Neither PD153035 nor 225 IgG was toxic to keratinocytes, as judged by calcein-AM uptake. PD153035 completely abrogated the proliferative phase of keratinocyte outgrowth in skin explant cultures, whereas it had no effect on the antecedent migratory phase. Based on these results, we conclude that EGF receptor activation by highly inducible, keratinocyte-derived heparin-binding ligands is an important mechanism for amplification and transmission of the cutaneous wound healing signal.


Determinants of frequency-dependent regulation of Kv1.2-containing potassium channels.
Voltage-gated potassium channels are important regulators of electrical excitation in many tissues, with Kv1.2 standing out as an essential contributor in the CNS. Genetic deletion of Kv1.2 invariably leads to early lethality in mice. In humans, mutations affecting Kv1.2 function are linked to epileptic encephalopathy and movement disorders. We have demonstrated that Kv1.2 is subject to a unique regulatory mechanism in which repetitive stimulation leads to dramatic potentiation of current. In this study, we explore the properties and molecular determinants of this use-dependent potentiation/activation. First, we examine how alterations in duty cycle (depolarization and repolarization/recovery times) affect the onset and extent of use-dependent activation. Also, we use trains of repetitive depolarizations to test the effects of a variety of Thr252 (S2-S3 linker) mutations on use-dependent activation. Substitutions of Thr with some sterically similar amino acids (Ser, Val, and Met, but not Cys) retain use-dependent activation, while bulky or charged amino acid substitutions eliminate use-dependence. Introduction of Thr at the equivalent position in other Kv1 channels (1.1, 1.3, 1.4), was not sufficient to transfer the phenotype. We hypothesize that use-dependent activation of Kv1.2 channels is mediated by an extrinsic regulator that binds preferentially to the channel closed state, with Thr252 being necessary but not sufficient for this interaction to alter channel function. These findings extend the conclusions of our recent demonstration of use-dependent activation of Kv1.2-containing channels in hippocampal neurons, by adding new details about the molecular mechanism underlying this effect.


Predicting outcomes in radiation oncology--multifactorial decision support systems.
With the emergence of individualized medicine and the increasing amount and complexity of available medical data, a growing need exists for the development of clinical decision-support systems based on prediction models of treatment outcome. In radiation oncology, these models combine both predictive and prognostic data factors from clinical, imaging, molecular and other sources to achieve the highest accuracy to predict tumour response and follow-up event rates. In this Review, we provide an overview of the factors that are correlated with outcome-including survival, recurrence patterns and toxicity-in radiation oncology and discuss the methodology behind the development of prediction models, which is a multistage process. Even after initial development and clinical introduction, a truly useful predictive model will be continuously re-evaluated on different patient datasets from different regions to ensure its population-specific strength. In the future, validated decision-support systems will be fully integrated in the clinic, with data and knowledge being shared in a standardized, instant and global manner.


Variation in physical and biological properties of solid gold sodium thiomalate on dissolution: an electron microscopic and energy dispersive spectroscopic study.
The dissolution of solid gold sodium thiomalate (GSTM) in water results in loss of yellow color. We studied the initial reaction on dissolution. It was associated with the disappearance of 2 absorption peaks on ultraviolet spectrum, one a well defined peak at 335 nm and the other a shoulder at 370 nm. This solution caused platelet aggregation and on transmission electron microscopy, dense gold containing particles measuring 125 nm are seen. Within 10 min of onset of dissolution, no gold containing particulate matter was detectable on electron microscopy. By 20 min, fibrillar particles measuring 40-150 nm appear. These resembled in general morphology and element composition the particles seen within aurosomes in platelets treated with Myochrysine (GSTM) and in synovium and other tissues by other workers. Our data elaborate on previous physical and chemical studies and correlate with morphological variations of gold containing particles at different phases. These variations in GSTM may be due to polymer size and/or structural change within the polymer. The biochemical significance of our data should provide better understanding of the biological effects of these gold thiol compounds in vivo.


Using fMRI to quantify the time dependence of remifentanil analgesia in the human brain.
To understand and exploit centrally acting drugs requires reliable measures of their time course of action in the human brain. Functional magnetic resonance imaging (fMRI) is able to measure noninvasively, drug-induced changes in task-related brain activity. Here, we have characterized, in a specific region of the brain, the time of onset of action and the half-life of action of a clinically relevant dose of a potent opioid analgesic agent, remifentanil. These times were established from the temporal variation of the amplitude of the blood oxygen level-dependent response in the insular cortex contralateral to a painfully hot thermal stimulus, in volunteers receiving a remifentanil infusion. The insular cortex has repeatedly been reported as activated by noxious thermal stimulation. The times of onset and offset of drug action were each characterized by a half-life for changes in fMRI signal from within the insula. These characteristic times agreed with the observed drug-induced analgesia and previous pharmacokinetic-pharmacodynamic measurements for remifentanil. We have successfully measured, for the first time using fMRI, temporal pharmacological parameters for a CNS-active drug based on its effect on task-related activity in a specific brain region. Comparison of the time course of regional brain activity with pain perception could reveal those regions engaged in drug-induced analgesia.


Functional features of hemocyte subpopulations of the invasive mollusk species Dreissena polymorpha.
Dreissena polymorpha is a mussel species that invaded many lotic and lentic inland waters in Western Europe and North America. Its positive or negative interactions with biotic and abiotic components of ecosystems are numerous, making this bivalve the subject of numerous studies in ecology, ecophysiology and ecotoxicology. In these contexts, the functional characterization of the zebra mussel hemocytes is of particular interest, as hemocytes are central cells involved in vital functions (immunity, growth, reproduction) of molluscan physiology. Dreissena polymorpha circulating hemocytes populations were characterized by a combination of structural and functional analysis. Assessments were performed during two contrasted physiological periods for mussels (gametogenesis and spawning). Three hemocyte types were identified as hyalinocytes and blast-like cells for agranular hemocytes and one granulocyte population. Flow cytometry analysis of hemocytes functionalities indicated that blast-like cells had low oxidative and mitochondrial activities and low lysosomal content. Hyalinocytes and granulocytes are fully equipped to perform innate immune response. Hyalinocytes exhibit higher oxidative activity than granulocytes. Such observation is not common since numerous studies show that granulocytes are usually cells that have the highest cellular activities. This result demonstrates the significant functional variability of hemocyte subpopulations. Moreover, our findings reveal that spawning period of Dreissena polymorpha was associated with an increase of hyalinocyte percentage in relation to low levels of biological activities in hemocytes. This reduction in hemocyte activity would reflect the important physiological changes associated with the spawning period of this invasive species known for its high reproductive potential.


Value of bone scan imaging in predicting pain relief from percutaneous vertebroplasty in osteoporotic vertebral fractures.
Patient selection for percutaneous vertebroplasty is often complicated by the presence of multiple fractures or non-localizing pain. Our purpose was to determine whether increased activity revealed by bone scan imaging is predictive of a positive clinical response to percutaneous vertebroplasty. A retrospective chart review conducted at our institution yielded 28 vertebroplasty treatment sessions that had been performed after obtaining bone scan imaging for painful, osteoporotic compression fractures in 27 patients. Thirty-five compression fractures were treated during these 28 treatment sessions. In all cases, increased activity was revealed by bone scan imaging before treatment with vertebroplasty. Positive outcome was defined as subjective decrease in pain severity and/or increased level of patient mobility. Subjective pain relief was noted in 26 (93%) of 28 treatment sessions. In 14 (100%) of 14 cases with quantifiable pain levels, pain improved at least 3 points on a 10-point scale (range of improvement, 3-10 points; mean improvement, 7.4 points). Among the remaining 14 treatment sessions in which patients were unable or unwilling to quantify pain severity, the pain relief was described as complete or excellent pain relief in 11 (78%) of 14 cases. In 14 (100%) of 14 cases for which semiquantitative assessment of mobility was available, mobility improved at least one level (5-point graded scale; range of improvement, 1-4 points; mean improvement, 1.7 points). Increased activity revealed by bone scan imaging is highly predictive of positive clinical response to percutaneous vertebroplasty.


Immunomodulation Mechanism of Antidepressants: Interactions between Serotonin/Norepinephrine Balance and Th1/Th2 Balance.
Neurotransmitters and hormones regulate major immune functions, including the selection of T helper (Th)1 or Th2 cytokine responses, related to cell-mediated and humoral immunity, respectively. A role of imbalance and dynamic switching of Th1/Th2 system has been proposed, with relative displacement of the immune reserve in relation to complex interaction between Th1/Th2 and neuro-hormonal balance fluctuations, in the pathogenesis of various chronic human diseases, probably also including psychiatric disorders. Components of the stress system such as norepinephrine (NE) and glucocorticoids appear to mediate a Th2 shift, while serotonin (5-HT) and melatonin might mediate a Th1 shift. Some antidepressants would occur affecting these systems, acting on neurotransmitter balance (especially the 5-HT/NE balance) and expression levels of receptor subtypes, which in turn affect cytokine production and relative Th1/Th2 balance. It could be therefore hypothesized that the antidepressant-related increase in NE tone enhances the Th2 response, while the decrease in NE tone or the increase in 5-HT tone enhances the Th1 response. However, the neurotransmitter and Th1/Th2 balance modulation could be relative, aiming to restore physiological levels a previous imbalance in receptor sensitivity and cytokine production. The considerations on neuro-immunomodulation could represent an additional aid in the study of pathophysiology of psychiatric disorders and in the choice of specific antidepressants in specific clusters of symptoms, especially in comorbidity with internal pathologies. Furthermore limited data, reviewed here, have shown the effectiveness of some antidepressants as pure immunomodulators. However, these considerations are tentative and require experimental confirmation or refutation by future studies.


Bioinformatics Tools for Mass Spectroscopy-Based Metabolomic Data Processing and Analysis.
Biological systems are increasingly being studied in a holistic manner, using omics approaches, to provide quantitative and qualitative descriptions of the diverse collection of cellular components. Among the omics approaches, metabolomics, which deals with the quantitative global profiling of small molecules or metabolites, is being used extensively to explore the dynamic response of living systems, such as organelles, cells, tissues, organs and whole organisms, under diverse physiological and pathological conditions. This technology is now used routinely in a number of applications, including basic and clinical research, agriculture, microbiology, food science, nutrition, pharmaceutical research, environmental science and the development of biofuels. Of the multiple analytical platforms available to perform such analyses, nuclear magnetic resonance and mass spectrometry have come to dominate, owing to the high resolution and large datasets that can be generated with these techniques. The large multidimensional datasets that result from such studies must be processed and analyzed to render this data meaningful. Thus, bioinformatics tools are essential for the efficient processing of huge datasets, the characterization of the detected signals, and to align multiple datasets and their features. This paper provides a state-of-the-art overview of the data processing tools available, and reviews a collection of recent reports on the topic. Data conversion, pre-processing, alignment, normalization and statistical analysis are introduced, with their advantages and disadvantages, and comparisons are made to guide the reader.


Kallikrein 8 is involved in skin desquamation in cooperation with other kallikreins.
Kallikrein type serine proteases, KLK8/neuropsin, KLK6, and KLK7, have been implicated in the proliferation and differentiation of epidermal keratinocytes and in the pathogenesis of psoriasis. However, their mechanistic roles in these processes remain largely unknown. We applied 12-O-tetradecanoylphorbol-13-acetate on the wild type (WT) and the Klk8 gene-disrupted (Klk8(-/-)) mouse skin, inducing keratinocyte proliferation similar to the human psoriatic lesion. Klk8 mRNA as well as Klk6 and Klk7 mRNA were up-regulated after 12-O-tetradecanoylphorbol-13-acetate application in the WT mice. In contrast, Klk8(-/-) mice showed minimum increases of Klk6 and Klk7 transcripts, the proteins, and enzymatic activities. Relative to the WT, the Klk8(-/-) skin showed less proliferation and an increase in the number of cell layers in the stratum corneum. However, overexpression of Klk8 by adenovirus vector in knock-out keratinocytes did not result in an increase in Klk6 or Klk7 mRNA. The inefficient cleavage of adhesion molecules DSG1 and CDSN in Klk8(-/-) skin contributes to a delay in corneocyte shedding, resulting in the hyperkeratosis phenotype. We propose that in psoriatic lesion, KLK8 modulates hyperproliferation and prevents excessive hyperkeratosis by shedding the corneocytes.


Treatment benefits on metabolic syndrome with diet and physical activity.
The research has included 422 patients aged between 25 to 60, of whom 341 were men and 81 women. The purpose of research was to determine impact of diet and physical activity in the treatment of metabolic syndrome during the six month period. Processing of results through descriptive and discriminative analysis have indicated that 6 month treatment with diet and physical activity have had an impact in the: waistline decrease by 6.05 cm or 5.50% among males, and 4.92 cm or 5.10% among females; body mass index (BMI) decrease by 1.78 or 6.20% among males, and 2.3 or 8.16% among females; decrease of blood triglycerides levels by 0.35 mmol/L or 16.28% among males, and 0.27 mmol/L or 13.30% among females; increase of blood cholesterol HDL-C by 0.48 mmol/L or 34.78% among males, and 0.06 mmol/L or 4.28% among females; systolic arterial pressure decreased by 15 mmHg or 10.18%, and diastolic blood pressure by 8.74 mmHg or 9.47% among males, and systolic arterial pressure decreased by 7.39 mmHg or 5.17%, and diastolic blood pressure decreased by 5.18 mmHg or 5.75% among females; the level of blood glucose decreased by 0.45 mmol/L or 7.04% among males, and by 0.64 mmol/L or 9.92% decreased among females. The results show that physical exercise and diet are important factors in reducing the values symptoms of metabolic syndrome. In order to improve symptoms of metabolic syndrome, it is necessary to keep on with healthy diet and physical exercise that means the change of lifestyle.


Generalized osteoarthritis in women: pattern of joint involvement and approaches to definition for epidemiological studies.
To ascertain whether clustering between joint sites in osteoarthritis (OA) is more common than would be expected simply from the rising prevalence of the disorder with age, and to explore a definition of generalized OA (GOA) by determining the pattern of joint group involvement, in a population sample of peri and postmenopausal women. Radiographs of the hands, knees, and hips were obtained in a population sample of 702 women aged 45 to 64 years. Distal interphalangeal, proximal interphalangeal, carpometacarpal, knee, and hip OA were assessed using the Kellgren-Lawrence grading system. Logistic regression was used to test for overall clustering of OA between joint sites, and log linear models were used to study the patterns of association between different sites. Multiple involvement of the 5 joint groups studied occurred significantly more frequently than could be expected by chance alone (chi 2 = 52.3, df = 5, p < 0.001), and this clustering remained significant after age adjustment (chi 2 = 26.1, df = 5, p < 0.001). Thresholds could be defined for the number of involved joint groups that distinguished a polyarticular subset of OA. These thresholds varied with age and the radiographic cutoff at which OA was assigned. Thus, for grade 2+ disease, GOA could be defined by involvement of 2 or more joint groups at age 45-47 years, but required involvement of all 5 joint groups at age 60-64 years. Symmetry within joint groups was the most pronounced feature in the pattern of joint involvement in the sample as a whole, with associations between different joint groups being substantially weaker than those for symmetrical bilateral involvement of a particular joint. There is a clear tendency towards polyarticular OA among women aged 45-64 years. However, there is no single threshold number of joint sites that can be used to define GOA. The pattern of joint involvement in OA is primarily symmetrical, and this pattern strongly suggests a systemic etiology in this subset of postmenopausal women.


Effect of mitral inflow pattern on diagnosis of severe mitral regurgitation in patients with chronic organic mitral regurgitation.
To determine sensitivity and specificity of E wave velocity in patients with severe chronic organic mitral regurgitation (MR) and normal left ventricular ejection fraction (EF) and to evaluate prevalence of A wave dominance in patients with severe MR. We compared 35 patients with quantified severe, chronic, quantified, organic MR due to flail/prolapsed leaflets who had reparative surgery with 35 age-matched control subjects. EF < 60%, atrial fibrillation, and more than mild aortic regurgitation. Mean [standard deviation (SD)] age [70 (8) years vs. 69 (8) years; p = 0.94] and mean (SD) EF [66% (6%) vs. 65% (4%); p = 0.43] were not different between the two groups. Mean (SD) E wave velocity was greater in case patients than control subjects [1.2 (0.3) m/sec vs. 0.7 (0.15) m/sec; p < 0.001]. However, E wave velocity of 1.2 m/sec had a sensitivity of only 57% [95% confidence interval (CI), 41-7 and a specificity of 100% (95% CI, 90-100%) in identifying severe MR. E wave velocity of 0.9 m/sec had a more optimal combined sensitivity (89%; 95% CI, 74-95%) and specificity (86%; 95% CI, 71-94%). A wave dominance was seen in 18% of case patients and 66% of control subjects (p < 0.001). E wave velocity of 1.2 m/sec is specific not sensitive for severe organic MR; E wave velocity of 0.9 m/sec has better sensitivity and specificity. A wave dominance pattern alone cannot exclude patients with severe organic MR. Our findings highlight the importance of a comprehensive echocardiographic exam rather than relying on a few Doppler parameters in diagnosing MR.


Beneficial effects of Plantago albicans on high-fat diet-induced obesity in rats.
Obesity is a one of the main global public health problems associated with chronic diseases such as coronary heart disease, diabetes and cancer. As a solution to obesity, we suggest Plantago albicans, which is a medicinal plant with several biological effects. This study assesses the possible anti-obesity protective properties of Plantago albicans in high fat diet-fed rats. 28 male Wistar rats were divided into 4 groups; a group which received normal diet (C), the second group was fed HDF diet (HDF), the third group was given normal diet supplemented with Plantago albicans (P.AL), and the fourth group received HDF supplemented with Plantago albicans (HDF+P.AL) (30mg/kg/day) for 7 weeks. Our results showed an increase in body weight of HDF rats by ∼16% as compared to the control group with an increase in the levels of total cholesterol (TC) as well as LDL-cholesterol, triglycerides (TG) in serum. Also, the concentration of TBARS increased in the liver and heart of HDF-fed rats as compared to the control group. The oral gavage of Plantago albicans extract to obese rats induced a reduction in their body weight, lipid accumulation in liver and heart tissue, compared to the high-fat diet control rats. The obtained results proved that the antioxidant potency of Plantago albicans extracts was correlated with their phenolic and flavonoid contents. The antioxidant capacity of the extract was evaluated by DPPH test (as EC50=250±2.12μg/mL) and FRAP tests (as EC50=27.77±0.14μg/mL). These results confirm the phytochemical and antioxidant impact of Plantago albicans extracts. Plantago albicans content was determined using validated HPLC methodology.


Sleep deprivation during early-adult development results in long-lasting learning deficits in adult Drosophila.
Multiple lines of evidence indicate that sleep is important for the developing brain, although little is known about which cellular and molecular pathways are affected. Thus, the aim of this study was to determine whether the early adult life of Drosophila, which is associated with high amounts of sleep and critical periods of brain plasticity, could be used as a model to identify developmental processes that require sleep. Wild type Canton-S Drosophila melanogaster. DESIGN; Flies were sleep deprived on their first full day of adult life and allowed to recover undisturbed for at least 3 days. The animals were then tested for short-term memory and response-inhibition using aversive phototaxis suppression (APS). Components of dopamine signaling were further evaluated using mRNA profiling, immunohistochemistry, and pharmacological treatments. Flies exposed to acute sleep deprivation on their first day of life showed impairments in short-term memory and response inhibition that persisted for at least 6 days. These impairments in adult performance were reversed by dopamine agonists, suggesting that the deficits were a consequence of reduced dopamine signaling. However, sleep deprivation did not impact dopaminergic neurons as measured by their number or by the levels of dopamine, pale (tyrosine hydroxylase), dopadecarboxylase, and the Dopamine transporter. However, dopamine pathways were impacted as measured by increased transcript levels of the dopamine receptors D2R and dDA1. Importantly, blocking signaling through the dDA1 receptor in animals that were sleep deprived during their critical developmental window prevented subsequent adult learning impairments. These data indicate that sleep plays an important and phylogenetically conserved role in the developing brain.


Diuretics prime plant immunity in Arabidopsis thaliana.
Plant activators are agrochemicals that activate the plant immune system, thereby enhancing disease resistance. Due to their prophylactic and durable effects on a wide spectrum of diseases, plant activators can provide synergistic crop protection when used in combination with traditional pest controls. Although plant activators have achieved great success in wet-rice farming practices in Asia, their use is still limited. To isolate novel plant activators applicable to other crops, we screened a chemical library using a method that can selectively identify immune-priming compounds. Here, we report the isolation and characterization of three diuretics, bumetanide, bendroflumethiazide and clopamide, as immune-priming compounds. These drugs upregulate the immunity-related cell death of Arabidopsis suspension-cultured cells induced with an avirulent strain of Pseudomonas syringae pv. tomato in a concentration-dependent manner. The application of these compounds to Arabidopsis plants confers disease resistance to not only the avirulent but also a virulent strain of the pathogen. Unlike salicylic acid, an endogenous phytohormone that governs disease resistance in response to biotrophic pathogens, the three diuretic compounds analyzed here do not induce PR1 or inhibit plant growth, showing potential as lead compounds in a practical application.


Rat model demonstrates a high risk of tremolite but a low risk of anthophyllite for mesothelial carcinogenesis.
Asbestos was abundantly used in industry during the last century. Currently, asbestos confers a heavy social burden due to an increasing number of patients with malignant mesothelioma (MM), which develops after a long incubation period. Many studies have been conducted on the effects of the asbestos types that were most commonly used for commercial applications. However, there are few studies describing the effects of the less common types, or minor asbestos. We performed a rat carcinogenesis study using Japanese tremolite and Afghan anthophyllite. Whereas more than 50% of tremolite fibers had a diameter of < 500 nm, only a small fraction of anthophyllite fibers had a diameter of < 500 nm. We intraperitoneally injected 1 or 10 mg of asbestos into F1 Fischer-344/Brown-Norway rats. In half of the animals, repeated intraperitoneal injections of nitrilotriacetate (NTA), an iron chelator to promote Fenton reaction, were performed to evaluate the potential involvement of iron overload. Tremolite induced MM with a high incidence (96% with 10 mg; 52% with 1 mg), and males were more susceptible than females. Histology was confirmed using immunohistochemistry, and most MMs were characterized as the sarcomatoid or biphasic subtype. Unexpectedly NTA showed an inhibitory effect in females. In contrast, anthophyllite induced no MM after an observation period of 550 days. The results suggest that the carcinogenicity of anthophyllite is weaker than formerly reported, whereas that of tremolite is as potent as major asbestos as compared with our previous data.


Coarse-graining simulation approaches for polymer melts: the effect of potential range on computational efficiency.
The integral equation coarse-graining (IECG) approach is a promising high-level coarse-graining (CG) method for polymer melts, with variable resolution from soft spheres to multi CG sites, which preserves the structural and thermodynamical consistencies with the related atomistic simulations. When compared to the atomistic description, the procedure of coarse-graining results in smoother free energy surfaces, longer-ranged potentials, a decrease in the number of interaction sites for a given polymer, and more. Because these changes have competing effects on the computational efficiency of the CG model, care needs to be taken when studying the effect of coarse-graining on the computational speed-up in CG molecular dynamics simulations. For instance, treatment of long-range CG interactions requires the selection of cutoff distances that include the attractive part of the effective CG potential and force. In particular, we show how the complex nature of the range and curvature of the effective CG potential, the selection of a suitable CG timestep, the choice of the cutoff distance, the molecular dynamics algorithms, and the smoothness of the CG free energy surface affect the efficiency of IECG simulations. By direct comparison with the atomistic simulations of relatively short chain polymer melts, we find that the overall computational efficiency is highest for the highest level of CG (soft spheres), with an overall improvement of the computational efficiency being about 106-108 for various CG levels/resolutions. Therefore, the IECG method can have important applications in molecular dynamics simulations of polymeric systems. Finally, making use of the standard spatial decomposition algorithm, the parallel scalability of the IECG simulations for various levels of CG is presented. Optimal parallel scaling is observed for a reasonably large number of processors. Although this study is performed using the IECG approach, its results on the relation between the level of CG and the computational efficiency are general and apply to any properly-constructed CG model.


Erection of a new onchobothriid genus (Cestoda: Tetraphyllidea) and the description of five new species from whaler sharks (Carcharhinidae).
The onchobothriid Triloculatum n. gen. is erected to house species formerly considered members of Phoreiobothrium, but that bear 3, rather than 5 or more, bothridial subloculi. The species formerly known as Phoreiobothrium triloculatum is designated as its type. This species is redescribed based on 2 syntypes and on voucher material consistent with type material taken from the type host, Carcharhinus obscurus, from the type and 1 additional locality. Examination of the cestode fauna of a diversity of carcharhinid sharks resulted in the discovery of an additional 5 new tri-subloculate species belonging to the genus. These include: Triloculatum andersonorum n. sp. from Negaprion acutidens; Triloculatumr bullardi n. sp. from Carcharhinus brevipinna; Triloculatum geeceearelensis n. sp. from Carcharhinus isodon; Triloculatum jodyi n. sp. from Carcharhinus acronotus; and Triloculatum oregontwoae n. sp. from Carcharhinus plumbeus. The new species differ from one another in the number of proglottids, scolex size, number of testes, number of lateral columns of vitelline follicles, and whether they possess craspedote or acraspedote proglottids. Histology and scanning electron microscopy suggest that the new genus differs further from Phoreiobothrium in that its species possess an anterior margin of the posterior loculus that is fused to the anterior loculus, rather than free. The diagnosis of Phoreiobothrium is emended to accommodate the removal of tri-subloculate species and the new information on the condition of the locular interface, and the symmetrical ovary and vitelline follicles arranged in 2 lateral bands; each band consisting of 2 to many columns of follicles. Existing host data indicate that the new genus is restricted to only a subset of the sharks parasitized by species of Phoreiobothrium. Results from the examination of a diversity of carcharhinid species suggest that species in the new genus may have an affinity for the larger, i.e., >200 cm in total length, species of Carcharhinus and Negaprion. One of the new Triloculatum species was found to attach in the crypts lying between the larger ridges found on the mucosal surface of the posterior inner region of the scroll-type spiral intestine of C. brevipinna.


[Associated factors to the calcium intake in mexican pregnant adolescents].
To explore food habits, demographic and socioeconomic factors associated to calcium intake of pregnant adolescents. In a cross sectional study 321 participants of 13 to 19 years old attending to the division of gynecology- obstetrics of the Civil Hospital of Guadalajara were included. All participants were healthy, in any moment of pregnancy and belonging to the low and middle-low socioeconomic status. The calcium intake was obtained through a food frequency questionnaire and a 24-hour dietary recall. Demographic and socioeconomic data were also included. A chi square test, an odds ratio (95% CI) and a regression logistic model for the identification of the epidemiologic meaning of the associated variables to the calcium intake were obtained. Sixty one percent of adolescents consumed less that 80% of the diary recommended intake of calcium. The domestic labor occupation of adolescents [OR 2.66 (1.28-5.53)], low milk [OR 2.54 (1.37-4.0)] and dairy intake [OR 2.75 (1.09-7.0)], excess of carbonated beverages consumption [OR 1.84 (1.04-3.28)] and low literacy of mothers [OR 1.83 (1.15-2.90)] were the most epidemiological meaning factors associated to deficient calcium intake. The results suggest that the calcium intake was deficient in the majority of pregnant adolescents and that there are some risk factors that must be identified and attended. Likewise, it is necessary to evaluate the nutritional status of calcium in this especial group with more precise and specific methods.


Reduced synthesis of muscle proteins in chronic renal failure.
Muscle wasting and weakness occur frequently in patients with chronic renal failure. The mechanism(s) by which these abnormalities occur is unclear. We hypothesized that such findings were due to defective muscle protein synthesis. We measured synthetic rates of mixed muscle proteins, myosin heavy chain, and mitochondrial proteins in serial muscle biopsy samples during a continuous infusion of L[1-(13)C]leucine from 12 patients with chronic renal failure and 10 healthy control subjects under identical study conditions. Patients with chronic renal failure have significantly lower synthetic rates of mixed muscle proteins and myosin heavy chain (27 and 37% reductions, respectively, P < 0.05 and P < 0.02). Significant declines in the synthetic rates of muscle mitochondrial protein (27%) (P < 0.05), muscle cytochrome c-oxidase activity (42%) (P < 0.007), and citrate synthase (27%) (P < 0.007) were also observed in patients with chronic renal failure. The synthetic rates of muscle proteins and activity of mitochondrial enzymes were negatively correlated to the severity of renal failure. These results indicate that in chronic renal failure there is a decrease in the synthesis of muscle contractile and mitochondrial proteins and a decrease in muscle mitochondrial oxidative enzymes. Reduced synthetic rate of several muscle proteins is the likely biochemical basis of muscle loss and muscle weakness in people with chronic renal failure.


Human Lymph Nodes Maintain TCF-1hi Memory T Cells with High Functional Potential and Clonal Diversity throughout Life.
Translating studies on T cell function and modulation from mouse models to humans requires extrapolating in vivo results on mouse T cell responses in lymphoid organs (spleen and lymph nodes [LN]) to human peripheral blood T cells. However, our understanding of T cell responses in human lymphoid sites and their relation to peripheral blood remains sparse. In this study, we used a unique human tissue resource to study human T cells in different anatomical compartments within individual donors and identify a subset of memory CD8+ T cells in LN, which maintain a distinct differentiation and functional profile compared with memory CD8+ T cells in blood, spleen, bone marrow, and lungs. Whole-transcriptome and high-dimensional cytometry by time-of-flight profiling reveals that LN memory CD8+ T cells express signatures of quiescence and self-renewal compared with corresponding populations in blood, spleen, bone marrow, and lung. LN memory T cells exhibit a distinct transcriptional signature, including expression of stem cell-associated transcription factors TCF-1 and LEF-1, T follicular helper cell markers CXCR5 and CXCR4, and reduced expression of effector molecules. LN memory T cells display high homology to a subset of mouse CD8+ T cells identified in chronic infection models that respond to checkpoint blockade immunotherapy. Functionally, human LN memory T cells exhibit increased proliferation to TCR-mediated stimulation and maintain higher TCR clonal diversity compared with memory T cells from blood and other sites. These findings establish human LN as reservoirs for memory T cells with high capacities for expansion and diverse recognition and important targets for immunotherapies.


Soil microbial communities are shaped by plant-driven changes in resource availability during secondary succession.
Although we understand the ecological processes eliciting changes in plant community composition during secondary succession, we do not understand whether co-occurring changes in plant detritus shape saprotrophic microbial communities in soil. In this study, we investigated soil microbial composition and function across an old-field chronosequence ranging from 16 to 86 years following agricultural abandonment, as well as three forests representing potential late-successional ecosystems. Fungal and bacterial community composition was quantified from ribosomal DNA, and insight into the functional potential of the microbial community to decay plant litter was gained from shotgun metagenomics and extracellular enzyme assays. Accumulation of soil organic matter across the chronosequence exerted a positive and significant effect on fungal phylogenetic β-diversity and the activity of extracellular enzymes with lignocellulolytic activity. In addition, the increasing abundance of lignin-rich C4 grasses was positively related to the composition of fungal genes with lignocellulolytic function, thereby linking plant community composition, litter biochemistry, and microbial community function. However, edaphic properties were the primary agent shaping bacterial communities, as bacterial β-diversity and variation in functional gene composition displayed a significant and positive relationship to soil pH across the chronosequence. The late-successional forests were compositionally distinct from the oldest old fields, indicating that substantial changes occur in soil microbial communities as old fields give way to forests. Taken together, our observations demonstrate that plants govern the turnover of soil fungal communities and functional characteristics during secondary succession, due to the continual input of detritus and differences in litter biochemistry among plant species.


The effect of topiramate on energy balance in obese men: a 6-month double-blind randomized placebo-controlled study with a 6-month open-label extension.
Topiramate (TPM) has been reported to reduce body weight beyond a placebo in the treatment of obese participants, but the effect of this agent on components of energy balance has not yet been established in humans. Thus, the aim of this study was to study the impact of TPM on food preferences, measures of satiety, food intake, resting metabolic rate (RMR), and 24-h energy expenditure. The study design consisted of a 6-month, single-center, randomized, double-blind, parallel group, placebo-controlled trial with a 6-month open-label extension. The study included 68 sedentary men with abdominal obesity (waist circumference > or = 100 cm), of between 25 and 55 years of age, with a dyslipidemic profile and a body mass index (BMI) > or = 27 and < or = 40 kg/m(2). Treatment with TPM produced significant changes in anthropometric variables and body composition compared with placebo. However, at the end of the 1-year study, the placebo/TPM group showed similar weight loss and reduction in body fatness compared with the TPM/TPM group. For instance, at the end of the 12-month intervention, mean percentage of body weight loss from baseline was about -5% in both groups (-4 kg fat loss). Topiramate treatment reduced energy intake, be it in the context of an ad libitum buffet-type meal or under free living conditions. The 24-h daily energy expenditure (DEE) assessed by whole-body indirect calorimetry adjusted for body weight and age was not altered by TPM treatment. Topiramate treatment produced significantly greater weight loss than placebo and the majority of this loss was explained by a decrease in body fat stores. Most of the weight loss effect produced by TPM therapy was observed within a period of 6 months. Finally, TPM treatment had an impact on energy balance through a reduction in food intake that appears to have created an energy deficit of about 30,000-40,000 kcal compared with treatment with the placebo over 6 months.


Optimization of TAM16, a Benzofuran That Inhibits the Thioesterase Activity of Pks13; Evaluation toward a Preclinical Candidate for a Novel Antituberculosis Clinical Target.
With increasing drug resistance in tuberculosis (TB) patient populations, there is an urgent need for new drugs. Ideally, new agents should work through novel targets so that they are unencumbered by preexisting clinical resistance to current treatments. Benzofuran 1 was identified as a potential lead for TB inhibiting a novel target, the thioesterase domain of Pks13. Although, having promising activity against Mycobacterium tuberculosis, its main liability was inhibition of the hERG cardiac ion channel. This article describes the optimization of the series toward a preclinical candidate. Despite improvements in the hERG liability in vitro, when new compounds were assessed in ex vivo cardiotoxicity models, they still induced cardiac irregularities. Further series development was stopped because of concerns around an insufficient safety window. However, the demonstration of in vivo activity for multiple series members further validates Pks13 as an attractive novel target for antitubercular drugs and supports development of alternative chemotypes.


β-catenin enhances Oct-4 activity and reinforces pluripotency through a TCF-independent mechanism.
Understanding the mechanisms regulating pluripotency in embryonic and induced pluripotent stem cells is required to ensure their safe use in clinical applications. Glycogen synthase kinase-3 (GSK-3) has emerged as an important regulator of pluripotency, based primarily on studies with small-molecule GSK-3 inhibitors. Here, we use mouse embryonic stem cells (ESCs) lacking GSK-3 to demonstrate that a single GSK-3 substrate, β-catenin, controls the ability of ESCs to exit the pluripotent state and to differentiate into neurectoderm. Unexpectedly, the effects of β-catenin on pluripotency do not appear to be dependent on TCF-mediated signaling, based on experiments utilizing a β-catenin C-terminal truncation mutant or highly efficient dominant-negative TCF strategies. Alternatively, we find that stabilized β-catenin forms a complex with and enhances the activity of Oct-4, a core component of the transcriptional network regulating pluripotency. Collectively, our data suggest previously underappreciated, divergent TCF-dependent and TCF-independent roles for β-catenin in ESCs.


Strength and breaking mechanism of multiwalled carbon nanotubes under tensile load
The tensile strengths of individual multiwalled carbon nanotubes (MWCNTs) were measured with a "nanostressing stage" located within a scanning electron microscope. The tensile-loading experiment was prepared and observed entirely within the microscope and was recorded on video. The MWCNTs broke in the outermost layer ("sword-in-sheath" failure), and the tensile strength of this layer ranged from 11 to 63 gigapascals for the set of 19 MWCNTs that were loaded. Analysis of the stress-strain curves for individual MWCNTs indicated that the Young's modulus E of the outermost layer varied from 270 to 950 gigapascals. Transmission electron microscopic examination of the broken nanotube fragments revealed a variety of structures, such as a nanotube ribbon, a wave pattern, and partial radial collapse.


Quantitative comparison of 21 protocols for labeling hippocampal subfields and parahippocampal subregions in in vivo MRI: towards a harmonized segmentation protocol.
An increasing number of human in vivo magnetic resonance imaging (MRI) studies have focused on examining the structure and function of the subfields of the hippocampal formation (the dentate gyrus, CA fields 1-3, and the subiculum) and subregions of the parahippocampal gyrus (entorhinal, perirhinal, and parahippocampal cortices). The ability to interpret the results of such studies and to relate them to each other would be improved if a common standard existed for labeling hippocampal subfields and parahippocampal subregions. Currently, research groups label different subsets of structures and use different rules, landmarks, and cues to define their anatomical extents. This paper characterizes, both qualitatively and quantitatively, the variability in the existing manual segmentation protocols for labeling hippocampal and parahippocampal substructures in MRI, with the goal of guiding subsequent work on developing a harmonized substructure segmentation protocol. MRI scans of a single healthy adult human subject were acquired both at 3 T and 7 T. Representatives from 21 research groups applied their respective manual segmentation protocols to the MRI modalities of their choice. The resulting set of 21 segmentations was analyzed in a common anatomical space to quantify similarity and identify areas of agreement. The differences between the 21 protocols include the region within which segmentation is performed, the set of anatomical labels used, and the extents of specific anatomical labels. The greatest overall disagreement among the protocols is at the CA1/subiculum boundary, and disagreement across all structures is greatest in the anterior portion of the hippocampal formation relative to the body and tail. The combined examination of the 21 protocols in the same dataset suggests possible strategies towards developing a harmonized subfield segmentation protocol and facilitates comparison between published studies.


[Functional MR urography in patients with kidney transplantation].
To assess the value of functional magnetic resonance urology for the noninvasive postoperative evaluation of renal transplants. A saturation inversion projection sequence allows the selective imaging of strongly T1 weighted signal from the MR contrast agent. A control slab leads to images comparable to conventional urography which can be acquired as a sequence with four images per minute. 15 patients with urologic questionable findings after renal transplantation were studied. FMRU revealed in 6 patients normal findings, in 6 moderate dilatation of the renal pelvis without any urodynamic relevant obstruction. 3 pathologic findings, ureteral leak, ureteropelvic-junction obstruction and ureteral stenosis were diagnosed and consequently surgically treated. The imaging quality in all studies was diagnostic and urologically relevant. FMRU can be used as a noninvasive technique for the assessment of renal transplant in cases with suspicion of complication in the excretory system.


A pilot multiple-baseline study of a mobile cognitive behavioral therapy for the treatment of eating disorders in university students.
Eating disorders (EDs) are serious psychiatric disorders associated with substantial morbidity and mortality that are prevalent among university students. Because many students do not receive treatment due to lack of access on university campuses, mobile-health (mHealth) adaptations of evidence-based treatments represent an opportunity to increase treatment accessibility and engagement. The purpose of this study was to test the initial efficacy of Building Healthy Eating and Self-Esteem Together for University Students (BEST-U), which is a 10-week mHealth self-guided cognitive-behavioral therapy (CBT-gsh) app that is paired with a brief 25-30-min weekly telehealth coaching, for reducing ED psychopathology in university students. A non-concurrent multiple-baseline design (N = 8) was used to test the efficacy of BEST-U for reducing total ED psychopathology (primary outcome), ED-related behaviors and cognitions (secondary outcomes), and ED-related clinical impairment (secondary outcome). Data were examined using visual analysis and Tau-BC effect-size calculations. BEST-U significantly reduced total ED psychopathology and binge eating, excessive exercise, and restriction (effect sizes ranged from -0.39 to -0.92). Although body dissatisfaction decreased, it was not significant. There were insufficient numbers of participants engaging in purging to evaluate purging outcomes. Clinical impairment significantly reduced from pre-to-post-treatment. The current study provided initial evidence that BEST-U is a potentially efficacious treatment for reducing ED symptoms and ED-related clinical impairment. Although larger-scale randomized controlled trials are needed, BEST-U may represent an innovative, scalable tool that could reach greater numbers of underserved university students than traditional intervention-delivery models. Using a single-case experimental design, we found evidence for the initial efficacy of a mobile guided-self-help cognitive-behavioral therapy program for university students with non-low weight binge-spectrum eating disorders. Participants reported significant reductions in ED symptoms and impairment after completion of the 10-week program. Guided self-help programs show promise for filling an important need for treatment among university students with an ED.


Psychometric Properties of the Proxy-Reported Life-Space Assessment in Institutionalized Settings (LSA-IS-Proxy) for Older Persons with and without Cognitive Impairment.
(1) Background: Life-space mobility assessments for institutionalized settings are scarce and there is a lack of comprehensive validation and focus on persons with cognitive impairment (CI). This study aims to evaluate the psychometric properties of the Life-Space Assessment for Institutionalized Settings by proxy informants (LSA-IS-proxy) for institutionalized, older persons, with and without CI. (2) Methods: Concurrent validity against the self-reported version of the LSA-IS, construct validity with established construct variables, test-retest reliability, sensitivity to change during early multidisciplinary geriatric rehabilitation treatment, and feasibility (completion rate, floor/ceiling effects) of the LSA-IS-proxy, were assessed in 94 hospitalized geriatric patients (83.3 ± 6.1 years), with and without CI. (3) Results: The LSA-IS-proxy total score showed good-to-excellent agreement with the self-reported LSA-IS (Intraclass Correlations Coefficient, ICC3,1 = 0.77), predominantly expected small-to-high correlations with construct variables (r = 0.21-0.59), good test-retest reliability (ICC3,1 = 0.74), significant sensitivity to change over the treatment period (18.5 ± 7.9 days; p < 0.001, standardized response mean = 0.44), and excellent completion rates (100%) with no floor/ceiling effects. These results were predominantly confirmed for the sub-scores of the LSA-IS-proxy and were comparable between the sub-groups with different cognitive status. (4) Conclusions: The LSA-IS-proxy has proven to be feasible, valid, reliable, and sensitive to change in hospitalized, geriatric patients with and without CI.


Functional characterization of the MODY1 gene mutations HNF4(R127W), HNF4(V255M), and HNF4(E276Q).
Genetic studies have shown that mutations in the gene encoding hepatocyte nuclear factor (HNF)-4alpha, a member of the steroid/thyroid hormone receptor superfamily, give rise to early-onset type 2 diabetes (MODY1). The functional properties of mutant HNF-4alpha proteins and the molecular mechanisms by which they impair insulin secretion are largely unknown. In the present study, we have investigated transcriptional activation, DNA binding properties, and protein dimerization activity of three HNF-4alpha missense mutations--HNF4(R127W), HNF4(V255M), and HNF4(E276Q)--that have been associated with type 2 diabetes. We demonstrate that HNF4(E276Q) has lost its ability to bind to HNF-4 consensus binding sites and activate transcription. HNF4(E276Q) had no effect on the functional activity of wild-type HNF-4alpha in the pancreatic beta-cell line HIT-T15, but it exhibited weak dominant-negative activity in other cell types. Analysis of HNF4(E276Q) protein showed that it exists in two forms: a full length 54-kDa protein and a 40-kDa COOH-terminal protein lacking the NH2-terminal transactivation domain and the DNA binding domain. Immunoprecipitation experiments indicate that this truncated protein can bind to wild-type HNF-4alpha and may be responsible for the weak dominant-negative effects seen in these cells. In addition, we show that the transcriptional transactivation of HNF4(R127W) and HNF4(V255M) is indistinguishable from that of wild-type HNF-4alpha, suggesting that they are sequence polymorphisms. Our results demonstrate that HNF4(E276Q) is a loss-of-function mutation and that it identifies glutamic acid 276 in alpha-helix 8 of the ligand-binding domain of HNF-4alpha protein as a critical residue for DNA binding, transcriptional activation, and protein stability in vivo.


Numerical studies of biocontrol efficacies of foliar plant pathogens in relation to the characteristics of a biocontrol agent.
A previously published generic mathematic model has been used in a numerical study to understand the dynamics of foliar pathogens in relation to mechanisms, and timing and coverage of biocontrol agent (BCA) applications. With the model parameter values used, it was demonstrated that a BCA possessing either competition or induced resistance as the main mechanism of biological control was more effective in reducing disease development than a BCA with either mycoparasitism or antibiosis as its mechanism. Application coverage, ranging from 50 to 90%, had little effect on biocontrol efficacy, particularly for a BCA with competition and induced resistance as the main mechanism of biocontrol. Conversely, delayed application of BCA had more profound effects on biocontrol efficacy for those with competition or induced resistance as their main mechanism than those with mycoparasitism and antibiosis. Biocontrol efficacy was greatest for a single BCA combining competition with mycoparasitism or antibiosis. The efficacy for a single BCA combining induced resistance with competition critically depended on application time; the efficacy was greatly reduced for delayed applications. The present study suggests that development of an effective strategy for BCA application is critically dependent upon our quantitative understanding of several key biocontrol processes and their interactions. Without reliable quantitative estimation of these processes, it is impossible to make quantitative predictions about biological control and hence to optimize BCA application strategies.


Estrogenic compounds are not always cardioprotective and can be lethal in males with genetic heart disease.
Hypertrophic cardiomyopathy (HCM) is more severe in male than female mice eating a soy-based diet. We sought to determine whether the detrimental effects are mediated by the phytoestrogens present in soy, the mechanism by which phytoestrogens act, and to test whether estrogen modulates the sexually dimorphic phenotype. A soy-free diet (casein based) supplemented with the predominant phytoestrogens in soy, genistein and daidzein, recapitulated the fibrotic, proapoptotic and negative hemodynamic effects of soy in male hearts. As with the soy diet, the hearts of female HCM mice were not negatively affected by the phytoestrogen-containing diet. To determine the role of estrogen in the sex differences mediated by diet in HCM, gonadectomies were performed and estrogen was administered to male and female HCM mice on a casein- or phytoestrogen-supplemented diet. Somewhat surprisingly, estrogen was not protective in male or female mice with HCM and, in fact, was lethal in phytoestrogen-fed male mice with HCM. Because genistein is a potent tyrosine kinase inhibitor and tyrosine kinase inhibition has been associated with cardiotoxicity, we tested its effects in isolated adult cardiac myocytes. Genistein inhibited different tyrosine kinases depending on sex and, in combination with estrogen, resulted in apoptosis only in adult male cardiac myocytes. Finally, we show that phytoestrogens led to distinct programs of gene expression in hearts from males vs. females with HCM, suggesting mechanisms by which males are more sensitive to the detrimental effects of phytoestrogens and females are protected. These results implicate the phytoestrogen genistein in mediating cardiac pathology in males with HCM and, importantly, establish that estrogen is not protective in the setting of HCM.


Genome-wide association study identifies loci affecting blood copper, selenium and zinc.
Genetic variation affecting absorption, distribution or excretion of essential trace elements may lead to health effects related to sub-clinical deficiency. We have tested for allelic effects of single-nucleotide polymorphisms (SNPs) on blood copper, selenium and zinc in a genome-wide association study using two adult cohorts from Australia and the UK. Participants were recruited in Australia from twins and their families and in the UK from pregnant women. We measured erythrocyte Cu, Se and Zn (Australian samples) or whole blood Se (UK samples) using inductively coupled plasma mass spectrometry. Genotyping was performed with Illumina chips and > 2.5 m SNPs were imputed from HapMap data. Genome-wide significant associations were found for each element. For Cu, there were two loci on chromosome 1 (most significant SNPs rs1175550, P = 5.03 × 10(-10), and rs2769264, P = 2.63 × 10(-20)); for Se, a locus on chromosome 5 was significant in both cohorts (combined P = 9.40 × 10(-28) at rs921943); and for Zn three loci on chromosomes 8, 15 and X showed significant results (rs1532423, P = 6.40 × 10(-12); rs2120019, P = 1.55 × 10(-18); and rs4826508, P = 1.40 × 10(-12), respectively). The Se locus covers three genes involved in metabolism of sulphur-containing amino acids and potentially of the analogous Se compounds; the chromosome 8 locus for Zn contains multiple genes for the Zn-containing enzyme carbonic anhydrase. Where potentially relevant genes were identified, they relate to metabolism of the element (Se) or to the presence at high concentration of a metal-containing protein (Cu).


Continuous monitoring of cerebrovascular pressure reactivity allows determination of optimal cerebral perfusion pressure in patients with traumatic brain injury.
To define optimal cerebral perfusion pressure (CPPOPT) in individual head-injured patients using continuous monitoring of cerebrovascular pressure reactivity. To test the hypothesis that patients with poor outcome were managed at a cerebral perfusion pressure (CPP) differing more from their CPPOPT than were patients with good outcome. Retrospective analysis of prospectively collected data. Neurosciences critical care unit of a university hospital. A total of 114 head-injured patients admitted between January 1997 and August 2000 with continuous monitoring of mean arterial blood pressure (MAP) and intracranial pressure (ICP). MAP, ICP, and CPP were continuously recorded and a pressure reactivity index (PRx) was calculated online. PRx is the moving correlation coefficient recorded over 4-min periods between averaged values (6-sec periods) of MAP and ICP representing cerebrovascular pressure reactivity. When cerebrovascular reactivity is intact, PRx has negative or zero values, otherwise PRx is positive. Outcome was assessed at 6 months using the Glasgow Outcome Scale. A total of 13,633 hrs of data were recorded. CPPOPT was defined as the CPP where PRx reaches its minimum value when plotted against CPP. Identification of CPPOPT was possible in 68 patients (60%). In 22 patients (27%), CPPOPT was not found because it presumably lay outside the studied range of CPP. Patients' outcome correlated with the difference between CPP and CPPOPT for patients who were managed on average below CPPOPT (r =.53, p <.001) and for patients whose mean CPP was above CPPOPT (r = -.40, p <.05). CPPOPT could be identified in a majority of patients. Patients with a mean CPP close to CPPOPT were more likely to have a favorable outcome than those whose mean CPP was more different from CPPOPT. We propose use of the criterion of minimal achievable PRx to guide future trials of CPP oriented treatment in head injured patients.


Population genetics analysis of Phlebotomus papatasi sand flies from Egypt and Jordan based on mitochondrial cytochrome b haplotypes.
Phlebotomus papatasi sand flies are major vectors of Leishmania major and phlebovirus infection in North Africa and across the Middle East to the Indian subcontinent. Population genetics is a valuable tool in understanding the level of genetic variability present in vector populations, vector competence, and the development of novel control strategies. This study investigated the genetic differentiation between P. papatasi populations in Egypt and Jordan that inhabit distinct ecotopes and compared this structure to P. papatasi populations from a broader geographical range. A 461 base pair (bp) fragment from the mtDNA cytochrome b (cyt b) gene was PCR amplified and sequenced from 116 individual female sand flies from Aswan and North Sinai, Egypt, as well as Swaimeh and Malka, Jordan. Haplotypes were identified and used to generate a median-joining network, F ST values and isolation-by-distance were also evaluated. Additional sand fly individuals from Afghanistan, Iran, Israel, Jordan, Libya, Tunisia and Turkey were included as well as previously published haplotypes to provide a geographically broad genetic variation analysis. Thirteen haplotypes displaying nine variant sites were identified from P. papatasi collected in Egypt and Jordan. No private haplotypes were identified from samples in North Sinai, Egypt, two were observed in Aswan, Egypt, four from Swaimeh, Jordan and two in Malka, Jordan. The Jordan populations clustered separately from the Egypt populations and produced more private haplotypes than those from Egypt. Pairwise F ST values fall in the range 0.024-0.648. The clustering patterns and pairwise F ST values indicate a strong differentiation between Egyptian and Jordanian populations, although this population structure is not due to isolation-by-distance. Other factors, such as environmental influences and the genetic variability in the circulating Le. major parasites, could possibly contribute to this heterogeneity. The present study aligns with previous reports in that pockets of genetic differentiation exists between populations of this widely dispersed species but, overall, the species remains relatively homogeneous.


Global obesity study on drivers for weight reduction strategies.
To assess factors determining the reaction of individuals to the threats of overweight and obesity and to examine the interdependencies between weight-reducing strategies. Cross-country survey covering 19 countries and 13,155 interviews. Data were analysed using a bivariate probit model that allows simultaneously analysing two weight-reducing strategies. Results show that weight-reducing strategies chosen are not independent from each other. Findings also reveal that different strategies are chosen by different population segments. Women are more likely to change their dietary patterns and less likely to become physically active after surpassing a weight threshold. In addition, the probability of a dietary change in case of overweight differs considerably between countries. The study also reveals that attitudes are an important factor for the strategy choice. It is vital for public health policies to understand determinants of citizens' engagement in weight reduction strategies once a certain threshold is reached. Thus, results can support the design of public health campaigns and programmes that aim to change community or national health behaviour trends taking into account, e.g., national differences.


Recent advances in porous polyoxometalate-based metal-organic framework materials.
Polyoxometalate (POM)-based metal-organic framework (MOF) materials contain POM units and generally generate MOF materials with open networks. POM-based MOF materials, which utilize the advantages of both POMs and MOFs, have received increasing attention, and much effort has been devoted to their preparation and relevant applications over the past few decades. They have good prospects in catalysis owing to the electronic and physical properties of POMs that are tunable by varying constituent elements. In this review, we present recent developments in porous POM-based MOF materials, including their classification, synthesis strategies, and applications, especially in the field of catalysis.


The product of the imprinted H19 gene is an oncofetal RNA.
The H19 gene is an imprinted, maternally expressed gene in humans. It is tightly linked and coregulated with the imprinted, paternally expressed gene of insulin-like growth factor 2. The H19 gene product is not translated into protein and functions as an RNA molecule. Although its role has been investigated for more than a decade, its biological function is still not understood fully. H19 is abundantly expressed in many tissues from early stages of embryogenesis through fetal life, and is down regulated postnatally. It is also expressed in certain childhood and adult tumours. This study was designed to screen the expression of H19 in human cancer and its relation to the expression of H19 in the fetus. Using in situ hybridisation with a [35S] labelled probe, H19 mRNA was detected in paraffin wax sections of fetal tissues from the first and second trimesters of pregnancy and of a large array of human adult and childhood tumours arising from these tissues. The H19 gene is expressed in tumours arising from tissues which express this gene in fetal life. Its expression in the fetus and in cancer is closely linked with tissue differentiation. Based on these and previous data, H19 is neither a tumour suppressor gene nor an oncogene. Its product is an oncofetal RNA. The potential use of this RNA as a tumour marker should be evaluated.


Measurements of the ripple effect and geometric distribution of switched gradient fields inside a magnetic resonance scanner.
Knowledge of patient exposure during magnetic resonance imaging (MRI) procedures is limited, and the need for such knowledge has been demonstrated in recent in vitro and in vivo studies of the genotoxic effects of MRI. This study focuses on the dB/dt of the switched gradient field (SGF) and its geometric distribution. These values were characterized by measuring the peak dB/dt generated by a programmed gradient current of alternating triangles inside a 1.5T MR scanner. The maximum dB/dt exposure to the gradient field was 6-14 T/s, and this occurred at the edges of the field of view (FOV) 20-25 cm from the isocenter in the longitudinal direction. The dB/dt exposure dropped off to roughly half the maximum (3-7 T/s) at the edge of the bore. It was found that the dB/dt of the SGF was distorted by a 200 kHz ripple arising from the amplifier. The ripple is small in terms of B-field, but the high frequency content contributes to a peak dB/dt up to 18 times larger than that predicted by the slew rate (4 T/s m) and the distance from the isocenter. Measurements on a 3 T MRI scanner, however, revealed a much smaller filtered ripple of 100 kHz in dB/dt. These findings suggest that the gradient current to each coil together with information on the geometrical distribution of the gradient field and ripple effects could be used to assess the SGF exposure within an MRI bore.


[Study on the Tibetan medicine Swertia mussotii Franch and its extracts by Fourier transform infrared spectroscopy].
The objective of the present study is to research the herb of Swertia mussotii Franch and its different extracts by tristep infrared spectroscopy. The main constitute of Swertia mussotii Franch-gentiamarin, which is also the higher content constitute, was selected as the control components to analyze the infrared spectroscopy and second derivative infrared spectroscopy of different extracts of Swertia mussotii Franch, at the same time, the different concentration of ethanol extracts were also analyzed by two-dimensional correlation spectroscopy (2D-COS). The results indicated that the intensity of 1 611 and 1 075 cm(-1) of gentiamarin, which are its two main absorptions in the infrared spectra, has the positive correlation with the content change in different extracts. The infrared spectroscopy of extracts are similar if the polarity of extract solvents is close; with the decreases in solution polarity, the intensity of 2 853, 1 733, 1 464, 1 277 and 1 161 cm(-1) in infrared spectroscopy of different extracts is increased, the content of esters and the extraction percentage terpenoid compounds are also increased; the different concentration of ethanol extracts has obviously difference when they are analyzed by two-dimensional correlation spectroscopy (2D-COS). The positive correlation between the intensity of absorptions and the content of the gentiamarin indicates that the infrared spectroscopy can reflect the content change in constitute; the similar and the change trend of the different concentrations of ethanol extract infrared spectroscopy approve the scientificalness of decoction of traditional medicine; infrared spectroscopy that used in the research can be used as an accurate, rapid and effective method in the pharmacological activity tests of transitional herbal Swertia mussotii F. and it's different extracts, even in the research on the tibetan medicine.


The role and potential of umbilical cord blood in an era of new therapies: a review.
In light of pioneering findings in the 1980s and an estimation of more than 130 million global annual births, umbilical cord blood (UCB) is considered to be the most plentiful reservoir of cells and to have regenerative potential for many clinical applications. Although UCB is used mainly against blood disorders, the spectrum of diseases for which it provides effective therapy has been expanded to include non-hematopoietic conditions; UCB has also been used as source for regenerative cell therapy and immune modulation. Thus, collection and banking of UCB-derived cells have become a popular option. However, there are questions regarding the cost versus the benefits of UCB banking, and it also raises complex ethical and legal issues. This review discusses many issues surrounding the conservation of UCB-derived cells and the great potential and current clinical applications of UCB in an era of new therapies. In particular, we describe the practical issues inherent in UCB collection, processing, and long-term storage as well as the different types of 'stem' or progenitor cells circulating in UCB and their uses in multiple clinical settings. Given these considerations, the trend toward UCB will continue to provide growing assistance to health care worldwide.


Task-evoked pulse wave amplitude tracks cognitive load.
Cognitive load is a crucial factor in mentally demanding activities and holds significance across various research fields. This study aimed to investigate the effectiveness of pulse wave amplitude (PWA) as a measure for tracking cognitive load and associated mental effort in comparison to heart rate (HR) during a digit span task. The data from 78 participants were included in the analyses. Participants performed a memory task in which they were asked to memorize sequences of 5, 9, or 13 digits, and a control task where they passively listened to the sequences. PWA and HR were quantified from photoplethysmography (PPG) and electrocardiography (ECG), respectively. Pupil dilation was also assessed as a measure of cognitive load. We found that PWA showed a strong suppression with increasing memory load, indicating sensitivity to cognitive load. In contrast, HR did not show significant changes with task difficulty. Moreover, when memory load exceeded the capacity of working memory, a reversal of the PWA pattern was observed, indicating cognitive overload. In this respect, changes in PWA in response to cognitive load correlated with the dynamics of pupil dilation, suggesting a potential shared underlying mechanism. Additionally, both HR and PWA demonstrated a relationship with behavioral performance, with higher task-evoked HR and lower PWA associated with better memory performance. Our findings suggest that PWA is a more sensitive measure than HR for tracking cognitive load and overload. PWA, measured through PPG, holds significant potential for practical applications in assessing cognitive load due to its ease of use and sensitivity to cognitive overload. The findings contribute to the understanding of psychophysiological indicators of cognitive load and offer insights into the use of PWA as a non-invasive measure in various contexts.


Accumulation of ricinoleic, lesquerolic, and densipolic acids in seeds of transgenic Arabidopsis plants that express a fatty acyl hydroxylase cDNA from castor bean.
A cDNA encoding the oleate 12-hydroxylase from castor bean (Ricinus communis L.) has previously been shown to direct the synthesis of small amounts of ricinoleic acid (12-hydroxyoctadec-cis-9-enoic acid) in seeds of transgenic tobacco plants. Expression of the cDNA under control of the Brassica napus napin promoter in transgenic Arabidopsis thaliana plants resulted in the accumulation of up to 17% of seed fatty acids as ricinoleate and two novel fatty acids that have been identified by gas chromatography-mass spectrometry as lesquerolic (14-hydroxyeicos-cis-11-enoic acid) and densipolic (12-hydroxyoctadec-cis-9,15-dienoic acid) acids. Traces of auricolic acid were also observed. These results suggest that either the castor hydroxylase can utilize oleic acid and eicosenoic acid as substrates for ricinoleic and lesquerolic acid biosynthesis, respectively, or Arabidopsis contains an elongase that accepts ricinoleic acid as a substrate. These observations are also consistent with indirect biochemical evidence that an n-3 desaturase is capable of converting ricinoleic acid to densipolic acid. Expression of the castor hydroxylase also caused enhanced accumulation of oleic acid and a corresponding decrease in the levels of polyunsaturated fatty acids. Since the steady-state level of mRNA for the oleate-12 desaturase was not affected, it appears that the presence of the hydroxylase, directly or indirectly, causes posttranscriptional inhibition of desaturation.


A single-cell analysis of early retinal ganglion cell differentiation in Xenopus: from soma to axon tip.
Intracellular injections of Lucifer yellow (LY) were made into the cell bodies of Xenopus retinal ganglion cells from the earliest stages of axonogenesis to the beginning of target innervation. Embryos were intact during the injection so that the entire cell (cell body, dendrites, axon, and growth cone) could be visualized. The purpose of the study was 3-fold: (1) to characterize the early steps in retinal ganglion cell differentiation before the axon reaches its target; (2) to determine whether guidepost cells exist as possible navigation cues in the vertebrate optic pathway; and (3) to investigate whether the morphology of early retinal ganglion cell growth cones varies in a position-dependent manner along the primordial optic pathway. Axons were generally initiated before dendrites and followed a well-defined course along the primordial optic pathway without branching. Surprisingly, at least 5% of the retinal ganglion cells sent more than one axon into the optic pathway. Sister axons from the same parent cell traveled separately in the pathway, indicating that their growth cones navigated independently. Examination of dendrite genesis showed that dendrites usually begin to emerge from the cell body well before the axon tip reaches the target. This observation argues against the possibility that target contact influences dendrite initiation. Nascent dendrites were commonly tipped with pronounced varicosities that did not resemble axon growth cones. Their number and branching correlated well with axon length, indicating that the age of the retinal ganglion cell itself, rather than the age of its presynaptic cells or local environment, is the strongest influence on dendrite genesis. Examination of LY-filled growth cones at varying points in the pathway showed no evidence of dye transfer to adjacent cells. This indicates that gap junctional contacts probably do not form during axonal pathfinding and suggests that direct intercellular communication between growing axons and other cells in the pathway does not play a major role in axon guidance. Growth cone morphology was analyzed quantitatively and found to vary at different positions along the pathway. Growth cones entering the optic nerve head were the largest and most complex; those on the retinal surface were the smallest and showed a simple morphology. Growth cones in the chiasm and optic tract showed a degree of complexity similar to those in the optic nerve head but were smaller.(ABSTRACT TRUNCATED AT 400 WORDS)


Report of chronic myeloid leukemia SMS Medical College Hospital, Jaipur.
This is a retrospective analysis of patients of chronic myeloid leukemia (CML) registered and under treatment at the Leukemia Lymphoma Clinic at the Birla Cancer Center, SMS Medical College Hospital, Jaipur. Approximately, two-thirds of the patients are getting imatinib mesylate (IM) through the Glivec International Patient Assistance Program while the rest are on generic IM. In addition to comparison of hematological and molecular responses in the Glivec versus the genetic group, in this analysis, an attempt is also made to assess the socio-economic (SE) status of the patients and its effect on the response rates. Of the 213 patients studied, most (28.6%) are in the age group between 30 years and 40 years and the mean age of the patients in 39 years, a good decade younger that in the west. There is a suggestion that patients in lower SE class present with higher Sokal scores and with more disease burden. Possibly hematological responses are similar with both Glivec and generic IM. No comment can be made with regards to molecular response between the two groups as a significant number of patients in the Glivec arm (42%) do not have molecular assessment because of economic reasons. CML is a common and challenging disease in the developing world with patients presenting at an earlier age with more advanced disease. SE factors play a significant role in therapy and disease monitoring decision making and may impact on response rates and prognosis.


Multifunctions of Excited Gold Nanoparticles Decorated Artificial Kidney with Efficient Hemodialysis and Therapeutic Potential.
Chronic kidney disease (CKD) is inflammation-related. Patients with chronic renal failure who undergo hemodialysis (HD) have some acute adverse effects caused by dialysis-induced oxidative stress, protein adsorption, platelet adhesion, and activation of coagulation and inflammation. Here, resonantly illuminated gold nanoparticles-modified artificial kidney (AuNPs@AK) for achieving high efficiency accompanying therapeutic strategy for CKD during HD is proposed. The efficiency in removing uremic toxins increased obviously, especially in the presence of protein (closer to the real blood). The excited AuNPs@AK expressed negatively charged surface reduced some acute adverse effects caused by dialysis-induced protein adsorption, platelet adhesion, and activation of coagulation, thus avoiding thrombosis during HD. Unlike to traditional HD which provides only one function of removing uremic toxins, the solution collected from the outlet of the sample channel of excited AuNPs@AK showed an efficient free radical scavenger that could decrease dialysis-induced oxidative stress. In the CKD mouse model, this antioxidative solution from excited AuNPs@AK further decreased fibronectin expression and attenuated renal fibrosis, suggesting a reduced inflammatory response. These successful in vitro and in vivo approaches suggest that resonantly illuminated AuNPs@AK in HD take multiadvantages in shortening treatment time and reducing risk of adverse effects, which promise trailblazing therapeutic strategies for CKD.


The prevalence of epilepsy and association with traumatic brain injury in veterans of the Afghanistan and Iraq wars.
To examine the association of epilepsy with traumatic brain injury (TBI) in Afghanistan and Iraq (Operation Enduring Freedom [OEF]/Operation Iraqi Freedom [OIF]) Veterans. Cross-sectional observational study. A total 256 284 OEF/OIF Veterans who received inpatient and outpatient care in the Veterans Health Administration in fiscal years 2009-2010. We used algorithms developed for use with International Classification of Diseases, Ninth Revision, Clinical Modification, codes to identify epilepsy, TBI (penetrating TBI [pTBI]/other TBI), and other risk factors for epilepsy (eg, stroke). TBI and other risk factors were identified prior to the index date (first date of seizure or October 1, 2009) for primary analyses. Epilepsy prevalence was 10.6 per 1000 (N = 2719) in fiscal year 2010; age-adjusted prevalence was 6.1. Of 37 718 individuals with a diagnosis of TBI, 29 297 Veterans had a diagnosis of TBI prior to the index date. Statistically significant associations were found between epilepsy and prior TBI diagnosis (pTBI: adjusted odds ratio = 18.77 [95% confidence interval, 9.21-38.23]; other TBI: adjusted odds ratio = 1.64 [1.43-1.89]). Among OEF/OIF Veterans, epilepsy was associated with previous TBI diagnosis, with pTBI having the strongest association. Because war-related epilepsy in Vietnam War Veterans with TBI continued 35 years postwar, a detailed, prospective study is needed to understand the relationship between epilepsy and TBI severity in OEF/OIF Veterans.


Estimating age of mature adults from the degeneration of the sternal end of the clavicle.
The sternal end of the clavicle has been illustrated to be useful in aging young adults, however, no studies have investigated what age-related changes occur to the sternal end post epiphyseal fusion. In this study, three morphological features (i.e., surface topography, porosity, and osteophyte formation) were examined and scored using 564 clavicles of individuals of European ancestry (n = 318 males; n = 246 females), with known ages of 40+ years, from four documented skeletal collections: Hamann-Todd, Pretoria, St. Bride's, and Coimbra. An ordinal scoring method was developed for each of the three traits. Surface topography showed the strongest correlation with age, and composite scores (formed by summing the three separate trait scores) indicated progressive degeneration of the surface with increasing chronological age. Linear regression analyses were performed on the trait scores to produce pooled-sample age estimation equations. Blind tests of the composite score method and regression formulae on 56 individuals, aged 40+ years, from Christ Church Spitalfields, suggest accuracies of 96.4% for both methods. These preliminary results display the first evidence of the utility of the sternal end of the clavicle in aging older adult individuals. However, in the current format, these criteria should only be applied to individuals already identified as over 40 years in order to refine the age ranges used for advanced age. These findings do suggest the sternal end of the clavicle has potential to aid age estimates beyond the traditional "mature adult" age category (i.e., 46+ years), and provides several suggestions for future research.


Outbreak of aseptic meningitis associated with mass vaccination with a urabe-containing measles-mumps-rubella vaccine: implications for immunization programs.
A mass immunization campaign with a Urabe-containing measles-mumps-rubella vaccine was carried out in 1997 in the city of Salvador, northeastern Brazil, with a target population of children aged 1-11 years. There was an outbreak of aseptic meningitis following the mass campaign. Cases of aseptic meningitis were ascertained through data collected from the records of children admitted to the local referral hospital for infectious diseases between March and October of 1997, using previously defined eligibility criteria. Vaccination histories were obtained through home visits or telephone calls. Eighty-seven cases fulfilled the study criteria. Of those, 58 cases were diagnosed after the vaccination campaign. An elevated risk of aseptic meningitis was observed 3 weeks after Brazil's national vaccination day compared with the risk in the prevaccination period (relative risk = 14.3; 95% confidence interval: 7.9, 25.7). This result was confirmed by a case series analysis (relative risk = 30.4; 95% confidence interval: 11.5, 80.8). The estimated risk of aseptic meningitis was 1 in 14,000 doses. This study confirms a link between measles-mumps-rubella vaccination and aseptic meningitis. The authors discuss the implications of this for the organization and planning of mass immunization campaigns.


[The antibacterial activity of cinnamon oil on the selected gram-positive and gram-negative bacteria].
The aim of our study was to determine the antibacterial activity of cinnamon bark oil against Gram-positive and Gram-negative isolates belonging to Staphylococcus, Enterococcus, Enterobacter and Acinetobacter genera come from different clinical specimens. The microdilution method was used to determine the minimum inhibitory concentration--MIC for cinnamon bark oil. Susceptibility testing to antibiotics was carried out using disc-diffusion method. Our investigations showed that the tested cinnamon bark oil was inhibiting activity against all isolates. The MIC for Gram-positive bacteria were between 01.25 and 1.5 μl/ml and for Gram-negative between 1.0 and 1.75 μl/ml. The tested bacteria come from Staphylococcus, Enterococcus, Enterobacter and Acinetobacter genera were susceptible to essential oil obtained from Cinnamomum zeylanicum Ness in low concentrations, despite the fact that the bacteria characterized the high resistance to recommended antibiotics. No correlation was found between the antibiotic resistance of the bacterial strains and their sensitivity to essential oil. The cinnamon bark oil due to the strong activity can be used as alternative antibacterial agents in cosmetics, toiletries and disinfectants applied in hospital environment.