Analysis of time-resolved X-ray scattering data from solution-state systems.
As ultrafast time-resolved studies of liquid systems with the laser pump/X-ray scattering probe method have come of age over the past decade, several groups have developed methods for the analysis of such X-ray scattering data. The present article describes a method developed primarily with a focus on determining structural parameters in the excited states of medium-sized molecules (approximately 30 atoms) in solution. The general methodology is set in a maximum-likelihood framework and is introduced through the analysis of the photoactive platinum compound PtPOP, in particular the structure of its lowest triplet excited state ((3)A(2u)). Emphasis is put on structure determination in terms of model comparisons and on the information content of difference scattering signals as well as the related experimental variables. Several suggestions for improving the accuracy of these types of measurements are presented.


Mutations at the Ser50 residue of translation factor eIF-2alpha dominantly affect developmental rate, body weight, and viability of Drosophila melanogaster.
Phosphorylation of the translation initiation factor eIF-2alpha downregulates protein synthesis by sequestering the guanylate exchange factor eIF-2B. The importance of this regulation has been demonstrated in the context of stress and virally induced repression of protein synthesis but has not been investigated relative to the control of protein synthesis during development. Transgenic Drosophila strains bearing aspartic acid or alanine substitutions at the presumed regulatory phosphorylation site (Ser50) of Drosophila eIF-2alpha were established. The expression of the eIF-2alpha mutant transgenes, under the transcriptional control of the hsp70 promoter, was induced at various times during development to assess the developmental and biochemical effects. Flies bearing the aspartic acid eIF-2alpha mutant (HD) transgene displayed a slow growth phenotype and small body size. Repeated induction of the HD transgene resulted in cessation of development. In contrast, flies bearing the alanine eIF-2alpha mutant (HA) displayed a fast growth phenotype and females were significantly larger than nontransgenic control sisters. The HD transgenic flies exhibit a relatively lower level of global protein synthesis than the HA transgenic flies, although the difference is statistically insignificant.


The opinions and feelings about their educational needs and role of familial caregivers of Parkinson's Disease patients: a qualitative study.
In the advanced stages of Parkinson's Disease, patients need complex care and support, especially at home, where they often receive assistance by familial caregivers. However, caregivers may be or feel unable to cope with their role and, despite the needs of caregivers are often assessed in the literature, their opinions and feelings about these needs are not widely explored yet. This study aimed at exploring the opinions and feelings about their educational needs and role of familial caregivers of Parkinson's Disease patients. A qualitative study was conducted from October to December 2017 in a polyclinic of central Italy. Fourteen caregivers voluntarily participated in the study; semi-structured face-to-face interviews were conducted, and audio recorded until data saturation. Two investigators reviewed the transcribed notes, created Meaning Units, Sub-categories and finally the Categories with emerged themes. The analysis of the 14 interviews generated three categories: supportiveness of healthcare educational programs; sense of inability to manage caregiver tasks; need for interaction with other familial caregivers. The caregivers declared their belief that healthcare educational courses can be useful in helping them live and understand the caregiving tasks and expressed their need to share their experiences with other caregivers. In fact, they often they felt abandoned and poorly trained for the patient's management at the home. The clinical practice should allow healthcare professionals to meet the training and emotional needs of caregivers and create a trust relationship with them to make caregivers skilled in caring for patients.


Insomnia, Sleep Duration, Depressive Symptoms, and the Onset of Chronic Multisite Musculoskeletal Pain.
The temporal relationships among sleep, depressive symptoms, and pain are unclear. This longitudinal study examines whether insomnia and sleep duration predict the onset of chronic multisite musculoskeletal pain over 6 years and whether this association is mediated by depressive symptoms. 1860 subjects of the Netherlands Study of Depression and Anxiety, free from chronic multisite musculoskeletal pain at baseline, were followed up for the onset of chronic multisite musculoskeletal pain over 6 years (Chronic Pain Grade Questionnaire). We determined baseline insomnia (Women's Health Initiative Insomnia Rating Scale ≥9) and sleep duration (short: ≤6 hr, normal: 7-9 hr, long: ≥10 hr). Depressive symptoms were assessed at baseline and as a change score over time (Inventory of Depressive Symptomatology). Insomnia (hazard ratio [HR] [95% confidence interval, 95%CI] = 1.60 [1.30-1.96], p < .001) and short sleep duration (HR [95%CI] = 1.52 [1.22-1.90], p < .001) were associated with chronic pain onset. Adding baseline depressive symptoms as a mediator attenuated the associations for insomnia and short sleep with chronic pain onset (∆B = 40% and 26%, respectively). Adding the change score of depressive symptoms further weakened the association for insomnia (∆B = 16%) but not for short sleep. All direct effects for sleep measures with chronic pain onset remained statistically significant (p < .05). This longitudinal study shows that insomnia and short sleep duration are risk factors for developing chronic pain. Depressive symptoms partially mediate the effect for insomnia and short sleep with developing chronic pain.


Redo-EVAR After Surgical Repair in Ruptured Abdominal Aortic Aneurysm.
Endovascular aneurysm repair (EVAR) is an adequate means for treating infrarenal abdominal aortic aneurysms (AAA). However, secondary interventions are required in approximately 15% to 20% of patients. The aim of this paper was to report our knowledge with stent grafts in secondary interventions after EVAR in a 73-year-old patient. One of the exceptional complications of EVAR are endoleaks which may lead to expansion of aneurysm and rupture if not repaired.


The evolution of donation after circulatory death donor kidney repair in the United Kingdom.
The increasing reliance on marginal donors has driven research to investigate ways to repair and improve the quality of kidneys for transplantation. Normothermic perfusion technologies provide an opportunity for improved preservation, organ assessment and resuscitation/repair of damaged kidneys. This review describes the evolution of normothermic perfusion in kidney transplantation in the United Kingdom. One hour of normothermic perfusion can be used to restore function and improve early graft function of extended criteria donor kidneys. A large multicentre trial is investigating the impact of normothermic perfusion on delayed graft function in a series of donation after circulatory death kidneys. Normothermic perfusion is also a platform for the delivery of therapies to the kidney to upregulate and modulate repair mechanisms or prevent injurious processes, such as activation of caspase-3 with the delivery of caspase-3 targeted small interfering RNAs. Normothermic perfusion can also be used to assess the quality and anatomical structure of a kidney to judge suitability for transplantation. Normothermic perfusion technology is a useful adjunct in kidney transplantation. It can improve early graft function by upregulating protective mechanisms. It also has the advantage of providing a functional assessment of the kidney and as a platform for the delivery of therapies or graft manipulation to target ischaemia reperfusion injury or the immune response. This technology can be used to expand the organ donor pool and prevent the unnecessary discard of kidneys.


Role of Intrinsic (Graft) Versus Extrinsic (Host) Factors in the Growth of Transplanted Organs Following Allogeneic and Xenogeneic Transplantation.
In our studies of life-supporting α-1,3-galactocyltransferase knockout (GalT-KO) pig-to-baboon kidneys, we found that some recipients developed increased serum creatinine with growth of the grafts, without histological or immunological evidence of rejection. We hypothesized that the rapid growth of orthotopic pig grafts in smaller baboon recipients may have led to deterioration of organ function. To test this hypothesis for both kidneys and lungs, we assessed whether the growth of outbred (Yorkshire) organ transplants in miniature swine was regulated by intrinsic (graft) or extrinsic (host environment) factors. Yorkshire kidneys exhibited persistent growth in miniature swine, reaching 3.7 times their initial volume over 3 mo versus 1.2 times for miniature swine kidneys over the same time period. Similar rapid early growth of lung allografts was observed and, in this case, led to organ dysfunction. For xenograft kidneys, a review of our results suggests that there is a threshold for kidney graft volume of 25 cm3 /kg of recipient body weight at which cortical ischemia is induced in transplanted GalT-KO kidneys in baboons. These results suggest that intrinsic factors are responsible, at least in part, for growth of donor organs and that this property should be taken into consideration for growth-curve-mismatched transplants, especially for life-supporting organs transplanted into a limited recipient space.


Muscle and cerebral oxygenation during exercise in athletes with exercise-induced hypoxemia: A comparison between sea level and acute moderate hypoxia.
The objective of the present study was to evaluate the influence of exercise-induced hypoxemia (EIH) on muscle and cerebral oxygenation responses during maximal exercise in normoxia and in acute moderate hypoxia (fraction of inspired oxygen: 15.3%, 2400 m). EIH was defined as a drop in hemoglobin saturation of at least 4% for at least three consecutive minutes during maximal exercise at sea level. Twenty-five athletes performed incremental treadmill tests to assess maximal oxygen consumption (VO2max) in normoxia and in hypoxia. Oxygenation of the vastus lateralis muscle and the left prefrontal cortex of the brain was monitored using near-infrared spectroscopy. During the normoxic test, 15 athletes exhibited EIH; they displayed a larger change in muscle levels of oxyhemoglobin (ΔO2Hb) (p = 0.04) and a greater change in cerebral levels of deoxyhemoglobin (ΔHHb) (p = 0.02) than athletes without EIH (NEIH group). During the hypoxic test, muscle ΔO2Hb was lower in the EIH group than in the NEIH group (p = 0.03). At VO2max, hypoxia was associated with a smaller cerebral ΔO2Hb in both groups, and a greater cerebral ΔHHb compared to normoxia in the NEIH group only (p = 0.02). No intergroup differences in changes in muscle oxygenation were observed. The severity of O2 arterial desaturation was negatively correlated with changes in total muscle hemoglobin in normoxia (r = -0.48, p = 0.01), and positively correlated with the cerebral ΔHHb in normoxia (r = 0.45, p = 0.02). The occurrence of EIH at sea level was associated with specific muscle and cerebral oxygenation responses to exercise under both normoxia and moderate hypoxia.


Alterations in the level of OFQ/N-IR in rat brain regions by cocaine.
We have previously shown that administration of orphanin FQ/nociceptin (OFQ/N), the endogenous ligand of the opioid receptor-like (ORL-1) receptor, into the lateral ventricles or VTA blocked cocaine sensitization. In the present study, we determined the effect of acute and chronic cocaine treatment on the level of endogenous OFQ/N in rat brain regions. Male Sprague Dawley rats were tested for motor activity in response to saline or cocaine (20 mg/kg) injection once daily for three consecutive days. To determine the effect of single or repeated cocaine administration on the level of OFQ/N, rats were sacrificed 1 h following saline or cocaine injection either on day 1 or 3, respectively. Additional groups of rats were treated similarly with saline or cocaine on days 1-3 and sacrificed or tested for locomotor sensitization on day 8. Consistent with previous studies, repeated cocaine administration induced locomotor sensitization to a challenge dose of cocaine (7.5 mg/kg) given on day 8. Measurements of tissue content of OFQ/N-IR using radioimmunoassay indicated that the rat hypothalamus and striatum, respectively, contained the highest and lowest levels of the peptide among the brain regions tested. Acute cocaine decreased the level of OFQ-IR in the rat midbrain and to a lesser extent in the striatum. On the other hand, the level of OFQ/N was higher in rats treated with cocaine on days 1-3 and sacrificed on day 8. These findings suggest that endogenous OFQ/N may be involved in the actions of cocaine and possibly in cocaine-induced motor stimulation and locomotor sensitization.


Associations of cardiovascular variables and HAART with cognition in middle-aged HIV-infected and uninfected women.
Despite the use of highly active anti-retroviral treatment (HAART), cognitive impairment remains prevalent in HIV. Indeed a recent study suggested that in certain instances, stopping HAART was associated with improved cognitive function (Robertson et al. Neurology 74(16):1260-1266 2010). HAART is occasionally associated with cardiovascular pathology and such pathology may be associated with cognitive impairment. To explore these associations, we assessed the relative contributions of cardiovascular variables such as hypertension and atherosclerosis, of HIV and HAART to cognition. The participants were members of the Women's Interagency HIV Study. In the analysis of cross-sectional data using general linear models, we assessed the relationship between each cardiovascular variable and Stroop interference time and symbol digit modalities test while adjusting for age, HIV, education, depression, and race/ethnicity. We also analyzed the association of summary measures of HAART use with cognition. In multivariate models, significance was limited to carotid lesions and carotid intima-medial thickness quintile (CIMT) with Stroop interference time (for carotid lesions, coefficient = 10.5, CI 3.5 to 17.5, p = 0.003, N = 1,130; for CIMT quintile, coefficient = 8.6, CI = 1.7 to 15.4, p = 0.025, N = 1,130). The summary measures of protease inhibitor use and other HAART measures were in most cases not associated with cognitive score in multivariate models. We conclude that in the HAART era among middle-aged women with HIV, carotid disease may be significantly associated with some measures of cognitive impairment. In this cross-sectional study, we could detect neither positive nor negative effects of HAART on cognition.


Role of androgens in the growth of endometrial carcinoma: an in vivo animal model.
We sought to create an animal model for the development of endometrial cancer in women with androgen excess. We examined the effects of estradiol and androgen, both alone and as precursors to estrogen biosynthesis on human endometrial cancers transplanted into a nude mouse model. We transplanted an estrogen-responsive, well-differentiated, established human endometrial carcinoma, EnCa-101, subcutaneously into athymic male nude mice. We established, first, that aromatase was expressed in this cell line, inducible by estrogen. We measured the growth of the tumor in the various groups weekly with Vernier calipers. We examined the effects of estradiol and androgens, both aromatizable and nonaromatizable, on tumor growth. Estrogen-supplemented tumors showed the greatest rate of growth and were significantly greater than the growth rate in castrate mice. Androgen-supplemented tumors showed a growth rate similar to that of tumors without significant hormonal exposure (castrate mice). Dihydrotestosterone had no effect on tumor growth in comparison with an agonadal state. Aromatizable and nonaromatizable androgens have little growth-promoting effect on a well-differentiated endometrial carcinoma. Estradiol is the most potent growth stimulus in our model.


Influence of Nitrogen Doping on Device Operation for TiO₂-Based Solid-State Dye-Sensitized Solar Cells: Photo-Physics from Materials to Devices.
Solid-state dye-sensitized solar cells (ssDSSC) constitute a major approach to photovoltaic energy conversion with efficiencies over 8% reported thanks to the rational design of efficient porous metal oxide electrodes, organic chromophores, and hole transporters. Among the various strategies used to push the performance ahead, doping of the nanocrystalline titanium dioxide (TiO₂) electrode is regularly proposed to extend the photo-activity of the materials into the visible range. However, although various beneficial effects for device performance have been observed in the literature, they remain strongly dependent on the method used for the production of the metal oxide, and the influence of nitrogen atoms on charge kinetics remains unclear. To shed light on this open question, we synthesized a set of N-doped TiO₂ nanopowders with various nitrogen contents, and exploited them for the fabrication of ssDSSC. Particularly, we carefully analyzed the localization of the dopants using X-ray photo-electron spectroscopy (XPS) and monitored their influence on the photo-induced charge kinetics probed both at the material and device levels. We demonstrate a strong correlation between the kinetics of photo-induced charge carriers probed both at the level of the nanopowders and at the level of working solar cells, illustrating a direct transposition of the photo-physic properties from materials to devices.


Correlation analysis of electromyogram signals for multiuser myoelectric interfaces.
An inability to adapt myoelectric interfaces to a novel user's unique style of hand motion, or even to adapt to the motion style of an opposite limb upon which the interface is trained, are important factors inhibiting the practical application of myoelectric interfaces. This is mainly attributed to the individual differences in the exhibited electromyogram (EMG) signals generated by the muscles of different limbs. We propose in this paper a multiuser myoelectric interface which easily adapts to novel users and maintains good movement recognition performance. The main contribution is a framework for implementing style-independent feature transformation by using canonical correlation analysis (CCA) in which different users' data is projected onto a unified-style space. The proposed idea is summarized into three steps: 1) train a myoelectric pattern classifier on the set of style-independent features extracted from multiple users using the proposed CCA-based mapping; 2) create a new set of features describing the movements of a novel user during a quick calibration session; and 3) project the novel user's features onto a lower dimensional unified-style space with features maximally correlated with training data and classify accordingly. The proposed method has been validated on a set of eight intact-limbed subjects, left-and-right handed, performing ten classes of bilateral synchronous fingers movements with four electrodes on each forearm. The method was able to overcome individual differences through the style-independent framework with accuracies of > 83% across multiple users. Testing was also performed on a set of ten intact-limbed and six below-elbow amputee subjects as they performed finger and thumb movements. The proposed framework allowed us to train the classifier on a normal subject's data while subsequently testing it on an amputee's data after calibration with a performance of > 82% on average across all amputees.


Recruiting the next generation of nephrologists.
The nephrology physician workforce substantially expanded during the past decade, as did the number of fellowship training positions. However, the number of U.S. medical graduates choosing nephrology careers has declined precipitously. Although workforce diversity has improved, the gains are modest. Leadership in kidney disease research and innovation is threatened by significant disincentives to the pursuit of research track careers. Meanwhile, various factors challenge reliable predictions of physician workforce demand: marked growth of the CKD and ESRD populations, shifting health care economics and access, restricted opportunities for international medical graduates, expansion of advanced practitioner utilization, and aging of the contemporary practicing physician cohort. Changing demographics and cultural shifts, including perceptions of work-life balance and quality of life, increasingly influence medical student and resident career choices. Negative student and resident attitudes toward core nephrology educational experiences and perceptions of nephrology careers are disquieting. The American Society of Nephrology has initiated a series of programs aimed at renewing interest among students and residents in nephrology careers and research training and continuing to improve the diversity of the nephrology workforce, both critical to ensuring there will be enough nephrologists to care for a growing kidney disease population.


Excitation of the 180mTa isomer in (gamma,n) reactions and its astrophysical relevance
The yield has been determined for the excitation of 180gTa (Jpi = 1+) from the 181Ta(gamma,n) reaction by measurements of gamma rays emitted following the electron capture and beta-decays of the 8.15 h ground state. The probability sigmam/(sigmam + sigmag) for the production of the 180mTa isomer (Jpi = 9-) after gamma absorption in the energy region from 8 to 13 MeV was deduced. The role of the initial and final spins on the reaction yield, along with the relevance for nucleosynthesis of 180mTa, is discussed.


Interaction of reactive oxygen species with DNA. A review.
Data on direct and indirect effects of reactive oxygen species on DNA are reviewed. The classification of the types of DNA oxidative damage and repair enzymes including glycosylases and endo- and exonucleases is presented. The regulatory function of reactive oxygen species and their role in carcinogenesis are discussed.


[Increase in the lipid peroxide content in the blood and aortas of rabbits with experimental atherosclerosis].
Content of lipid peroxides was estimated in blood and aorta of intact rabbits by means of highly sensitive polarographic method, using a mercuric electrode. Content of lipoperoxides in blood and aorta was increased 4.4- and 3.6-fold, respectively, in animals with pronounced experimental atherosclerosis. The oxidation of lipoperoxides caused a distinct increase in content of intermolecular bindings in amino-containing phospholipids in aorta of rabbits with pronounced atheromatosis.


Simultaneous training of negatively correlated neural networks in an ensemble.
This paper presents a new cooperative ensemble learning system (CELS) for designing neural network ensembles. The idea behind CELS is to encourage different individual networks in an ensemble to learn different parts or aspects of a training data so that the ensemble can learn the whole training data better. In CELS, the individual networks are trained simultaneously rather than independently or sequentially. This provides an opportunity for the individual networks to interact with each other and to specialize. CELS can create negatively correlated neural networks using a correlation penalty term in the error function to encourage such specialization. This paper analyzes CELS in terms of bias-variance-covariance tradeoff. CELS has also been tested on the Mackey-Glass time series prediction problem and the Australian credit card assessment problem. The experimental results show that CELS can produce neural network ensembles with good generalization ability.


A proposal for a standardized system of reporting human lymph node morphology in relation to immunological function.
This Memorandum proposes a standardized system of reporting the histology of human lymph nodes based on commonly used simple staining techniques. The purpose is to provide a uniform, internationally acceptable system by which the histological structure of lymph nodes can be correlated with other parameters of immunological status. The proposed protocols are intended to provide information that is not available in conventional written reports, that use such terms as "hyperplasia" or "nonspecific lymphadenitis".


Inherited platelet disorders including Glanzmann thrombasthenia and Bernard-Soulier syndrome.
Inherited platelet disorders (IPDs) are a heterogeneous group of diseases affecting platelet production, morphology, and function. The degree of thrombocytopenia and functional abnormality of platelets determines the clinical manifestations. Although severe deficiencies may cause excessive bleeding beginning in early childhood, most of IPDs have mild bleeding tendencies and therefore are not always easy to distinguish from acquired platelet disorders. The diagnosis of IPD may require extensive laboratory investigation, because current routine laboratory tests are not satisfactory for differential diagnosis in some cases, and most of the specific tests are not readily available in many countries. This review summarizes the classification and clinical and molecular characteristics of known IPDs, including Bernard-Soulier syndrome and Glanzmann thrombasthenia, with a focus on current challenges in the laboratory diagnosis and management of bleeding in these patients.


Image dependency in the recognition of newly learnt faces.
Research investigating the effect of lighting and viewpoint changes on unfamiliar and newly learnt faces has revealed that such recognition is highly image dependent and that changes in either of these leads to poor recognition accuracy. Three experiments are reported to extend these findings by examining the effect of apparent age on the recognition of newly learnt faces. Experiment 1 investigated the ability to generalize to novel ages of a face after learning a single image. It was found that recognition was best for the learnt image with performance falling the greater the dissimilarity between the study and test images. Experiments 2 and 3 examined whether learning two images aids subsequent recognition of a novel image. The results indicated that interpolation between two studied images (Experiment 2) provided some additional benefit over learning a single view, but that this did not extend to extrapolation (Experiment 3). The results from all studies suggest that recognition was driven primarily by pictorial codes and that the recognition of faces learnt from a limited number of sources operates on stored images of faces as opposed to more abstract, structural, representations.


Effects of macrophage depletion on characteristics of cervix remodeling and pregnancy in CD11b-dtr mice.
To test the hypothesis that macrophages are essential for remodeling the cervix in preparation for birth, pregnant homozygous CD11b-dtr mice were injected with diphtheria toxin (DT) on days 14 and 16 postbreeding. On day 15 postbreeding, macrophages (F4/80+) were depleted in cervix and kidney, but not in liver, ovary, or other non-reproductive tissues in DT-compared to saline-treated dtr mice or wild-type controls given DT or saline. Within 24 h of DT-treatment, the density of cell nuclei and macrophages declined in cervix stroma in dtr mice versus controls, but birefringence of collagen, as an indication of extracellular cross-linked structure, remained unchanged. Only in the cervix of DT-treated dtr mice was an apoptotic morphology evident in macrophages. DT-treatment did not alter the sparse presence or morphology of neutrophils. By day 18 postbreeding, macrophages repopulated the cervix in DT-treated dtr mice so that the numbers were comparable to that in controls. However, at term, evidence of fetal mortality without cervix ripening occurred in most dtr mice given DT-a possible consequence of treatment effects on placental function. These findings suggest that CD11b+ F4/80+ macrophages are important to sustain pregnancy and are required for processes that remodel the cervix in preparation for parturition.


Plastic pollution as a novel reservoir for the environmental survival of the drug resistant fungal pathogen Candida auris.
The WHO recently classified Candida auris as a fungal pathogen of "critical concern". Evidence suggests that C. auris emerged from the natural environment, yet the ability of this pathogenic yeast to survive in the natural environment is still poorly understood. The aim of this study, therefore, was to quantify the persistence of C. auris in simulated environmental matrices and explore the role of plastic pollution for facilitating survival and potential transfer of C. auris. Multi-drug resistant strains of C. auris persisted for over 30 days in river water or seawater, either planktonically, or in biofilms colonising high-density polyethylene (HDPE) or glass. C. auris could be transferred from plastic beads onto simulated beach sand, particularly when the sand was wet. Importantly, all C. auris cells recovered from plastics retained their pathogenicity; therefore, plastic pollution could play a significant role in the widescale environmental dissemination of this recently emerged pathogen.


Joint Impact of Early Life Adversity and COMT Val158Met (rs4680) Genotypes on the Adult Cortisol Response to Psychological Stress.
Exposure to stress during critical periods of development can diminish stress reactivity by the hypothalamic-pituitary-adrenocortical axis. Genetic characteristics may further modify this effect of early adversity, leading to a gene by environment (G × E) interaction on stress reactivity in adulthood. Val-allele carriers of a common polymorphism of the COMT gene (Val158Met, rs4680) have rapid removal of catecholamines in the prefrontal cortex, limbic system, and reward centers. Carriers of the Val and Met alleles may therefore respond differently to the environment and differ in the long-term impact of exposure to early life adversity (ELA). We measured saliva cortisol reactivity to public speaking and mental arithmetic stress in 252 healthy young adults exposed to low, medium, and high levels of ELA and who were genotyped for the Val158Met polymorphism. Cortisol responses showed a G × E interaction (F(4,243) = 2.78, p = .028); simple effects tests showed that Met/Met carriers had progressively smaller cortisol responses with greater levels of ELA. In comparison, Val/Val homozygotes had blunted responses that did not vary with ELA exposure. Met/Met homozygotes seem sensitive to stressful events in childhood and adolescence, leading to environmental programming of the stress axis. Glucocorticoid responsivity may represent a common pathway revealing targeted genetic vulnerabilities to the long-term effects of early life stress. The results suggest that further G × E studies of ELA are warranted in relation to health behaviors and health outcomes in adulthood.


Apparent mineral retention is similar in control and hyperinsulinemic men after consumption of high amylose cornstarch.
The effects on apparent mineral retention after long-term consumption of a high amylose diet containing 30 g resistant starch (RS) were investigated in 10 control and 14 hyperinsulinemic men. Subjects consumed products (bread, muffins, cookies, corn flakes and cheese puffs) made with standard (70% amylopectin, 30% amylose; AP) or high amylose (70% amylose, 30% amylopectin; AM) cornstarch for two 14-wk periods in a crossover pattern. Starch products replaced usual starches in the habitual diet for 10 wk followed by 4 wk of consuming the controlled diets. During wk 12, all urine, feces and duplicate foods were collected for 7 d. Urinary chromium losses after a glucose tolerance test or 24-h collections of the hyperinsulinemic and control subjects did not differ and were not altered by diet. Except for zinc, the two subject types did not differ significantly in apparent mineral balance. Apparent retentions of calcium and magnesium were not significantly affected by diet (AM vs. AP) or type-by-diet interaction. Apparent iron retention tended to be greater after AM than AP consumption (P < 0.09). Apparent copper retention was greater after consuming AP than after AM (P < 0.02), whereas apparent zinc retention was greater after consuming AM than after AP (P < 0.018). Zinc also showed a significant type-by-diet interaction (P < 0.034) with control subjects retaining less zinc after consuming AP than after AM. In summary, a high amylose cornstarch diet containing 30 g RS could be consumed long term without markedly affecting, and possibly enhancing, retention of some minerals.


What Motivates Successful Marathon Runners? The Role of Sex, Age, Education, and Training Experience in Polish Runners.
The aim of this study was to compare the motivations of successful marathon finishers (n = 1,243) and inexperienced runners (control group, n = 296). A total of 1,537 runners with 380 women (24.7%) and 1,157 men (75.3%) completed the motivations of marathoners scales (MOMS) questionnaire and the relationships between general motivation categories and selected demographic (e.g., gender, age, and education) and training characteristics were analyzed. Successful marathon finishers did not differ significantly in motivations from the control group (p > 0.05). Trivial to small correlations with age, educational level, and training characteristics were observed. Female marathon finishers exceeded men on the motivational scales for weight concern, affiliation, psychological coping, life meaning, and self-esteem and they scored lower on competitive motivation (p < 0.05). There was also a significant relationship of some motivational aspects with level of education, experience and training frequency. These findings confirmed that age and gender differentiate motivations in both successful female and male marathon finishers and controls.


Development of marker genes for jasmonic acid signaling in shoots and roots of wheat.
The jasmonic acid (JA) signaling pathway plays key roles in a diverse array of plant development, reproduction, and responses to biotic and abiotic stresses. Most of our understanding of the JA signaling pathway derives from the dicot model plant Arabidopsis thaliana, while corresponding knowledge in wheat is somewhat limited. In this study, the expression of 41 genes implicated in the JA signaling pathway has been assessed on 10 day-old bread wheat seedlings, 24 h, 48 h, and 72 h after methyl-jasmonate (MeJA) treatment using quantitative real-time PCR. The examined genes have been previously reported to be involved in JA biosynthesis and catabolism, JA perception and signaling, and pathogen defense in wheat shoots and roots. This study provides evidence to suggest that the effect of MeJA treatment is more prominent in shoots than roots of wheat seedlings, and substantial regulation of the JA pathway-dependent defense genes occurs at 72 h after MeJA treatment. Results show that the expression of 22 genes was significantly affected by MeJA treatment in wheat shoots. However, only PR1.1 and PR3 were significantly differentially expressed in wheat roots, both at 24 h post-MeJA treatment, with other genes showing large variation in their gene expression in roots. While providing marker genes on JA signaling in wheat, future work may focus on elucidating the regulatory function of JA-modulated transcription factors, some of which have well-studied potential orthologs in Arabidopsis.


Topological network analysis of patient similarity for precision management of acute blood pressure in spinal cord injury.
Predicting neurological recovery after spinal cord injury (SCI) is challenging. Using topological data analysis, we have previously shown that mean arterial pressure (MAP) during SCI surgery predicts long-term functional recovery in rodent models, motivating the present multicenter study in patients. Intra-operative monitoring records and neurological outcome data were extracted (n = 118 patients). We built a similarity network of patients from a low-dimensional space embedded using a non-linear algorithm, Isomap, and ensured topological extraction using persistent homology metrics. Confirmatory analysis was conducted through regression methods. Network analysis suggested that time outside of an optimum MAP range (hypotension or hypertension) during surgery was associated with lower likelihood of neurological recovery at hospital discharge. Logistic and LASSO (least absolute shrinkage and selection operator) regression confirmed these findings, revealing an optimal MAP range of 76-[104-117] mmHg associated with neurological recovery. We show that deviation from this optimal MAP range during SCI surgery predicts lower probability of neurological recovery and suggest new targets for therapeutic intervention. NIH/NINDS: R01NS088475 (ARF); R01NS122888 (ARF); UH3NS106899 (ARF); Department of Veterans Affairs: 1I01RX002245 (ARF), I01RX002787 (ARF); Wings for Life Foundation (ATE, ARF); Craig H. Neilsen Foundation (ARF); and DOD: SC150198 (MSB); SC190233 (MSB).


[Development of the coping scale for interpersonal stress events related to the goals of the coping].
This study developed the coping scale for interpersonal stress events, and evaluated its validity. This scale is composed of the following subscales based on the goals of the coping: problem-focused coping, emotion-focused behavioral coping, and emotion-focused cognitive coping. Based on previous research, a pilot study was used to construct scale items, considering the goals of coping to reduce measurement error. In study 1 (N=348), the validity of the scale was examined using several statistical analyses. Study 2 (N=182) and study 3 (N=161) report correlations between the coping scale for interpersonal stress events and several theoretically relevant scales. Based on these results, it was concluded that the scale and subscales are valid for measuring interpersonal stress coping.


Low-dose FK506 after contralateral C7 transfer to the musculocutaneous nerve using two different tubes: a study in rats.
The purpose of this project was to study the effect of a subimmunosuppressive dose of FK506 (0.7 mg/kg per day) on nerve regeneration along a long nerve gap (4 cm), using the contralateral C7 nerve root transfer model for musculocutaneous nerve neurotization. Two types of tubes were applied to the nerve gap: a polycaprolactone tube and a collagen tube. Twenty adult male Sprague-Dawley rats were divided into 4 groups (n = 5). A polycaprolactone was used in groups 1 and 3 and a collagen tube in groups 2 and 4. Groups 1 and 2 were daily administered a subimmunosuppressive dose of FK506. Animals were euthanized on day 30. Evaluation consisted of behavioral assessment, needle electromyography studies, biceps muscle weight measurements, and qualitative and quantitative morphometry. Groups 1 and 2 showed higher mean values for fiber counts, axon diameters, myelin thickness and myelin area in C7, better functional evaluation results, and higher biceps weight left to right ratio than groups 3 and 4. There was no evidence of reinnervation potentials, and there were no axons detectable inside the tube lumen in any of the study groups. The present study demonstrated that there was nonsignificant improvement of the functional recovery, after systemic administration of a low dose of FK506. This was attributed to 3 factors: length of nerve gap; duration of follow up; and dose of FK506. However, FK506-treated animals tended to be in a more advanced stage of nerve regeneration compared with the control groups.


Temperature rise during drilling through bone.
Temperature was measured during drilling in bovine cortical bone specimens. A surgical drill fitted with a custom-designed speedometer and mounted on a drill press was used to drill holes at one speed, 49,000 rpm, and at forces in the range of 1.5 to 9.0 N. The resulting temperatures were recorded by thermocouples placed at various locations. The distribution of maximum local temperature rise (delta T) was best fitted by the function delta T = aR-b, where R is the distance from the center of the drilled hole and a and b are constants that were found by regression analysis. It was also found that the temperature increased with force, up to about 4.0 N, and then decreased at forces greater than that because of decreased drilling time. A separate series of tests revealed that temperatures were higher in the longitudinal direction than in the circumferential direction; this difference was attributed to the anisotropic thermal properties of bone.


Arcuate Angiotensin II Increases Arterial Pressure via Coordinated Increases in Sympathetic Nerve Activity and Vasopressin Secretion.
The arcuate nucleus (ArcN) is an integrative hub for the regulation of energy balance, reproduction, and arterial pressure (AP), all of which are influenced by Angiotensin II (AngII); however, the cellular mechanisms and downstream neurocircuitry are unclear. Here, we show that ArcN AngII increases AP in female rats via two phases, both of which are mediated via activation of AngII type 1 receptors (AT1aRs): initial vasopressin-induced vasoconstriction, followed by slowly developing increases in sympathetic nerve activity (SNA) and heart rate (HR). In male rats, ArcN AngII evoked a similarly slow increase in SNA, but the initial pressor response was variable. In females, the effects of ArcN AngII varied during the estrous cycle, with significant increases in SNA, HR, and AP occurring during diestrus and estrus, but only increased AP during proestrus. Pregnancy markedly increased the expression of AT1aR in the ArcN with parallel substantial AngII-induced increases in SNA and MAP. In both sexes, the sympathoexcitation relied on suppression of tonic ArcN sympathoinhibitory neuropeptide Y (NPY) inputs, and activation of proopiomelanocortin (POMC) projections, to the paraventricular nucleus (PVN). Few or no NPY or POMC neurons expressed the AT1aR, suggesting that AngII increases AP and SNA at least in part indirectly via local interneurons, which express tyrosine hydroxylase (TH) and VGat (i.e., GABAergic). ArcN TH neurons release GABA locally, and central AT1aR and TH neurons mediate stress responses; therefore, we propose that TH AT1aR neurons are well situated to locally coordinate the regulation of multiple modalities within the ArcN in response to stress.


[Argentophilic nucleolar organizers and prognosis for patients with surface and locally advanced transitional cell cancer of the urinary bladder].
The aim of the study was to estimate distribution of the nucleoli and argentophilic nucleolar organizers in surface and locally advanced transitional cell tumors of the urinary bladder (TCTUB), to analyse correlation between this distribution, tumor recurrence and survival of the patients. The data on primary examination and 5-year follow-up of 61 patients (47 male and 14 female, mean age 64 +/- 1 year) with surface and locally advanced TCTUB were studied retrospectively. All the patients were radically operated on, 5-year progression-free survival made up 62%, recurrences of the urinary bladder tumors were detected in 61% patients. In addition to the standard morphological examination, tumor tissue was stained with silver nitrate according to the Howell and Black technique and the number of the nucleoli and argentophilic granules in them was counted in magnification 1000. The findings were compared with the invasion depth, grade of cancer differentiation, tumor recurrence and 5-year survival. The count of argentophilic granules increased with reduction of differentiation grade and an increase of cancer invasion depth. Distribution of the nucleoli and granules significantly differed in the subgroups of patients with recurrent and recurrence-free course of the disease, depending on 5-year survival without progression. Probable duration of the recurrence-free period was estimated best by coefficient of variation of argentophilic granules distribution (p = 0.001). Parameters of distribution of the nucleoli and granules allowed specification of the risk of tumor progression for 5 years for all the patients (p = 0.035) and patients with surface tumors (p = 0.007) irrespective of categories T and G. Thus, the number of nucleoli and argentophilic nucleolar organizers increases with lowering of differentiation and deepening of tumor invasion. The analysis of nucleoli and argentophilic granules distribution provides additional information on recurrence and transient cell carcinomas probability.


[Repeat percutaneous transluminal angioplasty in coronary artery restenosis].
Early experience with repeat transcutaneous transluminal coronary angioplasty (TTCA) in 9 coronary patients is reviewed. The interval between the first and the repeat TTCA varied between 1 and 12 months averaging 4.9 +/- 4.7 months. Repeat dilatation of the anterior interventricular branch was performed in 7 patients, that of the right coronary artery, in 1, and that of the circumflex artery, in 1. All repeat operations were successful. Changes in the degree of stenosis and the mean arterial blood pressure gradient were actually similar in both dilatations.


Formative research to explore the acceptability and use of infant food grinders for the promotion of animal source foods and micronutrient powders in rural Peru.
According to global recommendations, quality diets for complementary feeding (CF) should include a diversity of foods including vitamin A-rich fruits and vegetables and sources of high-quality proteins and essential nutrients, particularly animal-source foods (ASF). A key barrier to feeding ASF surrounds beliefs that the preparation of foods of a thicker consistency may cause problems of digestion, "heaviness" or stomach problems, swallowing, and choking. The objective of this study was to explore, through systematic formative research, the acceptability, use, and feasibility of a simple technology, commercial infant food grinders, in two rural Peruvian settings where there is delayed and low consumption of complementary foods of a thick consistency, including ASF. Phase I explored the barriers, constraints, and opportunities related to the provision of foods of a thicker consistency with a focus on ASF. Phase II encompassed household behavioural trials with mothers and infants to assess the acceptability and use of the grinders in the home setting, using key concepts and messages developed from the information obtained during Phase I. The technology was highly acceptable, used by the majority of mothers (87.8%), and led to changes in cultural perceptions, facilitating increased feeding of appropriate textures (thick purees), ASF, and multimicronutrient powders. Energy, protein, and micronutrient intakes were all significantly greater after the household behavioural trials. This simple technology, paired with systematic formative research to appropriately promote its use across cultures, may have a significant effect on improving CF practices globally, particularly for young infants beginning CF at 6 months.


IL-7 contributes to the progression of human T-cell acute lymphoblastic leukemias.
The importance of microenvironmental factors for driving progression in leukemia has been debated. Previous evidence has pointed to interleukin-7 (IL-7), a fundamental cytokine to normal T-cell development and homeostasis, as an important determinant of the viability and proliferation of T-cell acute lymphoblastic leukemia (T-ALL) cells in vitro. In this study, we report that IL-7 is also a critical determinant of T-ALL progression. T-ALL cell lines and primary T-ALL samples initiated leukemia more slowly when engrafted to immunocompromised Rag2(-/-)IL2rg(-/-) mice lacking IL-7. This effect was not related to reduced engraftment or homing of transplanted cells to the bone marrow. Instead, IL-7 deficiency diminished expansion of leukemia cells in the bone marrow and delayed leukemia-associated death of transplanted mice. Moreover, infiltration of different organs by T-ALL cells, which characterizes patients with advanced disease, was more heterogeneous and generally less efficient in IL-7-deficient mice. Leukemia progression was associated with increased Bcl-2 expression and cell viability, reduced p27(Kip1) expression, and decreased cell-cycle progression. Clinical measurements of IL-7 plasma levels and IL-7 receptor (IL-7R) expression in T-ALL patients versus healthy controls confirmed that IL-7 stimulates human leukemia cells. Our results establish that IL-7 contributes to the progression of human T-cell leukemia, and they offer preclinical validation of the concept that targeting IL-7/IL-7R signaling in the tumor microenvironment could elicit therapeutic effects in T-ALL.


Hierarchical representation of waveforms.
Ehrich and Foith have proposed an approach to the hierarchical representation of waveforms based on peak dominance relations. This correspondence proposes an alternative approach, derived from concepts of fuzzy connectedness. It also discusses the possibility of extending this approach to the description of curves and of images.


Challenges to optimising uptake and delivery of a HPV vaccination programme for men who have sex with men.
Human papillomavirus (HPV) vaccine programmes targeted at men who have sex with men (MSM) may reduce HPV-related disease burden among this at-risk group in countries where uptake of the vaccine among adolescent girls is sub-optimal and where adolescent boys are not routinely vaccinated. There are challenges to optimising the impact of a MSM programme: ensuring good uptake, understanding the effectiveness of the vaccine in this population and considering the longevity of the programme. Furthermore, monitoring of uptake and ensuring that delivery of the programme does not deprive other aspects of sexual health service resources may present challenges to programme evaluation and delivery. We draw on experience from the UK HPV vaccination programme for MSM, delivered in sexual health and HIV clinics, to better understand these challenges with the aim of supporting the implementation of similar programmes elsewhere in the world.


Differentiation of capsular polysaccharides from Acetobacter diazotrophicus strains isolated from sugarcane.
Capsular polysaccharides (CPSs) from six representative strains of Acetobacter diazotrophicus were isolated and fractionated by gel filtration and anion-exchange chromatography. Purified CPSs obtained in the non-adsorbed fraction of a DEAE-Sephadex A-25 column were qualitatively and quantitatively analyzed for sugar composition. Uronic acid and amino sugars were not detected in all purified CPSs. Basically the CPSs of A. diazotrophicus are composed of rhamnose, mannose, galactose and glucose. The presence of fucose was only observed in the CPS of strains PR2 and PAL3. Based on these results, the six strains of A. diazotrophicus could be divided into four groups according to the sugar content of their capsules: (i) fucose-containing capsules (PR2 and PAL3, localized in roots), (ii) mannose-rich capsule (PAL5, localized in root), (iii) capsules with a high ratio of hexose to rhamnose (PR4 and PR20, localized in stems) and (iv) capsules with a low ratio of hexose to rhamnose (PR14, localized in rhizosphere). For all CPSs, sodium dodecy sulfate-polyacrylamide gel electrophoresis showed diffuse bands of slow mobility in silver-stained gels. The different CPS migration patterns could not be correlated with sugar composition. The purified CPS of strain PAL3 was found to be immunogenic and immunochemically similar to the CPS of strain PR2. The serological specificity to CPS of strains PAL3 and PR2 correlated well with the presence of focuse, indicating that this deoxyhexose is immunodominant.(ABSTRACT TRUNCATED AT 250 WORDS)


A placebo-controlled trial of didanosine plus stavudine, with and without hydroxyurea, for HIV infection. The Swiss HIV Cohort Study.
To explore the short-term effects on surrogate markers for HIV progression of didanosine (ddl) plus stavudine (d4T), with or without hydroxyurea. Randomized, double-blinded, prospective study. Swiss HIV Cohort Study. A total of 144 patients (75% antiretroviral-naive) were studied (mean baseline HIV-1 RNA, 4.53 log10 copies/ml; mean CD4 cell count, 370 x 10(6)/l). Patients received ddl (200 mg twice daily) plus d4T (40 mg twice daily), with additional hydroxyurea (500 mg twice daily) or placebo. The primary endpoint was a reduction of viraemia below 200 copies/ml after 12 weeks. At that time, patients who did not reach the primary endpoint were withdrawn in the hydroxyurea arm, whereas patients in the placebo group had the option of adding hydroxyurea to ddl and d4T. All patients were followed until week 24. After 12 weeks, 54% of the patients randomized to hydroxyurea had viraemia below 200 copies/ml, compared with 28% on placebo (P < 0.001). Using an ultrasensitive assay with a limit of detection of 20 copies/ml, 19% of patients receiving hydroxyurea had viraemia levels below 20 copies/ml, compared with 8% on placebo (P = 0.05). Mean decrease in HIV-1 RNA was 2.3 and 1.7 log10 copies/ml for hydroxyurea and placebo groups, respectively (P = 0.001). Hydroxyurea was found to induce lymphopenia (-124 x 10(6)/l). Increase in CD4 cell counts was +28 x 10(6)/l during hydroxyurea treatment compared with +107 x 10(6)/l on placebo (P = 0.001). Hydroxyurea improved the antiviral activity of d4T and ddl over a 12-week period, but was associated with a smaller increase in CD4 cell counts due to hydroxyurea-induced lymphopenia.


Accessibility of basic paediatric emergency care in Malawi: analysis of a national facility census.
Emergency care is among the weakest parts of health systems in low-income countries with both quality and accessibility constraints. Previous studies estimated accessibility to surgical or emergency care based on population travel times to nearest hospital with no assessment of hospital readiness to provide such care. We analysed a Malawi national facility census with comprehensive inventory audits and geocoded facility locations to identify hospitals equipped to provide basic paediatric emergency care with estimated travel times to these hospitals from non-equipped facilities and in relation to Malawi's population distribution. We analysed a Malawi national facility census in 2013-2014 to identify hospitals equipped to manage critically ill children according to an extended version of WHO Emergency Triage, Assessment and Treatment (ETAT) guidelines. These guidelines include 25 components including staff, transport, equipment, diagnostics, medications, fluids, feeds and consumables that defined an emergency-equipped hospital in our study. We estimated travel times to emergency-equipped hospitals from non-equipped facilities and relative to population distributions using geocoded facility locations and an established accessibility mapping approach using global road network datasets from OpenStreetMap and Google. Four (3.5, 95% CI: 1.3-8.9) of 116 Malawi hospitals were emergency-equipped. Least available items were nasogastric tubes in 34.5% of hospitals (95% CI: 26.4-43.6), blood typing services (40.4, 95% CI: 31.9-49.6), micro nebulizers (50.9, 95% CI: 41.9-60.0), and radiology (54.2, 95% CI: 45.1-63.0). Nationally, the median travel time from non-equipped facilities to the nearest emergency-equipped hospital was 73 min (95% CI: 67-77) ranging 1-507 min. Approximately one-quarter (27%) of Malawians lived over 120 min from an emergency-equipped hospital with significantly better accessibility in Central than North and South regions (16% vs. 38 and 35%, p < 0.001). There are unacceptable deficiencies in accessibility of basic paediatric emergency care in Malawi. Reliable supply chains for essential drugs and commodities are needed, particularly nasogastric tubes, asthma drugs and blood, along with improved capacity for time-sensitive referral. Further child mortality reductions will require substantial investments to expand basic paediatric emergency care into all Malawi hospitals for better managing critically ill children at highest mortality risk.


The putrescine analogue 1,4-diamino-2-butanone affects polyamine synthesis, transport, ultrastructure and intracellular survival in Leishmania amazonensis.
Polyamines are important regulators of growth and differentiation in a variety of cells, including parasitic protozoa. Promastigotes of Leishmania species have high levels of putrescine and spermidine and their growth can be inhibited by polyamine biosynthesis antagonists. The putrescine analogue 1,4-diamino-2-butanone (DAB) is microbicidal against Tritrichomonas foetus and Trypanosoma cruzi, so we tested its effects on Leishmania amazonensis proliferation, viability, organization, putrescine transport and synthesis as well as in vitro infectivity. DAB impaired promastigote proliferation dose-dependently (IC(50) 144 microM) and the parasite putrescine concentration was reduced by nearly 50 %. This analogue markedly inhibited both ornithine decarboxylase activity and [H(3)]putrescine uptake by promastigotes. Pre-treatment with DAB for 24 h led to compensatory enhancement of putrescine uptake, indicating an adaptive mechanism in DAB-treated parasites. Remarkably, DAB caused mitochondrial damage, assessed by transmission electron microscopy, and 3 h treatment with 1 mM DAB enhanced lipid peroxidation, whereas incubation with 10 mM DAB or for 24 h resulted in decreased peroxidation levels in the parasites. This effect was probably due to the loss of mitochondrial function, demonstrated by the diminished reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), not observed in macrophages. Murine macrophages infected with L. amazonensis amastigotes treated with DAB had parasite loads significantly (P<0.05) lower than controls, presumably due to interference with putrescine uptake and/or synthesis. These results suggest that putrescine may be involved in leishmanial survival, possibly by maintaining the parasite's mitochondrial function. The use of analogues to interfere with polyamine/diamine synthesis and transport may shed light on its function in intracellular parasite survival and lead to identification of new targets for leishmaniasis chemotherapy.


Mitochondrial dynamics in the mouse liver infected by Schistosoma mansoni.
Mitochondrial dynamics is crucial for regulation of cell homeostasis. Schistosoma mansoni is one of the most common parasites known to cause liver disease. Mice infected by S. mansoni show acute symptoms of schistosomiasis after 8 weeks. Hence, in this study, we attempted to assess the direct effects of S. mansoni infection on mice liver, and to explore the expression of mitochondrial morphology, dynamics, and function. Our recent findings show that S. mansoni infection changes mitochondrial morphology and affects mitochondrial functions, which attenuates mitochondrial membrane potential and ATP generation. S. mansoni-infected mice increases mitochondrial numbers by upregulating of genes involved in mitochondrial biogenesis, including peroxisome proliferator-activated receptor c co-activator 1α (PGC1α) and mitochondrial transcription factor A (Tfam). This may promote mitochondria generation for accelerating the recovery of mitochondrial functions. Moreover, S. mansoni would disrupt mitochondrial dynamics including induced mitochondrial fission and promoted mitochondrial fragmentation in mice liver. More importantly, S. mansoni further stimulated upregulation both extrinsic and intrinsic apoptosis pathway in infected mice liver. The intrinsic pathway was triggered by cytochrome c release. Additionally, NFκB (nuclear factor-kappa B, p65) could play a protective role to inhibit apoptosis through reducing active caspase-3 expression. Therefore, our results confirmed the liver damage mechanism of experimental schistosomiasis in mice model.


Crystal structure of cancer chemopreventive Bowman-Birk inhibitor in ternary complex with bovine trypsin at 2.3 A resolution. Structural basis of Janus-faced serine protease inhibitor specificity.
Understanding molecular recognition on a structural basis is an objective with broad academic and applied significance. In the complexes of serine proteases and their proteinaceous inhibitors, recognition is governed mainly by residue P1 in accord with primary serine protease specificity. The bifunctional soybean Bowman-Birk inhibitor (sBBI) should, therefore, interact at LysI16 (subdomain 1) with trypsin and at LeuI43 (subdomain 2) with chymotrypsin. In contrast with this prediction, a 2:1 assembly with trypsin was observed in solution and in the crystal structure of sBBI in complex with trypsin, determined at 2.3 A resolution by molecular replacement. Strikingly, P1LeuI43 of sBBI was fully embedded into the S(1) pocket of trypsin in contrast to primary specificity. The triple-stranded beta-hairpin unique to the BBI-family and the surface loops surrounding the active site of the enzyme formed a protein-protein-interface far extended beyond the primary contact region. Polar residues, hydrophilic bridges and weak hydrophobic contacts were predominant in subdomain 1, interacting specifically with trypsin. However, close hydrophobic contacts across the interface were characteristic of subdomain 2 reacting with both trypsin and chymotrypsin. A Met27Ile replacement shifted the ratio with trypsin to the predicted 1:1 ratio. Thus, the buried salt-bridge responsible for trypsin specificity was stabilised in a polar, and destabilized in a hydrophobic, environment. This may be used for adjusting the specificity of protease inhibitors for applications such as insecticides and cancer chemopreventive agents.


A rapid and simple UPLC-MS-MS method for determination of glipizide in human plasma and its application to bioequivalence study.
In this study, a simple, rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry method is described for the determination of glipizide in human plasma samples using carbamazepine as the internal standard (IS) from bioequivalence assays. Sample preparation was accomplished through protein precipitation with methanol, and chromatographic separation was performed on an Acquity BEH C18 column (2.1 mm × 50 mm, 1.7 μm) with gradient profile at a flow rate of 0.4 mL/min. Mass spectrometric analysis was performed using an QTrap5500 mass spectrometer coupled with an electrospray ionization source in the positive ion mode. The multiple reaction monitoring transitions of m/z 446.1 → 321.0 and m/z 237.1 → 194.2 were used to quantify for glipizide and IS. The linearity of this method was found to be within the concentration range of 10-1,500 ng/mL for glipizide in human plasma. Only 1.0 min was needed for an analytical run. The method was applied to a bioequivalence study of two drug products containing glipizide in human plasma samples.


The Transition of Photoreceptor Guanylate Cyclase Type 1 to the Active State.
Membrane-bound guanylate cyclases (GCs), which synthesize the second messenger guanosine-3', 5'-cyclic monophosphate, differ in their activation modes to reach the active state. Hormone peptides bind to the extracellular domain in hormone-receptor-type GCs and trigger a conformational change in the intracellular, cytoplasmic part of the enzyme. Sensory GCs that are present in rod and cone photoreceptor cells have intracellular binding sites for regulatory Ca2+-sensor proteins, named guanylate-cyclase-activating proteins. A rotation model of activation involving an α-helix rotation was described as a common activation motif among hormone-receptor GCs. We tested whether the photoreceptor GC-E underwent an α-helix rotation when reaching the active state. We experimentally simulated such a transitory switch by integrating alanine residues close to the transmembrane region, and compared the effects of alanine integration with the point mutation V902L in GC-E. The V902L mutation is found in patients suffering from retinal cone-rod dystrophies, and leads to a constitutively active state of GC-E. We analyzed the enzymatic catalytic parameters of wild-type and mutant GC-E. Our data showed no involvement of an α-helix rotation when reaching the active state, indicating a difference in hormone receptor GCs. To characterize the protein conformations that represent the transition to the active state, we investigated the protein dynamics by using a computational approach based on all-atom molecular dynamics simulations. We detected a swinging movement of the dimerization domain in the V902L mutant as the critical conformational switch in the cyclase going from the low to high activity state.


New lines of GFP transgenic rats relevant for regenerative medicine and gene therapy.
Adoptive cell transfer studies in regenerative research and identification of genetically modified cells after gene therapy in vivo require unequivocally identifying and tracking the donor cells in the host tissues, ideally over several days or for up to several months. The use of reporter genes allows identifying the transferred cells but unfortunately most are immunogenic to wild-type hosts and thus trigger rejection in few days. The availability of transgenic animals from the same strain that would express either high levels of the transgene to identify the cells or low levels but that would be tolerant to the transgene would allow performing long-term analysis of labelled cells. Herein, using lentiviral vectors we develop two new lines of GFP-expressing transgenic rats displaying different levels and patterns of GFP-expression. The "high-expresser" line (GFP(high)) displayed high expression in most tissues, including adult neurons and neural precursors, mesenchymal stem cells and in all leukocytes subtypes analysed, including myeloid and plasmacytoid dendritic cells, cells that have not or only poorly characterized in previous GFP-transgenic rats. These GFP(high)-transgenic rats could be useful for transplantation and immunological studies using GFP-positive cells/tissue. The "low-expresser" line expressed very low levels of GFP only in the liver and in less than 5% of lymphoid cells. We demonstrate these animals did not develop detectable humoral and cellular immune responses against both transferred GFP-positive splenocytes and lentivirus-mediated GFP gene transfer. Thus, these GFP-transgenic rats represent useful tools for regenerative medicine and gene therapy.


Unusually high mechanical stability of bacterial adhesin extender domains having calcium clamps.
To gain insight into the relationship between protein structure and mechanical stability, single molecule force spectroscopy experiments on proteins with diverse structure and topology are needed. Here, we measured the mechanical stability of extender domains of two bacterial adhesins MpAFP and MhLap, in an atomic force microscope. We find that both proteins are remarkably stable to pulling forces between their N- and C- terminal ends. At a pulling speed of 1 μm/s, the MpAFP extender domain fails at an unfolding force Fu = 348 ± 37 pN and MhLap at Fu = 306 ± 51 pN in buffer with 10 mM Ca2+. These forces place both extender domains well above the mechanical stability of many other β-sandwich domains in mechanostable proteins. We propose that the increased stability of MpAFP and MhLap is due to a combination of both hydrogen bonding between parallel terminal strands and intra-molecular coordination of calcium ions.


Endografting of the aortic arch.
In recent years, endovascular repair with stent-grafts has made great advances as a minimally invasive alternative to conventional open surgery in the treatment of aortic aneurysm and dissection. Although many commercial endograft systems are now used worldwide for the treatment of these pathologies in the abdominal aorta, only a few dedicated stent-grafts have been developed for use in the thoracic aorta. However, these second-generation commercial endografts have almost identical specifications and performance profiles in terms of structure, function, and delivery mechanism as stent-graft systems employed in the abdominal aorta. Thus, endografts have been used in the thoracic aorta with little consideration to the morphological and hemodynamic characteristics specific to the aortic arch and the deployment techniques needed to navigate this curved region of the thoracic aorta. This review will survey the literature on aortic arch stent-graft repair and identify key elements critical to the successful design of an endograft to treat lesions in the aortic arch.


Changes in microcystin concentration in Lake Taihu, 13 years (2007-2020) after the 2007 drinking water crisis.
Since the 2007 water crisis occurred in Lake Taihu, substantial measures have been taken to restore the lake. This study evaluates the effectiveness of these restoration activities. We examined the physicochemical parameters and the distribution of microcystin and Microcystis in both the water column and sediment during the bloom period of May 2020 to October 2020. The mean value of extracellular and intracellular microcystin content was 0.12 μg L-1 and 16.26 μg L-1, respectively. The mean value of microcystin in sediment was 172.02 ng g-1 and peaked in August. The concentration in the water and sediment was significantly lower than the historical average concentration. The abundance of toxigenic Microcystis and total Microcystis in the water column ranged from 2.61 × 102 to 2.25 × 109 copies·L-1 and 8.28 × 105 to 2.76 × 109 copies·L-1, respectively. The proportion of toxic Microcystis in the sediment ranging from 31.2% to 19.12%. The highest and lowest region was Meiliang Bay and Grass-algae type zone, respectively. The copy number of the 16S rRNA gene was 1-4 orders of magnitude higher than that of mcyA gene in populations of Microcystis, indicating that non-toxic Microcystis was the dominant form in the majority of the lake. The abundance of toxic Microcystis in the water column was positively correlated with total phosphorus, PO43--P and pH, while the water temperature played distinct role to the distribution of toxic Microcystis in sediment. Our research indicated phosphorus remains a key factor influencing the toxic Microcystis and microcystins in the water column. pH played distinct roles in the distribution of microcystins in sediment and water column. The increasing water temperature is a threat. Explicit management actions and policies, which take into account nutrient concentrations, pH, and increasing temperatures, are necessary to understand and control the distribution of microcystin and Microcystis in Lake Taihu.


Azodyes as markers for tumor hypoxia imaging and therapy: An up-to-date review.
Tumor hypoxia is the low tissue oxygen levels seen characteristically in rapidly proliferating and expanding neoplasms. It affects both malignant tumor cells and its microenvironment, resulting in dysfunctional neovascularization. This leads to epithelial-to-mesenchymal transition phenotype, facilitating tumor progression through cell mobility, invasion, and metastasis. The hypoxic condition in solid tumors is thus an indicator of the process of cancer progression towards an aggressive malignant phenotype with an enhanced possibility of metastasis and resistance to treatment. Advancements in the detection of tumor hypoxia and its utilization as a treatment modality in solid tumors are highly imperative. The use of fluorescent probes is an evolving field for detecting hypoxic tumors in biological systems. The present review is an attempt to provide a contextual knowledge on the prominent role of tumor hypoxia in cancer progression and dissemination. The use of azodyes in detecting tumor hypoxia aiding in cancer diagnosis through fluorescence off-on imaging and azodye-based hypoxia selective pro-drugs for assisting cancer therapy are presented. The limitations of fluorescence based hypoxia imaging and further investigations desired for clinical usage of azodye based hypoxic probes for fluorescence imaging are also considered.


Giant Epidermoid Cyst: A Rare Cause of Temporal Lobe Epilepsy.
Introduction Epidermoid tumors represent approximately 0.3 to 1.8% of all intracranial brain tumors. Only 1.5% of all intracranial epidermoid cysts (ECs) invade the brain and secondary epilepsy is extremely rare. Since August 2014, a 59-year-old male smoker had been presenting bad smell feelings, totaling four episodes with sudden onset and duration of 2 minutes. On September 2014, after a sense of smell episode, it evolved into loss of contact and automatic movements followed by generalized tonic-clonic movements. The brain magnetic resonance imaging revealed an extensive subtemporal lesion affecting anterior, middle, and posterior fossa with invasion of the choroidal fissure and projection to the temporal horn of the lateral ventricle. Pretemporal craniotomy with combined approaches, transsylvian and subtemporal, allowed for the excision of a white keratinized and softened lesion suggestive of EC. Discussion The optimal surgical strategy in individuals with ECs and seizures is not established. The evaluation of the cause and risk-benefit must be held to choose the appropriate surgical strategy: lesionectomy, lobectomy, or amygdalohippocampectomy. In this case, a lesionectomy was performed due to an absence of evidence of involvement of hippocampus and amygdala. Conclusion Epilepsy secondary to ECs is a rare association. Lesionectomy can be an option with good results without increasing the morbidity.


Detection of multiple scattering in optical coherence tomography by speckle correlation of angle-dependent B-scans.
Angular diversity is a successful speckle-reduction technique in optical coherence tomography (OCT). We employ angle-dependent detection for a different purpose: to distinguish the singly backscattered and multiply scattered signal components. Single backscattering is highly correlated over a large range of detection angles; multiple scattering rapidly decorrelates as the angle is varied. Theoretical justification is provided using a linear-systems description of the OCT imaging process; detection of multiple scattering is corroborated experimentally.


Endoscopic ultrasound-guided transduodenal placement of a fully covered metal stent for palliative biliary drainage in patients with malignant biliary obstruction.
Endoscopic ultrasound (EUS)-guided biliary drainage (EUSBD) has been described as a viable alternative to percutaneous transhepatic cholangiography (PTC) in patients in whom ERCP has been unsuccessful. The purpose of our study was to assess the utility of EUSBD using a newly released, fully covered, self-expanding, biliary metal stent (SEMS) for palliation in patients with an obstructing malignant biliary stricture. We collected data on all patients who presented with obstructive jaundice and who underwent transduodenal EUSBD after a failed ERCP. Eight patients presented with biliary obstruction from inoperable pancreatic cancer or cholangiocarcinoma. Reasons for failed ERCP were duodenum stenosis, high-grade malignant stenosis of the common bile duct, periampullary tumor infiltration, failure to access the common bile duct, and periampullary diverticulum. EUS was used to access the common bile duct from the duodenum after which a guidewire was advanced upwards toward the liver hilum. The metal stent was then advanced into the biliary tree. Technical success was defined as correct stent deployment across the duodenum. Clinical success was defined as serum bilirubin level decreased by 50% or more within 2 weeks after the stent placement. Technical and clinical success was achieved in all eight patients. No stent malfunction or occlusion was observed. Complications included one case of duodenal perforation, which required surgery, and one case of self-limiting abdominal pain. EUSBD with a fully covered SEMS in whom ERCP is unsuccessful is effective for palliation of biliary obstruction. The limitations of our study are that we had a small number of patients and a limited follow-up time.


Development of a murine mutant Ras CD8+ CTL peptide epitope variant that possesses enhanced MHC class I binding and immunogenic properties.
We recently identified a murine mutant Ras p21 CD8+ CTL epitope reflecting residues 4 to 12, containing the mutation of Gly to Val at codon 12, that bound weakly to H-2Kd in vitro and generated a weak primary CTL response in immunized BALB/c mice. Here, we explored the hypothesis that specific modifications to the Ras4-12 peptide sequence can improve MHC binding, leading to enhanced immunogenicity without altering immune specificity. We synthesized Ras4-12 peptides in which Val at residue 12 was replaced with the more dominant H-2Kd C-terminus anchor residue Leu or Ile. In functional H-2Kd binding assays, Ras4-12(L12 or I12) peptide variants competed more effectively than the Ras4-12(V12) peptide. Ras4-12(L12 or I12) peptide variants enhanced both in vitro cytotoxicity and proliferation responses of anti-Ras4-12 CTL compared with the mutant Ras4-12(V12) peptide. Additionally, the Ras4-12(L12) peptide variant induced a quantitatively greater T cell response in vivo compared with that produced by Ras4-12(V12) as determined by IFN-gamma production. Mice immunized with Ras4-12(L12) peptide elicited CD8+ CTL activity specific for target cells presenting the Ras4-12(V12) epitope exogenously and endogenously. Moreover, both anti-Ras4-12(V12)-derived and anti-Ras4-12(L12)-derived CTL lines were similar insofar as their TCR usage and amino acid contact residues in the Ras4-12(V12) peptide. These experiments demonstrate that modifications can be introduced in tumor-specific peptide epitopes to enhance both in vitro and in vivo immunogenicity. The design of oncogene-specific peptide epitope variants as immunogens may accelerate the generation of anti-tumor T cell responses for cancer immunotherapy.


ChewFree.com: evaluation of a Web-based cessation program for smokeless tobacco users.
The sizeable percentage of adults who use smokeless tobacco (ST) represents an important public health target since the majority of ST users have a strong desire to quit, but many lack resources. We tested the impact of an interactive, tailored Web-based intervention (Enhanced Condition) versus a more linear, text-based website (Basic Condition) in a randomized trial with 2523 adult ST users. As is common in Internet-based research, there was considerable attrition: follow-up rates at 3 months, 6 months, and for both 3 and 6 months were 48%, 45% and 34%, respectively. Results using repeated point prevalence of all tobacco use at 3 and 6 months showed that participants in the Enhanced Condition quit at significantly higher rates than those in the Basic Condition. Using a Complete Case analysis, abstinence was 40.6% in the Enhanced Condition vs. 21.2% in the Basic Condition (p< .001). Using intent-to-treat analysis, quit rates were 12.6% vs. 7.9%, respectively (p< .001). Similar results were obtained for only ST use. Unobtrusive measures of program exposure indicated that program use was significantly related to outcome as well as to attrition. We conclude that a tailored, interactive Web-assisted cessation program can be an efficacious method for assisting adult ST users to quit.


Relationships between the epileptic focus and hand area in central epilepsy: combining dipole models and anatomical landmarks.
When considering resection of epileptic generators near the central sulcus, it is essential to define the spatial relationship between the epileptic generator and the primary sensorimotor hand area. In this study, the authors assessed the accuracy of dipole modeling of electroencephalographic spikes and median nerve somatosensory evoked potentials (SSEPs) in defining this relationship preoperatively and noninvasively. Epileptic spikes and SSEPs in patients with focal central area epilepsy were represented by dipole models coregistered onto global magnetic resonance images. In patients who underwent surgery, spike dipoles were also compared with findings of electrocorticography (ECoG) and with the resection area. To improve the accuracy of the dipole models, anatomical landmarks of the hand area were used to assess the error in SSEP dipole location, and this error measure was used to correct the location of spike dipoles. Five patients with central epilepsy were studied, three of whom underwent ECoG-guided surgical resections. The location of SSEP dipoles correlated well with anatomical landmarks of the primary sensory hand area. The relative position of the spike and SSEP dipoles correlated well with the patients' ictal symptoms, ECoG findings, and the location of the epileptic focus (as defined by the resection cavity in patients who became seizure free postoperatively). Corrected spike dipoles were located even closer to the resection cavity. The calculation of the relative location of spike and SSEP dipoles is a simple noninvasive method of determining the relationship between the primary hand area and an epileptic focus in the central area. The spatial resolution of this technique can be further improved using easily identifiable anatomical landmarks.


A thematic analysis of causes attributed to weight gain: a female slimmer's perspective.
Obesity prevalence has shown a marked increase in recent years. Strategies designed to manage the trend are not always effective in the long term. This qualitative study investigated perceived causes of weight gain in a group of female slimmer's. Understanding beliefs about the causes of a problem can help explain behaviour and find solutions. It is therefore justified and timely to explore beliefs about causes of weight gain. A group of 11 (adult) slimmer's were interviewed using a semi-structured approach, and the data obtained were analysed thematically. Four main themes were identified; importance of habits, influence of learning early models about the world through food, eating beyond feeling full and use of food as therapy. Behavioural causes were given to explain weight gain, perceived to be mediated by modern lifestyles or changes in circumstances. In addition, beliefs about food and its function related to personal history or childhood experience, which subsequently were used negatively in adulthood. The potential contributions of these findings for practice are explored.


Is nebulized aerosol treatment necessary in the pediatric emergency department?
Infants and small children admitted to the pediatric emergency department (PED) with acute wheezing episodes (AWE) are currently treated with nebulized wet aerosol (NWA). To determine the efficacy of MDI with Nebuchamber (Astra AB; Lund, Sweden), a nonelectrostatic spacer device (NESD), as compared to NWA in the treatment of an unselected population of babies and small children with AWE. Randomized, double-blind, placebo-controlled trial. Forty-two children referred to the PED (median age +/- SD, 16 +/- 15 months) with AWE received either placebo MDI through a NESD (four puffs) and salbutamol 0.5 mL (2.5 mg) as a NWA (group I, n = 19), or salbutamol MDI and 0.5 mL of saline solution administered in the same manner as above (group II, n = 23). This treatment was repeated three times every 20 min. The respiratory rates (RRs) at baseline were as follows: group I, 45 +/- 11.2 breaths/min; and group II, 52.3 +/- 11.3 breaths/min (p = not significant [NS]). After the first, second, and third interventions, the percent fall from baseline of the RR were as follows: group I, 8.9, 13.1, and 17.9%, respectively; group II, 8. 6, 14.6, and 18.6%, respectively. There was no significant difference at any time in the results between the two groups. The clinical scores (CSs) at baseline were as follows: group I, 6.6 +/- 1.3; group II, 6.8 +/- 1.49 (p = NS). After the first, second, and third interventions, the percent fall from baseline of the CS were as follows: group I, 9.1, 17.9, and 23.2%, respectively; group II, 8. 6, 18.9, and 24.7%, respectively. These results, also, did not differ significantly at any time between the two groups. Hospitalization rate and side effects did not differ between the two groups. We conclude that even in the group of unselected very young children (mean age < 2 years) with AWE, the use of MDI with NESD is at least as effective as the use of NWA. As opposed to data from an adult population, no plateau was reached in the dose-response curve using the above doses over time.


Complete Monitoring of Coherent and Incoherent Spin Flip Domains in the Recombination of Charge-Separated States of Donor-Iridium Complex-Acceptor Triads.
The spin chemistry of photoinduced charge-separated (CS) states of three triads comprising one or two triarylamine donors, a cyclometalated iridium complex sensitizer and a naphthalene diimide (NDI) acceptor, was investigated by transient absorption spectroscopy in the ns-μs time regime. Strong magnetic-field effects (MFE) were observed for two triads with a phenylene bridge between iridium complex sensitizer and NDI acceptor. For these triads, the lifetimes of the CS states increased from 0.6 μs at zero field to 40 μs at about 2 T. Substituting the phenylene by a biphenyl bridge causes the lifetime of the CS state at zero field to increase by more than 2 orders of magnitude (τ = 79 μs) and the MFE to disappear almost completely. The kinetic MFE was analyzed in the framework of a generalized Hayashi-Nagakura scheme describing coherent (S, T0 ↔ T±) as well as incoherent (S, T0 ⇌ T±) processes by a single rate constant k±. The magnetic-field dependence of k± of the triads with phenylene bridge spans 2 orders of magnitude and exhibits a biphasic behavior characterized by a superposition of two Lorentzians. This biphasic MFE is observed for the first time and is clearly attributable to the coherent (B < 10 mT) and incoherent (10 mT < B < 2 T) domains of spin motion induced by isotropic and anisotropic hyperfine coupling. The parameters of both domains are well understood in terms of the structural properties of the two triads, including the effect of electron hopping in the triad with two donor moieties. The kinetic model also accounts for the reduction of the MFE on reducing the rate constant of charge recombination in the triad with the biphenyl bridge.


Image-based multiscale structural models of fibrous engineered tissues.
While it is firmly established that the mechanical behavior of most biological tissues, including bioengineered tissues, is governed by an underlying network of protein fibers, it is still not clear how best to obtain and utilize structural information to predict mechanical response. In this paper, methods are presented to (1) quantify the fiber arrangement in a tissue from different imaging tools, (2) incorporate that structure into a multiscale model, and (3) solve the model equations to predict both the microscopic and the macroscopic tissue response. In principle these concepts could be applied to any tissue (incorporating the specific tissue components as needed), but for demonstration purposes, the focus of the current work is on cell-compacted collagen gel, a model engineered tissue.


Ultra-trace determination of total mercury in Italian bottled waters.
Mercury (Hg) is a widespread, highly toxic persistent pollutant with adverse health effects on humans. So far, concentrations below the method detection limit have always been reported by studies on the concentration of mercury in bottled water when determined using instrumental analytical methods. These are often very expensive and are unaffordable for many laboratories. In this work, a less expensive method based on cold vapour atomic fluorescence spectrometry has been employed to determine total mercury (HgT) concentrations in bottled natural mineral waters. In all, 255 waters representing 164 different typologies were analysed. They came from 136 springs located in 18 Italian regions. In all samples, HgT concentrations were found in the range of sub-nanogram to a few nanograms per litre, well below the National and European regulatory limit (1 μg L-1). Differences in HgT concentrations were related not only to the environmental characteristics of the springs but also to the extent and impact of human activities. Higher concentrations were found in waters coming from regions with former mining and/or natural thermal and volcanic activity. These data allowed us to estimate the mercury intake by population (adults, children and toddlers) from drinkable mineral waters consumption. The mean mercury daily intake was found to be remarkably lower, not only than the provisional tolerable value (1 μg L-1 according to European and Italian legislation) but also than the estimated provisional tolerable weekly intake (PTWI) value (4 μg kg-1 body weight) recommended by the Joint FAO/WHO Expert Committee on Food Additives (JECFA).


The outpatient management and special considerations of nausea and vomiting in pregnancy.
With 50-90% of pregnant women experiencing nausea and vomiting of pregnancy (NVP), the burden of illness can become quite significant if symptoms are under-treated and/or under-diagnosed, thus allowing for progression of the disease. The majority of these women will necessitate at least one visit with a provider to specifically address NVP, and up to 10% or greater will require pharmacotherapy after failure of conservative measures to adequately control symptoms. As a result, initiation of prompt and effective treatment in the outpatient setting is ideal. Once NVP is diagnosed and treatment is started, it is crucial to track symptoms in order to assess for a decrease in or resolution of symptoms as well as an escalation in symptoms requiring additional therapy. Of note, co-existing gastroesophageal reflux disease (GERD), Helicobacter pylori infection, and psychosocial factors may have a negative impact on the management of NVP. Ultimately, every woman has her own perception of disease severity and desire for treatment. It is critical that both the provider and patient be proactive in the diagnosis and management of NVP.


The hypoglycemic effects of guava leaf (Psidium guajava L.) extract are associated with improving endothelial dysfunction in mice with diet-induced obesity.
Obesity is associated with a low-grade inflammatory status that affects vascular function. Previous studies have reported the beneficial effects of Psidium guajava L. (guava) on diabetes. Here we evaluate the how guava leaf extract at the dose of 5 mg/kg, affects vascular dysfunction in obese mice fed a high-fat diet for 7 weeks. Extract intake did not alter weight over time, although it reduced glycemia and insulin resistance, improving the serum lipid profile in obese mice. Additionally, guava leaf extract reversed the endothelial dysfunction found in obese mice in terms of endothelium- and NO (nitric oxide)-dependent vasodilatation induced by acetylcholine in aortic rings. In conclusion, the beneficial effects of guava leaf extract in obese mice were associated with improved vascular functions altered by obesity, probably due to its phenolic content.


In vivo factors influencing the freezing cycle during cryoablation of small renal masses.
The aim of this study is to present a procedural analysis of the cryoablations performed in our department for small renal tumors and to try to identify clinical parameters or factors that influence the freezing rate during the procedure. We collected all data from the procedures performed in our department until August 2007. Based on the intraoperative biopsy result, we grouped the cases in two groups: renal-cell carcinoma (RCC) and benign. We calculated the freezing rate in both groups and compared them. Finally, we performed a univariate and multivariate analysis to identify clinical parameters that significantly influence the freezing rate. A total of 70 cryoablations of small renal tumors in 67 patients were performed during this period. From these, 56 procedures met the inclusion criteria and were analyzed further. The RCC group consisted of 48 cases (39 RCC and 9 lesions with a nondiagnostic biopsy) while 8 formed the benign group. There was no difference in the freezing rate between these two groups. Preoperative creatinine levels above 120 IU, diabetes mellitus, American Society of Anesthesiologists score 3, and location of the tumor at the lower pole were found to increase the freezing rate. The only factor that significantly decreased the freezing rate was the presence of chronic obstructive pulmonary disease. The multivariate analysis showed that the location of the tumor and diabetes mellitus influence more significantly the temperature v time graph. The freezing rate during cryotherapy of small renal tumors is significantly influenced by various clinical factors, while there are no differences in the freezing rate of those proven small malignant tumors and the small benign lesions.


Diagnosis and therapy of sleep apnea.
The presenting symptom complex, diagnostic features, and therapeutic alternatives for obstructive and central sleep apnea are discussed in relation to two illustrative patients. Heavy snoring and restlessness during sleep in an obese individual, usually a male, may indicate obstructive apnea. Daytime hypersomnolence, intellectual deterioration, mental depression, impotence, cardiac arrhythmias, cor pulmonale, systemic hypertension, and erythrocytosis are the most common complications. Tracheostomy, the classic form of therapy, can be replaced by pharmacologic intervention in most patients. The clinical presentation of central apnea is less dramatic, but neurological and cardiac complications can occur. Therapy is less well established for this entity. Knowledge of the increased incidence of these disorders and awareness of more subtle complications indicate that sleep apnea should be placed in the differential diagnosis of pulmonary and systemic hypertension, hypersomnolence states, mental deterioration, psychiatric illness, and even insomnia.


[Effects of 460 MHz microwave radiation on Drosophila embryos under raised temperature].
Combined effect of 460-MHz microwave irradiation and increased (up to 40 degrees C) temperature on Drosophila embryos of definite age was studied. It was demonstrated that the effect of 5-min exposures to non-modulated microwaves with 6 W/kg SAR accompanied with heating is only a little stronger than at normal temperature (24.5 degrees C). Irradiation with pulse-modulated microwaves with pulse repetition rates of 6, 10, 16, and 22 p.p.s. with average SAR of 0.12 W/kg (pulsed SAR 3 W/kg) combined with increased temperature caused some changes in PID dependent on the pulse rate. At 6 and 22 p.p.s, the increase in PID was close to that observed at normal temperature while at 10 and 16 p.p.s. the microwave irradiation did not produce any noticeable effect on development of the Drosophilas.


Communicating with patients via e-mail: is it a good idea?
As e-mail becomes an everyday part of more people's lives--and an important part of the way business is done--optometrists are naturally beginning to use it with patients. However, e-mail communication with patients creates a new set of potential dangers that doctors must consider: What defines the doctor-patient relationship? Should diagnoses be made and delivered via e-mail? How can privacy and confidentiality be maintained? Can marketing be done tastefully via e-mail? This author addresses each of these issues from a medico-legal perspective and offers advice on professional, ethical ways to communicate with patients via e-mail.


Postsynaptic adenosine A2A receptors modulate intrinsic excitability of pyramidal cells in the rat basolateral amygdala.
The basolateral amygdala plays a critical role in the etiology of anxiety disorders and addiction. Pyramidal neurons, the primary output cells of this region, display increased firing following exposure to stressors, and it is thought that this increase in excitability contributes to stress responsivity and the expression of anxiety-like behaviors. However, much remains unknown about the underlying mechanisms that regulate the intrinsic excitability of basolateral amygdala pyramidal neurons. Ex vivo gramicidin perforated patch recordings were conducted in current clamp mode where hyper- and depolarizing current steps were applied to basolateral amygdala pyramidal neurons to assess the effects of adenosine A(2A) receptor modulation on intrinsic excitability. Activation of adenosine A(2A) receptors with the selective A(2A) receptor agonist CGS-21680 significantly increased the firing rate of basolateral amygdala pyramidal neurons in rat amygdala brain slices, likely via inhibition of the slow afterhyperpolarization potential. Both of these A(2A) receptor-mediated effects were blocked by preapplication of a selective A(2A) receptor antagonist (ZM-241385) or by intra-pipette infusion of a protein kinase A inhibitor, suggesting a postsynaptic locus of A(2A) receptors on basolateral amygdala pyramidal neurons. Interestingly, bath application of the A(2A) receptor antagonist alone significantly attenuated basolateral amygdala pyramidal cell firing, consistent with a role for tonic adenosine in the regulation of the intrinsic excitability of these neurons. Collectively, these data suggest that adenosine, via activation of A(2A) receptors, may directly facilitate basolateral amygdala pyramidal cell output, providing a possible balance for the recently described inhibitory effects of adenosine A1 receptor activation on glutamatergic excitation of basolateral amygdala pyramidal cells.


Systemic and local complications following low-friction arthroplasty of the hip joint. A study of 800 consecutive operations.
At the New York Orthopaedic Hospital, a study was made of postoperative complications in 800 consecutive total hip replacements of the Charnley low-friction arthroplasty type. Specially designed records made it possible to document and include all systemic and local complications of this procedure. While the rate of postoperative infection was low (less than 1%), thromboembolism and deep-vein thrombosis incidence was high despite the introduction of a prophylactic anticoagulation regimen. There were no deaths during or immediately after surgery, but six occurred within the first six weeks postoperatively. Two were due to a massive pulmonary embolus (proved at autopsy), two to myocardial infarction (clinical diagnosis), and one to a perforated cecum (proved at autopsy). The incidence of mechanical and technical failures in our series was relatively low and quite comparable with results reported by others.