Survival in patients with metastatic recurrent breast cancer after adjuvant chemotherapy: little evidence of improvement over the past 30 years.
Population-based studies have shown improved survival for patients diagnosed with metastatic breast cancer over time, presumably because of the availability of new and more effective therapies. The objective of the current study was to determine whether survival improved for patients who developed distant recurrence of breast cancer after receiving adjuvant therapy. Adjuvant chemotherapy trials coordinated by the Eastern Cooperative Oncology Group that accrued patients between 1978 and 2002 were reviewed. Survival after distant disease recurrence was estimated for progressive time periods, and adjusted for baseline covariates in a Cox proportional hazards model. Of the 13,785 patients who received adjuvant chemotherapy in 11 trials, 3447 (25%) developed distant disease recurrence; the median survival after recurrence was 20 months (95% confidence interval, 19 months-21 months). Factors associated with inferior survival included a shorter distant recurrence-free interval (DRFI), estrogen receptor-negative and progesterone receptor-negative disease, the number of positive axillary lymph nodes present at the time of diagnosis, and black race (P < .0001 for all). When the time period of recurrence was added to the model, it was not found to be significantly associated with survival for the general population with disease recurrence. Survival improved over time only in those patients with hormone receptor-negative disease with a DRFI ≤ 3 years, both among the 5 most recent and the entire trial data sets (P = .01 and P = .05, respectively). In contrast to reports from population-based studies, no general improvement in survival was observed over the last 30 years for patients who developed distant disease recurrence after adjuvant chemotherapy after adjusting for DRFI. Improved survival for patients with hormone receptor-negative disease with a short DRFI suggests a benefit from trastuzumab.


Land application of sugar beet by-products: effects on nitrogen mineralization and crop yields.
Land application of food processing wastes has become an acceptable practice because of the nutrient value of the wastes and potential cost savings in their disposal. Spoiled beets and pulp are among the main by-products generated by the sugar beet (Beta vulgaris L.) processing industry. Farmers commonly land apply these by-products at rates >224 Mg ha(-1) on a fresh weight basis. However, information on nutrient release in soils treated with these by-products and their subsequent impacts on crop yield is lacking. Field studies were conducted to determine the effects of sugar beet by-product application on N release and crop yields over two growing seasons. Treatments in the first year were two rates (224 and 448 Mg ha(-1) fresh weight) of pulp and spoiled beets and a nonfertilized control. In the second year after by-product application, the control treatment was fertilized with N fertilizer and an additional treatment was added as a nonfertilized control in buffer areas. Wheat (Triticum aestivum L.) was grown in the year of by-product application and sugar beet in the subsequent year. By-product treatments caused a significant reduction in wheat grain yield compared with the control. This was due to a decline in N availability as a result of immobilization. Based on microplots receiving 15N labeled beets, wheat took up <1% of spoiled beet-N (approximately 4.7 kg ha(-1)) during the year of by-product application. In the second cropping year, sugar beet root yields were significantly higher in the fertilized control and by-product treatments than the nonfertilized control. The lack of significant difference in sugar beet yield between the fertilized control and by-product treatments was likely due to the greater availability of N in the second year. Labeled 15N data also showed that the sugar beet crop recovered a 17% of sugar beet-N, an equivalent of 86 kg N ha(-1), during the second cropping year. There was no difference in sugar beet root yield, N uptake, or soil N mineralization during the sugar beet cropping season between the pulp and the spoiled beet treatments at comparable rates of application.


Advances in basic and clinical immunology in 2010.
Reports in basic and clinical immunology in 2010 reflected the use of state-of-the-art genetic and immunologic tools to characterize the pathogenesis of immunologic diseases and the development of novel therapies directed to these conditions. B-cell biology has been explained in greater detail, significantly with lessons from the genetic defects found in the humoral immunodeficiencies. Therapeutic mAbs are given for an increasing number of indications, such as anti-CD20 antibodies or rituximab, which was initially developed for non-Hodgkin lymphomas and is currently used in diverse autoimmune and inflammatory disorders. The report of an infant with severe combined immunodeficiency (SCID) in Massachusetts detected by means of newborn screening and successfully treated with hematopoietic stem cell transplantation validated recent efforts toward newborn screening for SCID. Improvement of survival outcomes for patients with primary immunodeficiencies treated with hematopoietic stem cell transplantation was demonstrated in a large European cohort, with significant appreciation of the type of donor graft, particularly the use of HLA-matched unrelated donors for patients with non-SCID. Progress in cellular mechanisms of drug hypersensitivity included the characterization of nitroso-modified drug metabolites as potent T-cell activators and the identification of the relocation of plasmacytoid dendritic cells from blood to skin as a potential risk factor for reactivation of viral disease.


Developing the tissue viability seating guidelines.
Costs for the prevention and management of pressure ulcers have increased significantly with limited published advice from health and social care organisations on seating and preventing pressure ulcers. At the request of the UK Tissue Viability Society the aim of the publication was to develop a practical guide for people, carers and health and social care professionals on how the research and evidence base on pressure ulcer prevention and management can be applied to those who remain seated for extended periods of time. The evidence base informing the guidelines was obtained by applying a triangulation of methods: a literature review, listening event and stakeholder group consultation. The purpose was to engage users and carers, academics, clinicians, inspectorate and charities, with an interest in seating, positioning and pressure management to: gather views, feedback, stories, and evidence of the current practices in the field to create a greater awareness of the issue. The new guidelines are inclusive of all people with short and long-term mobility issues to include all population groups. The document includes evidence on where pressure ulcers develop when seated, risk factors, best possible seated position and what seat adjustments are required, the ideal seating assessment, interventions, self-help suggestions and key seating outcomes. The updated TVS CPGs have been informed by the best available evidence, the insights and wisdom of experts, stakeholders and people who spend extended periods of time sitting.


Exploring the effects of immunity and life history on the dynamics of an endogenous retrovirus.
Mammalian DNA is littered with the signatures of past retroviral infections. For example, at least 8% of the human genome can be attributed to endogenous retroviruses (ERVs). We take a single-locus approach to develop a simple susceptible-infected-recovered model to investigate the circumstances under which a disease-causing retrovirus can become incorporated into the host genome and spread through the host population if it were to confer an immunological advantage. In the absence of any fitness benefit provided by the long terminal repeat (LTR), we conclude that signatures of ERVs are likely to go to fixation within a population when the probability of evolving cellular/humoral immunity to a related exogenous version of the virus is extremely small. We extend this model to examine whether changing the speed of the host life history influences the likelihood that an exogenous retrovirus will incorporate and spread to fixation. Our results reveal the parameter space under which incorporation of exogenous retroviruses into a host genome may be beneficial to the host. In our final model, we find that the likelihood of an LTR reaching fixation in a host population is not strongly affected by host life history.


Multispectral laser-induced fluorescence imaging system for large biological samples.
A laser-induced fluorescence imaging system developed to capture multispectral fluorescence emission images simultaneously from a relatively large target object is described. With an expanded, 355-nm Nd:YAG laser as the excitation source, the system captures fluorescence emission images in the blue, green, red, and far-red regions of the spectrum centered at 450, 550, 678, and 730 nm, respectively, from a 30-cm-diameter target area in ambient light. Images of apples and of pork meat artificially contaminated with diluted animal feces have demonstrated the versatility of fluorescence imaging techniques for potential applications in food safety inspection. Regions of contamination, including sites that were not readily visible to the human eye, could easily be identified from the images.


Aesthesiometric threshold changes over the course of a workshift in miners exposed to hand-arm vibration.
The objective of this study was to investigate whether aesthesiometric threshold changes occur over the course of a workshift in vibration exposed hard rock miners relative to workers unexposed to vibration during the shift. The subjects were 99 miners and 40 smelter workers; four subjects declined to participate and nine were excluded from the analysis because of apparent failure to comprehend the testing procedure. Two point discrimination and depth sense aesthesiometry were conducted at the beginning and at the end of the workshift in all digits of both hands excluding the thumbs. In addition to the use of a vibrating tool during the shift, age, digital temperature, signs of arm injury, presence of fingertip callus, and handedness were documented. In the analysis the difference between postshift and preshift readings was studied in relation to these variables, particularly exposure to the jackleg drill during the shift. With the exception of exposure of the jackleg drill, no associations were observed between these variables and change over the workshift in aesthesiometric results, on both unadjusted comparison of means and backward elimination regression analysis. A statistically significant association, however, was found between the use of a jackleg drill and change in two point discrimination and in depth sense aesthesiometric results over the course of the shift, for the right hand. Evidence of the occurrence of a learning effect, particularly for two point discrimination aesthesiometry, was observed. The occurrence of an effect in the right, but not the left, hand reflects dominant handedness and relatively greater vibration exposure in the right hand in our subjects. This study supports the incorporation of an exposure free interval before aesthesiometric testing of vibration exposed workers.


Pilot study on the influence of cold atmospheric plasma on bacterial contamination and healing tendency of chronic wounds.
Cold atmospheric plasma (CAP) has been used successfully for wound treatment, with thrice weekly treatment intervals. In this study, we wished to investigate whether comparably beneficial results can be achieved even with once weekly CAP treatment. In this randomized clinical pilot study (RCT) patients with therapy-refractory chronic wounds were examined over a maximum of twelve weeks. Groups 1 and 2 were treated with CAP once and twice a week, respectively. Patients in Group 3 received placebo therapy once a week. Wound area decreased significantly by 63.0 % in Group 1 (n = 14, P = 0.005) and by 46.8 % in Group 2 (n = 13, P = 0.007). In Group 3 (n = 10) the wounds grew on average 17.5 % larger. A significant reduction in pain was measured in both CAP-treated groups (Group 1: P = 0.042; Group 2: P = 0.027). Only in Group 2 was there a significant improvement in wound-specific quality of life (P = 0.005). After the 12-week CAP treatment, the reduction in bacterial load compared to the day of study inclusion averaged 50.4 % for Group 1 and 35.0 % for Group 2. Our RCT shows that treatment with CAP improves various aspects of wound healing in patients with therapy-refractory chronic wounds. The results obtained for once weekly treatment with CAP were not inferior to those obtained when CAP treatment was three times a week. Treatment once a week is also easier and more economical to implement in clinical routine.


An exact accelerated stochastic simulation algorithm.
An exact method for stochastic simulation of chemical reaction networks, which accelerates the stochastic simulation algorithm (SSA), is proposed. The present "ER-leap" algorithm is derived from analytic upper and lower bounds on the multireaction probabilities sampled by SSA, together with rejection sampling and an adaptive multiplicity for reactions. The algorithm is tested on a number of well-quantified reaction networks and is found experimentally to be very accurate on test problems including a chaotic reaction network. At the same time ER-leap offers a substantial speedup over SSA with a simulation time proportional to the 23 power of the number of reaction events in a Galton-Watson process.


Challenges and perspectives in quantitative NMR.
This perspective article summarizes, from the author's point of view at the beginning of 2016, the major challenges and perspectives in the field of quantitative NMR. The key concepts in quantitative NMR are first summarized; then, the most recent evolutions in terms of resolution and sensitivity are discussed, as well as some potential future research directions in this field. A particular focus is made on methodologies capable of boosting the resolution and sensitivity of quantitative NMR, which could open application perspectives in fields where the sample complexity and the analyte concentrations are particularly challenging. These include multi-dimensional quantitative NMR and hyperpolarization techniques such as para-hydrogen-induced polarization or dynamic nuclear polarization. Because quantitative NMR cannot be dissociated from the key concepts of analytical chemistry, i.e. trueness and precision, the methodological developments are systematically described together with their level of analytical performance. Copyright © 2016 John Wiley & Sons, Ltd.


Effect of inoculation of sarcoid tissue into athymic (nude) mice.
Previous reports have suggested that the inoculation of sterile homogenates of human sarcoidosis tissue produce pathological changes or death in T cell deficient mice, while other reports have challenged these results. Because of the importance of this point, the potential infectiousness of human sarcoid tissue was investigated using athymic (nude) mice. Eight tissue specimens were obtained from patients with sarcoidosis and inoculated once into a total of sixty-two nude mice. These experiments were conducted over a period of two years. The tissue specimens inoculated included biopsies of lung, lymph node and muscle. A non-tissue buffer was used as a sham control and inoculated into ten nude mice. Of the eight tissue specimens, six were found to contain non-caseating granulomas consistent with sarcoidosis. Only one of these six specimens induced significant pathological changes when injected into nude mice: two mice developed reticulum cell sarcoma and one developed membranous glomerulonephritis. Five inoculations of sarcoid tissue into a new athymic mouse colony housed in resterilized cages produced no detectable pathology. Two different tissue specimens not containing sarcoid granulomas were inoculated into two groups of nude mice. Both of these specimens induced pathological changes. One mouse developed a reticulum cell sarcoma, one developed lymphoma and one developed interstitial nephritis. A saline control inoculation produced no pathology in any mice. Mortality rates were similar in sarcoid inoculated, normal tissue inoculated and saline inoculated mice. These findings suggest that if sarcoidosis has an infectious etiology, the responsible agent is not one that easily infects athymic mice.(ABSTRACT TRUNCATED AT 250 WORDS)


SUPPORT Tools for evidence-informed health Policymaking (STP).
This article is the Introduction to a series written for people responsible for making decisions about health policies and programmes and for those who support these decision makers. Knowing how to find and use research evidence can help policymakers and those who support them to do their jobs better and more efficiently. Each article in this series presents a proposed tool that can be used by those involved in finding and using research evidence to support evidence-informed health policymaking. The series addresses four broad areas: 1. Supporting evidence-informed policymaking 2. Identifying needs for research evidence in relation to three steps in policymaking processes, namely problem clarification, options framing, and implementation planning 3. Finding and assessing both systematic reviews and other types of evidence to inform these steps, and 4. Going from research evidence to decisions. Each article begins with between one and three typical scenarios relating to the topic. These scenarios are designed to help readers decide on the level of detail relevant to them when applying the tools described. Most articles in this series are structured using a set of questions that guide readers through the proposed tools and show how to undertake activities to support evidence-informed policymaking efficiently and effectively. These activities include, for example, using research evidence to clarify problems, assessing the applicability of the findings of a systematic review about the effects of options selected to address problems, organising and using policy dialogues to support evidence-informed policymaking, and planning policy monitoring and evaluation. In several articles, the set of questions presented offers more general guidance on how to support evidence-informed policymaking. Additional information resources are listed and described in every article. The evaluation of ways to support evidence-informed health policymaking is a developing field and feedback about how to improve the series is welcome.


A critical role for ceramide synthase 2 in liver homeostasis: II. insights into molecular changes leading to hepatopathy.
We have generated a mouse that cannot synthesize very long acyl chain (C22-C24) ceramides (Pewzner-Jung, Y., Park, H., Laviad, E. L., Silva, L. C., Lahiri, S., Stiban, J., Erez-Roman, R., Brugger, B., Sachsenheimer, T., Wieland, F. T., Prieto, M., Merrill, A. H., and Futerman, A. H. (2010) J. Biol. Chem. 285, 10902-10910) due to ablation of ceramide synthase 2 (CerS2). As a result, significant changes were observed in the sphingolipid profile of livers from these mice, including elevated C16-ceramide and sphinganine levels. We now examine the functional consequences of these changes. CerS2 null mice develop severe nonzonal hepatopathy from about 30 days of age, the age at which CerS2 expression peaks in wild type mice, and display increased rates of hepatocyte apoptosis and proliferation. In older mice there is extensive and pronounced hepatocellular anisocytosis with widespread formation of nodules of regenerative hepatocellular hyperplasia. Progressive hepatomegaly and noninvasive hepatocellular carcinoma are also seen from approximately 10 months of age. Even though CerS2 is found at equally high mRNA levels in kidney and liver, there are no changes in renal function and no pathological changes in the kidney. High throughput analysis of RNA expression in liver revealed up-regulation of genes associated with cell cycle regulation, protein transport, cell-cell interactions and apoptosis, and down-regulation of genes associated with intermediary metabolism, such as lipid and steroid metabolism, adipocyte signaling, and amino acid metabolism. In addition, levels of the cell cycle regulator, the cyclin dependent-kinase inhibitor p21(WAF1/CIP1), were highly elevated, which occurs by at least two mechanisms, one of which may involve p53. We propose a functional rationale for the synthesis of sphingolipids with very long acyl chains in liver homeostasis and in cell physiology.


Perfusion regulation of hMSC microenvironment and osteogenic differentiation in 3D scaffold.
The combination of hMSCs with 3D scaffolds has become an important approach to creating functional bone constructs. Bioreactors are important tools to mitigate mass transfer limitations and to provide controlled physiochemical and biomechanical environments for the 3D bone construct development. Media flow in the bioreactor systems is generally controlled either parallel or transverse with respect to the 3D construct, creating different cellular and biomechanical microenvironments in the 3D constructs. In this study, a custom designed modular perfusion bioreactor system was operated under either the parallel or transverse flow. The influence of the flow patterns on the characteristics of the hMSCs' cellular microenvironment and subsequent construct development was investigated. The parallel flow configuration retained ECM proteins and mitogenic growth factors within the scaffold, effectively preserving hMSC progenicity and proliferation potential (e.g., CFU-F, proliferation, and OCT-4), whereas the transverse flow induced hMSC osteogenic differentiation with higher ALP activity and calcium deposition and up-regulation of osteogenic bone markers (e.g., BMP-2, ALP, RUNX2, OSX, and OC). These results demonstrate the regulatory role of the macroscopic flow on the cellular microenvironment of the 3D hMSC construct, and suggest configuring media flow as a strategy for directing hMSC fate and 3D bone construct development in the perfusion bioreactor.


Measurement of the effective nonlinear and dispersion coefficients in optical fibers by the induced grating autocorrelation technique.
The induced grating autocorrelation technique, a technique based on temporally resolved two-beam coupling in a photorefractive crystal, was used to measure the nonlinear coefficient γ of three photonic crystal fibers (PCFs): a 30-cm long highly nonlinear PCF, and two large mode area PCFs of 4.5-m and 4.9-m lengths. The measurement used intense 2-ps, 800-nm (850-nm in one case) pulses from a Ti: sapphire laser that experienced self-phase modulation and group velocity dispersion as it travels inside the fibers. This technique was also expanded to measure γ and the dispersion coefficient β2 simultaneously.


Precession of the Earth as the Cause of Geomagnetism: Experiments lend support to the proposal that precessional torques drive the earth's dynamo.
I have proposed that the precessional torques acting on the earth can sustain a turbulent hydromagnetic flow in the molten core. A gross balance of the Coriolis force, the Lorentz force, and the precessional force in the core fluid provided estimates of the fluid velocity and the interior magnetic field characteristic of such flow. Then these numbers and a balance of the processes responsible for the decay and regeneration of the magnetic field provided an estimate of the magnetic field external to the core. This external field is in keeping with the observations, but its value is dependent upon the speculative value for the electrical conductivity of core material. The proposal that turbulent flow due to precession can occur in the core was tested in a study of nonmagnetic laboratory flows induced by the steady precession of fluid-filled rotating spheroids. It was found that these flows exhibit both small wavelike instabilities and violent finite-amplitude instability to turbulent motion above critical values of the precession rate. The observed critical parameters indicate that a laminar flow in the core, due to the earth's precession, would have weak hydrodynamic instabilities at most, but that finite-amplitude hydromagnetic instability could lead to fully turbulent flow.


Improvement of the embryonic stem cell test endpoint analysis by use of field potential detection.
The embryonic stem cell test (EST) is a validated in vitro method to assess the embryotoxic potential of compounds and is a promising tool for drug screening. EST requires microscopic observation of beating cardiomyocytes differentiated from embryonic stem cells as a toxicological endpoint. However, this process is time-consuming and lacks throughput performance. To improve the analysis, we introduced an electrophysiological method with a microelectrode array system for the evaluation of differentiated cardiomyocytes. Embryotoxic (valproic acid, verapamil, and 5-fluorouracil) and non-embryotoxic (penicillin G, d-camphor, and isoniazid) compounds were assessed with the system. Mouse embryonic stem cells were differentiated into cardiomyocytes and treated with each compound during the differentiation process. The embryotoxicity of each compound was then assessed by measuring the field potentials of differentiated cardiomyocytes using the microelectrode array system, as well as by microscopic evaluation. All the embryotoxic compounds dose-dependently inhibited the field potential formation and the myocardial beating of differentiated cells, while the non-embryotoxic compounds did not affect either endpoint. The detection capabilities of the two assay methods were similar. These results indicated that the field potential measurements can be used as an alternative endpoint of EST. Moreover, the field potential can be measured automatically, introducing a high throughput performance compared to the conventional microscopic observation. We therefore concluded that the endpoint analysis with the microelectrode array system improves the original EST and can be useful for the assessment of the embryotoxic potential of compounds.


The physical signs of impending dehydration among elderly people in nursing homes: The association with axillary skin temperature, humidity, intraoral moisture content, and salivary components.
The aim of the present study was to examine the association between impending dehydration among elderly people in nursing homes and physical signs, including the axillary skin temperature, humidity, intraoral moisture content, and salivary components. The study included 78 elderly individuals who required long-term care in a nursing home (11 men and 67 women; average age, 86.6±7.3 years). The elderly subjects were classified in two groups according to their serum osmolality levels: those with levels between the upper limit reference value (292 mOsm/kg H2O) and the diagnostic reference value of dehydration (300 mOsm/kg H2O) were classified into the boundary zone group and those with levels of <292 mOsm/kg H2O were classified into the normal range group. The following parameters were measured: basic attributes (age, gender and level of care required), body mass index, diet, daily fluid intake per kilogram of body weight, physiological indicators (blood pressure, pulse rate, body temperature, axillary skin temperature, humidity, total body water, body water rate, internal liquid rate, external solution rate, blood components, intraoral water amount, and salivary components), and the indoor environment (room temperature and humidity). We then performed a statistical analysis to compare the boundary zone group with the normal range group. After adjusting for age and the daily fluid intake per kilogram of body weight (<25 ml/≥25 ml), we performed a logistic regression analysis (the boundary zone group was used as an independent variable) for variables that had significance levels of <0.05 (except for blood components). The univariate analysis revealed significant differences in the following parameters: the serum sodium, chloride, and creatinine levels; the blood sugar level; the urea nitrogen/creatinine ratio; the axillary skin temperature; and room humidity. Only the axillary skin temperature showed a significant association in the final model of the logistic regression analysis (odds ratio, 3.664; 95% confidence interval, 1.101-12.197; p = 0.034). As the axillary skin temperature increased by 1°C, there was a 3.67-fold risk of being classified into the boundary zone group instead of the normal range group. Thus, the axillary skin temperature was associated with impending dehydration.


Using phase information in ultrasonic backscatter for in vivo liver analysis.
In recent studies, it has been shown that information about scatterer spacing can be obtained from analyzing the phase of the ultrasound echo from various media. Such information proves to be useful when examining the ultrasonic backscatter from well-organized tissue, such as the liver. By quantifying the deviations in scatterer spacing and/or varying degrees of regularity, conclusions may be drawn about the underlying pathology of the tissue. This paper examines the physical basis of how the scatterer locations affect the phase of the data. Computer simulations were performed that mimic various scattering conditions and that display the effects of differing degrees of regularity, as well as increases in a diffuse random background scattering component. Results of studies on a phantom are also included to investigate and display the phase response under well-controlled scattering conditions. Finally, in vivo data taken from liver scans were analyzed. In this work, it was shown that the phase of the backscattered signal holds valuable information regarding the pathological state of liver tissue. It is suggested that this simple examination of the phase can be refined into a technique to be used as a method to consistently detect the onset of pathological change.


Defective secretion of an immunoglobulin caused by mutations in the heavy chain complementarity determining region 2.
We have investigated four secretion-deficient antibodies (Abs) derived from a panel of 46 mutant T15 anti-phosphocholine Abs, all of which have point mutations in the heavy chain (H) complementarity determining region 2 (CDR2). The level of secretion for these four Abs was < 10% of wild type when expressed together with the T15 light chain (L) in either SP2/0 or P3X63Ag8.653 myeloma cells although normal levels of H and L chain mRNA were produced. Moreover, abundant intracellular H and L chain proteins were detected. Three of the four mutants had little or no assembled H and L complexes intracellularly whereas one had a significant amount of intracellular immunoglobulin (Ig) which was shown to be capable of binding Ag. Thus, we demonstrate for the first time that point mutations confined to CDR2 of the H chain variable (V) region can impede Ab assembly and secretion. We then introduced the same CDR2 mutations into a related H chain which is encoded by the same T15 VH gene but different diversity (D) and joining (J) genes. When these H chains were expressed with a non-T15 L chain, the resulting Abs were secreted normally. The results thus suggest that the effects of the CDR2 mutations on Ab secretion are dependent on their interactions with L and/or H chain D-J sequences. These results also reveal a novel mechanism that could contribute to B cell wastage.


Medical Anthropology in, of, for and with Africa: Three Hotspots.
Medical anthropologists offer an empirically rich and conceptually nuanced account of how and why people in Africa engage with diverse forces influencing their ways of experiencing illness and practicing medicine in an unequal world. Expanding the research focus from healers to patients and, since 2000, to biomedicine and global health, they have deepened our understanding of the intricate, though not immediately visible networks of connecting, diverging and crisscrossing healing routes within and beyond Africa. In this review article, we revisit three much debated issues in this burgeoning research field: making African global health, framing traditional medicine, and tackling culturalism.


Depression and the relationship between sleep disturbances, nightmares, and suicidal ideation in treatment-seeking Canadian Armed Forces members and veterans.
Research on the relationship between insomnia and nightmares, and suicidal ideation (SI) has produced variable findings, especially with regard to military samples. This study investigates whether depression mediated the relationship between: 1) sleep disturbances and SI, and 2) trauma-related nightmares and SI, in a sample of treatment-seeking Canadian Armed Forces (CAF) personnel and veterans (N = 663). Regression analyses were used to investigate associations between sleep disturbances or trauma-related nightmares and SI while controlling for depressive symptom severity, posttraumatic stress disorder (PTSD) symptom severity, anxiety symptom severity, and alcohol use severity. Bootstrapped resampling analyses were used to investigate the mediating effect of depression. Approximately two-thirds of the sample (68%; N = 400) endorsed sleep disturbances and 88% (N = 516) reported experiencing trauma-related nightmares. Although sleep disturbances and trauma-related nightmares were both significantly associated with SI on their own, these relationships were no longer significant when other psychiatric conditions were included in the models. Instead, depressive symptom severity emerged as the only variable significantly associated with SI in both equations. Bootstrap resampling analyses confirmed a significant mediating role of depression for sleep disturbances. The findings suggest that sleep disturbances and trauma-related nightmares are associated with SI as a function of depressive symptoms in treatment-seeking CAF personnel and veterans. Treating depression in patients who present with sleep difficulties may subsequently help mitigate suicide risk.


Silver Enhancement for Transmission Electron Microscopy Imaging of Antibody Fragment-Gold Nanoparticles Conjugates Immobilized on Ordered Mesoporous Silica.
Ordered mesoporous silica (OMS) materials are receiving great attention as possible carriers for valuable but unstable drugs as, for example, therapeutic proteins. A key issue is to prove that the therapeutic protein is effectively able to penetrate the pores of OMS during the adsorption step. Here, we immobilized an antibody fragment [F(ab')GAMIgG] conjugated with ultrasmall gold nanoparticles (GNPs) onto amino-functionalized SBA-15 (SBA-NH2) mesoporous silica. The aim of this work is the visualization of the location of the conjugates adsorbed onto SBA-NH2 with transmission electron microscopy (TEM). Because of the ultrasmall size of GNPs (<1 nm), we use the silver enhancement procedure to amplify their size. In this procedure, ultrathin sections of conjugate-loaded SBA-NH2 particles are prepared by a ultramicrotome sectioning technique. The ultrasmall GNPs located on the top side of the 70-90 nm thick slices act as microcrystallization nucleation sites for the deposition of reduced metallic silver. Consequently, the ultrasmall GNPs increase their size. This allows for the direct imaging of the conjugates adsorbed. We clearly localize the F(ab')GAMIgG-GNPs conjugates either on the external surface of the particles or inside the mesopores of SBA-NH2 through TEM.


Interaction of the tricyclic antidepressant amitriptyline with prejunctional alpha and muscarinic receptors in the dog saphenous vein.
Amitriptyline can cause tachycardia and arrhythmia associated with an excessive release of cardiac catecholamines. We have investigated its effects on norepinephrine release from adrenergic nerves by using the dog saphenous vein as a model of the sympathetic neuroeffector junction. Isolated strips of vein were mounted for isometric tension recording or incubated with [3H]norepinephrine and mounted for superfusion, tension recording and the superfusate. Amitriptyline (10(-6); 5 x 10(-6) M) increased the overflow of [3H]norepinephrine but decreased that of [3,4-3H]dihydroxyphenylglycol from electrically stimulated strips. The selective decreased in the overflow of this metabolite indicates that amitriptyline inhibits neuronal uptake. However, the increased overflow of [3H]norepinephrine caused by amitriptyline also occurred when neuronal uptake was blocked by cocaine (3 x 10(-5) M) but was abolished when prejunctional alpha receptors were blockade by phentolamine (10(-5) M). Amitriptyline attenuated the prejunctional inhibitory action of exogenous norepinephrine, this indicates that the drug interacts with prejunctional alpha receptors. Amitriptyline also antagonized the prejunctional inhibitory action of acetylcholine, both in the absence and presence of cocaine and phentolamine. These effects were not due to a nonspecific action of the drug as it did not reduce the prejunctional inhibitory effect of histamine. Thus, amitriptyline can increase the concentration of norepinephrine at the neuroeffector junction by blockade of neuronal uptake and by interacting with prejunctional alpha and muscarinic receptors. Since the cardiac adrenergic nerves also possess these receptors, the results could help to explain the cardiotoxic effects of the drug.


All Components of Metabolic Syndrome Are Associated with Microalbuminuria in a Chinese Population.
Albuminuria is a well-known predictor of poor renal and cardiovascular outcomes and associated with increased risk of all-cause mortality. The study aimed to evaluate the associations between metabolic characteristics and the presence of albuminuria. This cross-sectional study included 18,384 adult Chinese who participated in health examinations during 2013-2014. Differences in clinical characteristics were compared for microalbuminuria (MAU) and albuminuria, and between genders. Potential risk factors associated with the risk of developing MAU and albuminuria were analyzed using univariate logistic regression. Multiple logistic regression was applied to further identify the independent associations between different levels of risk factors and the presence of MAU and albuminuria. The area under the ROC curve (AUC) was used to determine the discriminatory ability of metabolic risk factors in detecting albuminuria. There were significant gender differences in clinical characteristics according to albuminuria status. Risk for the presence of albuminuria was significantly associated with age, male gender, waist circumference (WC), waist-to-height ratio (WHtR), hypertension, fasting plasma glucose (FPG), and triglycerides to high-density lipoprotein cholesterol ratio (TG/HDL-C) in univariate logistic regression. Multiple logistic regression analysis indicated that the factors significantly associated with the presence of MAU were WC > 90cm, WHtR at 0.6-0.7, hypertension, FPG > 6.1 mmole/L, and TG/HDL-C ratio > 1.6. The optimal cutoffs for risk factors of metabolic syndrome (MetS) to predict albuminuria in males and females were: WC, 90.8 vs. 80.0 cm; WHtR, 0.53 vs. 0.52; MAP, 97.9 vs. 91.9 mmHg; FPG, 5.40 vs. 5.28 mmole/L; and TG/HDL-C, 1.13 vs. 1.08. MetS and all its components were associated with the presence of MAU in a health check-up population in China. Gender specific and optimal cutoffs for MetS components associated with the presence of MAU were determined.


Intention, false beliefs, and delusional jealousy: insights into the right hemisphere from neurological patients and neuroimaging studies.
Jealousy sits high atop of a list comprised of the most human emotional experiences, although its nature, rationale, and origin are poorly understood. In the past decade, a series of neurological case reports and neuroimaging findings have been particularly helpful in piecing together jealousy's puzzle. In order to understand and quantify the neurological factors that might be important in jealousy, we reviewed the current literature in this specific field. We made an electronic search, and examined all literature with at least an English abstract, through Mars 2010. The search identified a total of 20 neurological patients, who experienced jealousy in relation with a neurological disorder; and 22 healthy individuals, who experienced jealousy under experimental neuroimaging settings. Most of the clinical cases of reported jealousy after a stroke had delusional-type jealousy. Right hemispheric stroke was the most frequently reported neurological disorder in these patients, although there was a wide range of more diffuse neurological disorders that may be reported to be associated with different other types of jealousy. This is in line with recent neuroimaging data on false beliefs, moral judgments, and intention [mis]understanding. Together the present findings provide physicians and psychologists with a potential for high impact in understanding the neural mechanisms and treatment of jealousy. By combining findings from case reports and neuroimaging data, the present article allows for a novel and unique perspective, and explores new directions into the neurological jealous mind.


Make it better but don't change anything.
With massive amounts of data being generated in electronic format, there is a need in basic science laboratories to adopt new methods for tracking and analyzing data. An electronic laboratory notebook (ELN) is not just a replacement for a paper lab notebook, it is a new method of storing and organizing data while maintaining the data entry flexibility and legal recording functions of paper notebooks. Paper notebooks are regarded as highly flexible since the user can configure it to store almost anything that can be written or physically pasted onto the pages. However, data retrieval and data sharing from paper notebooks are labor intensive processes and notebooks can be misplaced, a single point of failure that loses all entries in the volume. Additional features provided by electronic notebooks include searchable indices, data sharing, automatic archiving for security against loss and ease of data duplication. Furthermore, ELNs can be tasked with additional functions not commonly found in paper notebooks such as inventory control. While ELNs have been on the market for some time now, adoption of an ELN in academic basic science laboratories has been lagging. Issues that have restrained development and adoption of ELN in research laboratories are the sheer variety and frequency of changes in protocols with a need for the user to control notebook configuration outside the framework of professional IT staff support. In this commentary, we will look at some of the issues and experiences in academic laboratories that have proved challenging in implementing an electronic lab notebook.


Clinical validation of the Cervista HPV HR and 16/18 genotyping tests for use in women with ASC-US cytology.
High-risk (HR) human papillomavirus (HPV) testing is important in cervical cancer screening for triage to colposcopy. This study evaluated the clinical performance of the Cervista HPV HR and 16/18 genotyping tests for detection of HPV in cervical cytology specimens. The tests were prospectively evaluated in a multicenter clinical study. DNA was extracted from approximately 4000 residual liquid-based cytology specimens collected during routine liquid-based Papanicolaou tests at standard of care visits and was assessed for the presence of HR HPV and/or HPV types 16 and 18. All women with cytology results of atypical squamous cells of undetermined significance (ASC-US) or greater underwent colposcopic examination and biopsies were collected. Test results were compared with local colposcopy and histology results from a central pathology review panel. There were 1347 subjects with complete data sets of cytology, HR HPV, colposcopy, and histology included in the analysis of the HPV HR test. Sensitivity of the HPV HR test for detection of cervical intraepithelial neoplasia (CIN) 2+ among women with ASC-US cytology was 92.8% (95% confidence interval [CI]: 84.1-96.9) and the negative predictive value (NPV) was 99.1% (95% CI: 98.1-99.6). Sensitivity for detection of > or =CIN 3 in women with ASC-US was 100% (95% CI: 85.1-100) and the NPV was 100% (95% CI: 99.4-100). The specificity of the test for detection of > or =CIN 2 and > or =CIN 3 was 44.2% (95% CI: 41.5-46.9) and 43% (95% CI: 40.3-45.7), respectively. The HPV 16/18 genotyping test also performed as expected in women with ASC-US cytology who were positive for HR HPV. The Cervista HPV HR test can be clinically used for detecting HR HPV types in conjunction with cervical cytology for use in triage of women with ASC-US cytology during routine cervical cancer screening.


From the BMI paradox to the obesity paradox: the obesity-mortality association in coronary heart disease.
Despite a strong association between body weight and mortality in the general population, clinical evidence suggests better clinical outcome of overweight or obese individuals with established coronary heart disease. This finding has been termed the 'obesity paradox', but its existence remains a point of debate, because it is mostly observed when body mass index (BMI) is used to define obesity. Inherent limitations of BMI as an index of adiposity, as well as methodological biases and the presence of confounding factors, may account for the observed findings of clinical studies. In this review, our aim is to present the data that support the presence of a BMI paradox in coronary heart disease and then explore whether next to a BMI paradox a true obesity paradox exists as well. We conclude by attempting to link the obesity paradox notion to available translational research data supporting a 'healthy', protective adipose tissue phenotype. © 2016 World Obesity.


Perivascular drainage of solutes is impaired in the ageing mouse brain and in the presence of cerebral amyloid angiopathy.
The deposition of amyloid-β (Aβ) peptides in the walls of leptomeningeal and cortical blood vessels as cerebral amyloid angiopathy (CAA) is present in normal ageing and the majority of Alzheimer's disease (AD) brains. The failure of clearance mechanisms to eliminate Aβ from the brain contributes to the development of sporadic CAA and AD. Here, we investigated the effects of CAA and ageing on the pattern of perivascular drainage of solutes in the brains of naïve mice and in the Tg2576 mouse model of AD. We report that drainage of small molecular weight dextran along cerebrovascular basement membranes is impaired in the hippocampal capillaries and arteries of 22-month-old wild-type mice compared to 3- and 7-month-old animals, which was associated with age-dependent changes in capillary density. Age-related alterations in the levels of laminin, fibronectin and perlecan in vascular basement membranes were also noted in wild-type mice. Furthermore, dextran was observed in the walls of veins of Tg2576 mice in the presence of CAA, suggesting that deposition of Aβ in vessel walls disrupts the normal route of elimination of solutes from the brain parenchyma. These data support the hypothesis that perivascular solute drainage from the brain is altered both in the ageing brain and as a consequence of CAA. These findings have implications for the success of therapeutic strategies for the treatment of AD that rely upon the health of the ageing cerebral vasculature.


Inhibition of striatal dopamine release by the L-type calcium channel inhibitor isradipine co-varies with risk factors for Parkinson's.
Ca2+ entry into nigrostriatal dopamine (DA) neurons and axons via L-type voltage-gated Ca2+ channels (LTCCs) contributes, respectively, to pacemaker activity and DA release and has long been thought to contribute to vulnerability to degeneration in Parkinson's disease. LTCC function is greater in DA axons and neurons from substantia nigra pars compacta than from ventral tegmental area, but this is not explained by channel expression level. We tested the hypothesis that LTCC control of DA release is governed rather by local mechanisms, focussing on candidate biological factors known to operate differently between types of DA neurons and/or be associated with their differing vulnerability to parkinsonism, including biological sex, α-synuclein, DA transporters (DATs) and calbindin-D28k (Calb1). We detected evoked DA release ex vivo in mouse striatal slices using fast-scan cyclic voltammetry and assessed LTCC support of DA release by detecting the inhibition of DA release by the LTCC inhibitors isradipine or CP8. Using genetic knockouts or pharmacological manipulations, we identified that striatal LTCC support of DA release depended on multiple intersecting factors, in a regionally and sexually divergent manner. LTCC function was promoted by factors associated with Parkinsonian risk, including male sex, α-synuclein, DAT and a dorsolateral co-ordinate, but limited by factors associated with protection, that is, female sex, glucocerebrosidase activity, Calb1 and ventromedial co-ordinate. Together, these data show that LTCC function in DA axons and isradipine effect are locally governed and suggest they vary in a manner that in turn might impact on, or reflect, the cellular stress that leads to parkinsonian degeneration.


Molecular time-course and the metabolic basis of entry into dauer in Caenorhabditis elegans.
When Caenorhabditis elegans senses dauer pheromone (daumone), signaling inadequate growth conditions, it enters the dauer state, which is capable of long-term survival. However, the molecular pathway of dauer entry in C. elegans has remained elusive. To systematically monitor changes in gene expression in dauer paths, we used a DNA microarray containing 22,625 gene probes corresponding to 22,150 unique genes from C. elegans. We employed two different paths: direct exposure to daumone (Path 1) and normal growth media plus liquid culture (Path 2). Our data reveal that entry into dauer is accomplished through the multi-step process, which appears to be compartmentalized in time and according to metabolic flux. That is, a time-course of dauer entry in Path 1 shows that dauer larvae formation begins at post-embryonic stage S4 (48 h) and is complete at S6 (72 h). Our results also suggest the presence of a unique adaptive metabolic control mechanism that requires both stage-specific expression of specific genes and tight regulation of different modes of fuel metabolite utilization to sustain the energy balance in the context of prolonged survival under adverse growth conditions. It is apparent that worms entering dauer stage may rely heavily on carbohydrate-based energy reserves, whereas dauer larvae utilize fat or glyoxylate cycle-based energy sources. We created a comprehensive web-based dauer metabolic database for C. elegans (www.DauerDB.org) that makes it possible to search any gene and compare its relative expression at a specific stage, or evaluate overall patterns of gene expression in both paths. This database can be accessed by the research community and could be widely applicable to other related nematodes as a molecular atlas.


Modifying agricultural crops for improved nutrition.
The first generation of biotechnology products commercialized were crops focusing largely on input agronomic traits whose value was often opaque to consumers. The coming generations of crop plants can be grouped into four broad areas each presenting what, on the surface, may appear as unique challenges and opportunities. The present and future focus is on continuing improvement of agronomic traits such as yield and abiotic stress resistance in addition to the biotic stress tolerance of the present generation; crop plants as biomass feedstocks for biofuels and "bio-synthetics"; value-added output traits such as improved nutrition and food functionality; and plants as production factories for therapeutics and industrial products. From a consumer perspective, the focus on value-added traits, especially improved nutrition, is undoubtedly one of the areas of greatest interest. From a basic nutrition perspective, there is a clear dichotomy in demonstrated need between different regions and socioeconomic groups, the starkest being inappropriate consumption in the developed world and under-nourishment in Less Developed Countries (LDCs). Dramatic increases in the occurrence of obesity and related ailments in affluent regions are in sharp contrast to chronic malnutrition in many LDCs. Both problems require a modified food supply, and the tools of biotechnology have a part to play. Developing plants with improved traits involves overcoming a variety of technical, regulatory and indeed perception hurdles inherent in perceived and real challenges of complex traits modifications. Continuing improvements in molecular and genomic technologies are contributing to the acceleration of product development to produce plants with the appropriate quality traits for the different regions and needs. Crops with improved traits in the pipeline, the evolving technologies and the opportunities and challenges that lie ahead are covered.


Synthesis of adenosine derivatives as transcription initiators and preparation of 5' fluorescein- and biotin-labeled RNA through one-step in vitro transcription.
Expanding our previous finding of an adenosine-initiated transcription system, we now demonstrate that either the 5' site or the N6 site of adenosine nucleotides can be modified extensively without abolishing their ability to initiate transcription under the T7 phi2.5 promoter. Two series of amino derivatives of adenosine nucleotides were synthesized. Fluorescein and biotin groups were coupled to AMP derivatives through linkers of different sizes and hydrophobicities. Both fluorescein- and biotin-conjugated (at either the 5' or N6 site) adenosine nucleotides can act as efficient transcription initiators, producing fluorescein- and biotin-labeled RNA at the specific 5' end by a one-step transcription procedure, eliminating posttranscriptional modification. Furthermore, N6-modified adenosine derivative-initiated transcription synthesizes 5' end modified RNA with a free phosphate group, providing the possibility for further derivatization. The current finding makes easily available a variety of site-specifically functionalized RNA, which may be used in nucleic acid detection, RNA structural and functional investigation, and generation and isolation of novel functional RNA.


Streptococcus pneumoniae: a study of strains isolated from cerebrospinal fluid.
To determine the frequency of capsular serotypes and the antimicrobial susceptibility of strains of Streptococcus pneumoniae, as well as to provide recommendations on the use of available vaccines and antimicrobial drugs. In this retrospective study, standard procedures were followed to identify, serotype, and determine bacterial susceptibility to penicillin, cefotaxime, and vancomycin. Pneumococcal strains were isolated from the cerebrospinal fluid (CSF) of patients admitted to nine public and three private hospitals in Distrito Federal, Brazil, between January 1995 and December 2004. Identification and antimicrobial susceptibility tests were carried out at the Central Laboratory of Public Health (Laboratório Central de Saúde Pública). Serotyping was performed at Instituto Adolfo Lutz. A total of 232 pneumococcal strains were isolated, including 126 (54.31%) strains from male patients. Patients had an age range of 0 to 62 years and were distributed into four age groups: 0 to 5, 6 to 17, 18 to 50, and above 50. From the 36 distinct serotypes identified, eight were more prevalent: 14, 6B, 18C, 5, 19F, 23F, 9V, and 6A. The oxacillin test identified 67 penicillin-resistant strains, out of which 47 were confirmed by the E test as having intermediate level of resistance. None of the strains exhibited high-level resistance. Pneumococcal resistance to penicillin has gradually increased over the last 10 years in Distrito Federal. Serotypes more frequently isolated in the 0 to 5 years age group were the same involved in penicillin-resistance, all of which are covered by the 7-valent vaccine.


Enhancement of the intensity, persistence, and passive transfer of delayed-type hypersensitivity lesions by pertussigen in mice.
Pertussigen, a purified protein from Bordetella pertussis, was shown to increase delayed-type hypersensitivity (DTH) to protein antigens in mice. First, it caused an approximately twofold enhancement of the magnitude of 24-h DTH reactions. Second, the peak magnitude of DTH was delayed to 4-7 d after challenge, at which time it was five times more intense than in mice not receiving pertussigen. This reaction was antigen specific, and histologically was characterized by a dense mononuclear infiltrate. Third, pertussigen prolonged DTH so that it was still detectable 3-6 wk after challenge. The effect of pertussigen was seen only in antigen-driven reactions and was time and dose dependent, with 400 ng given 3 d after immunization resulting in the most prolonged reaction. The administration of pertussigen to the recipients of sensitized lymph node cells resulted in DTH that was more intense and prolonged than the reactions in control mice. Administration of pertussigen provides a model of prolonged and enhanced T cell-dependent inflammatory responses.


Population structure of Columbia spotted frogs (Rana luteiventris) is strongly affected by the landscape.
Landscape features such as mountains, rivers, and ecological gradients may strongly affect patterns of dispersal and gene flow among populations and thereby shape population dynamics and evolutionary trajectories. The landscape may have a particularly strong effect on patterns of dispersal and gene flow in amphibians because amphibians are thought to have poor dispersal abilities. We examined genetic variation at six microsatellite loci in Columbia spotted frogs (Rana luteiventris) from 28 breeding ponds in western Montana and Idaho, USA, in order to investigate the effects of landscape structure on patterns of gene flow. We were particularly interested in addressing three questions: (i) do ridges act as barriers to gene flow? (ii) is gene flow restricted between low and high elevation ponds? (iii) does a pond equal a 'randomly mating population' (a deme)? We found that mountain ridges and elevational differences were associated with increased genetic differentiation among sites, suggesting that gene flow is restricted by ridges and elevation in this species. We also found that populations of Columbia spotted frogs generally include more than a single pond except for very isolated ponds. There was also evidence for surprisingly high levels of gene flow among low elevation sites separated by large distances. Moreover, genetic variation within populations was strongly negatively correlated with elevation, suggesting effective population sizes are much smaller at high elevation than at low elevation. Our results show that landscape features have a profound effect on patterns of genetic variation in Columbia spotted frogs.


Relation between anterograde blood flow through a coronary artery and the size of the perfusion bed it supplies: experimental and clinical implications.
The relation between anterograde blood flow through a coronary artery and the size of the perfusion bed it supplies is not known. Accordingly, the left circumflex coronary artery was cannulated and perfused with arterial blood in 12 open chest mongrel dogs. In Group I dogs (n = 7), the goal was to correlate the size of the perfusion bed with the magnitude of anterogradely derived myocardial blood flow. The size of the perfusion bed was measured with use of two-dimensional myocardial contrast echocardiography, whereas anterograde myocardial blood flow was determined by injecting radiolabeled microspheres directly into the artery. In Group II dogs (n = 5), the goal was to study the effects of altering coronary blood flow on both anterogradely and collateral vessel-derived myocardial flow within the perfusion bed. In these dogs, microspheres were injected directly into both the coronary artery and the left atrium at each flow rate. In Group I dogs, the left circumflex perfusion bed size, as defined by myocardial contrast echocardiography, decreased at lower anterograde myocardial blood flow rates. The change in perfusion bed size occurred at the lateral zones. There was a linear relation between the normalized perfusion bed size and the normalized anterograde myocardial blood flow: y = 0.45x + 54.2 (p less than 0.001, r2 = 0.77). These results were substantiated in Group II dogs, in which the size of the perfusion bed was approximated with use of radiolabeled microspheres. The size of the perfusion bed was most affected when anterograde myocardial blood flow decreased to less than approximately 33% of normal. At the lowest flow rates, there was a linear relation between anterograde blood flow versus the fraction of the left circumflex flow derived anterogradely: y = 2.41x + 0.22 (p less than 0.001, r2 = 0.90). The lower the level of anterograde flow, the greater was the blood flow derived from remote vessels. It is concluded that the size of the area perfused by a coronary artery is significantly influenced by the magnitude of anterograde blood flow through that artery. These findings may have important implications in experimental and clinical models of myocardial ischemia.


Anorexia nervosa.
Anorexia nervosa is characterised by a low body mass index (BMI), fear of gaining weight, denial of current low weight and its impact on health, and amenorrhoea. Estimated prevalence is highest in teenage girls, and up to 0.7% of this age group may be affected. While most people with anorexia nervosa recover completely or partially, about 5% die of the condition, and 20% develop a chronic eating disorder. Young women with anorexia nervosa are at increased risk of bone fractures later in life. We conducted a systematic review, and aimed to answer the following clinical questions: What are the effects of treatments in anorexia nervosa? What are the effects of interventions to prevent or treat complications of anorexia nervosa? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 40 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: atypical antipsychotic drugs, benzodiazepines, cyproheptadine, inpatient/outpatient treatment setting, oestrogen treatment (HRT or oral contraceptives), older-generation antipsychotic drugs, psychotherapy, refeeding, selective serotonin reuptake inhibitors (SSRIs), and tricyclic antidepressants.


Safety and efficacy of outpatient parenteral antibiotic therapy in an academic infectious disease clinic.
Outpatient parenteral therapy (OPAT) has become a safe and effective modality for patients requiring intravenous or prolonged antimicrobial therapy since the 1970s. It is being increasingly utilized in various settings; however, studies evaluating the safety and efficacy of clinic-based OPAT are limited. Since 2012, patients being considered for OPAT have required an infectious disease (ID) consultation at our institution. Candidates receiving once-daily antimicrobials who were ineligible for home infusion or nursing home placement as determined by their insurance companies and those who preferred the clinic over nursing home or home infusion were referred to the ID clinic. This study assessed the safety and outcome of patients receiving OPAT in an academic inner-city ID clinic in Detroit, Michigan. This was a retrospective cross-sectional study of electronic medical records of patients, identified through clinic records, who received at least 2 days of OPAT from December 2012 to December 2015. Demographics, types of infections, antimicrobial regimen used, adverse events and outcome were evaluated. A total of 122 cases were identified during the study period. Mean age was 62 years with 55% male; 102 (84%) of 122 patients had peripherally inserted central catheter (PICC). Fifty-five per cent of patients participated in the clinic-based OPAT programme for insurance reasons, and 43% preferred the clinic over nursing home or home infusion. The most common infections were bone and joint (36%), followed by skin and soft tissue (18%) and urinary tract infections (12%). Ertapenem (44%) and daptomycin (41%) alone or in combination were used most frequently with 40% of patients receiving at least 4 weeks of treatment. Thirteen patients (11%) experienced one or more adverse drug events on daptomycin and/or ertapenem; of these, nine (69%) patients were receiving daptomycin monotherapy. Gastrointestinal symptoms (29%), cramping and myalgias (29%) and asymptomatic creatine phosphokinase (CPK) elevation (24%) were the most common adverse events. Three (3%) of 102 patients had PICC-related complications. Fourteen (88%) of 16 patients with adverse events or PICC-related complications required changing or stopping antibiotics; two (2%) had infection-related readmission. Conversely, 113 (93%) of 122 patients who completed treatment were considered cured and none had treatment failure at the end of 30 days of treatment. No patients died as a result of treatment or infection-related complications. Outpatient parenteral therapy in our academic ID clinic was a safe and effective alternative to home infusion or skilled nursing facilities for patients requiring long-term antibiotics with few adverse events and complications.


Tobacco Use and Its Relationship to Social Determinants of Health in LGBT Populations of a Midwestern State.
Researchers have documented that lesbian, gay, bisexual, and transgender (LGBT) people have a higher proportion of tobacco use as compared to general population smoking rates. This study examined the relationships between tobacco use and social determinants of health in a sample of self-identifying LGBT people who spend time in Nebraska. A community-based participatory research approach was used to develop an online survey to assess the physical, mental, social, and sexual health of LGBT populations who live, work, or play in Nebraska. Chi-squared and logistic regression analyses explored the use of tobacco among respondents. Of the 770 people who completed the survey, 763 respondents completed questions about smoking status. The prevalence of current smoking among these 763 respondents was 26.47%. Some LGBT-specific social determinants of health had significant relationships to smoking status. However, after controlling for known risk factors of smoking in logistic regression models, these variables were not related to smoking status. This study shows that there is a significant relationship between smoking and several general social determinants of health, including employment status, education, and income as well as binge drinking. Limitations include lack of adequate survey respondents to divide subgroups of LGBT individuals and inherent limitations of convenience sampling, which may not allow for an accurate representation of the situation faced by LGBT in Nebraska. In addition to this, the list of LGBT-specific determinants of health used in the survey may not be exhaustive, and there may be additional factors facing LGBT individuals. Public health professionals can use this information in designing smoking reduction campaigns for LGBT populations in Nebraska and culturally similar regions of the United States. These programs and interventions may want to consider a more holistic approach to smoking cessation grounded in the social-ecological model.


Regulation of adult human mesenchymal stem cells into osteogenic and chondrogenic lineages by different bioreactor systems.
The aim of this study was to examine the feasibility of expanding and regulating mesenchymal stem cells (MSCs) from isolated adult human bone marrow mononuclear cells, seeded on gelatin-hyaluronic acid biomatrices, and then to quantitatively compare the gene expression in three different culture systems. Individual and interactive effects of model system parameters on construct structure, function, and molecular properties were evaluated. The results showed that these adult human MSCs even at old age not only expressed primitive mesenchymal cell markers but also maintained a high level of colony-forming efficiency and were capable of differentiating into osteoblasts, chondrocytes, and adipocytes upon appropriate inductions. After 21 days of culture, we found that the osteoblastic and chondrocytic lineage gene expression were earlier and higher expressed in spinner flask bioreactor culture group when compared with the static culture and rotating wall vessel reactor culture. The osteogenic lineage proteins type I collagen, alkaline phosphatase, and osteocalcin were strongly stained in histological sections of spinner flask bioreactor culture, whereas these were less detected in the other two groups, especially in rotating wall vessel reactor culture. As for the markers associated with the chondrogenic lineage differentiation proteins, type II collagen was apparently expressed in spinner flask culture group, while the expression of proteoglycans (aggreacan, decorin) in three culture conditions took the lead of each other. We conclude that the spinner flask bioreactor with appropriate induction medium reported in this study may be used to rapidly expand adult MSCs and is likely to possess better induction results toward osteoblastic and chondrocytic lineages.


SU-E-J-38: Rotational Setup Errors in Pediatric Patients Receiving Radiation Therapy for Intracranial Tumors.
We have clinically observed that larger rotational setup errors are more prominent in pediatric patients who received radiation therapy for brain tumors. In this work, we quantitatively evaluated the daily setup corrections in pitch, roll, and yaw axes for children who received intracranial radiation therapy under x-ray image guidance. Daily localization data of 43 patients between the ages of 10 months and 21.9 years were analyzed in this study. Patients were immobilized with thermoplastic mask during treatments, and 2D orthogonal x-ray images wereacquired for setup corrections before each treatment. Rotational setup corrections in pitch, roll, and yaw axes were extracted from 873 treatment fractions, and were analyzed for the whole group of patients and for two age groups: < 5 and = 5 years old. The mean values for the pitch corrections were 1.91° and 1.65° (p:0.02), roll corrections were 1.37° and 1° (p<0.001), and yaw corrections were 1.93° and 1.47° (p<0.001), respectively. For patients < 5 years, 21.7% of treatments had pitch corrections more than 3°, versus 15.6% of treatments required pitch corrections more than 3° for patients >= 5 years. Similarly, 10.6% of roll corrections and 20.9% of yaw corrections were more than 3° for patients < 5 years. On the other hand, 2.1% of roll and 13.8% of yaw corrections were more than 3° for patients = 5 years old. Data indicate that children less than 5 years old are more prone to rotational setup errors during intracranial radiation therapy. This can be attributed to reduced efficacy of immobilization devices due to smaller and rounder anatomicalfeatures of pediatric patients, and challenges in setup while the patient is under anesthesia. The role of daily image guidance and rotational setup corrections becomes important to ensure target coverage, especially for children < 5 years old.


Dual-coded compressive hyperspectral imaging.
This Letter presents a new snapshot approach to hyperspectral imaging via dual-optical coding and compressive computational reconstruction. We demonstrate that two high-speed spatial light modulators, located conjugate to the image and spectral plane, respectively, can code the hyperspectral datacube into a single sensor image such that the high-resolution signal can be recovered in postprocessing. We show various applications by designing different optical modulation functions, including programmable spatially varying color filtering, multiplexed hyperspectral imaging, and high-resolution compressive hyperspectral imaging.


[Comparative evaluation of the neuroprotective activity of phenotropil and piracetam in laboratory animals with experimental cerebral ischemia].
The neuroprotective properties of phenotropil and piracetam were studied in Wistar rats with low and high sensitivity with respect to cerebral ischemia caused by bilateral irreversible simultaneous occlusion of carotid arteries and gravitational overload in craniocaudal vector. In addition, the effects of both drugs on microcirculation in the brain cortex under ischemic injury conditions were studied. Phenotropil and (to a lower extent) piracetam reduced the extent of neuralgic deficiency manifestations, retained the locomotor, research, and memory functions in animals with gravitational cerebral ischemia, increased the survival of experimental animals, and favored the restoration of local cerebral flow upon the occlusion of carotid arteries.


Knockout and transgenic mice of Trp53: what have we learned about p53 in breast cancer?
The human p53 tumor suppressor gene TP53 is mutated at a high frequency in sporadic breast cancer, and Li-Fraumeni syndrome patients who carry germline mutations in one TP53 allele have a high incidence of breast cancer. In the 10 years since the first knockout of the mouse p53 tumor suppressor gene (designated Trp53) was published, much has been learned about the contribution of p53 to biology and tumor suppression in the breast through the use of p53 transgenic and knockout mice. The original mice deficient in p53 showed no mammary gland phenotype. However, studies using BALB/c-Trp53-deficient mice have demonstrated a delayed involution phenotype and a mammary tumor phenotype. Together with other studies of mutant p53 transgenes and p53 bitransgenics, a greater understanding has been gained of the role of p53 in involution, of the regulation of p53 activity by hormones, of the effect of mouse strain and modifier genes on tumor phenotype, and of the cooperation between p53 and other oncogenic pathways, chemical carcinogens and hormonal stimulation in mammary tumorigenesis. Both p53 transgenic and knockout mice are important in vivo tools for understanding breast cancer, and are yet to be exploited for developing therapeutic strategies in breast cancer.


Clinical outcomes of unrelated donor umbilical cord blood transplantation for 30 adults with hematological malignancies.
Umbilical cord blood transplantation (CBT) has increasingly been used as a therapeutic option for adult patients for whom allogeneic stem-cell transplantation is not indicated, due to the availability of cord blood. However, myeloablative conditioning regimens are associated with significant mortality, and high relapse rates in reduced-intensity regimens may result in a poor rate of disease-free survival for those with advanced stages of hematological malignancies. Therefore, it remains unknown whether CBT is a truly effective option for such adults with high-risk disease, as well as for those with standard-risk disease. Thirty adult patients with a median age of 45 years (range: 16-67) with standard or high-risk disease underwent CBT from unrelated donors at Okayama University Hospital between October 2002 and May 2007. Twenty-one patients had diseases classified as high-risk for transplantation. The median number of nucleated cells in infused cord blood was 2.65 x 10(7)/kg (range: 1.73-4.87). Twenty-three patients achieved neutrophil engraftment at a median time of 22 days (range: 13-42) after CBT. The cumulative incidence of grade II to IV acute graft-versus-host disease (GVHD) was 53.6% . Out of the 30 patients, 11 were alive and disease-free at a median time of 446 days (range: 124-1153) after CBT. The cumulative 1-year overall survival in patients with standard-risk or high-risk disease was 63.5% and 15.4%, respectively (p=0.01). Although from a retrospective study, these results suggest that unrelated donor CBT could be safe and effective for adult patients with standard-risk disease who cannot find a suitable HLA-matched volunteer marrow or peripheral blood donor.


High-performance asymmetric supercapacitors based on monodisperse MnO nanocrystals with high energy densities.
Monodisperse spherical MnO nanocrystals (NCs) with a size of 22.5 nm were synthesized by the thermal decomposition of manganese oleate in the presence of oleic acid and 1-octadecene. The as-synthesized MnO NCs show superior electrochemical performances with a specific capacitance of 736.4 F g-1 at a current density of 1 A g-1 and retain 93.3% of initial specific capacitance after 5000 cycles. The MnO NC electrode was successfully assembled in an asymmetric supercapacitor as the cathode with an activated carbon (AC) electrode as the anode. The as-fabricated device can demonstrate remarkable performance with an energy density of 44.2 W h kg-1, a power density of 900 W kg-1, and excellent cycling stability. This work provides a new direction for MnO nanomaterials towards high-performance energy storage devices.


Genome-Wide Association Study of Behavioral Disinhibition in a Selected Adolescent Sample.
Behavioral disinhibition (BD) is a quantitative measure designed to capture the heritable variation encompassing risky and impulsive behaviors. As a result, BD represents an ideal target for discovering genetic loci that predispose individuals to a wide range of antisocial behaviors and substance misuse that together represent a large cost to society as a whole. Published genome-wide association studies (GWAS) have examined specific phenotypes that fall under the umbrella of BD (e.g. alcohol dependence, conduct disorder); however no GWAS has specifically examined the overall BD construct. We conducted a GWAS of BD using a sample of 1,901 adolescents over-selected for characteristics that define high BD, such as substance and antisocial behavior problems, finding no individual locus that surpassed genome-wide significance. Although no single SNP was significantly associated with BD, restricted maximum likelihood analysis estimated that 49.3 % of the variance in BD within the Caucasian sub-sample was accounted for by the genotyped SNPs (p = 0.06). Gene-based tests identified seven genes associated with BD (p ≤ 2.0 × 10(-6)). Although the current study was unable to identify specific SNPs or pathways with replicable effects on BD, the substantial sample variance that could be explained by all genotyped SNPs suggests that larger studies could successfully identify common variants associated with BD.


Monitoring sputum eosinophils in mucosal inflammation and remodelling: a pilot study.
Normalisation of eosinophil counts in sputum of asthmatic patients reduces eosinophilic exacerbations. However, the effect of this strategy on airway remodelling remains to be determined. We compared bronchial inflammation and collagen deposition after 2 yrs of treatment guided by either sputum eosinophils (sputum strategy, SS) or by clinical criteria (clinical strategy, CS). As a pilot study, 20 mild asthmatic patients were randomly assigned to CS or SS strategies. Bronchial biopsies were obtained when minimum treatment needed to maintain control was identified and this was continued for 2 yrs. Biopsies were immunostained for inflammatory cells, mucin 5A (MUC5A) and collagen. The mean dose of inhaled corticosteroids at the start and end of the study was similar in both SS and CS groups. Forced expiratory volume in 1 s increased in both groups at the study end. In SS, mucosal lymphocyte and eosinophil counts, but not neutrophils, were reduced at the end of the study. In CS, only activated eosinophil and neutrophil counts decreased. MUC5A staining decreased in SS but not CS. No change in collagen deposition underneath the basement membrane was observed in either strategy. Treatment strategies that normalise sputum eosinophils also reduce mucosal inflammatory cells and MUC5A expression, but do not change subepithelial collagen deposition in mild to moderate asthma.


Cholinergic signalling mechanisms and early implant healing phases in healthy versus generalized aggressive periodontitis patients: A prospective, case-control study.
Periodontal diseases negatively affect implant osseointegration. Perturbations in non-neuronal cholinergic signalling mechanisms are associated with periodontitis; however, their role in generalized aggressive periodontitis (GAgP) is unknown. The aim of this prospective case-control study was to determine the relationship between non-neuronal cholinergic signalling mechanisms, secreted Ly-6/uPAR-related protein-1 (SLURP-1), interleukin-17 (IL-17) family cytokines and healing of dental implants in health and GAgP. Thirteen GAgP patients and seven periodontally healthy individuals (PH) were recruited. Peri-implant crevicular fluid (PICF) was obtained at baseline and 1 month post-placement. Acetylcholine (ACh) levels and cholinesterase activity were determined biochemically. SLURP-1, IL-17A and IL-17E levels were determined by ELISA. Marginal bone loss (MBL) at 1 and 6 months post-placement was determined radiographically. The concentration of ACh, cholinesterase activity and IL-17A levels was elevated in PICF of patients with GAgP compared to PH individuals at baseline and 1 month post-placement. The concentration of ACh and cholinesterase activity levels in PICF correlated with levels of IL-17A and MBL around implants 1 month post-placement in patients with GAgP. Non-neuronal cholinergic mechanisms may play a role in the aetiopathogenesis of GAgP and may directly or indirectly, through modulation of IL-17A, influence early implant osseointegration and potential long-term implant survival.


Testicular morphology and spermatogenesis in harbour porpoises (Phocoena phocoena).
Knowledge about reproductive parameters in male harbour porpoises such as testicular histology and germ cell maturation as well as seasonal changes in spermatogenesis is scarce. Thus, the aim of the present study was to report changes in the histological appearance of the testicular morphology of neonatal and juvenile harbour porpoises during maturation, to identify stages of spermatogenesis in adult males and to detect seasonal modifications. The identification of these stages can be used to assess the developmental profile of gene expression during spermatogenesis and to identify defects in spermatogenesis arising in pathological conditions. Testes of adult male harbour porpoises from the North and Baltic Sea that became stranded or by-caught in the years 1998-2016 were histologically examined using Haematoxylin and Eosin - staining. The Periodic Acid Schiff (PAS) staining was used for spermatogenic staging and the evaluation of the development of the acrosomic cap. For the identification of changes in testes morphology and morphometry during the course of the year, histological characteristics like germ cell associations and diameter of the convoluted seminiferous tubules were noted for each month. The analysis showed that in adult males more than one stage of spermatogenesis could be found per cross section of the convoluted seminiferous tubules similar to findings in men and some ape species. This rare phenomenon is called multi-stage-arrangement. In sexually active males from the peak breeding season (June and July) eight stages of spermatogenesis were identified and all stages occurred simultaneously, while during the low breeding season (August to May) only residual spermatogenesis or constituent germ cell populations were found. Missing germ cell generations were recorded in specimens from July to September. Our investigations provide a detailed staging of spermatogenesis and give new insight into the reproductive biology of male harbour porpoises. With these new basic parameters, indicators for endocrine disruptors can be developed in the future, aiming to detect how environmental factors could affect male fertility in wildlife.


Changes in community mobility in older men and women. A 13-year prospective study.
Community mobility, defined as "moving [ones] self in the community and using public or private transportation", has a unique ability to promote older peoples' wellbeing by enabling independence and access to activity arenas for interaction with others. Early predictors of decreased community mobility among older men and women are useful in developing health promoting strategies. However, long-term prediction is rare, especially when it comes to including both public and private transportation. The present study describes factors associated with community mobility and decreased community mobility over time among older men and women. In total, 119 men and 147 women responded to a questionnaire in 1994 and 2007. Respondents were between 82 and 96 years old at follow-up. After 13 years, 40% of men and 43% of women had decreased community mobility, but 47% of men and 45% of women still experienced some independent community mobility. Cross-sectional independent community mobility among men was associated with higher ratings of subjective health, reporting no depression and more involvement in sport activities. Among women, cross-sectional independent community mobility was associated with better subjective health and doing more instrumental activities of daily living outside the home. Lower subjective health predicted decreased community mobility for both men and women, whereas self-reported health conditions did not. Consequently, general policies and individual interventions aiming to improve community mobility should consider older persons' subjective health.


The impact of endometrioma on IVF/ICSI outcomes: a systematic review and meta-analysis.
Endometriosis is a disease known to be detrimental to fertility. Women with endometriosis, and the presence of endometrioma, may require artificial reproductive techniques (ART) to achieve a pregnancy. The specific impact of endometrioma alone and the impact of surgical intervention for endometrioma on the reproductive outcome of women undergoing IVF/ICSI are areas that require further clarification. The objectives of this review were as follows: (i) to determine the impact of endometrioma on IVF/ICSI outcomes, (ii) to determine the impact of surgery for endometrioma on IVF/ICSI outcome and (iii) to determine the effect of different surgical techniques on IVF/ICSI outcomes. We performed a systematic review and meta-analysis examining subfertile women who have endometrioma and are undergoing IVF/ICSI, and who have or have not had any surgical management for endometrioma before IVF/ICSI. The primary outcome was live birth rate (LBR). Our secondary outcomes were clinical pregnancy rate (CPR), mean number of oocyte retrieved (MNOR), miscarriage rate (MR), fertilization rate, implantation rate, antral follicle count (AFC), total stimulating hormone dose, and any rates of adverse effects such as cancellation and associated complications during the IVF/ICSI treatment. We included 33 studies for the meta-analysis. The majority of the studies were retrospective (30/33), and three were RCTs. Compared with women with no endometrioma undergoing IVF/ICSI, women with endometrioma had a similar LBR (odds ratio [OR] 0.98; 95% CI [0.71, 1.36], 5 studies, 928 women, I(2) = 0%) and a similar CPR (OR 1.17; 95% CI [0.87, 1.58], 5 studies, 928 women, I(2) = 0%), a lower mean number of oocytes retrieved (SMD -0.23; 95% CI [-0.37, -0.10], 5 studies, 941 cycles, I(2) = 37%) and a higher cycle cancellation rate compared with those without the disease (OR 2.83; 95% CI [1.32, 6.06], 3 studies, 491 women, I(2) = 0%). Compared with women with no surgical treatment, women who had their endometrioma surgically treated before IVF/ICSI had a similar LBR (OR 0.90; 95% CI [0.63, 1.28], 5 studies, 655 women, I(2) = 32%), a similar CPR (OR 0.97; 95% CI [0.78, 1.20], 11 studies, 1512 women, I(2) = 0%) and a similar mean number of oocytes retrieved (SMD -0.17; 95% CI [-0.38, 0.05], 9 studies, 810 cycles, I(2) = 63%). Women with endometrioma undergoing IVF/ICSI had similar reproductive outcomes compared with those without the disease, although their cycle cancellation rate was significantly higher. Surgical treatment of endometrioma did not alter the outcome of IVF/ICSI treatment compared with those who did not receive surgical intervention. Considering that the reduced ovarian reserve may be attributed to the presence of endometrioma per se, and the potential detrimental impact from surgical intervention, individualization of care for women with endometrioma prior to IVF/ICSI may help optimize their IVF/ICSI results.


Modular Traits of the Rhizobiales Root Microbiota and Their Evolutionary Relationship with Symbiotic Rhizobia.
Rhizobia are a paraphyletic group of soil-borne bacteria that induce nodule organogenesis in legume roots and fix atmospheric nitrogen for plant growth. In non-leguminous plants, species from the Rhizobiales order define a core lineage of the plant microbiota, suggesting additional functional interactions with plant hosts. In this work, genome analyses of 1,314 Rhizobiales isolates along with amplicon studies of the root microbiota reveal the evolutionary history of nitrogen-fixing symbiosis in this bacterial order. Key symbiosis genes were acquired multiple times, and the most recent common ancestor could colonize roots of a broad host range. In addition, root growth promotion is a characteristic trait of Rhizobiales in Arabidopsis thaliana, whereas interference with plant immunity constitutes a separate, strain-specific phenotype of root commensal Alphaproteobacteria. Additional studies with a tripartite gnotobiotic plant system reveal that these traits operate in a modular fashion and thus might be relevant to microbial homeostasis in healthy roots.


Allergic rhinitis: evidence for impact on asthma.
This paper reviews the current evidence indicating that comorbid allergic rhinitis may have clinically relevant effects on asthma. Allergic rhinitis is very common in patients with asthma, with a reported prevalence of up to 100% in those with allergic asthma. While the temporal relation of allergic rhinitis and asthma diagnoses can be variable, the diagnosis of allergic rhinitis often precedes that of asthma. Rhinitis is an independent risk factor for the subsequent development of asthma in both atopic and nonatopic individuals. Controlled studies have provided conflicting results regarding the benefits for asthma symptoms of treating comorbid allergic rhinitis with intranasal corticosteroids. Effects of other treatments for comorbid allergic rhinitis, including antihistamines, allergen immunotherapy, systemic anti-IgE therapy, and antileukotriene agents, have been examined in a limited number of studies; anti-IgE therapy and antileukotriene agents such as the leukotriene receptor antagonists have benefits for treating both allergic rhinitis and asthma. Results of observational studies indicate that treating comorbid allergic rhinitis results in a lowered risk of asthma-related hospitalizations and emergency visits. Results of several retrospective database studies in the United States and in Europe indicate that, for patients with asthma, the presence of comorbid allergic rhinitis is associated with higher total annual medical costs, greater prescribing frequency of asthma-related medications, as well as increased likelihood of asthma-related hospital admissions and emergency visits. There is therefore evidence suggesting that comorbid allergic rhinitis is a marker for more difficult to control asthma and worsened asthma outcomes. These findings highlight the potential for improving asthma outcomes by following a combined therapeutic approach to comorbid allergic rhinitis and asthma rather than targeting each condition separately.


Out and down: incarceration and psychiatric disorders.
Psychiatric disorders are unusually prevalent among current and former inmates, but it is not known what this relationship reflects. A putative causal relationship is contaminated by assorted influences, including childhood disadvantage, the early onset of most disorders, and the criminalization of substance use. Using the National Comorbidity Survey Replication (N = 5692), we examine the relationship between incarceration and psychiatric disorders after statistically adjusting for multidimensional influences. The results indicate that (1) some of the most common disorders found among former inmates emerge in childhood and adolescence and therefore predate incarceration; (2) the relationships between incarceration and disorders are smaller for current disorders than lifetime disorders, suggesting that the relationship between incarceration and disorders dissipates over time; and (3) early substance disorders anticipate later incarceration and other psychiatric disorders simultaneously, indicating selection. Yet the results also reveal robust and long-lasting relationships between incarceration and certain disorders, which are not inconsequential for being particular. Specifically, incarceration is related to subsequent mood disorders, related to feeling "down," including major depressive disorder, bipolar disorder, and dysthymia. These disorders, in turn, are strongly related to disability, more strongly than substance abuse disorders and impulse control disorders. Although often neglected as a health consequence of incarceration, mood disorders might explain some of the additional disability former inmates experience following release, elevating their relevance for those interested in prisoner reintegration.


Mechanism of pingyangmycin-induced apoptosis of cultured human umbilical vein endothelial cells.
In this study, we investigated the effects of pingyangmycin (PYM) on the growth inhibition and apoptosis of human umbilical vein endothelial cells (HUVEC). In this study, we aimed to explore the optimal concentration of PYM to induce the apoptosis of HUVEC and to determine its mechanism of action. After treatment of HUVEC with different concentrations of PYM for 24 h, cell counting kit-8 (CCK-8) was used to detect growth inhibiting effects. Annexin V-FITC/propidium iodide stain was used to detect apoptosis, and western blot was used to detect the expression of glucose-related protein 78 (GPR78) and C/EBP homologous protein (CHOP) endoplasmic reticulum stress proteins. With increasing PYM concentration, the growth inhibition of HUVEC increased (P < 0.05), the apoptotic numbers of HUVEC increased (P < 0.05), with higher PYM concentrations inducing necrosis, and the protein expression of GRP78 and CHOP increased (P < 0.05). PYM could obviously inhibit the proliferation and promote the apoptosis of HUVEC. Necrotic cells were more prevalent than apoptotic cells at high PYM concentrations. This study helped to determine the proper concentration of PYM to induce more apoptosis than necrosis, which is critical to minimize inflammation, enhance the healing of the skin, and maintain safety for the patient. PYM might induce HUVEC apoptosis through the endoplasmic reticulum stress pathway.


PRL1, an RNA-binding protein, positively regulates the accumulation of miRNAs and siRNAs in Arabidopsis.
The evolutionary conserved WD-40 protein PRL1 plays important roles in immunity and development. Here we show that PRL1 is required for the accumulation of microRNAs (miRNAs) and small interfering RNAs (siRNAs). PRL1 positively influences the processing of miRNA primary transcripts (pri-miRNAs) and double-stranded RNAs (dsRNAs). Furthermore, PRL1 interacts with the pri-miRNA processor, DCL1, and the dsRNA processors (DCL3 and DCL4). These results suggest that PRL1 may function as a general factor to promote the production of miRNAs and siRNAs. We also show that PRL1 is an RNA-binding protein and associates with pri-miRNAs in vivo. In addition, prl1 reduces pri-miRNA levels without affecting pri-miRNA transcription. These results suggest that PRL1 may stabilize pri-miRNAs and function as a co-factor to enhance DCL1 activity. We further reveal the genetic interaction of PRL1 with CDC5, which interacts with PRL1 and regulates transcription and processing of pri-miRNAs. Both miRNA and pri-miRNA levels are lower in cdc5 prl1 than those in either cdc5 or prl1. However, the processing efficiency of pri-miRNAs in cdc5 prl1 is similar to that in cdc5 and slightly lower than that in prl1. Based on these results, we propose that CDC5 and PRL1 cooperatively regulate pri-miRNA levels, which results in their synergistic effects on miRNA accumulation, while they function together as a complex to enhance DCL1 activity.