Closing the gap: cardiovascular disease in women.

Cardiovascular disease (CVD) in women remains understudied, under-recognized, underdiagnosed and undertreated. Initiatives such as the Lancet Women and Cardiovascular Disease Commission help to identify sex and gender-related gaps in research, care and outcomes and to guide next steps in addressing them. This article highlights important aspects of the Lancet Commission report and expands on the evidence and proposed strategies for reducing the global burden of CVD in women. Furthermore, the article explores the benefits of cross-specialty collaborations for the treatment and prevention of CVD in women and discusses the impact of gender-related disparities in academic cardiology.

Primary prevention of cardiovascular disease in women.

Ischemic heart disease is the primary cause of cardiovascular disease (CVD) mortality in both men and women. Strategies targeting traditional modifiable risk factors are essential - including hypertension, smoking, dyslipidemia and diabetes mellitus - particularly for atherosclerosis, but additionally for stroke, heart failure and some arrhythmias. However, challenges related to education, screening and equitable access to effective preventative therapies persist, and are particularly problematic for women around the globe and those from lower socioeconomic groups. The association of female-specific risk factors (e.g. premature menopause, gestational hypertension, small for gestational age births) with CVD provides a potential window for targeted prevention strategies. However, further evidence for specific effective screening and interventions is urgently required. In addition to population-level factors involved in increasing the risk of suffering a CVD event, efforts are leveraging the enormous potential of blood-based 'omics', improved imaging biomarkers and increasingly complex bioinformatic analytic approaches to strive toward more personalized early disease detection and personalized preventative therapies. These novel tactics may be particularly relevant for women in whom traditional risk factors perform poorly. Here we discuss established and emerging approaches for improving risk assessment, early disease detection and effective preventative strategies to reduce the mammoth burden of CVD in women.

Key Issues for Seamless Integrated Chemistry-Meteorology Modeling.

Online coupled meteorology-atmospheric chemistry models have greatly evolved in recent years. Although mainly developed by the air quality modeling community, these integrated models are also of interest for numerical weather prediction and climate modeling, as they can consider both the effects of meteorology on air quality and the potentially important effects of atmospheric composition on weather. This paper summarizes the main conclusions from the "Symposium on Coupled Chemistry-Meteorology/Climate Modelling: Status and Relevance for Numerical Weather Prediction, Air Quality and Climate Research," which was initiated by the European COST Action ES1004 "European Framework for Online Integrated Air Quality and Meteorology Modelling (EuMetChem)." It offers a brief review of the current status of online coupled meteorology and atmospheric chemistry modeling and a survey of processes relevant to the interactions between atmospheric physics, dynamics, and composition. In addition, it highlights scientific issues and emerging challenges that require proper consideration to improve the reliability and usability of these models for three main application areas: air quality, meteorology (including weather prediction), and climate modeling. It presents a synthesis of scientific progress in the form of answers to nine key questions, and provides recommendations for future research directions and priorities in the development, application, and evaluation of online coupled models.

The effectiveness of the paclitaxel-coated Luminor® balloon catheter versus an uncoated balloon catheter in superficial femoral and popliteal arteries in preventing vessel restenosis or reocclusion: study protocol for a randomized controlled trial.

BACKGROUND: The aim of this investigator-initiated trial is to evaluate the safety and efficacy of the novel Luminor® paclitaxel-coated drug-eluting balloon (DEB) catheter (iVascular, S.L.U., Barcelona, Spain) in inhibiting restenosis and in ensuring long-term vascular patency. METHODS/DESIGN: This is a multicenter randomized controlled trial to evaluate the Luminor® paclitaxel-coated DEB catheter for stenotic or occlusive lesions (length ≤15 cm) in the superficial femoral artery (SFA) and the popliteal artery (PA) up to the P1 segment compared to the noncoated, plain old balloon angioplasty (POBA) catheter. In total 172 subjects will be treated with either the DEB catheter or the POBA catheter in 11 German study centers in a 1:1 randomization study design. The primary endpoint is late lumen loss (LLL) at 6 months. Secondary endpoints are patency rate, target lesion/vessel revascularization, quality of life (assessed with the Walking Impairment Questionnaire (WIQ) and the EQ-5D), change of Rutherford stage and ankle-brachial index, major and minor amputation rate at the index limb, number of dropouts and all-cause mortality. DISCUSSION: EffPac represents a randomized controlled trial that will provide evidence on the effectiveness of the Luminor® paclitaxel-coated DEB catheter for the reduction of restenosis compared to the POBA catheter for the SFA and the PA. The results of EffPac will allow direct comparison to other already-completed RCTs applying paclitaxel-coated DEBs from different manufacturers with different coating technologies in the same target vessel. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02540018 , registered on 17 August 2015. Protocol version: CIP Version Final04, 11 February 2016. EUDAMED No: CIV-15-03-013204.

Renal Artery Stenosis - are there Patients who Benefit from Intervention?

Atherosclerotic renal artery stenosis (ARAS) is one of the most relevant long-term complications of atherosclerotic disease. It is associated both with hypertension and increased renal and cardiovascular risk and overall mortality. Diagnostic modalities include non-invasive duplex ultrasound, dynamic magnetic resonance angiography (MRA) and computer tomography angiography (CTA) and are confirmed by using invasive renal angiography. Percutaneous revascularization of renal artery stenosis has been studied in various clinical trials. With regard to hypertension, several case series could show a clinical response to revascularization. However, the majority of randomized clinical trials could not confirm the correlation between intervention and the improvement of hypertension, kidney function, cardiovascular events, and mortality. Based on this predication the crucial tool in the treatment of ARAS is an optimal medical therapy, including statins, antihypertensive agents and platelet inhibition. Today the core point is to select subgroups and appropriate indications for better outcomes and avoiding unnecessary procedures very carefully. Therefore in patients with typical manifestations of ARAS including resistant or malignant hypertension, progressive decline of renal function, flash pulmonary edema or angina, renal artery intervention remains a sensible therapeutic option - after hemodynamic testing prior to revascularization. In the future further trials targeting patients who fulfill rational selection criteria need to be undertaken to confirm the efficacy of revascularization.

Vaccination: Developing and implementing a competency-based-curriculum at the Medical Faculty of LMU Munich.

BACKGROUND: In Germany medical students should gain proficiency and specific skills in the vaccination field. Especially important is the efficient communication of scientific results about vaccinations to the community, in order to give professional counseling with a complete overview about therapeutic options. AIM OF THE PROJECT: The aim of this project is to set up a vaccination-related curriculum in the Medical Faculty at the Ludwig-Maximilians-University in Munich. The structure of the curriculum is based on the National catalogue for competency-based learning objectives in the field of vaccination (Nationaler Kompetenzbasierter Lernzielekatalog Medizin NKLM). Through this curriculum, the students will not only acquire the classical educational skills concerning vaccination in theory and practice, but they will also learn how to become independent in the decision-making process and counseling. Moreover, the students will become aware of consequences of action related to this specific topic. METHODS: According to defined guidelines, an analysis was performed on courses, which are currently offered by the university. A separate analysis of the NKLM was carried out. Both analyses identified the active courses related to the topic of vaccination as well as the NKLM learning objectives. The match between the topics taught in current courses and the NKLM learning objectives identified gaps concerning the teaching of specific content. Courses were modified in order to implement the missing NKLM learning objectives. RESULTS: These analyses identified 24 vaccination-related courses, which are currently taught at the University. Meanwhile, 35 learning objectives on vaccination were identified in the NKLM catalogue. Four of which were identified as not yet part of the teaching program. In summary, this interdisciplinary work enabled the development of a new vaccination-related curriculum, including 35 learning objectives, which are now implemented in regular teaching courses by the Medical Faculty. CONCLUSIONS: This project successfully describes a method to develop and implement a competency-based teaching program on the topic of vaccination. Importantly, the process presented here can serve as a guide to develop and implement similar teaching programs on other subjects and Universities.

Large scale water lens for solar concentration.

Properties of large scale water lenses for solar concentration were investigated. These lenses were built from readily available materials, normal tap water and hyper-elastic linear low density polyethylene foil. Exposed to sunlight, the focal lengths and light intensities in the focal spot were measured and calculated. Their optical properties were modeled with a raytracing software based on the lens shape. We have achieved a good match of experimental and theoretical data by considering wavelength dependent concentration factor, absorption and focal length. The change in light concentration as a function of water volume was examined via the resulting load on the foil and the corresponding change of shape. The latter was extracted from images and modeled by a finite element simulation.

Newborn screening for X-linked adrenoleukodystrophy in New York State: diagnostic protocol, surveillance protocol and treatment guidelines.

PURPOSE: To describe a diagnostic protocol, surveillance and treatment guidelines, genetic counseling considerations and long-term follow-up data elements developed in preparation for X-linked adrenoleukodystrophy (X-ALD) newborn screening in New York State. METHODS: A group including the director from each regional NYS inherited metabolic disorder center, personnel from the NYS Newborn Screening Program, and others prepared a follow-up plan for X-ALD NBS. Over the months preceding the start of screening, a series of conference calls took place to develop and refine a complete newborn screening system from initial positive screen results to long-term follow-up. RESULTS: A diagnostic protocol was developed to determine for each newborn with a positive screen whether the final diagnosis is X-ALD, carrier of X-ALD, Zellweger spectrum disorder, acyl CoA oxidase deficiency or D-bifunctional protein deficiency. For asymptomatic males with X-ALD, surveillance protocols were developed for use at the time of diagnosis, during childhood and during adulthood. Considerations for timing of treatment of adrenal and cerebral disease were developed. CONCLUSION: Because New York was the first newborn screening laboratory to include X-ALD on its panel, and symptoms may not develop for years, long-term follow-up is needed to evaluate the presented guidelines.

[Identification of city areas with an urgent need for early help in Munich: presentation of a new procedure on the basis of data on regional social structures and on the health risks of newborn babies]. / Ermittlung von Stadtgebieten mit hohem Bedarf an Frühen Hilfen in München: Vorstellung eines neuen Verfahrens auf Basis von Daten zur regionalen Sozialstruktur und zum gesundheitlichen Risiko von Neugeborenen.

BACKGROUND: In Germany, it is forbidden by law to physically punish children or to harm them mentally. Breaking these rules can result in severe health problems for the children. Home visiting programmes for families with young children are aimed at supporting young families who are facing large social problems, and at enhancing the chances of their children to grow up in a healthy way. Maps showing the regional distribution of the need for these home visiting programmes could be an important tool for local health policy planning. They could help to focus the resources on those families who are in greatest need. METHODS: The method proposed here for developing such a regional map is based on the following steps: (a) search for data that indicate the potential for child neglect, maltreatment or abuse, and that are available for each zip code in the city of Munich, Germany; (b) based on these data, calculation of a summary score that could indicate high need for these home visits; (c) grouping of the zip code areas according to this score; (d) presentation of the regional distribution in a map. RESULTS: After inspecting different data sources, we could identify 5 variables that could indicate the need for these home visits and that are available for each zip code: index of purchasing power, percentage of the population with low education, percentage of the population with migration background, percentage of single mothers, percentage of new-borns with low birth weight (<2 500 g). If 'high need' is defined as 'upper quintile of at least 3 among the 5 variables listed above, about 1 087 newborn babies would have to be visited per year (i. e., 10% of all newborn infants in Munich). CONCLUSION: These home visits should be as little stigmatising as possible, and especially those families should be reached that are in greatest need. If it is not possible to reach all families in the community, it can be recommended to focus on city districts with a high percentage of families in greatest need. As far as we know, this is the first scientifically based method for such a definition of city districts. The method proposed here could serve as starting point, and it would be important to develop it further. It is very flexible, though, and it can easily be transferred to other cities or districts.

Crush implantation of a self-expanding interwoven stent over a subintimally recanalized standard stent in a TASC D lesion of the superficial femoral artery.

We demonstrate feasibility of implantation of a self-expanding interwoven nitinol stent in a claudicant, where recanalization attempt of a heavily calcified, occluded superficial femoral artery (TASC D lesion) was complicated by a previously implanted, fractured standard stent. Wire passage through the occlusion and beyond the fractured stent could only be achieved through the subintimal space. A dedicated reentry device was used to allow distal wire entry into the true lumen at the level of the popliteal artery. Despite crushing of the fractured stent with a series of increasingly sized standard balloons, a significant recoil remainded in the area of the crushed stent. To secure patency of the femoro-popliteal artery we therefore decided to implant the novel self-expanding interwoven nitinol stent (Supera Veritas (TM), IDEV), whose unique feature is an exceptional high radial strength. Patient presented asymptomatic without any impairment of his walking capacity at three month follow up and duplex ultrasound confirmed patency of the stent. Subintimal recanalizations can be complicated by previously implanted stents, in particular in the presence of stent fracture, where intraluminal wire passage often can not be achieved. Considering the high radial strength and fracture resistance, interwoven nitinol stents represent a good treatment option in those challenging cases and they can be used to crush standard nitinol and ballonexpandable stents.

Antithrombotic therapy in patients with acute coronary syndrome and diabetes mellitus.

Acute coronary syndrome (ACS) is associated with high mortality even in the acute phase as well as in the post-acute (chronic) phase. Diabetes mellitus type 2 (DM-2), on the other hand, further increases mortality after ACS. Several new antiplatelet and antithrombotic drugs available for clinical use have also been investigated in patients with DM-2, and the guidelines of the European Society of Cardiology (ESC) were recently adapted. However, in daily clinical practice choosing the most suitable regimen is a challenge in many cases. This review article aims to shed light on and simplify antiplatelet and antithrombotic therapy in ACS patients with DM-2 in order to ease the clinician's decision-making.

Influence of updated guidelines on short- and long-term mortality in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS).

AIM: In 2002 the ACC/AHA guidelines for the management of patients with unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI) were updated. We aimed to answer whether the implementation of updated guidelines was capable of influencing short- and long-term mortality in these patients. METHODS: We analyzed data on 812 consecutive patients who were admitted with either UA or NSTEMI between 2001 and 2004. Patients admitted in the two years before the implementation of updated guidelines (UA(01/02) group and NSTEMI(01/02) group) were compared to patients admitted in the two years thereafter (UA(03/04) group and NSTEMI(03/04) group). Yearly follow-up concerning all-cause mortality was obtained up to four years. RESULTS: The rate of revascularizations, the percentage of procedures performed within 48 h of admission, and the administration of clopidogrel increased significantly. However, still many - especially high-risk - patients did not receive revascularization. Patients of both UA groups had an identical in-hospital mortality rate. Differences in mortality between groups gained statistical significance over time (four-year mortality; 15.1% for the UA(03/04) group vs. 26.5% for the UA(01/02) group, p=0.014; HR 0.49 95% CI 0.28-0.87). In patients with NSTEMI in-hospital mortality decreased from 18.4% in the NSTEMI(01/02) group to 9.6% in the NSTEMI(03/04) group (p=0.011; HR 0.47 95% CI 0.26-0.84), and 1-year mortality from 34.7% to 25.1% (p=0.038; HR 0.63 95% CI 0.41-0.98), respectively. Mortality rates beyond one year were still lower in the NSTEMI(03/04) group as compared to the NSTEMI(01/02) group but it did not reach statistical significance. Multivariate Cox-regression analysis revealed furthermore that also patients with higher age and/or renal dysfunction benefit from an early invasive strategy. CONCLUSION: The implementation of updated guidelines for NSTE-ACS had significant impact on short- and long-term mortality. However, an early invasive strategy is still withheld to a significant number of high-risk patients, who would benefit from an invasive treatment.

Listeria monocytogenes survival of UV-C radiation is enhanced by presence of sodium chloride, organic food material and by bacterial biofilm formation.

The bactericidal effect on food processing surfaces of ceiling-mounted UV-C light (wavelength 254 nm) was determined in a fish smoke house after the routine cleaning and disinfection procedure. The total aerobic counts were reduced during UV-C light exposure (48 h) and the number of Listeria monocytogenes positive samples went from 30 (of 68) before exposure to 8 (of 68). We therefore in a laboratory model determined the L. monocytogenes reduction kinetics by UV-C light with the purpose of evaluating the influence of food production environmental variables, such as presence of NaCl, organic material and the time L. monocytogenes was allowed to adhere to steel before exposure. L. monocytogenes grown and attached in tryptone soy broth (TSB) with glucose were rapidly killed (after 2 min) by UV-C light. However, bacteria grown and adhered in TSB with glucose and 5% NaCl were more resistant and numbers declined with 4-5 log units during exposure of 8-10 min. Bacteria grown in juice prepared from cold-smoked salmon were protected and numbers were reduced with 2-3 log when UV-C light was used immediately after attachment whereas numbers did not change at all if bacteria had been allowed to form a biofilm for 7 days before exposure. It is not known if this enhanced survival is due to physiological changes in the attached bacterial cells, a physical protection of the cells in the food matrix or a combination. In conclusion, we demonstrate that UV-C light is a useful extra bacteriocidal step and that it, as all disinfecting procedures, is hampered by the presence of organic material.

Tacrolimus-eluting carbon-coated stents versus sirolimus-eluting stents for prevention of symptom-driven clinical end points.

BACKGROUND: Coating of stents has been shown to minimize the interactions between platelets, stent surface and vascular response following stent implantation. The aim of our study was to compare the tacrolimus-eluting carbon-coated JANUS(®) stent with sirolimus-eluting CYPHER(®) stent for the prevention of symptom-driven clinical end points in a real world clinical setting. METHODS: This prospective registry with a follow-up period of 24 months was conducted in 90 consecutive patients undergoing coronary artery stenting receiving CYPHER(®) (n = 48) or JANUS(®) (n = 42) stents. The primary end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction and target vessel revascularisation, and the secondary end point was clinically driven in-stent restenosis. RESULTS: The primary combined endpoint occurred in 38% of patients (n = 16) in the JANUS(®) group compared to 10% (n = 5) in the CYPHER(®) group. The relative risk increase of the composite end point was therefore 63% higher in patients receiving JANUS(®) stents compared to the CYPHER(®) stents (crude HR = 1.63, 95% CI = 1.17-2.28, p = 0.004; adjusted HR = 1.79, CI = 1.26-2.55, p = 0.001). Interestingly, 75% of events in the JANUS(®) group occurred during the first 6 months after stent implantation. Similarly, the rate of clinically driven in-stent restenosis was higher in patients receiving JANUS(®) stent (n = 10, 2%) compared to the CYPHER(®) stent (n = 2, 4%). Concordantly, the relative risk for clinically driven in-stent restenosis was 81% higher in the JANUS(®) group compared to the CYPHER(®) group (crude HR = 1.81, 95% CI = 1.08-3.02, p = 0.02; adjusted HR = 2.24, CI = 1.26-3.96, p = 0.006). CONCLUSION: The use of tacrolimus-eluting carbon coated JANUS(®) stent was associated with worse clinical outcome compared to the sirolimus-eluting CYPHER(®) stent in clinical routine use.

[Implementation of a routine gradual psycho-diagnostic programme in somatic rehabilitation centres - results of a pilot study]. / Implementierung eines psychodiagnostischen Stufenplans in der medizinischen Rehabilitation - Ergebnisse einer Pilotstudie.

STUDY AIM: A pilot study was conducted to implement and evaluate a routine gradual psycho-diagnostic programme to improve diagnostics and treatment of mental disorders in somatic rehabilitation centres. First of all, implementation strategies were acquired in trainings together with psychologists and physicians. The psycho-diagnostic programme consists of a screening instrument (PHQ-9) designed to permit time-effective detection of comorbid mental disorders. Besides evaluation of the training, the aim of the study was to analyze the extent to which it is possible to implement the routine gradual psycho-diagnostic programme in practice. Additionally, it was intended to identify beneficial and obstructive conditions for implementation. METHODOLOGY: The pilot study was conducted in two orthopaedic and one cardiological rehabilitation centre. The training was evaluated directly after its completion using a questionnaire. Three months after its implementation, the introduction of the psycho-diagnostic programme was evaluated using interviews with n=11 physicians and psychologists. RESULTS: The training was rated positively by the participants . Implementation of the entire gradual psycho-diagnostic programme was possible in one centre and to some degree in the other two. Beneficial for implementation were a frank organisational climate, sufficient time resources, and physicians' biopsychosocial understanding of disease. A dismissive attitude towards psycho-diagnostics, little communication between staff members, little perceived advantage for one's own work and fear to stigmatise patients by psychiatric diagnoses were obstructive. CONCLUSION: Essential for a successful implementation are sufficient time and personal resources, a motivation for change in staff and centre management, and a positive attitude regarding psycho-diagnostics in clinic staff. Furthermore, flexibility in implementation strategies and the opportunity to participate in the implementation process are important.

Ionizing radiation in secret services' conspirative actions.

INTRODUCTION: The death of Litvinenko has been reported by the media. It has raised the question whether this case had been unique. The fall of the wall has allowed a glimpse in the planning and comporting of a secret service. MATERIAL AND METHOD: Documents of the secret service of the former German democratic republic (GDR), books of defectors, and media reports about secret service actions with radiating substances have been analyzed. RESULTS: Since decades, secret services have been using radioactive nuclides and radiation for their tasks. Several killings with radiation have been reported. A complicated logistic had been developed. CONCLUSION: Only singular cases of the employment of radiating substances have become known. It is probable that the majority rests unknown. Government support seems necessary in secret services' conspirative actions with radiating substance.

Clinical and financial impact of obesity on the outcome of liver transplantation.

The purpose of this study was to determine whether body mass index (BMI) influences the clinical outcomes and overall cost of transplantation in adult liver transplantation (OLT) using records of 700 adult OLT recipients. Patients were divided into BMI range groups over the range of 15 to 42 (mean = 26.7), namely: <25, n = 288 (41%); 25 to 30, n = 245 (35%); > or =30, n = 167 (24%). Only a small subset of this last group was morbidly obese (BMI > or = 35, n = 37, 5% of total). We did not detect an effect of BMI on patient or graft survival, the incidence of acute graft rejection, or major surgical complications. BMI was not related to length of hospital stay. There were no statistical differences between the three groups with respect to the ratio of overall hospital cost in a general linear model, corrected for age, gender, calculated Model for End-Stage Liver Disease score, retransplant status, or return to the operating room. In conclusion, obesity did not influence either the costs or the clinical outcomes following OLT. Further analysis of the morbidly obese population with respect to cost and outcome is warranted.

Bovine eotaxin (CCL11)--an unusual member of the eotaxin group--attracts eosinophils in vitro but is not responsible for eosinophilia in the ovary.

Under physiological conditions normally characterised by low tissue infiltration of eosinophils, a conspicuous number of these cells are attracted into the human and ruminant ovary. Eosinophils suddenly increase in the thecal layer of the preovulatory follicle and corpus luteum at very early development. Currently, we only have a limited understanding of the mechanism for the recruitment of the ovarian eosinophils. Eotaxin (CCL11) may be one of the chemoattractants involved in stimulating eosinophils to migrate selectively into ovary. As a prerequisite for the analysis of eotaxin expression in the bovine ovary, we determined the complete bovine eotaxin mRNA sequence since it was not available from databases. The bovine eotaxin is the first member of the monocyte chemoattractant protein (MCP)/eotaxin subfamily with two mRNA isoforms varying in length in the untranslated 3'-untranslated region. The unusual amino-acid sequence of bovine eotaxin contains structural features that are so far known to be characteristic for MCP, but not eotaxin. In our microchemotaxis assays, recombinant bovine eotaxin showed a functional pattern orthologous to known eotaxins. Thus, the chimeric structure of bovine eotaxin did not affect the favoured chemotactic activity on eosinophils. Semiquantitative RT-PCR was used to investigate the expression of eotaxin in different regions of the bovine ovary. We only detected faint eotaxin mRNA signals that did not indicate physiological significance even in stimulated granulosa cell cultures, follicle-derived macrophages or fibroblasts. Taken together, bovine eotaxin attracts eosinophils in vitro but is not responsible for eosinophilia in the ovary. Its unusual chimeric structure confirms the unity of the MCP/eotaxin subfamily of CC chemokines and distinguishes it from other CC chemokine subfamilies.