Sensitivity and specificity of fluorescence microlymphography for detecting lymphedema of the lower extremity

Fluorescence microlymphography (FML) is used to visualize the lymphatic capillaries. A maximum spread of the fluorescence dye of ≥ 12 mm has been suggested for the diagnosis of lymphedema. However, data on sensitivity and specificity are lacking. The aim of this study was to investigate the accuracy of FML for diagnosing lymphedema in patients with leg swelling. Patients with lower extremity swelling were clinically assessed and separated into lymphedema and non-lymphatic edema groups. FML was studied in all affected legs and the maximum spread of lymphatic capillaries was measured. Test accuracy and receiver operator characteristic (ROC) analysis was performed to assess possible threshold values that predict lymphedema. Between March 2008 and August 2011 a total of 171 patients (184 legs) with a median age of 43.5 (IQR 24, 54) years were assessed. Of those, 94 (51.1%) legs were diagnosed with lymphedema. The sensitivity, specificity, positive and negative likelihood ratio and positive and negative predictive value were 87%, 64%, 2.45, 0.20, 72% and 83% for the 12-mm cut-off level and 79%, 83%, 4.72, 0.26, 83% and 79% for the 14-mm cut-off level, respectively. The area under the ROC curve was 0.82 (95% CI: 0.76, 0.88). Sensitivity was higher in the secondary versus primary lymphedema (95.0% vs 74.3%, p = 0.045). No major adverse events were observed. In conclusion, FML is a simple and safe technique for detecting lymphedema in patients with leg swelling. A cut-off level of ≥ 14-mm maximum spread has a high sensitivity and high specificity of detecting lymphedema and should be chosen.

[(99m)Tc]Demotate 2 in the detection of sst(2)-positive tumours: a preclinical comparison with [(111)In]DOTA-tate

PURPOSE: The aim of this study was to evaluate [(99m)Tc]Demotate 2 ([(99m)Tc-N(4) (0-1),Asp(0),Tyr(3)]octreotate) as a candidate for in vivo imaging of sst(2)-positive tumours and to compare it with [(111)In]DOTA-tate ([(111)In-DOTA(0),Tyr(3)]octreotate). METHODS: Labelling of Demotate 2 with (99m)Tc was performed at room temperature using SnCl(2) as reductant in the presence of citrate at alkaline pH. Radiochemical analysis involved ITLC and HPLC methods. Peptide conjugate affinities for sst(2) were determined by receptor autoradiography on rat brain cortex sections using [DOTA(0),(125)I-Tyr(3)]octreotate as the radioligand. The affinity profile of Demotate 2 for human sst(1)-sst(5) was studied by receptor autoradiography in cell preparations using the universal somatostatin radioligand [(125)I][Leu(8),(D: )Trp(22),Tyr(25)]somatostatin-28. The internalisation rates of [(99m)Tc]Demotate 2 and [(111)In]DOTA-tate were compared in sst(2)-positive and -negative control cell lines. Biodistribution of radiopeptides was studied in male Lewis rats bearing CA20948 tumours. RESULTS: Peptide conjugates showed selectivity and a high affinity binding for sst(2) (Demotate 2 IC(50)=3.2 nM and DOTA-tate IC(50)=5.4 nM). [(99m)Tc]Demotate 2, like [(111)In]DOTA-tate, internalised rapidly in all sst(2)-positive cells tested, but not in sst(2)-negative control cells. After injection in CA20948 tumour-bearing rats both radiopeptides showed high and specific uptake in the sst(2)-positive organs and in the implanted tumour and rapid excretion from non-target tissues via the kidneys. CONCLUSION: [(99m)Tc]Demotate 2, similarly to the known sst(2)-targeting agent [(111)In]DOTA-tate, showed promising biological qualities for application in the scintigraphy of sst(2)-positive tumours.

Microalbuminuria in diabetes mellitus: efficacy of a new screening method in comparison with timed overnight urine collection

Diabetic nephropathy and end-stage renal failure are still a major cause of mortality amongst patients with diabetes mellitus (DM). In this study, we evaluated the Clinitek-Microalbumin (CM) screening test strip for the detection of microalbuminuria (MA) in a random morning spot urine in comparison with the quantitative assessment of albuminuria in the timed overnight urine collection ("gold standard"). One hundred thirty-four children, adolescents, and young adults with insulin-dependent DM Type 1 were studied at 222 outpatient visits. Because of urinary tract infection and/or haematuria, the data of 13 visits were excluded. Finally, 165 timed overnight urine were collected in the remaining 209 visits (79% sample per visit rate). Ten (6.1%) patients presented MA of > or =15 microg/min. In comparison however, 200 spot urine could be screened (96% sample/visit rate) yielding a significant increase in compliance and screening rate (P<.001, McNemar test). Furthermore, at 156 occasions, the gold standard and CM could be directly compared. The sensitivity and the specificity for CM in the spot urine (cut-off > or =30 mg albumin/l) were 0.89 [95% confidence interval (CI) 0.56-0.99] and 0.73 (CI 0.66-0.80), respectively. The positive and negative predictive value were 0.17 (CI 0.08-0.30) and 0.99 (CI 0.95-1.00), respectively. Considering CM albumin-to-creatinine ratio, the results were poorer than with the albumin concentration alone. Using CM instead of quantitative assessment of albuminuria is not cost-effective (35 US dollars versus 60 US dollars/patient/year). In conclusion, to exclude MA, the CM used in the random spot urine is reliable and easy to handle, but positive screening results of > or =30 mg albumin/l must be confirmed by analyses in the timed overnight collected urine. Although the screening compliance is improved, in terms of analysing random morning spot urine for MA, we cannot recommend CM in a paediatric diabetic outpatient setting because the specificity is far too low.

[Bisexuality and AIDS. Implications for heterosexual HIV infections in women]

One of the possible pathways into heterosexual population is the transfer of HIV-virus from bisexual men to their female partners. Therefore sexual behaviour of HIV-positive and -negative bisexual men (n = 31) before and after Aids-disease was analysed. Prior to the Aids-epidemic promiscuous behavior towards male partners (about one female partner per year versus 10 male partners per year). Relatively common contacts to woman occurred within steady relationships. After contact with HIV-test and personal counselling sexual practice became significantly different. The number of female and male contacts was markedly reduced, especially female chance acquaintances were avoided; safer sex was preferred and readiness to inform female partners about bisexuality was increased. This study suggests that reduction of risk for HIV-infection of female partners by homosexual men can be achieved by means of a HIV-test and personal counselling, a possibility that should be considered in preventive concepts.

Crizotinib inhibits migration and expression of ID1 in MET-positive lung cancer cells: implications for MET targeting in oncology

ABSTRACT Aims: ID1 is an important component of the MET-SRC signaling pathway, which is a regulator of cell migration and invasion. We hypothesized that the ALK/MET inhibitor crizotinib inhibits migration via MET-SRC-ID1, rather than ALK. Materials & methods: We used ALK fusion-positive and -negative lung cancer cell lines; crizotinib, PHA-665752, and saracatinib, and stable transfection with shMET. We performed western blotting for p-ALK, ALK, p-MET, MET, p-SRC, SRC and ID1, and quantitative real-time PCR for ID1. Results: Crizotinib decreased p-MET, p-SRC and ID1 levels in ALK- and or MET-positive cell lines and inhibited cell migration. Knockdown of MET was comparable with the effect of crizotinib. Conclusion: The effects of crizotinib on ID1 expression and cancer cell migration were associated with the presence of activated MET, rather than ALK fusion.

Positive Affect and Sleep in Spousal Alzheimer Caregivers: A Longitudinal Study.

This article examines the longitudinal relation between positive affect (PA) and sleep in 126 spousal Alzheimer's disease caregivers. Caregivers underwent 4 yearly assessments for the Positive and Negative Affect Schedule, the self-rated Pittsburgh Sleep Quality Index, and actigraphy to objectify nighttime total sleep time, wake after sleep onset, and percentage of sleep. Increased levels of PA and a greater positivity (i.e., positive-to-negative affect) ratio were significantly associated with better subjective sleep over the entire study period. Yearly increases in PA-even when controlling for negative affect (NA)-and in the positivity ratio were also associated with better subjective sleep. PA and actigraphy measures showed no significant relations. Increased PA is longitudinally associated with better sleep in dementia caregivers largely independent of NA.

Warm Conveyor Belts in the ERA-Interim Dataset (1979–2010): Part I: Climatology and Potential Vorticity Evolution

A global climatology of warm conveyor belts (WCBs) is presented for the years 1979–2010, based on trajectories calculated with Interim ECMWF Re-Analysis (ERA-Interim) data. WCB trajectories are identified as strongly ascending air parcels (600 hPa in 2 days) near extratropical cyclones. Corroborating earlier studies, WCBs are more frequent during winter than summer and they ascend preferentially in the western ocean basins between 25° and 50° latitude. Before ascending, WCB trajectories typically approach from the subtropics in summer and from more midlatitude regions in winter. Considering humidity, cloud water, and potential temperature along WCBs confirms that they experience strong condensation and integrated latent heating during the ascent (typically >20 K). Liquid and ice water contents along WCBs peak at about 700 and 550 hPa, respectively. The mean potential vorticity (PV) evolution shows typical tropospheric values near 900 hPa, followed by an increase to almost 1 potential vorticity unit (PVU) at 700 hPa, and a decrease to less than 0.5 PVU at 300 hPa. These low PV values in the upper troposphere constitute significant negative anomalies with amplitudes of 1–3 PVU, which can strongly influence the downstream flow. Considering the low-level diabatic PV production, (i) WCBs starting at low latitudes (<40°) are unlikely to attain high PV (due to weak planetary vorticity) although they exhibit the strongest latent heating, and (ii) for those ascending at higher latitudes, a strong vertical heating gradient and high absolute vorticity are both important. This study therefore provides climatological insight into the cloud diabatic formation of significant positive and negative PV anomalies in the extratropical lower and upper troposphere, respectively.

CD14-Dependent Monocyte Isolation Enhances Phagocytosis of Listeria monocytogenes by Proinflammatory, GM-CSF-Derived Macrophages

Macrophages are an important line of defence against invading pathogens. Human macrophages derived by different methods were tested for their suitability as models to investigate Listeria monocytogenes (Lm) infection and compared to macrophage-like THP-1 cells. Human primary monocytes were isolated by either positive or negative immunomagnetic selection and differentiated in the presence of granulocyte macrophage colony-stimulating factor (GM-CSF) or macrophage colony-stimulating factor (M-CSF) into pro- or anti-inflammatory macrophages, respectively. Regardless of the isolation method, GM-CSF-derived macrophages (GM-Mφ) stained positive for CD206 and M-CSF-derived macrophages (M-Mφ) for CD163. THP-1 cells did not express CD206 or CD163 following incubation with PMA, M- or GM-CSF alone or in combination. Upon infection with Lm, all primary macrophages showed good survival at high multiplicities of infection whereas viability of THP-1 was severely reduced even at lower bacterial numbers. M-Mφ generally showed high phagocytosis of Lm. Strikingly, phagocytosis of Lm by GM-Mφ was markedly influenced by the method used for isolation of monocytes. GM-Mφ derived from negatively isolated monocytes showed low phagocytosis of Lm whereas GM-Mφ generated from positively selected monocytes displayed high phagocytosis of Lm. Moreover, incubation with CD14 antibody was sufficient to enhance phagocytosis of Lm by GM-Mφ generated from negatively isolated monocytes. By contrast, non-specific phagocytosis of latex beads by GM-Mφ was not influenced by treatment with CD14 antibody. Furthermore, phagocytosis of Lactococcus lactis, Escherichia coli, human cytomegalovirus and the protozoan parasite Leishmania major by GM-Mφ was not enhanced upon treatment with CD14 antibody indicating that this effect is specific for Lm. Based on these observations, we propose macrophages derived by ex vivo differentiation of negatively selected human primary monocytes as the most suitable model to study Lm infection of macrophages.

A Research Roadmap for Complementary and Alternative Medicine – What We Need to Know by 2020

Background: The CAMbrella coordination action was funded within the Framework Programme 7. Its aim is to provide a research roadmap for clinical and epidemiological research for complementary and alternative medicine (CAM) that is appropriate for the health needs of European citizens and acceptable to their national research institutes and healthcare providers in both public and private sectors. One major issue in the European research agenda is the demographic change and its impact on health care. Our vision for 2020 is that there is an evidence base that enables European citizens to make informed decisions about CAM, both positive and negative. This roadmap proposes a strategic research agenda for the field of CAM designed to address future European health care challenges. This roadmap is based on the results of CAMbrella’s several work packages, literature reviews and expert discussions including a consensus meeting. Methods: We first conducted a systematic literature review on key issues in clinical and epidemiological research in CAM to identify the general concepts, methods and the strengths and weaknesses of current CAM research. These findings were discussed in a workshop (Castellaro, Italy, September 7–9th 2011) with international CAM experts and strategic and methodological recommendations were defined in order to improve the rigor and relevance of CAM research. These recommendations provide the basis for the research roadmap, which was subsequently discussed in a consensus conference (Järna, Sweden, May 9–11th 2012) with all CAMbrella members and the CAMbrella advisory board. The roadmap was revised after this discussion in CAMbrella Work Package (WP) 7 and finally approved by CAMbrella’s scientific steering committee on September 26th 2012. Results: Our main findings show that CAM is very heterogenous in terms of definitions and legal regulations between the European countries. In addition, citizens’ needs and attitudes towards CAM as well as the use and provision of CAM differ significantly between countries. In terms of research methodology, there was consensus that CAM researchers should make use of all the commonly accepted scientific research methods and employ those with utmost diligence combined in a mixed methods framework. Conclusions: We propose 6 core areas of research that should be investigated to achieve a robust knowledge base and to allow stakeholders to make informed decisions. These are: Research into the prevalence of CAM in Europe: Reviews show that we do not know enough about the circumstances in which CAM is used by Europeans. To enable a common European strategic approach, a clear picture of current use is of the utmost importance. Research into differences regarding citizens’ attitudes and needs towards CAM: Citizens are the driver for CAM utilization. Their needs and views on CAM are a key priority, and their interests must be investigated and addressed in future CAM research. Research into safety of CAM: Safety is a key issue for European citizens. CAM is considered safe, but reliable data is scarce although urgently needed in order to assess the risk and cost-benefit ratio of CAM. Research into the comparative effectiveness of CAM: Everybody needs to know in what situation CAM is a reasonable choice. Therefore, we recommend a clear emphasis on concurrent evaluation of the overall effectiveness of CAM as an additional or alternative treatment strategy in real-world settings. Research into effects of context and meaning: The impact of effects of context and meaning on the outcome of CAM treatments must be investigated; it is likely that they are significant. Research into different models of CAM health care integration: There are different models of CAM being integrated into conventional medicine throughout Europe, each with their respective strengths and limitations. These models should be described and concurrently evaluated; innovative models of CAM provision in health care systems should be one focus for CAM research. We also propose a methodological framework for CAM research. We consider that a framework of mixed methodological approaches is likely to yield the most useful information. In this model, all available research strategies including comparative effectiveness research utilising quantitative and qualitative methods should be considered to enable us to secure the greatest density of knowledge possible. Stakeholders, such as citizens, patients and providers, should be involved in every stage of developing the specific and relevant research questions, study design and the assurance of real-world relevance for the research. Furthermore, structural and sufficient financial support for research into CAM is needed to strengthen CAM research capacity if we wish to understand why it remains so popular within the EU. In order to consider employing CAM as part of the solution to the health care, health creation and self-care challenges we face by 2020, it is vital to obtain a robust picture of CAM use and reliable information about its cost, safety and effectiveness in real-world settings. We need to consider the availability, accessibility and affordability of CAM. We need to engage in research excellence and utilise comparative effectiveness approaches and mixed methods to obtain this data. Our recommendations are both strategic and methodological. They are presented for the consideration of researchers and funders while being designed to answer the important and implicit questions posed by EU citizens currently using CAM in apparently increasing numbers. We propose that the EU actively supports an EUwide strategic approach that facilitates the development of CAM research. This could be achieved in the first instance through funding a European CAM coordinating research office dedicated to foster systematic communication between EU governments, public, charitable and industry funders as well as researchers, citizens and other stakeholders. The aim of this office would be to coordinate research strategy developments and research funding opportunities, as well as to document and disseminate international research activities in this field. With the aim to develop sustainability as second step, a European Centre for CAM should be established that takes over the monitoring and further development of a coordinated research strategy for CAM, as well as it should have funds that can be awarded to foster high quality and robust independent research with a focus on citizens health needs and pan-European collaboration. We wish to establish a solid funding for CAM research to adequately inform health care and health creation decision-making throughout the EU. This centre would ensure that our vision of a common, strategic and scientifically rigorous approach to CAM research becomes our legacy and Europe’s reality. We are confident that our recommendations will serve these essential goals for EU citizens.

Entwicklung der Fünf-Item-Kurzskala STAI-SKD zur Messung von Zustandsangst

Das State-Trait-Angstinventar (STAI) ist eines der am häufigsten eingesetzten Erhebungsinstrumente im Bereich der Angstdiagnostik. Die STAI-Skala zur Erfassung von Zustandsangst umfasst 20 Items. Unter bestimmten Erhebungsbedingungen erweist es sich als relativ schwierig, eine große Menge an Items zu bearbeiten oder aber es steht nicht ausreichend Testzeit zur Verfügung. Daher war es das Ziel der vorliegenden Studie, eine Kurzform der State-Version des STAI zu entwickeln. An einer Stichprobe von N = 65 Studierenden wurde aufgrund inhaltlicher und statistischer Kriterien eine Kurzform der State-Version des STAI, das STAI-SKD, mit fünf Items generiert. Eine konfirmatorische Faktorenanalyse an einer zweiten Stichprobe von N = 191 Studierenden zeigte, dass das STAI-SKD die Angstkomponenten Emotionality und Worry abbildet. Die Beziehungen des STAI-SKD zu positivem und negativem Affekt sowie dessen Veränderungssensitivität fielen in einer dritten Stichprobe (N = 80 Studierende) erwartungsgemäß aus. Die neue Kurzform der State-Version des STAI erlaubt eine ökonomische Erfassung der Zustandsangst.

Examining invisible social control as predictor of daily smoking and negative affect after a self-set quit date

Objectives: The dual-effects model of social control proposes that social control leads to better health practices, but also arouses psychological distress. However, findings are inconsistent in relation to health behavior and psychological distress. Recent research suggests that the most effective control is unnoticed by the receiver (i.e., invisible). There is some evidence that invisible social control is beneficial for positive and negative affective reactions. Yet, investigations of the influence of invisible social control on daily smoking and distress have been limited. In daily diaries, we investigated how invisible social control is associated with number of cigarettes smoked and negative affect on a daily basis. Methods: Overall, 99 smokers (72.0% men, mean age M = 40.48, SD = 9.82) and their non-smoking partners completed electronic diaries from a self-set quit date for 22 consecutive days within the hour before going to bed, reporting received and provided social control, daily number of cigarettes smoked, and negative affect. Results: Multilevel analyses indicated that between-person levels of invisible social control were associated with lower negative affect, whereas they were unrelated to number of cigarettes smoked. On days with higher-than-average invisible social control, smokers reported less cigarettes smoked and more negative affect. Conclusions: Between-person level findings indicate that invisible social control can be beneficial for negative affect. However, findings on the within-person level are in line with the assumptions of the dual-effects model of social control: Invisible social control reduced daily smoking and simultaneously increased daily negative affect within person.

Life-span development of self-esteem and its effects on important life outcomes

We examined the life-span development of self-esteem and tested whether self-esteem influences the development of important life outcomes, including relationship satisfaction, job satisfaction, occupational status, salary, positive and negative affect, depression, and physical health. Data came from the Longitudinal Study of Generations. Analyses were based on 5 assessments across a 12-year period of a sample of 1,824 individuals ages 16 to 97 years. First, growth curve analyses indicated that self-esteem increases from adolescence to middle adulthood, reaches a peak at about age 50 years, and then decreases in old age. Second, cross-lagged regression analyses indicated that self-esteem is best modeled as a cause rather than a consequence of life outcomes. Third, growth curve analyses, with self-esteem as a time-varying covariate, suggested that self-esteem has medium-sized effects on life-span trajectories of affect and depression, small to medium-sized effects on trajectories of relationship and job satisfaction, a very small effect on the trajectory of health, and no effect on the trajectory of occupational status. These findings replicated across 4 generations of participants— children, parents, grandparents, and their great-grandparents. Together, the results suggest that self-esteem has a significant prospective impact on real-world life experiences and that high and low self-esteem are not mere epiphenomena of success and failure in important life domains.

Longitudinal associations between causal sexual relationships and stressful life events in emerging adults

Findings on the consequences of casual sexual relationships (CSR) are inconsistent and range from positive to negative outcomes. The longitudinal association between stressful live events and CSR was investigated in a random sample of 2844 Swiss emerging adults. Cross-lagged panel models with baseline, two- and five-year follow-up data showed that life events predicted more subsequent CSR across emerging adulthood. In contrast, CSR predicted life events only from the first to the second wave. Results suggest that the link between stressful life events and CSR was mainly explained by romantic breakups as stressful life event. Environment-related life events were not substantially associated with casual sexual relationships. Thus, engaging in CSR did not seem to be a general emotion-focused coping strategy in the context of life events nor can the engagement in casual sex be seen as a result of stressful life events affecting general self-regulation.

Enhanced emotional empathy after psychosocial stress in young healthy men

Empathy is a core prerequisite for human social behavior. Relatively, little is known about how empathy is influenced by social stress and its associated neuroendocrine alterations. The current study was designed to test the impact of acute stress on emotional and cognitive empathy. Healthy male participants were exposed to a psychosocial laboratory stressor (trier social stress test, (TSST)) or a well-matched control condition (Placebo-TSST). Afterwards they participated in an empathy test measuring emotional and cognitive empathy (multifaceted empathy test, (MET)). Stress exposure caused an increase in negative affect, a rise in salivary alpha amylase and a rise in cortisol. Participants exposed to stress reported more emotional empathy in response to pictures displaying both positive and negative emotional social scenes. Cognitive empathy (emotion recognition) in contrast did not differ between the stress and the control group. The current findings provide initial evidence for enhanced emotional empathy after acute psychosocial stress.

The Psychological Outcome of Religious Coping with Stressful Life Events in a Swiss Sample of Church Attendees

Background: Recent research suggested thatreligious coping, based on dispositional religiousness and spirituality (R/S), is an important modulating factor in the process of dealing with adversity. In contrast to the United States, the effect of R/S on psychological adjustment to stress is a widely unexplored area in Europe. Methods: We examined a Swiss sample of 328 church attendees in the aftermath of stressful life events to explore associations of positive or negative religious coping with the psychological outcome. Applying a cross-sectional design, we used Huber’s Centrality Scale to specify religiousness and Pargament’s measure of religious coping (RCOPE) for the assessment of positive and negative religious coping. Depressive symptoms and anxiety as outcome variables were examined by the Brief Symptom Inventory. The Stress-Related Growth Scale and the Marburg questionnaire for the assessment of well-being were used to assess positive outcome aspects. We conducted Mann-Whitney tests for group comparisons and cumulative logit analysis for the assessmentof associations of religious coping with our outcome variables. Results: Both forms of religious coping were positively associated with stress-related growth (p < 0.01). However, negative religious coping additionally reduced well-being (p = 0.05, β = 0.52, 95% CI = 0.27–0.99) and increased anxiety (p = 0.02, β = 1.94, 95% CI = 1.10–3.39) and depressive symptoms (p = 0.01, β = 2.27, 95% CI = 1.27–4.06). Conclusions: The effects of religious coping on the psychological adjustment to stressful life events seem relevant. These findings should be confirmed in prospective studies.