The effects of on-pump and off-pump coronary artery bypass grafting on intraoperative graft flow in arterial and venous conduits defined by a flow/pressure ratio.
Despite profound differences in the neurohumoral milieu in patients undergoing on-pump and off-pump coronary artery bypass grafting, it is uncertain how this affects graft blood flow. We prospectively recorded intraoperative transit-time flow measurements (MediStim BF 2004; MediStim AS, Oslo, Norway) in all internal thoracic artery, radial artery, and long saphenous vein conduits in patients undergoing off-pump and on-pump bypass grafting by a single surgeon. We calculated a flow/pressure ratio as a ratio of mean graft flow to mean arterial pressure for all the conduits just before chest closure. Transit-time flow measurements were recorded in 266 grafts (203 off-pump; 63 on-pump) in 100 patients (80 off-pump; 20 on-pump). Overall, mean graft flow (milliliters per minute) was higher for all grafts in the on-pump group despite a significantly lower mean arterial pressure compared with the off-pump group (P < .05). Consequently the flow/pressure ratio was greater for all grafts in the on-pump group (internal thoracic artery 0.55 vs 0.35, radial artery 0.61 vs 0.36, long saphenous vein 0.77 vs 0.55). Overall mean graft flow was significantly greater in the long saphenous vein than in the internal thoracic artery (P < .001) and radial artery (P = .001), but there was no significant difference in mean graft flow in internal thoracic artery or radial artery grafts within each group. In comparison with the off-pump group, the overall mean graft flow and flow/pressure ratio were significantly higher and mean arterial pressure significantly lower for all grafts in the on-pump group. These findings are probably a result of vasodilatation resulting from cardiopulmonary bypass and reactive hyperemia resulting from a period of ischemia. There was no difference in the mean graft flow and flow/pressure ratio of arterial grafts, which were significantly less than for long saphenous vein grafts. In patients with unstable angina and/or hemodynamic instability, in whom rapid and maximum restoration of myocardial perfusion is a priority, potentially lower graft flow in arterial grafts and off-pump surgery should be considered.


IL-18 inhibits growth of murine orthotopic prostate carcinomas via both adaptive and innate immune mechanisms.
Interleukin(IL)-18 is a pleiotrophic cytokine with functions in immune modulation, angiogenesis and bone metabolism. In this study, the potential of IL-18 as an immunotherapy for prostate cancer (PCa) was examined using the murine model of prostate carcinoma, RM1 and a bone metastatic variant RM1(BM)/B4H7-luc. RM1 and RM1(BM)/B4H7-luc cells were stably transfected to express bioactive IL-18. These cells were implanted into syngeneic immunocompetent mice, with or without an IL-18-neutralising antibody (αIL-18, SK113AE4). IL-18 significantly inhibited the growth of both subcutaneous and orthotopic RM1 tumors and the IL-18 neutralizing antibody abrogated the tumor growth-inhibition. In vivo neutralization of interferon-gamma (IFN-γ) completely eliminated the anti-tumor effects of IL-18 confirming an essential role of IFN-γ as a down-stream mediator of the anti-tumor activity of IL-18. Tumors from mice in which IL-18 and/or IFN-γ was neutralized contained significantly fewer CD4(+) and CD8(+) T cells than those with functional IL-18. The essential role of adaptive immunity was demonstrated as tumors grew more rapidly in RAG1(-/-) mice or in mice depleted of CD4(+) and/or CD8(+) cells than in normal mice. The tumors in RAG1(-/-) mice were also significantly smaller when IL-18 was present, indicating that innate immune mechanisms are involved. IL-18 also induced an increase in tumor infiltration of macrophages and neutrophils but not NK cells. In other experiments, direct injection of recombinant IL-18 into established tumors also inhibited tumor growth, which was associated with an increase in intratumoral macrophages, but not T cells. These results suggest that local IL-18 in the tumor environment can significantly potentiate anti-tumor immunity in the prostate and clearly demonstrate that this effect is mediated by innate and adaptive immune mechanisms.


A cross-sectional study of the association between family conflicts and children's health: Lolland-Falster Health Study.
Few family interaction processes are more detrimental to children's health than family conflicts. Conflictual relationships in childhood predict a host of adverse health outcomes across the life course. The current study examines associations between household conflicts and the health of children aged 6-12 years and explores to which extent this may vary by socioeconomic status (SES) and multimorbidity (MM) in the household. Cross-sectional study using questionnaire data gathered between 2016 and 2020 as part of the Lolland-Falster Health Study (LOFUS) combined with routine register data on health care use and socio-demography from the Danish nationwide administrative databases. The study sample consisted of 1065 children 6-12 years old, who answered LOFUS4 or LOFUS11, from 777 households for which at least one adult answered LOFUS18. Main outcome was children's health complaints, defined as headache, abdominal pain, back pain, and sleep difficulties. Covariates included MM, SES, and conflicts, all three measured at household level. Multivariable logistic regression models were used. Conflicts were negatively associated with children's health. This was most pronounced for general conflicts in the household, with increased complaints of abdominal pain, back pain, and sleep difficulties. The associations varied when we stratified the households according to MM and SES. Significant associations were found within households without MM for abdominal pain, and within households with MM and low SES, and without MM and with high SES for sleep difficulties. While the higher level of abdominal pain for the above indicated households were found for both internal and external conflicts in the household, the higher level in sleep difficulties was mostly driven by internal conflicts. Children reporting frequent health complaints have a higher future health care use compared with children without such complaints. Our results indicate that growing up in a household with a high conflict level might be a predisposing factor.


Alpha proteobacterial ancestry of the [Fe-Fe]-hydrogenases in anaerobic eukaryotes.
Eukaryogenesis, a major transition in evolution of life, originated from the symbiogenic fusion of an archaea with a metabolically versatile bacterium. By general consensus, the latter organism belonged to α proteobacteria, subsequently evolving into the mitochondrial organelle of our cells. The consensus is based upon genetic and metabolic similarities between mitochondria and aerobic α proteobacteria but fails to explain the origin of several enzymes found in the mitochondria-derived organelles of anaerobic eukaryotes such as Trichomonas and Entamoeba. These enzymes are thought to derive from bacterial lineages other than α proteobacteria, e.g., Clostridium - an obligate anaerobe. [FeFe]-hydrogenase constitues the characteristic enzyme of this anaerobic metabolism and is present in different types also in Entamoeba and other anaerobic eukaryotes. Here we show that α proteobacteria derived from metagenomic studies possess both the cytosolic and organellar type of [FeFe]-hydrogenase, as well as all the proteins required for hydrogenase maturation. These organisms are related to cultivated members of the Rhodospirillales order previously suggested to be close relatives of mitochondrial ancestors. For the first time, our evidence supports an α proteobacterial ancestry for both the anaerobic and the aerobic metabolism of eukaryotes. This article was reviewed by William Martin and Nick Lane, both suggested by the Authors.


Surface plasmon resonance binding kinetics of Alzheimer's disease amyloid beta peptide-capturing and plaque-binding monoclonal antibodies.
Several different monoclonal antibodies (mAbs) have been actively developed in the field of Alzheimer's disease (AD) for basic science and clinical applications; however, the binding kinetics of many of the mAbs with the beta-amyloid peptides (Abeta) are poorly understood. A panel of mAbs with different Abeta recognition sites, including our plaque-binding antibody (IgG4.1), a peptide-capturing antibody (11A50), and two classical mAbs (6E10 and 4G8) used for immunohistochemistry, were chosen for characterization of their kinetics of binding to monomeric and fibrillar forms of Abeta40 using surface plasmon resonance and their amyloid plaque binding ability in AD mouse brain sections using immunohistochemistry. The plaque-binding antibody (IgG4.1) with epitope specificity of Abeta(2-10) showed a weaker affinity (512 nM) for monomeric Abeta40 but a higher affinity (1.5 nM) for Abeta40 fibrils and labeled dense core plaques better than 6E10 as determined by immunohistochemistry. The peptide-capturing antibody (11A50) showed preferential affinity (32.5 nM) for monomeric Abeta40 but did not bind to Abeta40 fibrils, whereas antibodies 6E10 and 4G8 had moderate affinity for monomeric Abeta40 (22.3 and 30.1 nM, respectively). 4G8, which labels diffuse plaques better than 6E10, had a higher association rate constant than 6E10 but showed similar association and dissociation kinetics compared to those of 11A50. Enzymatic digestion of IgG4.1 to the F(ab')(2)4.1 fragments or their polyamine-modified derivatives that enhance blood-brain barrier permeability did not affect the kinetic properties of the antigen binding site. These differences in kinetic binding to monomeric and fibrillar Abeta among various antibodies could be utilized to distinguish mAbs that might be useful for immunotherapy or amyloid plaque imaging versus those that could be utilized for bioanalytical techniques.


Human immunodeficiency virus infection of human-PBL-SCID mice.
Severe combined immunodeficient (SCID) mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID mice) have inducible human immune function and may be useful as a small animal model for acquired immunodeficiency syndrome (AIDS) research. Hu-PBL-SCID mice infected with human immunodeficiency virus-1 (HIV-1) contained virus that was recoverable by culture from the peritoneal cavity, spleen, peripheral blood, and lymph nodes for up to 16 weeks after infection; viral sequences were also detected by in situ hybridization and by amplification with the polymerase chain reaction (PCR). Mice could be infected with multiple strains of HIV-1, including LAV-1/Bru, IIIB, MN, SF2, and SF13. HIV-1 infection affected the concentration of human immunoglobulin and the number of CD4+ T cells in the mice. These results support the use of the hu-PBL-SCID mouse for studies of the pathogenesis and treatment of AIDS.


Progressive changes of regional macular thickness after macular hole surgery with internal limiting membrane peeling.
To determine the changes of regional macular thickness after successful macular hole surgery (MHS) with internal limiting membrane (ILM) peeling during a 24-month follow-up period. In a prospective, interventional case study, the authors evaluated 24 eyes of 24 patients who underwent 23-gauge transconjunctival pars plana vitrectomy with triamcinolone-assisted ILM peeling to treat idiopathic macular hole. Examinations were performed before and 1, 2, 3, 6, 9, 12, and 24 months after surgery. Average regional macular thicknesses in the Early Treatment Diabetic Retinopathy Study sectors were measured by spectral-domain optical coherence tomography. The four inner sectors showed a significant reduction in the average retinal thickness at 1 month after surgery (P ≤ 0.0001-0.020), and the thickness continued to decrease for 24 months except in the nasal sector. The four outer sectors had a significant increase at postoperative 1 month (P = 0.0003-0.029) and then progressively decreased during the postoperative 24 months. The postoperative regional macular thinning was statistically significant even between 12 and 24 months (P = 0.0007-0.026) in all sectors except in the inner nasal sector (P = 0.13). The postoperative percent reduction rate was significantly different among four inner sectors after postoperative 3 months (P = 0.0029-0.039) in the order of temporal > superior > inferior > nasal sectors. These results suggest that a progressive macular thinning occurs for at least 2 years with different patterns of the changes in the macular regions after successful MHS with ILM peeling.


Classification and retrieval on macroinvertebrate image databases.
Aquatic ecosystems are continuously threatened by a growing number of human induced changes. Macroinvertebrate biomonitoring is particularly efficient in pinpointing the cause-effect structure between slow and subtle changes and their detrimental consequences in aquatic ecosystems. The greatest obstacle to implementing efficient biomonitoring is currently the cost-intensive human expert taxonomic identification of samples. While there is evidence that automated recognition techniques can match human taxa identification accuracy at greatly reduced costs, so far the development of automated identification techniques for aquatic organisms has been minimal. In this paper, we focus on advancing classification and data retrieval that are instrumental when processing large macroinvertebrate image datasets. To accomplish this for routine biomonitoring, in this paper we shall investigate the feasibility of automated river macroinvertebrate classification and retrieval with high precision. Besides the state-of-the-art classifiers such as Support Vector Machines (SVMs) and Bayesian Classifiers (BCs), the focus is particularly drawn on feed-forward artificial neural networks (ANNs), namely multilayer perceptrons (MLPs) and radial basis function networks (RBFNs). Since both ANN types have been proclaimed superior by different investigations even for the same benchmark problems, we shall first show that the main reason for this ambiguity lies in the static and rather poor comparison methodologies applied in most earlier works. Especially the most common drawback occurs due to the limited evaluation of the ANN performances over just one or few network architecture(s). Therefore, in this study, an extensive evaluation of each classifier performance over an ANN architecture space is performed. The best classifier among all, which is trained over a dataset of river macroinvertebrate specimens, is then used in the MUVIS framework for the efficient search and retrieval of particular macroinvertebrate peculiars. Classification and retrieval results present high accuracy and can match an experts' ability for taxonomic identification.


Micro/milliflow processing with selective catalyst microwave heating in the Cu-catalyzed Ullmann etherification reaction: a μ(2)-process.
A μ(2)-process in the Ullmann-type C-O coupling of potassium phenolate and 4-chloropyridine was successfully performed in a combined microwave (MW) and microflow process. Selective MW absorption in a micro-fixed-bed reactor (μ-FBR) by using a supported Cu nanocatalyst resulted in an increased activity compared to an oil-bath heated process. Yields of up to 80 % were attained by using a multisegmented μ-FBR without significant catalyst deactivation. The μ-FBR was packed with beads coated with Cu/TiO(2) and CuZn/TiO(2) catalysts. Temperature measurements along axial positions of the reactor were performed by using a fiber-optic probe in the catalyst bed. The simultaneous application of MW power and temperature sensors resulted in an isothermal reactor at 20 W. Initially, only solvent was used to adjust the MW field density in the cavity and optimize the power utility. Subsequently, the reaction mixture was added to ensure the maximum MW power transfer by adjusting the waveguide stub tuners to steady-state operations as a result of the changed reaction mixture composition and, therefore, the dielectric properties. Finally, the beneficial influence of the Cu/TiO(2)- and CuZn/TiO(2)-coated glass beads (200 μm) on the MW absorption as a result of the additional absorbing effect of the metallic Cu nanoparticles was optimized in a fine-tuning step. For the catalyst synthesis, various sol-gel, deposition, and impregnation methods provided Cu catalyst loadings of around 1 wt %. The addition of Zn to the Cu nanocatalyst revealed an increased catalyst activity owing to the presence of stable Cu(0). Multilaminar mixing was necessary because of the large difference in fluid viscosities. To the best of our knowledge, this work is the first extended experimental survey of the decisive parameters to combine microprocess and single-mode MW technology following the concepts of "novel process windows" for organic syntheses.


Incontinence in women prisoners: an exploration of the issues.
This paper is a report of a study exploring the extent and management of bladder and bowel problems in order to inform the provision and practice of prison nursing services and health care services in women's prisons. Nurses and general practitioners provide primary care services inside prisons in the United Kingdom. While high levels of mental health and addiction problems in women prisoners are recognized, there has been less focus on physical problems. Incontinence symptoms are perceived as shameful and stigmatizing, and frequently help is not sought from healthcare professionals. Guidance for assessing prisoner health does not refer to bladder and bowel symptoms. Women prisoners in a large, closed prison in the United Kingdom were surveyed in 2005 using an anonymous self-completed questionnaire. Women resident in the detoxification unit and the hospital unit, absent from their unit at the time of questionnaire distribution or deemed vulnerable by prison health staff were excluded. Questionnaires were offered to 283 women and 246 agreed to take it. Of those taken, 148 (60%) were returned. Twenty-four per cent indicated that they disclosed information about bladder and bowel problems in the survey not previously disclosed to anyone else. Forty-three per cent reported urinary symptoms. Five per cent reported nocturnal enuresis. The majority of women with symptoms reported using sanitary pads and toilet paper for containment of leakage. Prison nurses and nurse practitioners involved in reception into prison assessments should ask direct but sensitive questions about women's bladder and bowel symptoms.


Association between infancy BMI peak and body composition and blood pressure at age 5-6 years.
The development of overweight is often measured with the body mass index (BMI). During childhood the BMI curve has two characteristic points: the adiposity rebound at 6 years and the BMI peak at 9 months of age. In this study, the associations between the BMI peak and body composition measures and blood pressure at age 5-6 years were investigated. Measurements from the Amsterdam Born Children and their Development (ABCD) study were available for this study. Blood pressure (systolic and diastolic) and body composition measures (BMI, waist-to-height ratio, fat percentage) were gathered during a health check at about 6 years of age (n = 2822). All children had multiple BMI measurements between the 0-4 years of age. For boys and girls separately, child-specific BMI peaks were extracted from mixed effect models. Associations between the estimated BMI peak and the health check measurements were analysed with linear models. In addition, we investigated the potential use of the BMI at 9 months as a surrogate measure for the magnitude of the BMI peak. After correction for the confounding effect of fetal growth, both timing and magnitude of the BMI peak were significantly and positively associated (p<0.001) with all body composition measures at the age of 5-6 years. The BMI peak showed no direct association with blood pressure at the age 5-6 year, but was mediated by the current BMI. The correlation between the magnitude of the BMI peak and BMI at 9 months was approximately 0.93 and similar associations with the measures at 5-6 years were found. The magnitude of the BMI peak was associated with body composition measures at 5-6 years of age. Moreover, the BMI at 9 months could be used as surrogate measure for the magnitude of the BMI peak.


Early morning surge in blood pressure.
Early-morning blood pressure is generally viewed as an important therapeutic target, for two reasons. First, for antihypertensive agents taken once daily in the morning, the timing of the trough plasma drug level, and thereby the lowest pharmacodynamic effect, often coincides with the early morning rise in blood pressure and heart rate. Evidence has been accumulated to suggest that blood pressure control throughout the 24 h period may be necessary to gain complete benefit from antihypertensive medication. In fact, in a longitudinal study, the regression of cardiac hypertrophy in patients with hypertension was more accurately predicted by treatment-induced changes in average 24 h ambulatory blood pressure than by clinic or home-monitored blood pressure readings. The other reason for the importance of morning blood pressure is that cardiovascular risk is heightened at this time of day. A morning surge in sympathetic activity alters haemodynamic forces and predisposes vulnerable coronary atherosclerotic plaques to rupture. At the same time as this risk of plaque rupture is greatest, circadian variations in haemostatic and fibrinolytic factors result in morning hypercoagulability and hypofibrinolysis, promoting the formation of intraluminal thrombi. We recently showed that, in older hypertensives, a greater morning blood pressure surge, mediated at least in part by an exaggerated alpha-sympathetic activity, is associated with more advanced silent cerebrovascular disease as well as a higher future incidence of stroke. The early morning surge in blood pressure could become a new therapeutic target for preventing target-organ damage and subsequent cardiovascular events in hypertension. Of greatest interest is the potential benefit of a chronotherapeutic approach, involving, for example, long-acting chronoformulations, which has not yet been extensively studied.


Pursuing minimally disruptive medicine: disruption from illness and health care-related demands is correlated with patient capacity.
Chronic conditions burden patients with illness and treatments. We know little about the disruption of life by the work of dialysis in relation to the resources patients can mobilize, that is, their capacity, to deal with such demands. We sought to determine the disruption of life by dialysis and its relation to patient capacity to cope. We administered a survey to 137 patients on dialysis at an academic medical center. We captured disruption from illness and treatment, and physical, mental, personal, social, financial, and environmental aspects of patient capacity using validated scales. Covariates included number of prescriptions, hours spent on health care, existence of dependents, age, sex, and income level. On average, patients reported levels of capacity and disruption comparable to published levels. In multivariate regression models, limited physical, financial, and mental capacity were significantly associated with greater disruption. Patients in the top quartile of disruption had lower-than-expected physical, financial, and mental capacity. Our sample generally had capacity comparable to other populations and may be able to meet the demands imposed by treatment. Those with reduced physical, financial, and mental capacity reported higher disruption and represent a vulnerable group that may benefit from innovations in minimally disruptive medicine.


Assessing DSM-5-oriented level of personality functioning: Development and psychometric evaluation of the Semi-Structured Interview for Personality Functioning DSM-5 (STiP-5.1).
The alternative model for personality disorders (AMPD) in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) features a Level of Personality Functioning Scale, measuring intrinsic personality processes that include identity, self-direction, empathy, and intimacy. This study describes the development and psychometric evaluation of a semistructured interview schedule for the multi-item assessment of the level of personality functioning, the Semi-Structured Interview for Personality Functioning DSM-5 (STiP-5.1). Eighty patients and 18 community subjects completed the STiP-5.1. Patients additionally completed the Brief Symptom Inventory, the Severity Indices of Personality Problems, and the Structured Clinical Interview for DSM-IV Axis I and Axis II Personality Disorders. Good interrater reliability was observed in subsamples of patients (n = 40) and nonpatients (n = 18). Associations between the interview scores and conceptually relevant external measures consistently supported the construct validity of the instrument. The STiP-5.1 thus offers a brief, relatively user-friendly instrument with generally favorable psychometric properties for the assessment of level of personality functioning of the DSM-5 AMPD. (PsycINFO Database Record


Urotensin II induces rat cardiomyocyte hypertrophy via the transient oxidization of Src homology 2-containing tyrosine phosphatase and transactivation of epidermal growth factor receptor.
Urotensin II (U-II) is implicated in cardiomyocyte hypertrophy, which results in cardiac remodeling. We recently demonstrated that both reactive oxygen species (ROS) generation and epidermal growth factor receptor (EGFR) transactivation play critical roles in U-II signal transduction. However, the detailed intracellular mechanism(s) underlying cardiac hypertrophy and remodeling remain unclear. In this study, we used rat cardiomyocytes treated with U-II to investigate the association between ROS generation and EGFR transactivation. U-II treatment was found to stimulate cardiomyocyte hypertrophy through phosphorylation of EGFR and ROS generation. Apocynin, an NAD(P)H oxidase inhibitor, and N-acetyl cysteine (NAC), an ROS scavenger, both inhibited EGFR transactivation induced by U-II. In contrast, 4-(3'-chloroanilino)-6,7-dimethoxy-quinazoline (AG1478, an EGFR inhibitor) failed to inhibit intracellular ROS generation induced by U-II. Src homology 2-containing tyrosine phosphatase (SHP-2), but not protein tyrosine phosphatase 1B (PTP 1B), was shown to be associated with EGFR during U-II treatment by EGFR coimmunoprecipitation. ROS have been reported to transiently oxidize the catalytic cysteine of phosphotyrosine phosphatases, subsequently inhibiting their activity. We examined the effect of U-II on SHP-2 and PTP 1B in cardiomyocytes using a modified malachite green phosphatase assay. SHP-2, but not PTP 1B, was transiently oxidized during U-II treatment, which could be repressed by NAC treatment. In SHP-2 knockdown cells, U-II-induced phosphorylation of EGFR and myocyte hypertrophy were dramatically elevated, and these effects were not influenced by NAC. Our data suggest that U-II-mediated ROS generation can transiently inhibit SHP-2 activity, thereby facilitating EGFR transactivation and hypertrophic signal transduction in rat cardiomyocytes.


Sustained Effects on Lung Function in Community Members Following Exposure to Hazardous PM2.5 Levels from Wildfire Smoke.
Extreme wildfire events are becoming more common and while the immediate risks of particulate exposures to susceptible populations (i.e., elderly, asthmatics) are appreciated, the long-term health effects are not known. In 2017, the Seeley Lake (SL), MT area experienced unprecedented levels of wildfire smoke from July 31 to September 18, with a daily average of 220.9 μg/m3. The aim of this study was to conduct health assessments in the community and evaluate potential adverse health effects. The study resulted in the recruitment of a cohort (n = 95, average age: 63 years), for a rapid response screening activity following the wildland fire event, and two follow-up visits in 2018 and 2019. Analysis of spirometry data found a significant decrease in lung function (FEV1/FVC ratio: forced expiratory volume in first second/forced vital capacity) and a more than doubling of participants that fell below the lower limit of normal (10.2% in 2017 to 45.9% in 2018) one year following the wildfire event, and remained decreased two years (33.9%) post exposure. In addition, observed FEV1 was significantly lower than predicted values. These findings suggest that wildfire smoke can have long-lasting effects on human health. As wildfires continue to increase both here and globally, understanding the health implications is vital to understanding the respiratory impacts of these events as well as developing public health strategies to mitigate the effects.


The potential contribution of cardiac replacement to the control of cardiovascular diseases. A population-based estimate.
The potential number of individuals who might benefit from a cardiac replacement procedure (either cardiac transplantation or insertion of a total artificial heart) was retrospectively estimated from medical records for residents of Olmsted County, Minnesota, who had died during a 5-year period. Residents were divided into two age groups: those younger than 15 years (pediatric) and those 15 to 69 years (adult). During the 5-year period of observation, cardiac disease led to death in 17 of the 8342 live births in Olmsted County. Cardiac disease also caused the deaths of 248 adults meeting the age criteria. Five children and 35 adults met all criteria for cardiac replacement. Extrapolation to the total population of the United States suggests that 2167 children (a 95% confidence interval of 361 to 3972) and 16,500 adults (a 95% confidence interval of 11,456 to 22,959) per year could potentially benefit from cardiac replacement.


Reactivity of heteropolymolybdates and heteropolytungstates in the cationic polymerization of styrene.
The two heteropolyacids H(3)PW(12)O(40) and H(3)PMo(12)O(40), and their homologous salts (NH(4))(3)PW(12)O(40), and (NH(4))(3)PMo(12)O(40) were prepared and tested in the cationic polymerization of styrene. The results showed that the heteropolytungstates were more reactive than the heteropolymolybdates. It has been found that the yield and the viscosity average molecular weight (M(v)) of polystyrene are directly proportional to the acidity strength of the heteropolyanions (H(3)PW(12)O(40) > H(3)PMo(12)O(40) > (NH(4))(3)PW(12)O(40) > (NH(4))(3)PMo(12)O(40)). The highest yield (68.0%) and M(v) (7,930) were obtained by using H(3)PW(12)O(40). In addition, H(3)PW(12)O(40) polymerized the styrene under mild conditions and was recyclable, and could behave as a truly heterogeneous catalyst.


Electron-beam induced terahertz radiation from graded metallic grating.
We have numerically analyzed, based on a simplified particle-in-cell finite-difference time-domain (PIC-FDTD) method, an electron-beam (e-beam) induced terahertz (THz) radiation from metallic grating structures with graded depths (graded grating). Upon exciting with e-beam, directional THz radiations with wide-band spectrum containing several sharp peaks are obtained only from the one of the edge of the grating, which cannot be expected from the conventional theory of Smith-Purcell radiation. It was clarified that each modes originate from different locations on the graded grating reflecting different dispersion characteristics of spoof surface plasmon polariton (spoof SPP) at each locations, and they can propagate toward only the shallower groove as a surface wave due to the cutoff at each locations, and all of these modes eventually emitted from the one of the edge of the graded grating. These directional radiations can be directed toward either backward or forward by making the groove depth deeper or shallower. The lowest and the highest frequency of the radiation can be chosen by appropriately designing the deepest and the shallowest groove depths, respectively. These unique radiations cannot be obtained from the uniformly grooved grating. Our findings may open the way for a development of novel THz radiation source based on the spoof SPP on the wide variety of metallic grating structures or metasurfaces.


Relamorelin Relieves Constipation and Accelerates Colonic Transit in a Phase 2, Placebo-Controlled, Randomized Trial.
Ghrelin receptors are located in the colon. Relamorelin is a pentapeptide selective agonist of ghrelin receptor 1a with gastric effects, but its effects in the colon are not known. We aimed to evaluate the effects of relamorelin on bowel movements (BMs) and gastrointestinal and colonic transit (CT) in patients with chronic constipation. We performed a study of 48 female patients with chronic constipation who fulfilled the Rome III criteria and had 4 or fewer spontaneous BMs (SBMs)/wk. In a randomized (1:1), double-blind, parallel-group, placebo-controlled trial, the effects of relamorelin (100 μg/d, given subcutaneously) were tested during 14 days after a 14-day baseline, single-blind phase in which patients were given placebo at 2 Mayo Clinic sites. The participants' mean age was 40.6 ± 1.5 y, with a mean body mass index of 25.7 ± 0.6 kg/m(2), with 1.7 ± 0.1 SBM/wk, and a mean stool consistency of 1.2 ± 0.1 on the Bristol scale during this baseline period. The effect of treatment on transit was measured in 24 participants with colonic transit of less than 2.4 (geometric center at 24 h) during the baseline period. Gastric emptying, small-bowel transit, and CT were measured during the last 2 days that patients received relamorelin or placebo. Bowel function was determined from daily diaries kept by patients from days 1 through 28. Study end points were time to first BM, SBMs/wk, complete SBMs/wk, stool form, and ease of stool passage. Effects of relamorelin were assessed by analysis of covariance. Compared with placebo, relamorelin accelerated gastric emptying half-time (P = .027), small-bowel transit (P = .051), and CT at 32 hours (P = .040) and 48 hours (P = .017). Relamorelin increased the number of SBMs (P < .001) and accelerated the time to first BM after the first dose was given (P = .004) compared with placebo, but did not affect stool form. Adverse events associated with relamorelin included increased appetite, fatigue, and headache. Relamorelin acts in the colon to significantly reduce symptoms of constipation and accelerate CT in patients with chronic constipation, compared with placebo. ClinicalTrial.Gov registration number: NCT01781104.


Neurofeedback and Attention-Deficit/Hyperactivity-Disorder (ADHD) in Children: Rating the Evidence and Proposed Guidelines.
Stimulant medication and behaviour therapy are the most often applied and accepted treatments for Attention-Deficit/Hyperactivity-Disorder (ADHD). Here we explore where the non-pharmacological clinical intervention known as neurofeedback (NFB), fits on the continuum of empirically supported treatments, using standard protocols. In this quantitative review we utilized an updated and stricter version of the APA guidelines for rating 'well-established' treatments and focused on efficacy and effectiveness using effect-sizes (ES) and remission, with a focus on long-term effects. Efficacy and effectiveness are compared to medication and behaviour therapy using benchmark studies. Only recent systematic reviews and meta-analyses as well as multi-centre randomized controlled trials (RCT's) will be included. Two meta-analyses confirmed significant efficacy of standard neurofeedback protocols for parent and teacher rated symptoms with a medium effect size, and sustained effects after 6-12 months. Four multicenter RCT's demonstrated significant superiority to semi-active control groups, with medium-large effect sizes end of treatment or follow-up and remission rates of 32-47%. Effectiveness in open-label studies was confirmed, no signs of publication bias were found and no significant neurofeedback-specific side effects have been reported. Standard neurofeedback protocols in the treatment of ADHD can be concluded to be a well-established treatment with medium to large effect sizes and 32-47% remission rates and sustained effects as assessed after 6-12 months.


Predicting the Valence of a Scene from Observers' Eye Movements.
Multimedia analysis benefits from understanding the emotional content of a scene in a variety of tasks such as video genre classification and content-based image retrieval. Recently, there has been an increasing interest in applying human bio-signals, particularly eye movements, to recognize the emotional gist of a scene such as its valence. In order to determine the emotional category of images using eye movements, the existing methods often learn a classifier using several features that are extracted from eye movements. Although it has been shown that eye movement is potentially useful for recognition of scene valence, the contribution of each feature is not well-studied. To address the issue, we study the contribution of features extracted from eye movements in the classification of images into pleasant, neutral, and unpleasant categories. We assess ten features and their fusion. The features are histogram of saccade orientation, histogram of saccade slope, histogram of saccade length, histogram of saccade duration, histogram of saccade velocity, histogram of fixation duration, fixation histogram, top-ten salient coordinates, and saliency map. We utilize machine learning approach to analyze the performance of features by learning a support vector machine and exploiting various feature fusion schemes. The experiments reveal that 'saliency map', 'fixation histogram', 'histogram of fixation duration', and 'histogram of saccade slope' are the most contributing features. The selected features signify the influence of fixation information and angular behavior of eye movements in the recognition of the valence of images.


Assessment of Mandibular Surface Area Changes in Bruxers Versus Controls on Panoramic Radiographic Images: A Case Control Study.
Bruxism is the commonest of the many parafunctional activities of the masticatory system. Opinions on the causes of bruxism were numerous and widely varying. It can occur during sleep as well as wakefulness. Bruxism was for long considered a major cause of tooth wear. Other effects of bruxism may include tooth movement and tooth mobility, as well as changes in oral soft tissues and jaw bone. Since the exact etiology and manifestations are unclear, it was difficult to diagnose Bruxism. In this study, we evaluated the area change as measured from digital panoramic radiographs that can occur in the lower jaw bone in those with Bruxism and compared the results with non-bruxers. To determine the surface area changes of the mandible, condylar and coronoid processes in Bruxers from Panoramic radiographs and to compare and contrast the changes with age and gender matched controls. The study was conducted in the department of Oral Medicine and Radiology. The total sample size was 40. The sample was divided into two groups, Bruxers and non-bruxers with 20 subjects in each group. Healthy volunteers aged between 20- 30 years diagnosed with Bruxism and Healthy volunteers aged between 20- 30 years diagnosed without Bruxism were included in group II (Non-Bruxers). Bruxchecker was made use of in confirming the Bruxism in Group I. The Panoramic radiograph was used as the imaging modality for the study. The measurements were made with the help of software, Image J. All the measurements were tabulated and statistical analysis was made using ANOVA (Post hoc) followed by Dunnett's test and unpaired t test. A comparison of the mandibular surface area as a whole and also condylar and coronoid processes individually were carried out. Significant results were obtained in case of condylar and coronoid processes between the two groups. The surface area of condylar process of Group I was found to be lower than that of Group II. The surface area of the right coronoid process of group I was found to be less when compared to that of group II but the values of the left coronoid process of group I was found to be more when compared with group II. The surface area of the mandible showed no significant difference between the groups. There was significant difference between the genders in case of mandible, condyle and coronoid. The surface area of mandible and condylar process was found to be lower in female when compared to male. The surface area of coronoid process was found to be more in case of females when compared to that of males in Group I.The results of our study show that while the overall surface area of bruxers remain unaffected when compared to controls, the condylar and coronoid process show significant change. The hitherto belief that the primary brunt of bruxism is borne by the masseter would require a revisit since alteration in tonicity of the masseter would reflect in surface area change of the mandible as a whole. An increase in the surface area of the coronoid process in bruxers was observed in our study which could be attributed to altered activity of the temporalis, a muscle largely responsible for the posture of the mandible. This could imply that bruxers show alteration in temporalis activity which would explain several clinical manifestations such as headache, neck pain, shoulder pain and altered posture and so on which we have observed in the clinical practice of neuromuscular dentistry. Further studies examining the activity of the temporalis and masseter would further corroborate our findings and form the basis for future research in this arena. This original research was carried out to assess the surface area changes in mandible and condylar and coronoid processes of Bruxers and non-bruxers. The results showed significant changes in the surface area of condylar and coronoid process in Bruxers when compared to the controls. This is an area of study with paucity of available literature. This study would be a stepping stone for future studies in this arena.


Renshaw cells and Ia inhibitory interneurons are generated at different times from p1 progenitors and differentiate shortly after exiting the cell cycle.
Spinal interneurons modulating motor output are highly diverse but surprisingly arise from just a few embryonic subgroups. The principles governing their development, diversification, and integration into spinal circuits are unknown. This study focuses on the differentiation of adult Renshaw cells (RCs) and Ia inhibitory interneurons (IaINs), two subclasses that respectively mediate recurrent and reciprocal inhibition of motoneurons from embryonic V1 interneurons (V1-INs). V1-INs originate from p1 progenitors and, after they become postmitotic, specifically express the transcription factor engrailed-1, a property that permits genetic labeling of V1 lineages from embryo to adult. RCs and IaINs are V1 derived, but differ in morphology, location, calcium-binding protein expression, synaptic connectivity, and function. These differences are already present in neonates, and in this study we show that their differentiation starts in the early embryo. Using 5'-bromodeoxyuridine birth dating we established that mouse V1-INs can be divided into early (E9.5-E10.5) and late (E11.5-E12.5) groups generated from the p1 domain (where E is embryonic day). The early group upregulates calbindin expression soon after becoming postmitotic and includes RCs, which express the transcription factor MafB during early differentiation and maintain calbindin expression throughout life. The late group includes IaINs, are calbindin-negative, and express FoxP2 at the start of differentiation. Moreover, developing RCs follow a characteristic circumferential migratory route that places them in unique relationship with motor axons with whom they later synaptically interact. We conclude that the fate of these V1-IN subclasses is determined before synaptogenesis and circuit formation by a process that includes differences in neurogenesis time, transcription factor expression, and migratory pathways.


CTLA-4 gene polymorphisms predispose to autoimmune endocrinopathies but not to celiac disease.
The aim of the study was to determine the association of two CTLA-4 gene polymorphisms (CT60, +49 A/G) with Hashimoto thyroiditis (HT), type 1 diabetes mellitus (T1DM) and celiac disease (CD) as well as with the occurrence of multi-organ involvement by autoimmunity in children. Genotyping was done by RFLP analysis in Slovak children with HT (n=63) and CD (n=120) and both Slovak and Slovene children with T1DM (n=320) and healthy controls (n=231). We found a significant association of the G allele of the CT60 polymorphism with HT (p<0,0005) in the Slovak population and T1DM in both Slovak (p<0.01) and Slovene populations (p<0.005). The G allele of the +49A/G polymorphism was significantly, though less strongly, associated with T1DM (p<0.05) and HT (p<0.05). Distribution of genotypes of CTLA-4 gene polymorphisms in CD patients did not differ significantly from controls. None of the polymorphisms was associated with multi-organ involvement by autoimmunity. The G allele of both examined CTLA-4 gene polymorphisms predisposes to HT and T1DM, but not to CD. No association with multi-organ involvement was found. The GG genotype of the CT60 polymorphism may identify CD patients at an increased risk for concomitant T1DM and HT. Further studies to assess the predictive value of CTLA-4 polymorphisms for the co-occurrence of HT and T1DM in CD patients are needed.


Host-parasite relationship of Leishmania mexicana mexicana and Lutzomyia abonnenci (Diptera: Psychodidae).
The life cycle of Leishmania mexicana mexicana in the gut of the sand fly, Lutzomyia abonnenci, was studied by light and electron microscopy. Development was suprapylarian with initial establishment of parasites in the bloodmeal (posterior midgut), and anterior migration of parasites to the cardia/stomodeal valve region beginning at 2.5 days post-infection. Flagellates were first observed in the esophagus at 3.5 days, in the posterior armature region of the pharynx at 5 days, and in the anterior pharynx at 7 days; but they were not detected in the cibarium or proboscis. Infection of the pylorus region of the hindgut and of the Malpighian tubules was also commonly observed. Three different morphological forms of L. m. mexicana developed in the gut: nectomonad promastigotes, short promastigotes, and paramastigotes. Nectomonads occurred primarily in the abdominal midgut after bloodmeal digestion, where they were oriented in longitudinal masses in the lumen, or interdigitated with epithelial microvilli via the flagellum. Short promastigotes found in the cardia/stomodeal valve region are described for the first time. These forms were smaller than nectomonads, showed an amplification of the kinetoplast, apposition of kinetoplast and nucleus, and were embedded in a gel-like matrix. To maintain position in the cardia, parasites commonly inserted the flagellum deep into microvilli or cytoplasm of the epithelium; adherence to the cuticular intima of the stomodeal valve was by flagellar modification and formation of hemidesmosome plaques. Paramastigotes occurred in the esophagus, were sometimes degenerated in appearance, and were attached via flagellar hemidesmosomes. Paramastigotes observed in the lumen of the pharynx were commonly degenerated and were not attached to the intima. L. m. mexicana was able to colonize the various gut habitats of Lu. abonnenci by a number of adaptations; this sand fly appears to be a suitable biological host for the parasite.


Poseidonibacter parvus sp. nov., isolated from a squid.
A Gram-stain-negative, aerobic, short rod-shaped, motile, brownish-coloured bacterium, termed strain LPB0137T, was isolated from a squid. Its cells could grow weakly on marine agar 2216 with 0.04 % 2,3,5-triphenyl tetrazolium chloride (TTC). Each cell of strain LPB0137T has a circular chromosome with a length of 2.87 Mb and 27.7 mol% DNA G+C content. The genome includes 2698 protein-coding genes and six rRNA operons. In 16S rRNA gene sequence trees, strain LPB0137T formed a robust monophyletic clade with Poseidonibacter antarcticus SM1702T with a sequence similarity of 98.3 %. However, the average nucleotide identity and in silico DNA-DNA hybridization values between the two type strains were low (83.9 and 28.1 %, respectively). The overall phenotypic and genomic features of strain LPB0137T supported its assignment to the genus Poseidonibacter. However, the relatively low gene and genome sequence similarity between this strain and other type strains of the genus Poseidonibacter and several enzymatic characteristics indicated the taxonomic novelty of the isolated strain as a new member of the genus Poseidonibacter. Therefore, based on the phylogenetic and phenotypic characteristics of LPB0137T, we proposed a novel species of the genus Poseidonibacter for it, with the name Poseidonibacter parvus sp. nov. The type strain of this new species is thus LPB0137T (=KACC 18888T=JCM 31548T).


Phenotype and genotype in Nicolaides-Baraitser syndrome.
Nicolaides-Baraitser syndrome (NCBRS) is an intellectual disability (ID)/multiple congenital anomalies syndrome caused by non-truncating mutations in the ATPase region of SMARCA2, which codes for one of the two alternative catalytic subunits of the BAF chromatin remodeling complex. We analyzed 61 molecularly confirmed cases, including all previously reported patients (n = 47) and 14 additional unpublished individuals. NCBRS is clinically and genetically homogeneous. The cardinal features (ID, short stature, microcephaly, typical face, sparse hair, brachydactyly, prominent interphalangeal joints, behavioral problems and seizures), are almost universally present. There is variability however, as ID can range from severe to mild, and sparse hair may be present only in certain age groups. There may be a correlation between the severity of the ID and presence of seizures, absent speech, short stature and microcephaly. SMARCA2 mutations causing NCBRS are likely to act through a dominant-negative effect. There may be some genotype-phenotype correlations (mutations at domain VI with severe ID and seizures; mutations affecting residues Pro883, Leu946, and Ala1201 with mild phenotypes) but numbers are still too small to draw definitive conclusions.


Selective serotonin reuptake inhibitors modify the effect of beta-blockers on long-term survival of patients with end-stage heart failure and major depression.
Major depression (MD) is a key feature in heart failure (HF), and it is unclear whether common antidepressive medications interact with cardiovascular drugs used for the treatment of patients with MD and HF, affecting their efficacy. We examined the impact of MD on long-term survival of patients with end-stage severe HF. We also evaluated the interaction between antidepressive medication and beta-blockers on the clinical outcome of these patients. The study population consisted of 250 patients with end-stage severe HF. Sixty-one percent of these patients suffered MD and were receiving selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants (TCA). All patients were followed prospectively for 18 months. The primary end point was cardiovascular death. At baseline, patients with severe MD had higher serum interleukin 6 (P < .05) and soluble vascular cell adhesion molecule (P < .01). During the follow-up, 167 cardiovascular deaths were reported, and MD was 1 of the major predictors of cardiovascular death (P = .031), whereas treatment with angiotensin receptor inhibitors and statins were also important negative predictors of mortality (P = .036 and P = .039, respectively). Although beta-blockers had a borderline nonsignificant effect on cardiovascular mortality in the overall population, they had a striking beneficial effect among those patients with major depression receiving SSRIs (P = .006), whereas they had a negative effect on mortality in those patients receiving SNRIs/TCAs (P = .025). MD is an independent predictor of cardiovascular death in patients with end-stage HF. beta-blockers are associated with lower cardiovascular mortality in patients with end-stage HF and depression only when they are combined with SSRIs.


Neuroendocrine carcinoma of the head and neck: a 20-year case series.
Neuroendocrine carcinoma (NEC) can be an aggressive disease with locoregional and distant metastasis. We present this article (1) to highlight the typical presentation of NEC in head and neck primary sites such as the parotid gland, paranasal sinuses, and supraglottis and (2) to discuss the prognosis of these tumors based on their histologic subtype and stage. We base our comments on the findings of our retrospective review of the cases of 16 adults-10 men and 6 women, aged 43 to 88 years (mean: 65.8)-who had been diagnosed with pathologically confirmed NEC of the head and neck. Analysis of subtypes revealed that 11 of these patients (68.8%) had presented with poorly differentiated NEC, 4 (25.0%) with moderately differentiated NEC, and 1 (6.3%) with well-differentiated NEC. The most common primary sites were the salivary glands (n = 5; 31.3%), paranasal sinuses (n = 4, 25.0%), and larynx (n = 4). There was no statistically significant difference in survival at 24 months between the patients with moderately differentiated NEC and those with poorly differentiated NEC (37.5 vs. 35.4%; p = 0.86); at the end of the study period, the patient with well-differentiated NEC was still living, 129 months after diagnosis. Taken together, patients with stage I, II, and III disease had a combined survival of 77.8% at 12 months, which was significantly higher (p = 0.023) than the 57.1% survival at 12 months for patients with stage IV disease.


Plants, endosymbionts and parasites: Abscisic acid and calcium signaling.
It was recently discovered that the protozoan parasite, Toxoplasma gondii produces and uses the plant hormone, abscisic acid (ABA), for communication. Following intracellular replication, ABA production influences the timing of parasite egress from the host cell. This density-dependent signal may serve to coordinate exit from the host cell in a synchronous manner by triggering calcium-dependent activation of motility. In the absence of ABA production, parasites undergo differentiation to the semidormant, tissue cyst. The pathway for ABA production in T. gondii may be derived from a relict endosymbiont, acquired by ingestion of a red algal cell. Although the parasite has lost the capacity for photosynthesis, the plant-like nature of this signaling pathway may be exploited to develop new drugs. In support of this idea, an inhibitor of ABA biosynthesis protected mice against lethal infection with T. gondii. Here, we compare the role of ABA in parasites to its activities in plants, where it is know to control development and stress responses.


Neutrophil gelatinase-associated lipocalin, a sensitive urinary biomarker of acute kidney injury in dogs receiving gentamicin.
A sensitive urinary biomarker for acute kidney injury (AKI) was investigated in beagle dogs with nephrotoxicity induced by gentamicin. Gentamicin sulphate at 25 or 50 mg/kg was injected (s.c.) for 9 days, and conventional urinalysis, ELISA assay of neutrophil gelatinase-associated lipocal (NGAL) in urine, blood chemistry, and pathological examinations were performed. The dog given gentamicin at 25 mg/kg only showed slight deposition of lysosomal granules in the proximal tubular epithelium of the kidneys without any other significant changes even though urinary NGAL was elevated on Day 10 (day of necropsy). In the dog receiving gentamicin at 50 mg/kg, increases in urinary NGAL were observed on Days 3 and 5, and absence of urination, marked increases in serum urea nitrogen and creatinine, enlargement and discoloration of the kidneys with marked necrosis, and swelling of proximal epithelium were observed. In conclusion, urinary NGAL is considered to be a candidate as a sensitive predictable biomarker of AKI in the gentamicin-induced nephrotoxicity model in dogs.


Increased cancer awareness among British adolescents after a school-based educational intervention: a controlled before-and-after study with 6-month follow-up.
There is a lack of evidence around the effectiveness of school-based interventions designed to raise adolescents' cancer awareness. To address this deficit this study assessed the impact of an intervention delivered in the United Kingdom by Teenage Cancer Trust on: recall (open question) and recognition (closed question) of cancer warning signs; knowledge of common childhood, teenage, male and female cancers; awareness of the relationship between cancer and age; anticipated medical help-seeking delay; perceived barriers to seeking medical advice about cancer; and examined variation of intervention effect by gender and whether adolescents reported that they knew someone with cancer. The Cancer Awareness Measure (CAM) was completed by 422 adolescents (male: 221, 52.4%) aged 11-17 years old (mean age=13.8, standard deviation=1.26) two weeks before and two weeks after the intervention in three schools, and on two occasions four weeks apart in a fourth (control) school. Intervention schools were followed-up 6-months post-intervention. Recognition of nine common cancer warning signs significantly increased two weeks after the intervention (4.6 to 6.8, p<0.001) and was maintained at 6-month follow-up (6.2, p<0.001). Endorsement of emotional barriers to help-seeking 'not confident to talk about symptoms' (53% to 45%, p=0.021) and 'worried about what the doctor might find' (70% to 63%, p=0.021) significantly decreased two weeks after the intervention but changes were not maintained at 6-months. The intervention had a greater impact on females and those who knew someone with cancer. The intervention is an effective way to raise adolescents' cancer awareness, especially of cancer symptoms. Further development and evaluation is required to maximise intervention impact, particularly on barriers to help-seeking behaviour.


Inhibitory effect of t-butyl hydroperoxide on mitochondrial oxidative phosphorylation in isolated rat hepatocytes.
Using high-resolution oxygraphy, we tested the changes of various parameters characterizing the mitochondrial energy provision system that were induced by peroxidative damage. In the presence of succinate as respiratory substrate, 3 mM t-butyl hydroperoxide increased respiration in the absence of ADP, which indicated partial uncoupling of oxidative phosphorylation. Low activity of coupled respiration was still maintained as indicated by the ADP-activated and oligomycin-inhibited respiration. However, during the incubation the phosphorylative capacity decreased as indicated by the continuous decrease of the mitochondrial membrane potential. Under these experimental conditions the maximum capacity of the succinate oxidase system was inhibited by 50% in comparison with values obtained in the absence of t-butyl hydroperoxide. Our data thus indicate that the oxygraphic evaluation of mitochondrial function represents a useful tool for evaluation of changes participating in peroxidative damage of cell energy metabolism.


At three years, patients with acute lymphoblastic leukaemia are still at risk for relapse. Results of the international MRC UKALLXII/ECOG E2993 trial.
Late relapse [>3 years from complete remission (CR)] in acute lymphoblastic leukaemia (ALL), is unusual. Data from the MRC UKALLXII/ECOG E2993 trial are presented to evaluate the incidence and characteristics of late relapse in adult ALL. Of 1,909 patients, 1,752 (92%) achieved CR and among these 757 (43·2%) relapsed; 691 (91·3%) within three years and 66 (8·7%) beyond. Among these 66 patients, median time to relapse was 47 (37-144) months. Relapse beyond three years occurred in 3·8% of all who achieved CR. The cumulative risk of relapse was 40%, 43% and 45% at three, five and ten years respectively. Out of the 1 752 patients who achieved CR, 11·7% underwent autologous and 40·6% allogeneic transplant, while in CR1. Of the autologous patients, 43·2% relapsed early and 3·4% relapsed late. However, among the allogeneic patients, 13·2% relapsed early and only 1·3% late. The five-year overall survival from relapse was 5·8% and 20% in the early and late relapse patients respectively. In conclusion, late relapse in adults with ALL is not uncommon, and is associated with better outcome after relapse compared to early relapse.


Cytochemical differences in bacterial glycocalyx.
To examine new cytochemical aspects of the bacterial adhesion, a strain 41452/01 of the oral commensal Streptococcus sanguis and a wild strain of Staphylococcus aureus were grown with and without sucrose supplementation for 6 days. Osmiumtetraoxyde (OsO4), uranyl acetate (UA), ruthenium red (RR), cupromeronic blue (CB) staining with critical electrolytic concentrations (CECs), and the tannic acid-metal salt technique (TAMST) were applied for electron microscopy. Cytochemically, only RR-positive fimbriae in S. sanguis were visualized. By contrast, some types of fimbriae staining were observed in S. aureus glycocalyx: RR-positive, OsO4-positive, tannophilic and CB-positive with ceasing point at 0.3 M MgCl2. The CB staining with CEC, used for the first time for visualization of glycoproteins of bacterial glycocalyx, also reveals intacellular CB-positive substances-probably the monomeric molecules, that is, subunits forming the fimbriae via extracellular assembly. Thus, glycosylated components of the biofilm matrix can be reliably related to single cells. The visualization of intracellular components by CB with CEC enables clear distinction between S. aureus and other bacteria, which do not produce CB-positive substances. The small quantities of tannophilic substances found in S. aureus makes the use of TAMST for the same purpose difficult. The present work protocol enables, for the first time, a partial cytochemical differentiation of the bacterial glycocalyx.


Suppression by an h current of spontaneous Na+ action potentials in human cone and rod photoreceptors.
The sense of vision in humans is robust, and visual flickering is rarely experienced. To investigate this mechanism, electrophysiological and molecular biological techniques were used on human cone and rod photoreceptors. Voltage-gated currents were recorded using the patch-clamp technique on isolated human cones, and especially their voltage-gated Na+ currents were analyzed in detail. Whether Na+ channel transcripts could be detected in single photoreceptors using RT-PCR was also examined, to test the expression of voltage-gated Na+ channels in cones and/or rods. Under current-clamp conditions, blocking h currents (hyperpolarization-activated cationic currents) with Cs+, Tl+, or ZD7288 hyperpolarized the resting potentials of cones and rods by approximately 10 to 15 mV, and surprisingly generated spontaneous action potentials. The spontaneous spikes were blocked by 1 microM tetrodotoxin, but not by 1 mM Co2+, suggesting that they were Na+ spikes rather than Ca2+ spikes. Under voltage-clamp conditions, application of Cs+ and ZD7288 markedly decreased the steady inward current through the h channel. This is consistent with Cs+-induced hyperpolarization under a current-clamp condition. SCN2 Na+ channel was observed in both cones and rods by single-cell RT-PCR analysis, suggesting that human photoreceptors express the SCN2 Na+ channel. The data confirmed that voltage-gated Na+ channels were expressed not only in human rods but also in cones by electrophysiological and molecular biological experiments. These results suggest that the h current may contribute to preventing visual flickering by inhibiting the generation of spontaneous Na+ spikes in human photoreceptors.


Future Research Directions in Pneumonia. NHLBI Working Group Report.
Pneumonia is a complex pulmonary disease in need of new clinical approaches. Although triggered by a pathogen, pneumonia often results from dysregulations of host defense that likely precede infection. The coordinated activities of immune resistance and tissue resilience then dictate whether and how pneumonia progresses or resolves. Inadequate or inappropriate host responses lead to more severe outcomes such as acute respiratory distress syndrome and to organ dysfunction beyond the lungs and over extended time frames after pathogen clearance, some of which increase the risk for subsequent pneumonia. Improved understanding of such host responses will guide the development of novel approaches for preventing and curing pneumonia and for mitigating the subsequent pulmonary and extrapulmonary complications of pneumonia. The NHLBI assembled a working group of extramural investigators to prioritize avenues of host-directed pneumonia research that should yield novel approaches for interrupting the cycle of unhealthy decline caused by pneumonia. This report summarizes the working group's specific recommendations in the areas of pneumonia susceptibility, host response, and consequences. Overarching goals include the development of more host-focused clinical approaches for preventing and treating pneumonia, the generation of predictive tools (for pneumonia occurrence, severity, and outcome), and the elucidation of mechanisms mediating immune resistance and tissue resilience in the lung. Specific areas of research are highlighted as especially promising for making advances against pneumonia.


How cyanophage S-2L rejects adenine and incorporates 2-aminoadenine to saturate hydrogen bonding in its DNA.
Bacteriophages have long been known to use modified bases in their DNA to prevent cleavage by the host's restriction endonucleases. Among them, cyanophage S-2L is unique because its genome has all its adenines (A) systematically replaced by 2-aminoadenines (Z). Here, we identify a member of the PrimPol family as the sole possible polymerase of S-2L and we find it can incorporate both A and Z in front of a T. Its crystal structure at 1.5 Å resolution confirms that there is no structural element in the active site that could lead to the rejection of A in front of T. To resolve this contradiction, we show that a nearby gene is a triphosphohydolase specific of dATP (DatZ), that leaves intact all other dNTPs, including dZTP. This explains the absence of A in S-2L genome. Crystal structures of DatZ with various ligands, including one at sub-angstrom resolution, allow to describe its mechanism as a typical two-metal-ion mechanism and to set the stage for its engineering.


A novel human CC chemokine PARC that is most homologous to macrophage-inflammatory protein-1 alpha/LD78 alpha and chemotactic for T lymphocytes, but not for monocytes.
By searching the expressed sequence tag (EST) database, we identified partial cDNA sequences encoding a polypeptide with significant sequence identity to the human CC chemokine macrophage-inflammatory protein-1 alpha (MIP-1 alpha)/LD78 alpha. We determined the complete cDNA sequence that contained a reading frame of 89 amino acids with 61% identity to human MIP-1 alpha/LD78 alpha. The mRNA was expressed constitutively at high levels in human lung and at low levels in some lymphoid tissues. Furthermore, the mRNA was strongly induced in several human cell lines, including monocytic U937 cells, by PMA. From these results, we designated this novel CC chemokine as PARC from pulmonary and activation-regulated chemokine. In situ hybridization analyses showed that alveolar macrophages, follicular dendritic cells in the germinal centers of regional lymph nodes, and peripheral blood monocytes stimulated with LPS express PARC mRNA. Using the human CC chemokine yeast artificial chromosome contig that we constructed recently, we mapped the PARC gene (SCYA18) within one of the two subregions of the CC chemokine gene cluster at chromosome 17q11.2. To investigate its biologic activity, the PARC protein was expressed in insect cells. PARC was chemotactic for both activated (CD3+) T cells and nonactivated (CD14-) lymphocytes, but not for monocytes or granulocytes. Binding analysis using PARC fused with alkaline phosphatase-(His)6 showed the presence of a single class of receptors for PARC on lymphocytes with a Kd of 1.9 nM and 590 sites/cell. Thus, PARC is a novel CC chemokine with a close phylogenic relationship with MIP-1 alpha/LD78 alpha, but with a highly selective activity on lymphocytes.


The effect of genomic inversions on estimation of population genetic parameters from SNP data.
In recent years it has emerged that structural variants have a substantial impact on genomic variation. Inversion polymorphisms represent a significant class of structural variant, and despite the challenges in their detection, data on inversions in the human genome are increasing rapidly. Statistical methods for inferring parameters such as the recombination rate and the selection coefficient have generally been developed without accounting for the presence of inversions. Here we exploit new software for simulating inversions in population genetic data, invertFREGENE, to assess the potential impact of inversions on such methods. Using data simulated by invertFREGENE, as well as real data from several sources, we test whether large inversions have a disruptive effect on widely applied population genetics methods for inferring recombination rates, for detecting selection, and for controlling for population structure in genome-wide association studies (GWAS). We find that recombination rates estimated by LDhat are biased downward at inversion loci relative to the true contemporary recombination rates at the loci but that recombination hotspots are not falsely inferred at inversion breakpoints as may have been expected. We find that the integrated haplotype score (iHS) method for detecting selection appears robust to the presence of inversions. Finally, we observe a strong bias in the genome-wide results of principal components analysis (PCA), used to control for population structure in GWAS, in the presence of even a single large inversion, confirming the necessity to thin SNPs by linkage disequilibrium at large physical distances to obtain unbiased results.


Laboratory selection at different temperatures modifies heat-shock transcription factor (HSF) activation in Drosophila melanogaster.
The magnitude and time course of activation of the heat-shock transcription factor (HSF) differ among Drosophila melanogaster lines evolving at 18 degrees C, 25 degrees C or 28 degrees C for more than 20 years. At lower heat-shock temperatures (27-35 degrees C), flies from the 18 degrees C population had higher levels of activated HSF (as detected by an electrophoretic mobility shift assay) than those reared at 25 degrees C and 28 degrees C. At higher temperatures (36 and 37 degrees C), however, the 28 degrees C flies had the highest levels of HSF. These differences persisted after one generation of acclimation at 25 degrees C, suggesting that phenotypic plasticity was limited. In addition, larvae from the 28 degrees C lines activated HSF less rapidly after a 35 degrees C heat shock than those from the 18 degrees C and 25 degrees C populations. These results are similar but not identical to previously reported differences in expression of Hsp70 (the major heat-inducible stress protein in Drosophila melanogaster) among the experimental lines. We conclude that HSF activation evolves rapidly during laboratory culture at diverse temperatures and could play an important role in the evolution of the heat-shock response.


The role of the renin--angiotensin--aldosterone system in cardiovascular homeostasis in normal man.
1. To examine the role of angiotensin II in the maintenance of blood pressure and control of aldosterone secretion, eight normal human subjects were studied on a tilt table in sodium-replete and sodium-depleted states, before and after the administration of an angiotensin converting-enzyme inhibitor (CEI). 2. Administration of CEI was followed by a marked fall in blood pressure on tilting in sodium-depleted, but not in sodium-replete, subjects. CEI administration also resulted in a rise in plasma renin activity in the supine position, in the absence of haemodynamic change. The rise in plasma aldosterone observed both in response to tilting and sodium depletion did not occur after CEI, even though plasma renin activities were higher. 3. These results indicate that: (a) angiotensin II is essential for blood pressure control in the sodium-depleted individual; (b) angiotensin II exerts direct feedback control on renin secretion; (c) angiotensin II is the primary stimulus to aldosterone secretion in response to both sodium depletion and posture.


Access to post-discharge inpatient care after lower limb trauma.
Most hospitals in the United States are required to provide emergency care to all patients, regardless of insurance status. However, uninsured patients might be unable to access non-acute services, such as post-discharge inpatient care (PDIC). This could result in prolonged acute hospitalization. We tested the hypothesis that insurance status would be independently associated with both PDIC and length of stay (LOS). An observational study was undertaken using the California State Inpatient Database (2007-2011), which captures 98% of patients admitted to hospital in California. All patients with a diagnosis of orthopedic lower limb trauma were identified using International Classification of Diseases, 9th Revision, Clinical Modification codes 820-828. Multivariable logistic and generalized linear regression models were used to adjust odds of PDIC and LOS for patient and hospital characteristics. There were 278,573 patients with orthopedic lower limb injuries, 160,828 (57.7%) of which received PDIC. Uninsured patients had lower odds of PDIC (adjusted odds ratio 0.20, 95% confidence interval 0.17-0.24) and significantly longer hospital LOS (predicted mean difference 1.06 [95% confidence interval 0.78-1.34] d) than those with private insurance. Lack of health insurance is associated with reduced access to PDIC and prolonged hospital LOS. This potential barrier to hospital discharge could reduce the number of trauma beds available for acutely injured patients.


Giant Kohn anomaly and the phase transition in charge density wave ZrTe3.
A strong Kohn anomaly in ZrTe3 is identified in the mostly transverse acoustic phonon branch along the modulation vector q_{P} with polarization along the a;{*} direction. This soft mode freezes to zero frequency at the transition temperature T_{P}, and the temperature dependence of the frequency is strongly affected by fluctuation effects. Diffuse x-ray scattering of the incommensurate superstructure shows a power-law scaling of the intensity and the correlation length that is compatible with an order parameter of dimension n=2.


How Stress Gets Under the Skin: Early Life Adversity and Glucocorticoid Receptor Epigenetic Regulation.
Early life adversity is associated with both persistent disruptions in the hypothalamic-pituitary-adrenal (HPA) axis and psychiatric symptoms. Glucocorticoid receptors (GRs), which are encoded by the NR3C1 gene, bind to cortisol and other glucocorticoids to create a negative feedback loop within the HPA axis to regulate the body's neuroendocrine response to stress. Excess methylation of a promoter sequence within NR3C1 that attenuates GR expression, however, has been associated with both early life adversity and psychopathology. As critical regulators within the HPA axis, GRs and their epigenetic regulation may mediate the link between early life adversity and the onset of psychopathology. The present review discusses this work as one mechanism by which stress may get under the skin to disrupt HPA functioning at an epigenetic level and create long-lasting vulnerabilities in the stress regulatory system that subsequently predispose individuals to psychopathology. Spanning prenatal influences to critical periods of early life and adolescence, we detail the impact that early adversity has on GR expression, physiological responses to stress, and their implications for long-term stress management. We next propose a dual transmission hypothesis regarding both genomic and non-genomic mechanisms by which chronic and acute stress propagate through numerous generations. Lastly, we outline several directions for future research, including potential reversibility of methylation patterns and its functional implications, variation in behavior determined solely by NR3C1, and consensus on which specific promoter regions should be studied.


Phospholipide turnover in microsomal membranes of the pancreas during enzyme secretion.
After incubation of pigeon pancreas slices with P(32) and isolation of various fractions by differential centrifugation the deoxycholate extract of the microsome fraction was found to account for over half of the phospholipide P and over half of the P(32) incorporated into the phospholipides. The remaining phospholipide P and P(32) were fairly evenly distributed in the nuclei, zymogen granules, mitochondria, microsomal ribonucleoprotein particles, and the soluble fraction. When enzyme secretion was stimulated with acetylcholine about two-thirds of the increment in radioactivity in the total phospholipides was found in deoxycholate soluble components of the microsome fraction. The remainder of the increment was distributed in the other fractions. This indicates that the cellular component in which the increase in phospholipide turnover occurs on stimulation of secretion is a membranous structure. Evidence is presented which indicates that the increment in radioactivity in the non-microsomal fractions on stimulation of secretion is due to contamination of these fractions with fragments of the stimulated membranous structure. The distribution of P(32) radioactivity in each of the chromatographically separated phospholipides in the various fractions from unstimulated tissue paralleled the distribution of radioactivity in the total phospholipide fraction, indicating that individual phospholipides are not concentrated in different fractions but are associated together in the membranous structures of the microsome fraction. The major proportion of the stimulation of the turnover of the individual phospholipides also occurred in the microsome fraction. The distribution of radioactivity from glycerol-1-C(14) in the total phospholipides and in the individual phospholipides in the various fractions was similar to the distribution of P(32). In the microsome fraction acetylcholine stimulated the incorporation of glycerol-1-C(14) in each phospholipide which showed a stimulation of P(32) incorporation. The significance of the turnover of phosphatides in microsomal membranes in relation to the mechanism of secretion is discussed.


Chagas disease in the State of Pernambuco, Brazil: analysis of admissions and mortality time series.
A time series study of admissions, deaths and acute cases was conducted in order to evaluate the context of Chagas disease in Pernambuco. Data reported to the Information Technology Department of the Brazilian National Health Service between 1980 and 2008 was collected for regions and Federal Units of Brazil; and microregions and municipalities of Pernambuco. Rates (per 100,000 inhabitants) of hospitalization, mortality and acute cases were calculated using a national hospital database (SIH), a national mortality database (SIM) and the national Information System for Notifiable Diseases (SINAN), respectively. The national average for Chagas disease admissions was 0.99 from 1995 to 2008. Pernambuco obtained a mean of 0.39 in the same period, with the highest rates being concentrated in the interior of the state. The state obtained a mean mortality rate of 1.56 between 1980 and 2007, which was lower than the national average (3.66). The mortality rate has tended to decline nationally, while it has remained relatively unchanged in Pernambuco. Interpolating national rates of admissions and deaths, mortality rates were higher than hospitalization rates between 1995 and 2007. The same occurred in Pernambuco, except for 2003. Between 2001 and 2006, rates for acute cases were 0.56 and 0.21 for Brazil and Pernambuco, respectively. Although a decrease in Chagas mortality has occurred in Brazil, the disease remains a serious public health problem, especially in the Northeast region. It is thus essential that medical care, prevention and control regarding Chagas disease be maintained and improved.


Selective induction of mucin-3 by hypoxia in intestinal epithelia.
Epithelial cells line mucosal surfaces (e.g., lung, intestine) and critically function as a semipermeable barrier to the outside world. Mucosal organs are highly vascular with extensive metabolic demands, and for this reason, are particularly susceptible to diminished blood flow and resultant tissue hypoxia. Here, we pursue the hypothesis that intestinal barrier function is regulated in a protective manner by hypoxia responsive genes. We demonstrate by PCR confirmation of microarray data and by avidin blotting of immunoprecipitated human Mucin 3 (MUC3), that surface MUC3 expression is induced in T84 intestinal epithelial cells following exposure to hypoxia. MUC3 RNA is minimally detectable while surface protein expression is absent under baseline normoxic conditions. There is a robust induction in both the mRNA (first evident by 8 h) and protein expression, first observed and maximally expressed following 24 h hypoxia. This is followed by a subsequent decline in protein expression, which remains well above baseline at 48 h of hypoxia. Further, we demonstrate that this induction of MUC3 protein is associated with a transient increase in the barrier restorative peptide, intestinal trefoil factor (ITF). ITF not only colocalizes with MUC3, by confocal microscopy, to the apical surface of T84 cells following exposure to hypoxia, but is also found, by co-immunoprecipitation, to be physically associated with MUC3, following 24 h of hypoxia. In exploration of the mechanism of hypoxic regulation of mucin 3 expression, we demonstrated by luciferase assay that the full-length promoter for mouse Mucin 3 (Muc3) is hypoxia-responsive with a 5.08 +/- 1.76-fold induction following 24 h of hypoxia. Furthermore, analysis of both the human (MUC3A) and mouse (Muc3) promoters revealed potential HIF-1 binding sites which were shown by chromatin immunoprecipitation to bind the pivotal hypoxia-regulating transcription factor HIF-1alpha. Taken together, these studies implicate the HIF-1alpha mediated hypoxic induced expression of mucin 3 and associated ITF in the maintenance of intestinal barrier function under hypoxic conditions.


Circulating Vitamin D and Overall Survival in Breast Cancer Patients: A Dose-Response Meta-Analysis of Cohort Studies.
Studies have shown that vitamin D could have a role in breast cancer survival; however, the evidence of the relationship between patients' vitamin D levels and their survival has been inconsistent. This meta-analysis explores possible dose-response relationships between vitamin D levels and overall survival by allowing for differences in vitamin D levels among populations of the various studies. Studies relating vitamin D (25-OH-D [25-hydroxyvitamin D]) levels in breast cancer patients with their survival were identified by searching PubMed and Embase. A pooled HR (hazard ratio) comparing the highest with the lowest category of circulating 25-OH-D levels were synthesized using the Mantel-Haenszel method under a fixed-effects model. A two-stage fixed-effects dose-response model including both linear (a log-linear dose-response regression) and nonlinear (a restricted cubic spline regression) models were used to further explore possible dose-response relationships. Six studies with a total number of 5984 patients were identified. A pooled HR comparing the highest with the lowest category of circulating 25-OH-D levels under a fixed-effects model was 0.67 (95% confidence interval = 0.56-0.79, P < .001). Utilizing a dose-response meta-analysis, the pooled HR for overall survival in breast cancer patients was 0.994 (per 1 nmol/L), Pfor linear trend < .001. At or above a 23.3 nmol/L threshold, for a 10 nmol/L, 20 nmol/L, or 25 nmol/L increment in circulating 25-OH-D levels, the risk of breast cancer overall mortality decreased by 6%, 12%, and 14%, respectively. There was no significant nonlinearity in the relationship between overall survival and circulating 25-OH-D levels. Our findings suggest that there is a highly significant linear dose-response relationship between circulating 25-OH-D levels and overall survival in patients with breast cancer. However, better designed prospective cohort studies and clinical trials are needed to further confirm these findings.


Cancer mortality among woodworkers.
The mortality experience of 10,322 men employed in woodworking industries was compared with that of 406,798 nonwoodworkers. All subjects were enrolled in an American Cancer Society study and followed prospectively from 1959 through 1972. Age-adjusted rates of death from all causes and from all cancers were not higher in the woodworker group, but excess rates were observed for cancers of the lung, stomach, and bladder, as well as nonmelanoma skin cancer and possibly leukemia. Woodworkers experienced significantly decreased rates of colon-rectum cancer and coronary heart disease. The elevated cancer rates could not be explained by cigarette smoking habits. If anything, there is evidence to suggest a possible interaction between employment in woodworking trades and heavy cigarette smoking, in increasing the risk of lung and bladder cancer.


Human T cell leukemia virus type 1 Tax inhibits innate antiviral signaling via NF-kappaB-dependent induction of SOCS1.
Human T cell leukemia virus type 1 (HTLV-1) inhibits host antiviral signaling pathways although the underlying mechanisms are unclear. Here we found that the HTLV-1 Tax oncoprotein induced the expression of SOCS1, an inhibitor of interferon signaling. Tax required NF-κB, but not CREB, to induce the expression of SOCS1 in T cells. Furthermore, Tax interacted with SOCS1 in both transfected cells and in HTLV-1-transformed cell lines. Although SOCS1 is normally a short-lived protein, in the presence of Tax, the stability of SOCS1 was greatly increased. Accordingly, Tax enhanced the replication of a heterologous virus, vesicular stomatitis virus (VSV), in a SOCS1-dependent manner. Surprisingly, Tax required SOCS1 to inhibit RIG-I-dependent antiviral signaling, but not the interferon-induced JAK/STAT pathway. Inhibition of SOCS1 by RNA-mediated interference in the HTLV-1-transformed cell line MT-2 resulted in increased IFN-β expression accompanied by reduced HTLV-1 replication and p19(Gag) levels. Taken together, our results reveal that Tax inhibits antiviral signaling, in part, by hijacking an interferon regulatory protein.


Brassica napus L. cultivars show a broad variability in their morphology, physiology and metabolite levels in response to sulfur limitations and to pathogen attack.
Under adequate sulfur supply, plants accumulate sulfate in the vacuoles and use sulfur-containing metabolites as storage compounds. Under sulfur-limiting conditions, these pools of stored sulfur-compounds are depleted in order to balance the nitrogen to sulfur ratio for protein synthesis. Stress conditions like sulfur limitation and/or pathogen attack induce changes in the sulfate pool and the levels of sulfur-containing metabolites, which often depend on the ecotypes or cultivars. We are interested in investigating the influence of the genetic background of canola (Brassica napus) cultivars in sulfur-limiting conditions on the resistance against Verticillium longisporum. Therefore, four commercially available B. napus cultivars were analyzed. These high-performing cultivars differ in some characteristics described in their cultivar pass, such as several agronomic traits, differences in the size of the root system, and resistance to certain pathogens, such as Phoma and Verticillium. The objectives of the study were to examine and explore the patterns of morphological, physiological and metabolic diversity in these B. napus cultivars at different sulfur concentrations and in the context of plant defense. Results indicate that the root systems are influenced differently by sulfur deficiency in the cultivars. Total root dry mass and length of root hairs differ not only among the cultivars but also vary in their reaction to sulfur limitation and pathogen attack. As a sensitive indicator of stress, several parameters of photosynthetic activity determined by PAM imaging showed a broad variability among the treatments. These results were supported by thermographic analysis. Levels of sulfur-containing metabolites also showed large variations. The data were interrelated to predict the specific behavior during sulfur limitation and/or pathogen attack. Advice for farming are discussed.


Motor learning in people with Parkinson's disease: Implications for fall prevention across the disease spectrum.
Falls are a significant burden for people with Parkinson's disease (PD), however, individuals across the spectrum of disease severity respond differently to fall prevention interventions. Despite the multifactorial causes of falls in people with PD, recent work has provided insight into interventions that hold promise for fall prevention. Further, studies have begun to identify patient characteristics that may predict responsiveness to such interventions. We discuss (i) the postural motor learning abilities of people with mild versus severe PD that could affect their ability to benefit from fall prevention interventions, (ii) how people with different severity of PD respond to such interventions, and (iii) the practical considerations of providing effective fall prevention interventions for people with PD across the spectrum of disease severity. This narrative review consolidates recent work on postural motor learning and fall prevention rehabilitation involving exercise in people with PD. People with PD are able to improve postural motor control through practice, enabling them to benefit from exercise which challenges their gait and balance to reduce falling. Worsening of axial and cognitive symptoms may result in diminished learning, and those with more severe PD may require fully supervised, high intensity programs to reduce falls. Understanding how people with PD across the spectrum of disease severity differ in their postural motor learning ability and response to different fall prevention interventions will enable researchers and clinicians to refine such interventions and their delivery to minimize falls and their negative sequelae in people with PD.


Characteristics of oral mucosal events related to bevacizumab treatment.
Bevacizumab, a monoclonal antibody targeting a vascular endothelial growth factor (VEGF) protein, has been reported to induce mucosal toxicities. However, the clinical characteristics of these particular toxicities have not been well characterized. We aimed at providing a detailed clinical description of signs and symptoms limited to the tongue mucosa in patients treated with bevacizumab. A retrospective review of medical records and clinical photographs was performed with specific attention to clinical presentation, evolution, associated symptoms, concomitant medications, and treatment methods. In total, four patients presented to the dermatology service with clinical findings characterized by multifocal, erythematous circinate and serpiginous erosions on the dorsal tongue surrounded by white hyperkeratotic rims that were temporally related to bevacizumab therapy. Associated increased sensitivity to spicy foods was frequently observed. These characteristic clinical findings are consistent with geographic tongue. However, large prospective evaluations are necessary to confirm this potential relationship. If bevacizumab is indeed associated with geographic tongue, increased awareness may result in improved reporting and characterization of this particular adverse event.


'That would have been beneficial': LGBTQ education for home-care service providers.
This paper reports qualitative findings from a pilot study that explored the lesbian, gay, bisexual, transgender and queer (LGBTQ) education needs of home-care service providers working in one large, urban Canadian city. The pilot study builds upon research that has documented barriers to health services for diversely situated LGBTQ people, which function to limit access to good-quality healthcare. LGBTQ activists, organisations and allies have underscored the need for health provider education related to the unique health and service experiences of sexual and gender minority communities. However, the home-care sector is generally overlooked in this important body of research literature. We used purposeful convenience sampling to conduct four focus groups and two individual interviews with a total of 15 professionally diverse home-care service providers. Data collection was carried out from January 2011 to July 2012 and data were analysed using grounded theory methods towards the identification of the overarching theme, 'provider education' and it had two sub-themes: (i) experiences of LGBTQ education; and (ii) recommendations for LGBTQ education. The study findings raise important questions about limited and uneven access to adequate LGBTQ education for home-care service providers, suggest important policy implications for the education and health sectors, and point to the need for anti-oppression principles in the development of education initiatives.


A lifetime experience of violence and adverse reproductive outcomes: findings from population surveys in India.
Intimate partner violence (IPV) is a global public health issue that threatens the reproductive health of women. Despite a growing demand for research on the potential threat of IPV in relation to adverse reproductive outcomes, there have been no population-based studies of India. The current study analyzed the National Family Health Survey 3, which contained detailed information on types of violence in relation to the single question of pregnancy outcomes. The dataset was used to assess the association between a lifetime experience of IPV and terminated pregnancies among married Indian women. Multiple logistic regression analysis was then used to assess the association between these variables, controlling for socio-demographic characteristics. Results showed that 39.6% of Indian women have experienced violence by their husbands, while 18.3% of women have terminated a pregnancy during their lifetimes. The odds ratio of a terminated pregnancy among women who had experienced any type of partner violence was 1.62 (95% CI (confidence interval) = 1.51-1.73). All combinations of violence except a combination of emotional and sexual violence were associated with an increased risk of a terminated pregnancy. These results suggest that prevention of IPV would reduce the high incidence of terminated pregnancies, thus improving maternal health in India.


Multipurpose surface functionalization on AZ31 magnesium alloys by atomic layer deposition: tailoring the corrosion resistance and electrical performance.
An environmentally friendly atomic layer deposition (ALD) method with excellent atomic scale roughness controllability is developed to fabricate a highly conformal, corrosion preventive and conducting Al doped ZnO (AZO) film on a plasma electrolytic oxidation (PEO) layer coated AZ31 magnesium alloy. Compared with the insulated PEO coated magnesium alloy, the electrical conductivity of the composite coating increases to 25 S m-1, and in the meantime the anticorrosion performance of the PEO/AZO coating is greatly improved compared to the bare Mg alloy. The enhanced electrical properties of the composite coating are due to the abundant oxygen deficiency in the AZO film generated during the ALD process. The improvement of the corrosion resistance is attributed to the changes in the bond angle and the distance between the surface coating molecule and adsorbent H2O molecule. As a result, the hydrophilic surface of PEO changes to the hydrophobic surface of AZO, providing a novel process to protect the surface of the magnesium alloy. It is believed that this technique may provide a novel and controllable strategy to expand the practical applications of magnesium alloys.


Financing strategies for drug abuse treatment programs.
Contemporary drug abuse treatment programs exist in an extremely complex financing environment. Programs face a myriad of funding sources with different eligibility requirements and payment mechanisms that make it difficult for programs to develop a single financing strategy. To complicate the financing process, current funding sources are in a state of flux as managed care gains significance in health care reimbursement. This article will assist drug abuse treatment programs in several ways. First, it summarizes information about funding, eligibility requirements and payment mechanisms. Second, the information is geared toward drug treatment programs and less toward policymakers. Third, the article describes strategies for obtaining funding, including strategies for interacting with managed care. By using these methods for obtaining revenues, it is hoped that drug treatment programs will be able to increase their financing effectiveness.


Pituitary macroadenoma presenting with pituitary apoplexy, acromegaly and secondary diabetes mellitus - a case report.
Pituitary adenomas are associated with significant morbidity. The usual symptoms on presentation are of endocrine dysfunction and mass effects. A 31-year-old African female presented with headache, irregular menses, blurring of vision in the right eye and complete loss of vision in the left eye for 1 year. She had coarse facial features, enlarged hands and feet. Her right eye had temporal hemianopia with decreased visual acuity and her left eye had no perception of light. Investigations revealed an elevated fasting blood sugar and an elevated prolactin and growth hormone level. A CT scan and MRI done showed a hemorrhagic pituitary macroadenoma. She was put on bromocriptine, ocreotide, analgesics and insulin. Thereafter, she underwent transphenoidal surgery, where near total resection of the tumor was achieved. Patient is doing well post-operatively. This case highlights the importance of the use of a high clinical index of suspicion and radiological findings in diagnosis.