Combination of computed tomography angiography with coronary artery calcium score for improved diagnosis of coronary artery disease: a collaborative meta-analysis of stable chest pain patients referred for invasive coronary angiography.

OBJECTIVES: Coronary computed tomography angiography (CCTA) has higher diagnostic accuracy than coronary artery calcium (CAC) score for detecting obstructive coronary artery disease (CAD) in patients with stable chest pain, while the added diagnostic value of combining CCTA with CAC is unknown. We investigated whether combining coronary CCTA with CAC score can improve the diagnosis of obstructive CAD compared with CCTA alone. METHODS: A total of 2315 patients (858 women, 37%) aged 61.1 ± 10.2 from 29 original studies were included to build two CAD prediction models based on either CCTA alone or CCTA combined with the CAC score. CAD was defined as at least 50% coronary diameter stenosis on invasive coronary angiography. Models were built by using generalized linear mixed-effects models with a random intercept set for the original study. The two CAD prediction models were compared by the likelihood ratio test, while their diagnostic performance was compared using the area under the receiver-operating-characteristic curve (AUC). Net benefit (benefit of true positive versus harm of false positive) was assessed by decision curve analysis. RESULTS: CAD prevalence was 43.5% (1007/2315). Combining CCTA with CAC improved CAD diagnosis compared with CCTA alone (AUC: 87% [95% CI: 86 to 89%] vs. 80% [95% CI: 78 to 82%]; p < 0.001), likelihood ratio test 236.3, df: 1, p < 0.001, showing a higher net benefit across almost all threshold probabilities. CONCLUSION: Adding the CAC score to CCTA findings in patients with stable chest pain improves the diagnostic performance in detecting CAD and the net benefit compared with CCTA alone. CLINICAL RELEVANCE STATEMENT: CAC scoring CT performed before coronary CTA and included in the diagnostic model can improve obstructive CAD diagnosis, especially when CCTA is non-diagnostic. KEY POINTS: • The combination of coronary artery calcium with coronary computed tomography angiography showed significantly higher AUC (87%, 95% confidence interval [CI]: 86 to 89%) for diagnosis of coronary artery disease compared to coronary computed tomography angiography alone (80%, 95% CI: 78 to 82%, p < 0.001). • Diagnostic improvement was mostly seen in patients with non-diagnostic C. • The improvement in diagnostic performance and the net benefit was consistent across age groups, chest pain types, and genders.

Global brain network modularity dynamics after local optic nerve damage following noninvasive brain stimulation: an EEG-tracking study.

Tightly connected clusters of nodes, called communities, interact in a time-dependent manner in brain functional connectivity networks (FCN) to support complex cognitive functions. However, little is known if and how different nodes synchronize their neural interactions to form functional communities ("modules") during visual processing and if and how this modularity changes postlesion (progression or recovery) following neuromodulation. Using the damaged optic nerve as a paradigm, we now studied brain FCN modularity dynamics to better understand module interactions and dynamic reconfigurations before and after neuromodulation with noninvasive repetitive transorbital alternating current stimulation (rtACS). We found that in both patients and controls, local intermodule interactions correlated with visual performance. However, patients' recovery of vision after treatment with rtACS was associated with improved interaction strength of pathways linked to the attention module, and it improved global modularity and increased the stability of FCN. Our results show that temporal coordination of multiple cortical modules and intermodule interaction are functionally relevant for visual processing. This modularity can be neuromodulated with tACS, which induces a more optimal balanced and stable multilayer modular structure for visual processing by enhancing the interaction of neural pathways with the attention network module.

Influence of visual acuity, manual dexterity and handgrip strength on oral and denture hygiene ability of non-frail older people: Development of the Gerostomatological Assessment Battery.

BACKGROUND: Due to the heterogeneity of older people, it is difficult to identify reliable factors influencing oral health. OBJECTIVE: The aim was to illustrate the influence of visual acuity, manual dexterity, and handgrip strength on the oral and denture hygiene ability of older non-frail people. METHODS: In a cross-sectional study, conducted at a specialized dental clinic, at baseline, all participants received professional prophylaxis and instruction on daily oral and denture hygiene regimes for a 6-week intervention period. Data on the Quigley and Hein modified plaque index (QHI), respectively, the Denture Hygiene Index (DHI), visual acuity, manual dexterity and handgrip strength in non-frail participants (≥ 65 years) were collected. Recruitment was done within the clinic's patient clientele and within the staff (control cohort). RESULTS: Women showed significantly better manual dexterity than men (Mann-Whitney U, p = .01), while women's mean handgrip strength was significantly lower (Mann-Whitney U, p < .01). Manual dexterity (Mann-Whitney U, p = .003) and handgrip strength (Mann-Whitney U, p = .052) were associated with age. However, visual acuity, manual dexterity and handgrip strength had no influence on oral or denture hygiene. CONCLUSION: Visual acuity, manual dexterity and handgrip strength have no influence on oral and denture hygiene ability in older non-frail people. Further studies should investigate whether these factors also have no influence on oral and denture hygiene in vulnerable older patients. Therefore, an assessment tool for the evaluation of potential influencing factors of oral and denture hygiene is proposed in a dental context. This Gerostomatological Assessment Battery (G-AB) can be used as a helpful tool to check the individual cognitive function and comprehension, dental therapy approaches and their individual adaption.

An in silico model of the capturing of magnetic nanoparticles in tumour spheroids in the presence of flow.

One of the main challenges in improving the efficacy of conventional chemotherapeutic drugs is that they do not reach the cancer cells at sufficiently high doses while at the same time affecting healthy tissue and causing significant side effects and suffering in cancer patients. To overcome this deficiency, magnetic nanoparticles as transporter systems have emerged as a promising approach to achieve more specific tumour targeting. Drug-loaded magnetic nanoparticles can be directed to the target tissue by applying an external magnetic field. However, the magnetic forces exerted on the nanoparticles fall off rapidly with distance, making the tumour targeting challenging, even more so in the presence of flowing blood or interstitial fluid. We therefore present a computational model of the capturing of magnetic nanoparticles in a test setup: our model includes the flow around the tumour, the magnetic forces that guide the nanoparticles, and the transport within the tumour. We show how a model for the transport of magnetic nanoparticles in an external magnetic field can be integrated with a multiphase tumour model based on the theory of porous media. Our approach based on the underlying physical mechanisms can provide crucial insights into mechanisms that cannot be studied conclusively in experimental research alone. Such a computational model enables an efficient and systematic exploration of the nanoparticle design space, first in a controlled test setup and then in more complex in vivo scenarios. As an effective tool for minimising costly trial-and-error design methods, it expedites translation into clinical practice to improve therapeutic outcomes and limit adverse effects for cancer patients.

Machine learning instructed microfluidic synthesis of curcumin-loaded liposomes.

The association of machine learning (ML) tools with the synthesis of nanoparticles has the potential to streamline the development of more efficient and effective nanomedicines. The continuous-flow synthesis of nanoparticles via microfluidics represents an ideal playground for ML tools, where multiple engineering parameters - flow rates and mixing configurations, type and concentrations of the reagents - contribute in a non-trivial fashion to determine the resultant morphological and pharmacological attributes of nanomedicines. Here we present the application of ML models towards the microfluidic-based synthesis of liposomes loaded with a model hydrophobic therapeutic agent, curcumin. After generating over 200 different liposome configurations by systematically modulating flow rates, lipid concentrations, organic:water mixing volume ratios, support-vector machine models and feed-forward artificial neural networks were trained to predict, respectively, the liposome dispersity/stability and size. This work presents an initial step towards the application and cultivation of ML models to instruct the microfluidic formulation of nanoparticles.

Computed tomography angiography versus Agatston score for diagnosis of coronary artery disease in patients with stable chest pain: individual patient data meta-analysis of the international COME-CCT Consortium.

OBJECTIVES: There is conflicting evidence about the comparative diagnostic accuracy of the Agatston score versus computed tomography angiography (CTA) in patients with suspected obstructive coronary artery disease (CAD). PURPOSE: To determine whether CTA is superior to the Agatston score in the diagnosis of CAD. METHODS: In total 2452 patients with stable chest pain and a clinical indication for invasive coronary angiography (ICA) for suspected CAD were included by the Collaborative Meta-analysis of Cardiac CT (COME-CCT) Consortium. An Agatston score of > 400 was considered positive, and obstructive CAD defined as at least 50% coronary diameter stenosis on ICA was used as the reference standard. RESULTS: Obstructive CAD was diagnosed in 44.9% of patients (1100/2452). The median Agatston score was 74. Diagnostic accuracy of CTA for the detection of obstructive CAD (81.1%, 95% confidence interval [CI]: 77.5 to 84.1%) was significantly higher than that of the Agatston score (68.8%, 95% CI: 64.2 to 73.1%, p < 0.001). Among patients with an Agatston score of zero, 17% (101/600) had obstructive CAD. Diagnostic accuracy of CTA was not significantly different in patients with low to intermediate (1 to < 100, 100-400) versus moderate to high Agatston scores (401-1000, > 1000). CONCLUSIONS: Results in our international cohort show CTA to have significantly higher diagnostic accuracy than the Agatston score in patients with stable chest pain, suspected CAD, and a clinical indication for ICA. Diagnostic performance of CTA is not affected by a higher Agatston score while an Agatston score of zero does not reliably exclude obstructive CAD. KEY POINTS: • CTA showed significantly higher diagnostic accuracy (81.1%, 95% confidence interval [CI]: 77.5 to 84.1%) for diagnosis of coronary artery disease when compared to the Agatston score (68.8%, 95% CI: 64.2 to 73.1%, p < 0.001). • Diagnostic performance of CTA was not affected by increased amount of calcium and was not significantly different in patients with low to intermediate (1 to <100, 100-400) versus moderate to high Agatston scores (401-1000, > 1000). • Seventeen percent of patients with an Agatston score of zero showed obstructive coronary artery disease by invasive angiography showing absence of coronary artery calcium cannot reliably exclude coronary artery disease.

Undergraduate Dental Education in Gerodontology in Germany between 2004 and 2019-A case for compulsory teaching?

INTRODUCTION: The study surveys the present state of undergraduate dental education in gerodontology in Germany and highlights changes between 2004 and 2019. MATERIALS AND METHODS: In 2019, questionnaires were emailed to the department heads of all German dental schools. Data were analysed descriptively and compared to existing data from 2004, 2009 and 2014. RESULTS: Thirty-nine (86.7%) out of forty-five responding department heads stated to teach aspects of gerodontology in traditional core subject lecture series. Overall, 15 (55.6%) out of 27 responding dental university schools are offering special education in gerodontology (dedicated lecture series and/or practical training). A stronger focus on non-dental topics has been observed over the years. DISCUSSION: The 15-year observation period in Germany shows that teaching gerodontology should be mandatory. There is a lack of specialists in gerodontology at the dental schools, although specialisation has been possible for many years in the German professional association. Students should be sure that, as in other subjects, they are well trained for the very heterogeneous patient group of seniors. The financial and personnel prerequisites for the universities need to be established. CONCLUSION: Inclusion of gerodontology in the national syllabus is a decisive factor for the integration of the subject into undergraduate courses. The recommendations of the European College of Gerodontology (2009) and of the German Association of Gerodontology (DGAZ) regarding didactical and practical teaching should be implemented in the respective compulsory syllabus to prepare current undergraduate dental students for the demographic challenges of tomorrow.

Recipient sex and estradiol levels affect transplant outcomes in an age-specific fashion.

Sex-specific influences have been shown for a variety of diseases. Whether donor or recipient sex and sex hormone levels impact alloimmune responses remains unclear. In unifactorial and multifactorial analyses of more than 400 000 SRTR listed kidney transplant patients, we found that younger female recipients had an inferior death-censored graft survival that was independent of donor sex. In contrast, graft survival was superior in older female recipients, suggesting the impact of recipient sex hormones over chromosomal sex mismatches. Those clinical changes were delineated in experimental skin and heart transplant models showing a prolongation of graft survival in ovariectomized young female recipients. In contrast, graft survival was comparable in ovariectomized and naïve old female recipients. Young ovariectomized mice showed reduced amounts and a compromised T cell proliferation. Deprivation of female hormones dampened the production of interferon (IFN)-γ and interleukin (IL)-17+ by CD4+ T cells while augmenting systemic counts of Tregs. Increasing estradiol concentrations in vitro promoted the switch of naïve CD4+ T cells into Th1 cells; high physiological estradiol concentrations dampening Th1 responses, promoted Tregs, and prolonged graft survival. Thus, clinical observations demonstrate age-specific graft survival patterns in female recipients. Estrogen levels, in turn, impact the fate of T cell subsets, providing relevant and novel information on age- and sex-specific alloimmunity.

Detection of polymer compatibility by means of self-organization: poly(ethylene oxide) and poly(sodium 4-styrenesulfonate).

Information on the miscibility of different polymers A and B on a molecular level is important in many ways. However, along the traditional lines this knowledge is difficult and time consuming to achieve. The current study presents a simple alternative, based on the determination of the intrinsic viscosities (specific hydrodynamic volume of isolated coils) for blend solutions in a common solvent. In the case of incompatible polymers, isolated coils contain one macromolecule only, either A or B. In contrast, compatible polymers form mixed isolated coils, because of favorable interactions. The present investigation was carried out for the system water/poly(ethylene oxide)/poly(sodium 4-polystyrenesulfonate), for which the reason of compatibility lies in the formation Na+ bridges between the sulfonate groups of the polyelectrolyte and the OH groups of the poly(ethylene oxide). Zero shear viscosities were measured as a function of polymer concentration for blends of different compositions and modeled quantitatively by means of relations yielding the excess intrinsic viscosities ε (zero in the case of incompatibility) and viscometric interaction parameters. Particular attention is being paid to the role the molar masses of the polymers play for the resulting ε values.

An Aerosol Containment and Filtration Tent for Intubation During the COVID-19 Pandemic.

Background. Exposure to infectious droplets confers a high risk for infection transmission by the SARS-CoV-2 coronavirus. Aerosolizing procedures pose particular concern for increasing healthcare workers' (HCWs) risks of infection. Multiple creative personal protective equipment solutions have been utilized to minimize exposure to infectious particles; however, the overall benefit of many of these devices is limited by a number of factors. Methods. We designed an intubation tent consisting of a metal frame and a clear plastic sheet. The flexible walls of our tent offer increased maneuverability & access, although the efficacy in reducing risk of transmission to HCWs remained unclear. Using an atomizer, particle generator, and matchstick smoke, we simulated the generation of infectious respiratory droplets and aerosols and tested whether our device effectively decreased the concentration of these particles to which a provider might be exposed. Finally, we tested whether the addition of a vacuum fan fit with a high efficiency particulate air filter designed to evacuate contaminated air would influence particle concentrations inside and outside the tent. Results. Droplet dispersion tests with the tent in place showed that the simulated droplet distribution was limited to surfaces within the tent. Aerosol testing under a variety of circumstances consistently showed only a minor rise in particle concentration in the air outside the tent despite an initial peak of particle concentration during generation within. All testing demonstrated declining inside concentrations over time. Conclusions. Our simulations suggest our device has the potential to effectively decrease HCWs' exposure to infectious droplets and aerosolized viral particles.

Interrater reliability and concurrent validity of oral/dental items in the resident assessment instrument minimum data set 2.0.

OBJECTIVE: To examine interrater reliability and concurrent validity of oral/dental items in the Resident Assessment Instrument Minimum Data Set (RAI-MDS) 2.0. BACKGROUND: RAI-MDS is a standardised instrument used in nursing to determine health status and nursing needs. The extent to which oral/dental items in the RAI-MDS describe dental treatment needs concerning oral health has been questioned. MATERIALS AND METHODS: This study evaluated the interrater reliability (dentist vs. nurse) and validity of oral/dental items in the Swiss version of RAI-MDS 2.0 (areas: K-nutritional status, L-oral/dental status) using professional oral examinations as a benchmark. Data of 168 residents of five long-term care facilities in the canton of Zurich, Switzerland, were collected within 1 year between October 2017 and December 2018. The statistical evaluation used descriptive statistics and Cohen's kappa (95% CI). RESULTS: RAI-MDS items K1a, chewing (κ 0.098, 95% CI: 0.004-0.19); K1c, pain (κ 0.039, 95% CI: -0.03 to 0.11); L1a, debris (κ 0.117, 95% CI: 0.02-0.21); L1c, dental status (κ 0.229, 95% CI: 0.12-0.34); L1d, dental disease (κ 0.129, 95% CI: 0.02-0.24); L1e, periodontal diseases (κ -0.005, 95% CI: -0.07 to -0.03); and L1f, daily cleaning (κ -0.031, 95% CI: -0.05 to -0.01) showed weak or no agreement, whereas L1b, denture status (κ 0.634, 95% CI: 0.52-0.75), showed substantial agreement. CONCLUSION: Oral/dental items in RAI-MDS lack reliability and validity. Recognition of oral health situation/treatment needs by nursing staff does not seem to be possible with the current version of this tool.

Is Mental Stress the Primary Cause of Glaucoma? / Ist Stress die primäre Ursache von Glaukom?

The prognosis of going blind is very stressful for patients diagnosed with "glaucoma". Worries and fear of losing independence is a constant mental burden, with secondary risks of depression and social isolation. But stress is not only a result of glaucoma but also a possible cause (risk factor). This should not be surprising, given that chronic stress can trigger "psychosomatic" organ dysfunctions anywhere in the body. Why should the organ "eye" be an exception? Indeed, glaucoma patients often suspect that severe emotional stress caused their visual field loss or "foggy vision". The hypothesis that stress is a possible cause of glaucoma is supported by different observations: (i) acute and chronic stress increases intraocular pressure and (ii) long-term stress can lead to vascular dysregulation of the microcirculation in the eye and brain ("Flammer's syndrome"), leading to partial hypoxia and hypoglycaemia (hypo-metabolism). Even if nerve cells do not die, they may then become inactive ("silent" neurons). (iii) Degenerative changes have been reported in the brain of glaucoma patients, affecting not only anterograde or transsynaptic areas of the central visual pathway, but degeneration is also found (iv) in brain areas involved in emotional appraisal and the physiological regulation of stress hormones. There are also psychological hints indicating that stress is a cause of glaucoma: (v) Glaucoma patients with Flammer's syndrome show typical personality traits that are associated with low stress resilience: they often have cold hands or feet, are ambitious (professionally successful), perfectionistic, obsessive, brooding and worrying a lot. (vi) If stress hormone levels and inflammation parameters are reduced in glaucoma patients by relaxation with meditation, this correlates with normalisation of intraocular pressure, and yet another clue is that (vii) visual field improvements after non-invasive current stimulation therapy, that are known to improve circulation and neuronal synchronisation, are much most effective in patients with stress resilient personalities. An appreciation of stress as a "cause" of glaucoma suggests that in addition to standard therapy (i) stress reduction through relaxation techniques should be recommended (e.g. meditation), and (ii) self-medication compliance should not be induced by kindling anxiety and worries with negative communication ("You will go blind!"), but communication should be positive ("The prognosis is optimistic").

Aspects of oral health and dementia among Swiss nursing home residents.

BACKGROUND: Little empirical evidence of high levels of oral diseases of people in need of care and the impact of dementia is available. The resident assessment instrument minimum data set (RAI-MDS) is an evaluation tool for caregivers. OBJECTIVE: The aim of this study was to show oral health of nursing home residents through RAI-MDS 2.0 data as a function of the cognitive impairment. METHODS: A retrospective analysis of RAI-MDS (general, cognitive, oral health variables) of 357 long-term care facilities in Switzerland (data of 105,835 residents) was carried out. The final sample size was 7922 residents after applying the inclusion/exclusion criteria in four evaluation groups (no dementia, moderate, severe and incident dementia). RESULTS: As dementia developed and severity increased over time, subjects often had fewer or no teeth and did not wear removable dentures. Chewing problems increased over time regardless of the dementia severity. Oral complaints increased over time in subjects with severe dementia, which in turn led to low body mass index (BMI) values (<23 kg/m2) and was associated with an higher risk of mortality. CONCLUSION: This dataset provides an overview on dental aspects in patients with dementia in nursing homes. The accuracy of the assessment of a given dental situation by nursing staff is to be questioned. The results indicated an underdetection of oral illnesses by nurses.

Rapid turnover of DnaA at replication origin regions contributes to initiation control of DNA replication.

DnaA is a conserved key regulator of replication initiation in bacteria, and is homologous to ORC proteins in archaea and in eukaryotic cells. The ATPase binds to several high affinity binding sites at the origin region and upon an unknown molecular trigger, spreads to several adjacent sites, inducing the formation of a helical super structure leading to initiation of replication. Using FRAP analysis of a functional YFP-DnaA allele in Bacillus subtilis, we show that DnaA is bound to oriC with a half-time of 2.5 seconds. DnaA shows similarly high turnover at the replication machinery, where DnaA is bound to DNA polymerase via YabA. The absence of YabA increases the half time binding of DnaA at oriC, showing that YabA plays a dual role in the regulation of DnaA, as a tether at the replication forks, and as a chaser at origin regions. Likewise, a deletion of soj (encoding a ParA protein) leads to an increase in residence time and to overinitiation, while a mutation in DnaA that leads to lowered initiation frequency, due to a reduced ATPase activity, shows a decreased residence time on binding sites. Finally, our single molecule tracking experiments show that DnaA rapidly moves between chromosomal binding sites, and does not arrest for more than few hundreds of milliseconds. In Escherichia coli, DnaA also shows low residence times in the range of 200 ms and oscillates between spatially opposite chromosome regions in a time frame of one to two seconds, independently of ongoing transcription. Thus, DnaA shows extremely rapid binding turnover on the chromosome including oriC regions in two bacterial species, which is influenced by Soj and YabA proteins in B. subtilis, and is crucial for balanced initiation control, likely preventing fatal premature multimerization and strand opening of DnaA at oriC.

Outpatient dental care for people with disabilities under general anaesthesia in Switzerland.

BACKGROUND: Life expectancy of people with permanent disabilities has increased. The dental care of these vulnerable patients is one of the greatest challenges for the dentist and the dental team due to limited or non-existent cooperation and the associated lack of health competence. In order to be able to provide safe and acceptable, quality dental treatment without psychological and physical stress for these patients, it is therefore necessary to resort to sedation or general anaesthesia (GA) under medical supervision. The aim of the analysis is to highlight the need for dental treatment performed under GA for people with disabilities and the associated indications and treatment patterns. METHODS: Ten-year retrospective analysis of outpatient dental care under GA for people with disabilities. RESULTS: Of all adult patients (n = 221) who attended the GA pre-assessment, 69.7% (n = 154) received dental treatment under GA based on the clinical findings or in cases of suspected pain. Most patients received one GA. A total of 205 dental treatment sessions were performed under GA mostly for conservative (n = 442, 52%) and surgical (n = 389, 45.8%) procedures. Endodontic treatment (n = 19, 2.2%) was rare. The failure rate related to all teeth in need of treatment (n = 850) was 5.1% (n = 43), in most cases due to secondary caries (n = 40; 93.0%). Patients were enrolled in an annual recall for dental examination and prophylaxis without GA. Non-compliant patients for whom oral hygiene was impossible received a periodic GA. CONCLUSION: There is a high need of people with disabilities for dental treatment under GA. Main indications for treatment under GA are dental complaints, pain or suspected pain. Dental care can be successful if, for the benefit of patients with special needs, all carers cooperate closely. Caregivers have to be trained in nutrition control as well as in oral hygiene. These factors in conjunction help to prevent dental emergencies.

Aggression modulates neural correlates of hostile intention attribution to laughter in children.

The tendency to interpret nonverbal social signals as hostile in intention is associated with aggressive responding, poor social functioning and mental illness, and can already be observed in childhood. To investigate the neural correlates of such hostile attributions of social intention, we performed a functional magnetic imaging study in 10-18 year old children and adolescents. Fifty healthy participants rated videos of laughter, which they were told to imagine as being directed towards them, as friendly versus hostile in social intention. Hostile intention ratings were associated with neural response in the right temporal voice area (TVA). Moreover, self-reported trait physical aggression modulated this relationship in both the right TVA and bilateral lingual gyrus, with stronger associations between hostile intention ratings and neural activation in children with higher trait physical aggression scores. Functional connectivity results showed decreased connectivity between the right TVA and left dorsolateral prefrontal cortex with increasing trait physical aggression for making hostile social intention attributions. We conclude that children's social intention attributions are more strongly related to activation of early face and voice-processing regions with increasing trait physical aggression.

Heart rate reserve is a long-term risk predictor in women undergoing myocardial perfusion imaging.

BACKGROUND: Although women with cardiovascular disease experience relatively worse outcomes as compared to men, substantial knowledge gaps remain regarding the unique female determinants of cardiovascular risk. Heart rate (HR) responses to vasodilator stress mirror autonomic activity and may carry important long-term prognostic information in women. METHODS AND RESULTS: Hemodynamic changes during adenosine stress were recorded in a total of 508 consecutive patients (104 women) undergoing clinically indicated 13N-ammonia Positron-Emission-Tomography (PET) at our institution. Following propensity matching, 202 patients (101 women, mean age 61.3 ± 12.6 years) were analyzed. During a median follow-up of 5.6 years, 97 patients had at least one cardiac event, including 17 cardiac deaths. Heart rate reserve (% HRR) during adenosine infusion was significantly higher in women as compared to men (23.8 ± 19.5 vs 17.3 ± 15.3, p = 0.009). A strong association between 10-year cardiovascular endpoints and a blunted HRR was observed in women, while this association was less pronounced in men. Accordingly, in women, but not in men, reduced HRR was selected as a strong predictor for adverse cardiovascular events in a Cox regression model fully adjusted for imaging findings and traditional risk factors (HR 2.41, 95% CI 1.23-4.75, p = 0.011). Receiver operating characteristics (ROC) curves revealed that a blunted HRR <21% was a powerful predictor for MACE in women with a sensitivity of 77% and a specificity of 68%. CONCLUSION: Blunted HRR to adenosine stress adds incremental prognostic value for long-term cardiovascular outcomes in women beyond that provided by traditional risk factors and imaging findings.

Coupling tumor growth and bio distribution models.

We couple a tumor growth model embedded in a microenvironment, with a bio distribution model able to simulate a whole organ. The growth model yields the evolution of tumor cell population, of the differential pressure between cell populations, of porosity of ECM, of consumption of nutrients due to tumor growth, of angiogenesis, and related growth factors as function of the locally available nutrient. The bio distribution model on the other hand operates on a frozen geometry but yields a much refined distribution of nutrient and other molecules. The combination of both models will enable simulating the growth of a tumor in a whole organ, including a realistic distribution of therapeutic agents and allow hence to evaluate the efficacy of these agents.

How Nanoparticle Physicochemical Parameters Affect Drug Delivery to Cells in the Retina via Systemic Interactions.

Minor changes in the composition of poloxamer 188-modified, DEAE-dextran-stabilized (PDD) polybutylcyanoacrylate (PBCA) nanoparticles (NPs), by altering the physicochemical parameters (such as size or surface charge), can substantially influence their delivery kinetics across the blood-retina barrier (BRB) in vivo. We now investigated the physicochemical mechanisms underlying these different behaviors of NP variations at biological barriers and their influence on the cellular and body distribution. Retinal whole mounts from rats injected in vivo with fluorescent PBCA NPs were processed for retina imaging ex vivo to obtain a detailed distribution of NPs with cellular resolution in retinal tissue. In line with previous in vivo imaging results, NPs with a larger size and medium surface charge accumulated more readily in brain tissue, and they could be more easily detected in retinal ganglion cells (RGCs), demonstrating the potential of these NPs for drug delivery into neurons. The biodistribution of the NPs revealed a higher accumulation of small-sized NPs in peripheral organs, which may reduce the passage of these particles into brain tissue via a "steal effect" mechanism. Thus, systemic interactions significantly determine the potential of NPs to deliver markers or drugs to the central nervous system (CNS). In this way, minor changes of NPs' physicochemical parameters can significantly impact their rate of brain/body biodistribution.

A standardized low-cost peer role-playing training intervention improves medical student competency in communicating bad news to patients in Botswana.

OBJECTIVE: The purpose of this study was to demonstrate effectiveness of an educational training workshop using role-playing to teach medical students in Botswana to deliver bad news. METHOD: A 3-hour small group workshop for University of Botswana medical students rotating at the Princess Marina Hospital in Gaborone was developed. The curriculum included an overview of communication basics and introduction of the validated (SPIKES) protocol for breaking bad news. Education strategies included didactic lecture, handouts, role-playing cases, and open forum discussion. Pre- and posttraining surveys assessed prior exposure and approach to breaking bad news using multiple-choice questions and perception of skill about breaking bad news using a 5-point Likert scale. An objective structured clinical examination (OSCE) with a standardized breaking bad news skills assessment was conducted; scores compared two medical student classes before and after the workshop was implemented.ResultForty-two medical students attended the workshop and 83% (35/42) completed the survey. Medical students reported exposure to delivering bad news on average 6.9 (SD = 13.7) times monthly, with 71% (25/35) having delivered bad news themselves without supervision. Self-perceived skill and confidence increased from 23% (8/35) to 86% (30/35) of those who reported feeling "good" or "very good" with their ability to break bad news after the workshop. Feedback after the workshop demonstrated that 100% found the SPIKES approach helpful and planned to use it in clinical practice, found role-playing helpful, and requested more sessions. Competency for delivering bad news increased from a mean score of 14/25 (56%, SD = 3.3) at baseline to 18/25 (72%, SD = 3.6) after the workshop (p = 0.0002).Significance of resultsThis workshop was effective in increasing medical student skill and confidence in delivering bad news. Standardized role-playing communication workshops integrated into medical school curricula could be a low-cost, effective, and easily implementable strategy to improve communication skills of doctors.