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Solid organ transplantation mobilizes myeloid cells, including monocytes and macrophages, which are central protagonists of allograft rejection. However, myeloid cells can also be functionally reprogrammed by perioperative costimulatory blockade to promote a state of transplantation tolerance. Transplantation tolerance holds promise to reduce complications from chronic immunosuppression and promote long-term survival in transplant recipients. We sought to identify different mediators of transplantation tolerance by performing single-cell RNA sequencing of acute rejecting or tolerized cardiac allografts. This led to the unbiased identification of the transcription factor, hypoxia inducible factor (HIF)-2α, in a subset of tolerogenic monocytes. Using flow cytometric analyses and mice with conditional loss or gain of function, we uncovered that myeloid cell expression of HIF-2α was required for costimulatory blockade-induced transplantation tolerance. While HIF-2α was dispensable for mobilization of tolerogenic monocytes, which were sourced in part from the spleen, it promoted the expression of colony stimulating factor 1 receptor (CSF1R). CSF1R mediates monocyte differentiation into tolerogenic macrophages and was found to be a direct transcriptional target of HIF-2α in splenic monocytes. Administration of the HIF stabilizer, roxadustat, within micelles to target myeloid cells, increased HIF-2α in splenic monocytes, which was associated with increased CSF1R expression and enhanced cardiac allograft survival. These data support further exploration of HIF-2α activation in myeloid cells as a therapeutic strategy for transplantation tolerance., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: Health professional programs can promote equitable healthcare delivery but few programs include disability in these efforts. Limited opportunities exist for health professional students to engage with disability education within the classroom or beyond. The Disability Advocacy Coalition in Medicine (DAC Med) is a national interprofessional student-led organization which hosted a virtual conference for health professional students in October 2021. We describe the impact of this single-day virtual conference on learning and the current state of disability education across health professional programs., Methods: This cross-sectional study utilized a 17-item post-conference survey. A 5-point Likert scale-based survey was distributed to conference registrants. Survey parameters included background in disability advocacy, curricular exposure to disability, and impact of the conference., Results: Twenty-four conference attendees completed the survey. Participants were enrolled in audiology, genetic counseling, medical, medical scientist, nursing, prosthetics and orthotics, public health, and 'other' health programs. Most participants (58.3%) reported not having a strong background in disability advocacy before the conference, with 26.1% indicating they learned about ableism in their program's curriculum. Almost all students (91.6%) attended the conference to learn how to be a better advocate for patients and peers with disabilities, and 95.8% reported that the conference provided this knowledge. Eighty-eight percent of participants agreed that they acquired additional resources to better care for patients with disabilities., Conclusions: Few health professional students learn about disability in their curriculum. Single-day virtual, interactive conferences are effective in providing advocacy resources and empowering students to employ them.

Immune cell function among the myocardium, now more than ever, is appreciated to regulate cardiac function and pathophysiology. This is the case for both innate immunity, which includes neutrophils, monocytes, dendritic cells, and macrophages, as well as adaptive immunity, which includes T cells and B cells. This function is fueled by cell-intrinsic shifts in metabolism, such as glycolysis and oxidative phosphorylation, as well as metabolite availability, which originates from the surrounding extracellular milieu and varies during ischemia and metabolic syndrome. Immune cell crosstalk with cardiac parenchymal cells, such as cardiomyocytes and fibroblasts, is also regulated by complex cellular metabolic circuits. Although our understanding of immunometabolism has advanced rapidly over the past decade, in part through valuable insights made in cultured cells, there remains much to learn about contributions of in vivo immunometabolism and directly within the myocardium. Insight into such fundamental cell and molecular mechanisms holds potential to inform interventions that shift the balance of immunometabolism from maladaptive to cardioprotective and potentially even regenerative. Herein, we review our current working understanding of immunometabolism, specifically in the settings of sterile ischemic cardiac injury or cardiometabolic disease, both of which contribute to the onset of heart failure. We also discuss current gaps in knowledge in this context and therapeutic implications., (© 2023 The Authors.)

Aims: Central venous catheters are essential for the management of pediatric cardiac surgery patients. Recently, an ultrasound-guided access via a supraclavicular approach to the brachiocephalic vein has been described. Central venous catheters are associated with a relevant number of complications in pediatric patients. In this study, we evaluated the frequency of complications of left brachiocephalic vein access compared with right internal jugular vein standard access in children undergoing cardiac surgery., Methods: Retrospective analysis of all pediatric cases at our tertiary care university hospital over a two-year period receiving central venous catheters for cardiac surgery., Primary Endpoint: Frequency of complications associated with central venous catheters inserted via the left brachiocephalic vein vs. right internal jugular vein. Complications were defined as: chylothorax, deep vein thrombosis, sepsis, or delayed chest closure. Secondary endpoints: Evaluation of the insertion depth of the catheter using a height-based formula without adjustment for side used., Results: Initially, 504 placed catheters were identified. Following inclusion and exclusion criteria, 480 placed catheters remained for final analysis. Overall complications were reported in 68/480 (14.2%) cases. There was no difference in the frequency of all complications in the left brachiocephalic vein vs. the right internal jugular vein group (15.49% vs. 13.65%; OR = 1.16 [0.64; 2.07]), nor was there any difference considering the most relevant complications chylothorax (7.7% vs. 8.6%; OR = 0.89 [0.39; 1.91]) and thrombosis (5.6% vs. 4.5%; OR = 1.28 [0.46; 3.31]). The mean deviation from the optimal insertion depth was left brachiocephalic vein vs. right internal jugular vein 5.38 ± 13.6 mm and 4.94 ± 15.1 mm, respectively., Conclusions: Among children undergoing cardiac surgery, there is no significant difference between the supraclavicular approach to the left brachiocephalic vein and the right internal jugular vein regarding complications. For both approaches, a universal formula can be used to determine the correct insertion depth., (© 2022 The Authors. Pediatric Anesthesia published by John Wiley & Sons Ltd.)

There currently exists an exciting impetus for increased diversity among medical trainees and improved equity in medical care received by patients. Yet, inclusion of disability within these efforts is often forgotten, allowing the current cultural narrative of ableism to shape medical training. National structural challenges as early as medical school admissions and ableist barriers throughout the educational pipeline have yielded 1) a concerningly low prevalence of medical students and physicians in the US who identify as disabled and 2) propagation of systemic misunderstandings on disability in our healthcare system. This perspective addresses the need for a re-evaluation of diversity in medicine which includes ability status and a commitment to anti-ableism as a critical part of the conversation. We propose reforms and important considerations that could have meaningful implications necessary for improving the culture of disability inclusion in medical education., Competing Interests: Declaration of Conflicting Interests: The Authors declare that there is no conflict of interest., (© The Author(s) 2022.)

Monitoring the humoral protective immune response and its durability after SARS-CoV-2 infections is essential for risk assessment of reinfections, the improvement of diagnostic methods and the evaluation of vaccine trials. We have analyzed neutralizing antibodies and IgG responses specific to different antigens, including the inactivated whole-virion of SARS-CoV-2, the spike subunit 1 protein and its receptor binding domain, as well as the nucleocapsid protein. We show the dynamic developments of the responses from the early convalescent stages up to 9 months post symptoms onset in follow-up samples from 57 COVID-19 patients with varying clinical severity. By correlating antibody signals to neutralizing titres, valid diagnostic markers for the estimation of neutralizing protection could be identified.

Cardiac Allograft Vasculopathy (CAV) is a leading contributor to late transplant rejection. Although implicated, the mechanisms by which bone marrow-derived cells promote CAV remain unclear. Emerging evidence implicates the cell surface receptor tyrosine kinase AXL to be elevated in rejecting human allografts. AXL protein is found on multiple cell types, including bone marrow-derived myeloid cells. The causal role of AXL from this compartment and during transplant is largely unknown. This is important because AXL is a key regulator of myeloid inflammation. Utilizing experimental chimeras deficient in the bone marrow-derived Axl gene, we report that Axl antagonizes cardiac allograft survival and promotes CAV. Flow cytometric and histologic analyses of Axl-deficient transplant recipients revealed reductions in both allograft immune cell accumulation and vascular intimal thickness. Co-culture experiments designed to identify cell-intrinsic functions of Axl uncovered complementary cell-proliferative pathways by which Axl promotes CAV-associated inflammation. Specifically, Axl-deficient myeloid cells were less efficient at increasing the replication of both antigen-specific T cells and vascular smooth muscle cells (VSMCs), the latter a key hallmark of CAV. For the latter, we discovered that Axl-was required to amass the VSMC mitogen Platelet-Derived Growth Factor. Taken together, our studies reveal a new role for myeloid Axl in the progression of CAV and mitogenic crosstalk. Inhibition of AXL-protein, in combination with current standards of care, is a candidate strategy to prolong cardiac allograft survival., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Serological severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody assays differ in the target antigen specificity, e.g. of antibodies directed against the viral spike or the nucleocapsid protein, and in the spectrum of detected immunoglobulins. The aim of the study was to evaluate the performance of two different routinely used immunoassays in hospitalized and outpatient COVID-19 cases., Methods: The test characteristics of commercially available spike1 protein-based serological assays (Euroimmun, EI-assays), determining IgA or IgG and nucleocapsid-based assays (Virotech, VT-assays) determining IgA, IgM or IgG were compared in 139 controls and 116 hospitalized and outpatient COVID-19 cases., Results: Hospitalized COVID-19 patients (n = 51; 115 samples) showed significantly higher concentrations of antibodies against SARS-CoV-2 and differed from outpatient cases (n = 65) by higher age, higher disease severity scores and earlier follow up blood sampling. Sensitivity of the two IgG assays was comparable in hospitalized patients tested ≥ 14 days (EI-assay: 88%, CI 95% 67.6-99.9; VT-assay: 96%, CI 95% 77.7-99.8). In outpatient COVID-19 cases sensitivity was significantly lower in the VT-assay (86.2%, CI 95% 74.8-93.1) compared with the EI-assay (98.5%, CI 95% 90.6-99.9). Assays for IgA and IgM demonstrated a lack of specificity or sensitivity., Conclusions: Our results indicate that SARS-CoV-2 serological assays may need to be optimized to produce reliable results in outpatient COVID-19 cases who are low or even asymptomatic. Assays for IgA and IgM have limited diagnostic performance and do not prove an additional value for population-based screening approaches., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

SARS-CoV-2 infection results in a mild-to-moderate disease course in most patients, allowing outpatient self-care and quarantine. However, in approx. 10% of cases a two- or three-phasic critical disease course with starting from day 7 to 10 is observed. To facilitate and plan outpatient care, biomarkers prognosing such worsening at an early stage appear of outmost importance. In this accelerated article, we report on the identification of urinary peptides significantly associated with SARS-CoV-2 infection, and the development of a multi-marker urinary peptide based test, COVID20, that may enable prognosis of critical and fatal outcomes in COVID-19 patients. COVID20 is composed of 20 endogenous peptides mainly derived from various collagen chains that enable differentiating moderate or severe disease from critical state or death with 83% sensitivity at 100% specificity. Based on the performance in this pilot study, testing in a prospective study on 1000 patients has been initiated. This article is protected by copyright. All rights reserved., (This article is protected by copyright. All rights reserved.)

Survival rates after heart transplant have significantly improved over the last decade. Nevertheless, long-term allograft viability after 10 years remains poor and the sequelae of transplant-associated immunosuppression increases morbidity. Although several studies have implicated roles for lymphocyte-mediated rejection, less is understood with respect to non-major histocompatibility, and innate immune reactivity, which influence graft viability. As immature and mature dendritic cells (DCs) engage in both Major Histocompatibility Complex (MHC)-dependent and MHC-independent immune responses, these cells are at the crossroads of therapeutic strategies that seek to achieve both allograft tolerance and suppression of innate immunity to the allograft. Here we review emerging roles of DC subsets and their molecular protagonists during allograft tolerance and allograft rejection, with a focus on cardiac transplant. New insight into emerging DC subsets in transplant will inform novel strategies for operational tolerance and amelioration of cardiac vasculopathy., (Copyright © 2020 Schroth, Glinton, Luo and Thorp.)

Recipient infusion of donor apoptotic cells is an emerging strategy for inducing robust transplantation tolerance. Daily clearance of billions of self-apoptotic cells relies on homeostatic engagement of phagocytic receptors, in particular, receptors of the tyrosine kinase family TAM (Tyro3, Axl, and MerTK), to maintain self-tolerance. However, an outstanding question is if allogeneic apoptotic cells trigger the same receptor system for inducing allogeneic tolerance. Here, we employed allogeneic apoptotic splenocytes and discovered that the efferocytic receptor MerTK on recipient phagocytes is a critical mediator for transplantation tolerance induced by this strategy. Our findings indicate that the tolerogenic properties of allogeneic apoptotic splenocytes require MerTK transmission of intracellular signaling to suppress the production of inflammatory cytokine interferon α (IFN-α). We further demonstrate that MerTK is crucial for subsequent expansion of myeloid-derived suppressor cells and for promoting their immunomodulatory function, including maintaining graft-infiltrating CD4 + CD25 + Foxp3 + regulatory T cells. Consequently, recipient MerTK deficiency resulted in failure of tolerance by donor apoptotic cells, and this failure could be effectively rescued by IFN-α receptor blockade. These findings underscore the importance of the efferocytic receptor MerTK in mediating transplantation tolerance by donor apoptotic cells and implicate MerTK agonism as a promising target for promoting transplantation tolerance., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

The Internet offers an easy and quick access to a vast amount of patient information. However, several studies point to the poor quality of many websites and the resulting hazards of false information. The aim of this study was to assess quality of information on thyroid cancer. A patients' search for information about thyroid cancer on German websites was simulated using the search engine Google and the patient portal "Patienten-Information.de". The websites were assessed using a standardized instrument with formal and content aspects from the German Cancer Society. Supporting the results of prior studies that analysed patient information on the Internet, the data showed that the quality of patient information on thyroid cancer is highly heterogeneous depending on the website providers. The majority of website providers are represented by media and health providers other than health insurances, practices and professionals offering patient information of relatively poor quality. Moreover, most websites offer patient information of low-quality content. Only a few trustworthy, high-quality websites exist. Especially Google, a common search engine, focuses more on the dissemination of information than on quality aspects. In order to improve the patient information from the Internet, the visibility of high-quality websites must be improved. For that, education programs to improve patients' eHealth literacy are needed. A quick and easy evaluation tool for online information suited for patients should be implemented, and patients should be taught to integrate such a tool into their research process.

In spite of a referral letter as an important document for communicating between physicians, whether it could also be useful as a source of information for patients has not yet established. We included cancer patients in palliative care setting, all of whom completed a standardized questionnaire regarding their opinion concerning the utility of a referral letter as a source of information and its requirements to achieve a better understanding. Completed questionnaires were received from 50 cancer patients. Ninety-four percent of participants agreed that a referral letter could be of great importance for procuring medical information to them. There was only minor divergence among the participants respecting age, gender, or education. Particular requirements were diagnosis, treatment plan, prognosis, list of drugs, and contact data of involved physicians. Additional important topics were laboratory values, alternatives to current therapy, side effects and supportive therapy, and advices regarding lifestyle and naturopathy. The majority of patients also concluded to accept technical terms in doctor's letters if a glossary supported their comprehension. The majority of patients prefer a concise description of medical information in a referral letter. This form of a letter would boost patients' involvement and help them transfer medical information to other therapists or relatives.

Objectives: The optimal surgical treatment strategy for transposition of the great arteries (TGA) associated with ventricular septal defect (VSD) and left ventricular outflow tract obstruction (LVOTO) leading to the best long-term outcome has not been established yet. The wide range of anatomical variability has led to the development of different surgical treatment options. In a retrospective single-centre review, we aimed to report the long-term outcome in patients who underwent biventricular repair., Methods: Between 1992 and 2015, 49 patients underwent biventricular repair for TGA with VSD and LVOTO. On the basis of anatomical substrate, the type of repair was chosen. According to the type of repair, the patients were divided into two groups. Group A (n = 30 patients) includes all patients who underwent intraventricular rerouting (Rastelli, n = 22; réparation à l'étage ventriculaire, n = 8); Group B patients (n = 14) had repair on an arterial level (arterial switch operation + VSD closure + LVOTO resection, n = 10; Bex-Nikaidoh, n = 4)., Results: The follow-up was completed in 90% with a median follow-up of 12.3 years (17.1-17.7 years). There was no difference in survival (Group A: 97% at 5, 10 and 15 years; Group B: 92% at 5, 10 and 15 years) and functional outcome between the groups. All patients were in New York Heart Association class I, having sinus rhythm and normal left ventricular (LV) function. Neurological and educational development was adequate for age in all but one who suffered from attention-deficit hyperactivity disorder. Group A exhibited significantly less freedom from right ventricular outflow tract (RVOT) reoperations/reintervention (79, 48 and 21% at 5, 10 and 15 years) (P = 0.008) due to RVOT dysfunction and endocarditis. Event-free LVOTO survival in Group A at 5, 10 and 15 years amounted to 96, 91 and 91% and was similar to Group B with event-free LVOTO survival at 5, 10 and 15 years of 100, 88 and 88%, respectively., Conclusions: LV function is well preserved irrespective of the type of procedure. Patients who had undergone intraventricular rerouting (Group A) suffered from recurrent RVOT interventions due to RVOT dysfunction and endocarditis. The neurological outcome and the educational level were adequate for age in both groups. Executing the appropriate type of surgery for the individual patient's anatomy provides excellent functional and event-free outcome., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: With growing complexity of diagnostics and therapy, as well as increasing involvement of patients in the decision-making process, there is more and more demand for second opinions in oncology. This literature review aims at analyzing the benefits and risks involved, as well as the tools needed to establish a structured program for second opinion within a modern healthcare system., Methods: A systematic literature search was performed using MEDLINE and Embase and the databases SocINDEX, ERIC and CINAHL. Thirteen articles met the inclusion criteria and offered a relevant insight into the topic of second opinions., Results: Depending on the study, between 6.5 and 36 % of patients search for a second opinion, due to a variety of reasons. Changes in diagnosis, treatment recommendations or prognosis as a result of the second opinion occurred in 12-69 % of cases. In 43-82 % of cases, the original diagnosis or treatment was verified. Patient satisfaction was high, and the second opinion was deemed as helpful and reassuring in most cases. Yet, data on patient-relevant outcomes or on the quality of the second opinion are missing., Conclusion: In general, outcome data on second opinion are divergent and scarce. Yet, with patients' demand for second opinion and influence of second opinion on treatment decisions, a structured, high quality and transparent second-opinion program seems mandatory. Such a program may support patient-physician communication and improve the flow of information, as well as decision-making. Its evaluation should be independent from the provider of the second opinion.

The objective of this study was to describe and compare husbandry practices on organic and conventional dairy farms of similar sizes in Minnesota. Organic (ORG, n=35), same-sized conventional (SC, n=15, <200 cows) and medium-sized conventional (MC, n=13, ≥200 cows) dairy herds were visited in 2012, and farmers were interviewed once about their farm, herd demographics, and herd management practices concerning nutrition, housing, and reproductive programs. Organic farms had been established as long as conventional farms, and ORG producers had most commonly selected ORG farming because of a negative perception of pesticides for human health. The distribution of cattle breeds and ages differed across farm types. Organic farms had more crossbred cows and a greater number of older cows than conventional farms, who had mainly Holstein cattle. Organic farms did not dock tails, were more likely to use breeding bulls, and were less likely to conduct pregnancy diagnoses in cattle. All conventional farmers fed corn, corn silage, and hay, but no forage or feed supplement was fed by all ORG farms with the exception of pasture. Kelp was supplemented on most ORG farms but on none of the conventional farms. In summary, although there were differences across farm types regarding the use of pasture, feeds, and feed additives, breed and age distribution, reproductive management, and the use of tail docking, observations in other management areas showed large overlap across herd types., (Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Purpose: In traumatic brain injury, diffusion-weighted and diffusion tensor imaging of the brain are essential techniques for determining the pathology sustained and the outcome. Postmortem cross-sectional imaging is an established adjunct to forensic autopsy in death investigation. The purpose of this prospective study was to evaluate postmortem diffusion tensor imaging in forensics for its feasibility, influencing factors and correlation to the cause of death compared with autopsy., Methods: Postmortem computed tomography, magnetic resonance imaging, and diffusion tensor imaging with fiber tracking were performed in 10 deceased subjects. The Likert scale grading of colored fractional anisotropy maps was correlated to the body temperature and intracranial pathology to assess the diagnostic feasibility of postmortem diffusion tensor imaging and fiber tracking., Results: Optimal fiber tracking (>15,000 fiber tracts) was achieved with a body temperature at 10°C. Likert scale grading showed no linear correlation (P > 0.7) to fiber tract counts. No statistically significant correlation between total fiber count and postmortem interval could be observed (P = 0.122). Postmortem diffusion tensor imaging and fiber tracking allowed for radiological diagnosis in cases with shearing injuries but was impaired in cases with pneumencephalon and intracerebral mass hemorrhage., Conclusions: Postmortem diffusion tensor imaging with fiber tracking provides an exceptional in situ insight "deep into the fibers" of the brain with diagnostic benefit in traumatic brain injury and axonal injuries in the assessment of the underlying cause of death, considering influencing factors for optimal imaging technique.

The objective of this study was to describe the prevalence and practices used to manage internal helminth parasites and external arthropod parasites on organic and conventional dairy herds in Minnesota. All organic (ORG) dairy herds in Minnesota (n=114) and a convenience sample of conventional herds were invited to participate in the study. Thirty-five ORG herds and 28 conventional herds were visited once in summer and fall of 2012. Conventional dairy herds were split into small conventional (SC,<200 cows) and medium-sized conventional herds (MC, ≥200 cows) so that SC herds were comparable in size to the ORG herds. Dairy managers were surveyed to assess their farm management practices and perceptions about parasites, hygiene scores were recorded for adult stock, and fecal samples were collected from a nominal 20 breeding-age heifers to characterize abundance of internal parasites. Nonparametric tests were used to compare fecal egg counts per gram (FEC) among farms grouped by management systems and practices. Organic farms had more designated pasture and were more likely to use rotational grazing compared with conventional farms, but the stocking densities of animals on pasture were similar among farm types. The overall FEC were very low, and only a few individual ORG heifers had FEC >500 eggs/gram. Samples from heifers on ORG farms had significantly more strongyle-type eggs than those on SC and MC farms (ORG: 6.6±2.1; SC: 0.5±0.3; MC: 0.8±0.7), but egg counts of other types of gastrointestinal parasites did not differ significantly among the 3 herd groups. Fly control measures were applied mainly to milking cows and preweaned calves and were used on 88.6% of ORG herds, 60.0% of SC herds, and 91.7% of MC herds. Approximately half of the producers reported having seen skin conditions suggestive of lice or tail mange in their cattle during the previous winter (ORG: 48.6%, SC: 57.1%, MC: 53.9%). Although most conventional producers reported treating these skin conditions, most organic producers stated they had not treated them. In conclusion, gastrointestinal parasite egg counts were low overall at the time of the survey, and most surveyed producers did not perceive gastrointestinal parasites to be a problem for their animals' health. Independent of the herd type, fly control was mostly targeted at the lactating herd and preweaned calves., (Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The presence of humic substances (HS) has previously been shown to alter sorption properties of multi-walled carbon nanotubes (MWCNTs). To systematically study this process, three alkane pairs were selected as molecular probe sorbates. The influence of HS on sorption affinity, sorption linearity, and the dominant sorption mode (i.e., ad- or absorption) by MWCNTs was investigated. The addition of HS led to a continuous decrease in sorption affinity and an increase in sorption linearity with increasing HS addition. Furthermore, the comparison of distribution coefficients of n- and cycloalkanes showed that the dominant sorption mode remains to be adsorption regardless of the presence of HS on MWCNT surface. From this, it can be concluded that instead of a change in sorption mode to absorption of sorbates into HS-coated MWCNT, HS blocks high-energy sorption sites for subsequently added sorbates and that sorbates continuously sorb on the MWCNT surface., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Acute Aspergillus fumigatus infection in immunocompetent patients is rare. This is the first known case of a patient who survived Aspergillus sepsis after being treated early with veno-venous extracorporeal membrane (ECMO) and antifungal therapy., Case Presentation: An immunocompetent 54-year-old woman was exposed to plant mulch during gardening and subsequently developed pulmonary failure that progressed to sepsis with multiorgan failure. Owing to her severe clinical condition, she was treated for acute respiratory distress syndrome (ARDS) with veno-venous ECMO. Empiric antifungal therapy comprising voriconazole was also initiated owing to her history and a previous case report of aspergillosis after plant mulch exposure, though there was no microbiological proof at the time. A. fumigatus was later cultured and detected on antibody testing. The patient recovered, and ECMO was discontinued 1 week later. After 7 days of antifungal treatment, Aspergillus antibodies were undetectable., Conclusions: In cases of sepsis that occur after gardening, clinicians should consider Aspergillus inhalation as an aetiology, and early antimycotic therapy is recommended.

The accurate prediction of distribution coefficients of organic compounds from water to carbon-based nanomaterials (CNM) is of major importance for the understanding of environmental processes and a risk assessment of released CNM. Poly-parameter linear free-energy relationships (ppLFER) have previously been shown to offer such an accurate prediction of sorption processes. The aim of this study was to identify and quantify the contribution of individual molecular interactions to overall sorption by multi-walled carbon nanotubes (MWCNTs). To this end, a large data set of experimental sorption isotherms by MWCNTs of 20 aliphatic and 14 aromatic compounds covering various relevant molecular interactions was produced. A thermodynamic cycle was used to obtain MWCNT-air distribution coefficients (KMWCNT/a) for the interpretation of direct sorbate-MWCNTs interactions. The thereby derived ppLFER log KMWCNT/a = (0.59 ± 0.59)E + (2.23 ± 0.59)S + (3.90 ± 0.67)A + (3.23 ± 0.71)B + (0.98 ± 0.17)L - (0.05 ± 0.50) shows the contribution of non-specific interactions, represented by the hexadecane-air partitioning constant (L), and specific interactions related to the solute polarity (S) as well as the H-bond interactions (A, B). Measured MWCNT-water distribution coefficients were clearly more accurately calculated by the ppLFER equations (R(2) 0.85-0.86) compared to the classical prediction by single parameter model based on the octanol-water partitioning constant (R(2) 0.64-0.78). In addition, the ppLFER presented here allow a more accurately prediction of sorption by MWCNTs compared to literature ppLFER, especially for aliphatic compounds and at environmentally relevant concentrations., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Few avenues exist to familiarize medical students with careers as clinician-educators, and the clinician-educator career pathway has not been well defined. In this article, the authors describe how they integrated a career-oriented student track into the 2011 Northeast Group on Educational Affairs (NEGEA) annual retreat to introduce students to careers in medical education. Annual education conferences are principal sources of educational scholarship, networking, collaboration, and information sharing; as such, they represent attractive venues for early exposure to the culture of medical education. The authors' goal in creating the NEGEA conference student track was to excite students about careers in medical education by providing them with an array of opportunities for active involvement in both student-specific and general conference activities.The authors draw from their experience to provide a guide for recruiting student participants to career-building student tracks. They also offer a guide for developing future student tracks, based on their experience and grounded in social cognitive career theory. Although their focus is on medical education, they believe these guides will be useful for educators planning a conference-based student track in any field.

Aim: We investigated the effect of mild hypothermia on the contractility and calcium response of atrial and ventricular myocardium., Methods: Human atrial tissue was excised during cannulation process from patients undergoing elective open heart surgery following informed consent. Trabeculae were carefully dissected and compared to rabbit atrial and ventricular trabeculae. All probes were electrically stimulated while clamped to a force transducer and suspended in buffer media. Developed force, time to peak tension and time to 50% of relaxation were measured during mild hypothermia (37-31 degrees C). SR Ca++-content was studied by rapid cooling contractures, Ca++-responsiveness by a stepwise increase of extracellular calcium concentration to 10 mM., Results: Hypothermia decreased twitch tension and SR Ca++-content in human atrial myocardium but increased contractility and SR Ca++-content in rabbit atrial and rabbit ventricular myocardium. Cooling induced a lengthening of contraction and relaxation times in all preparations. In all preparations the positive inotropic response to calcium was diminished at 34 degrees C and almost abolished at 31 degrees C., Conclusions: In contrast to rabbit ventricular and atrial myocardium, human atrial myocardium showed a negative inotropic effect when exposed to hypothermia. This alteration could be secondary to a declined SR-Ca++ storage and decreased atrial calcium sensitivity. Calcium dependent inotropy is suppressed at temperatures below 34 degrees C.

Background: alpha-1-Antitrypsin deficiency (AATD) is a rare condition with a prevalence of about 1/4000 individuals in Germany. The clinical manifestations are the early development of pulmonary emphysema or of liver cirrhosis. The low prevalence of AATD suggested the establishment of a registry with the aim to learn more details about the natural history and the quality of care for these patients., Methods, Patients, Results: Since 2004 the German registry for individuals with AATD is maintained in Marburg. Up to May 2008, 548 individuals were registered, 455 with the genotype PiZZ and 46 with PiSZ. The age range of the registered individuals extends from 2 to 82 years (mean 55, SD 20; men 54 [SD 19] years, women 55 [SD 21] years). Most patients are affected by chronic obstructive pulmonary disease (COPD, distribution to the GOLD stages: GOLD I = 16 %, GOLD II = 30 %, GOLD III = 33 %, GOLD IV = 21 %). Currently 109 subjects are under substitution therapy. The time period between the first symptom and the establishment of the correct diagnosis was on average 5.6 years., Conclusions: The data of the registry allow a detailed characterisation of the natural course of the disease and the levels of the patient care.

Background: In addition to their well-known ability to predict fluid responsiveness, functional pre-load parameters, such as the left ventricular stroke volume variation (SVV) and pulse pressure variation (PPV), have been proposed to allow real-time monitoring of cardiac pre-load. SVV and PPV result from complex heart-lung interactions during mechanical ventilation. It was hypothesized that, under open-chest conditions, when cyclic changes in pleural pressures during positive-pressure ventilation are less pronounced, functional pre-load indicators may be deceptive in the estimation of ventricular pre-load., Methods: Forty-five patients undergoing coronary artery bypass grafting participated in this prospective, observational study. PPV and SVV were assessed by pulse contour analysis. The thermodilution technique was used to measure the stroke volume index and global and right ventricular end-diastolic volume index. Trans-oesophageal echocardiography was used to determine the left ventricular end-diastolic area index. All parameters were assessed before and after sternotomy, and, in addition, after weaning from cardiopulmonary bypass before and after chest closure (pericardium left open). Patients were ventilated with constant tidal volumes (8 +/- 2 ml/kg) throughout the study period using pressure control., Results: SVV and PPV decreased after sternotomy and increased after chest closure. However, these changes could not be related to concomitant changes in the ventricular pre-load. The stroke volume index was correlated with SVV and PPV in closed-chest conditions only, whereas volumetric indices reflected cardiac pre-load in both closed- and open-chest conditions. SVV and PPV were correlated with left and right ventricular pre-load in closed-chest-closed-pericardium conditions only (with the best correlation found for the right ventricular end-diastolic volume index)., Conclusions: SVV and PPV may be misleading when estimating cardiac pre-load during open heart surgery.

The use of miniaturized cardiopulmonary bypass (CPB) circuits and avoidance of cardioplegic arrest are attempts to reduce the inflammatory response to cardiac surgery. We studied the effects of beating heart surgery (BHS) with assistance of simplified bypass systems (SBS) on global hemodynamics, myocardial function and the inflammatory response to CPB. We hypothesized that the use of SBS was associated with less hemodynamic instability after CPB resulting from attenuation of the inflammatory response when compared with surgery performed with a conventional CPB (cCPB) circuit. Forty-five patients undergoing coronary artery bypass grafting were prospectively studied. Fifteen patients were randomized to the use of a cCPB circuit, cold crystalloid cardioplegia, and moderate hypothermia. Two groups of 15 patients underwent BHS during normothermia with assistance of two different SBS consisting of only blood pump and oxygenator. Hemodynamic variables were assessed with transpulmonary thermodilution and transesophageal echocardiography. Plasma levels of proinflammatory and antiinflammatory mediators were measured perioperatively. After CPB, variables of global hemodynamics and systolic ventricular function did not differ among groups. Left ventricular diastolic function was impaired after CPB equally in all groups (P < 0.01 versus pre-CPB). At the end of surgery, there was more need for vasopressor (norepinephrine) support in both SBS groups than in the cCPB group (P < 0.01). After CPB, the release of interleukin (IL)-6 did not differ significantly among groups, whereas plasma levels of IL-10 were higher in the cCPB group (P < 0.01 versus SBS). The extent of myocardial necrosis (Troponin T) was comparable in all groups. We conclude that in our study, miniaturizing bypass systems and avoidance of cardioplegic arrest were not effective in improving hemodynamic performance and in attenuating the proinflammatory immune response after CPB.

Stroke rarely occurs in a young patient with migraine. Nevertheless, vascular headache can lead to catastrophic neurologic consequences, and severe headache associated with persistent neurologic deficits poses a complex diagnostic problem.