Search

Internal exposure of the human body to potentially harmful chemical substances can be assessed by Human Biomonitoring (HBM). HBM can be used to generate conclusive data that may provide an overview of exposure levels in entire or specific population groups. This knowledge can promote the understanding of potential risks of the substances of interest or help monitoring the success of regulatory measures taken on the political level. Study planning and design are key elements of any epidemiologic study to generate reliable data. In the field of HBM, this has been done using differing approaches on various levels of population coverage so far. Comparison and combined usage of the resulting data would contribute to understanding exposure and its factors on a larger scale, however, the differences between studies make this a challenging and somewhat limited endeavour. This article presents templates for documents that are required to set up an HBM study, thus facilitating the generation of harmonised HBM data as a step towards standardisation of HBM in Europe. They are designed to be modular and adaptable to the specific needs of a single study while emphasising minimum requirements to ensure comparability. It further elaborates on the challenges encountered during the process of creating these documents during the runtime of the European Joint Programme HBM4EU in a multi-national expert team and draws up lessons learnt in the context of knowledge management. This report was developed under the Horizon 2020 project HBM4EU (WP7 “Survey design and fieldwork preparation”) (www.hbm4eu.eu). HBM4EU has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 733032. This article reflects only the authors’ view and the European Commission is not responsible for any use that may be made of the information it contains. The authors would like to express their gratitude towards all partners participating in WP7, to wards the HBM4EU Chemical Group Leaders who have contributed with their valuable experiences and expertise to the creation of the described documents as well as towards the cofunding national authorities. Sí

Aim [99mTc]Tc-PSMA-based radioguided surgery (TPRS) represents a curative approach for localized relapse of prostate cancer. For its simplified regulatory permission, the radiation protection authorities require a 99mTc- activity below the exemption limit of 10 MBq at the time of surgery. Our aim was to determine the optimal amount of radioactivity (OAR) to comply with that limit and to estimate the maximum number of TPRS procedures per year and surgeon without triggering the full monitoring obligations. Methods In this retrospective study, a dose rate meter was calibrated using measurements on phantoms and from recently injected (1 min p. i.) patients to determine the activity in the patient from measured dose rates. The effective half-life of 99mTc-PSMA-I&S in patients was determined from repeated dose rate measurements to estimate dose parameters of relevance for radiation protection. External exposures of the surgeons were measured with personal dosimeters calibrated in Hp(10). The surgeon’s finger dose Hp(0.07) is estimated from radioactivity measured in resected lymph nodes. Potenzial incorporations were estimated for an activity of 10 MBq. Results From the first 6 subsequent patients, an effective half-life of 4.15 h was observed. Assuming an operation time 24 h p. i., the OAR was 550 MBq. Operations lasting in average 2 h in a distance of 0.25 m to the patient imply a body dose for surgeons of 4.16 µSv per procedure. Based on these estimates, the surgeon’s Hp(10) is less than 1 mSv per year with up to 241 operations per year. Hp(0.07) and potential incorporation of activity do not lead to further limitations. Summary All radiation protection regulations are met with adherence to OAR recommended here without triggering the full monitoring obligations from radiation protection regulations.

International audience; Although central venous catheter (CVC)-related thrombosis (CRT) is a severe complication of home parenteral nutrition (HPN), the amount and quality of data in the diagnosis and management of CRT remain low. We aimed to describe current practices regarding CVC management in French adult and pediatric HPN centers, with a focus on CVC obstruction and CRT. Current practices regarding CVC management in patients on HPN were collected by an online-based cross-sectional survey sent to expert physicians of French HPN centers. We compared these practices to published guidelines and searched for differences between pediatric and adult HPN centers' practices. Finally, we examined the heterogeneity of practices in both pediatric and adult HPN centers. The survey was completed by 34 centers, including 21 pediatric and 13 adult centers. We found a considerable heterogeneity, especially in the responses of pediatric centers. On some points, the centers' responses differed from the current guidelines. We also found significant differences between practices in adult and pediatric centers. We conclude that the management of CVC and CRT in patients on HPN is a serious and complex situation for which there is significant heterogeneity between HPN centers. These findings highlight the need for more well-designed clinical trials in this field.

A retrospective, single-center analysis of 14 cases of Candida endocarditis (from 355 candidemia cases during the years 2012–2019) revealed a high in-hospital mortality (57.1%), a high proportion of healthcare-associated infections (13/14) and a high treatment preference for echinocandins. Transthoracic echocardiography and 18F-FDG PET/CT had a sensitivity of 54.5% and 57.1%, respectively. Patients were older than previously described and most patients with Candida endocarditis had persistent candidemia for ≥ 3 days despite antifungal therapy. Electronic supplementary material The online version of this article (10.1007/s11046-020-00492-3) contains supplementary material, which is available to authorized users.

Background Overdose deaths related to illegal drugs in North American markets are now dominated by potent synthetic opioids such as fentanyl, a circumstance foreshadowed by often-overlooked events in Estonia since the turn of the century. Market transitions generate important and far-reaching implications for drug policy. Argument and analysis The supplier-driven introduction of illegally manufactured synthetic opioids into street opioids is elevating the risk of fatal overdose. Using the most recent overdose mortality and drug seizure data in North America, we find that overdose deaths and seizures involving synthetic opioids are geographically concentrated, but this might be changing. Examination here suggests that in some places fentanyl and its analogues have virtually displaced traditional opioids, such as heroin. The concealing of synthetic opioids in powders sold as heroin or pressed into counterfeit medications substantially increases harms. The nature and scale of the challenge posed by synthetic opioids is unprecedented in recent drug policy history. Conclusions There is urgent need for policy and technological innovation to meet the challenges posed by illegally produced synthetic opioids. Novel interventions worth examining include supervising drug use, proactively deterring on-line distribution and new technologies aimed at improving transparency, such as point-of-use drug content testing. Continuing to approach this problem only with existing policies and available methods, such as naloxone, is unlikely to be enough and will result in many premature deaths.

A silicalite-1 film (SF) deposited on Ti-6Al-4V alloy was investigated in this study as a promising coating for metallic implants. Two forms of SFs were prepared: as-synthesized SFs (SF-RT), and SFs heated up to 500 °C (SF-500) to remove the excess of template species from the SF surface. The SFs were characterized in detail by X-ray photoelectron spectroscopy (XPS), by Fourier transform infrared spectroscopy (FTIR), by scanning electron microscopy (SEM) and water contact angle measurements (WCA). Two types of bone-derived cells (hFOB 1.19 non-tumor fetal osteoblast cell line and U-2 OS osteosarcoma cell line) were used for a biocompatibility assessment. The initial adhesion of hFOB 1.19 cells, evaluated by cell numbers and cell spreading area, was better supported by SF-500 than by SF-RT. While no increase in cell membrane damage, in ROS generation and in TNF-alpha secretion of bone-derived cells grown on both SFs was found, gamma H2AX staining revealed an elevated DNA damage response of U-2 OS cells grown on heat-treated samples (SF-500). This study also discusses differences between osteosarcoma cell lines and non-tumor osteoblastic cells, stressing the importance of choosing the right cell type model.

LL-37 is a cationic antimicrobial peptide and the sole human member of cathelicidins. Besides its bactericidal properties, LL-37 is known to have direct immunomodulatory effects, among which enhancement of antiviral responses via endosomal toll-like receptors (TLRs). Omiganan pentahydrochloride is a synthetic cationic peptide in clinical development. Previously, omiganan was primarily known for its direct bactericidal and antifungal properties. We investigated whether omiganan enhances endosomal TLR responses, similar to LL-37. Human peripheral blood mononuclear cells were treated with endosomal TLR3, -7, -8, and -9 ligands in the presence of omiganan. Omiganan enhanced TLR-mediated interferon-alpha release. Subsequent experiments with TLR9 ligands showed that plasmacytoid dendritic cells were main contributors to omiganan-enhanced IFN production. Based on this type I interferon-enhancing effect, omiganan may qualify as potential treatment modality for virus-driven diseases. The molecular mechanism by which omiganan enhances endosomal TLR responses remains to be elucidated.

Background To evaluate predictive clinico-pathological characteristics on outcome in head and neck melanoma (HNM) in a population-based study with particular emphasis on the prognostic effect of sentinel lymph node biopsy (SLNB), Charlson comorbidity index (CCI) and distinct tumor localisations. Methods Here we primarily describe a retrospective multicenter population-based cohort study with 402 patients having undergone resection with curative intent of HNM between 2010 and 2017. SLNB was used in the diagnosis of 79 HNM patients. Outcome was analyzed, focusing on SLNB, CCI as well as tumor localisation. Overall survival (OAS) und recurrence free survival (RFS) was examined by uni- and multivariate analysis. Results Histopathologically verified lymph node metastasis according to SLNB was associated with impaired RFS in HNM patients (p = 0.004). Especially in higher tumor stages, the sole implementation of SLNB improved survival significantly in the present cohort (p = 0.042). With most of the HNM being located in the face, melanoma of the scalp and neck could be linked to deteriorated patient’s outcome in uni- as well as multivariate analysis (p = 0.021, p = 0.004). Conclusions SLNB is a useful tool in predicting development of distant metastasis after HNM resection with curative intent. Especially in higher tumor stages, performing a SLNB ameliorated survival of HNM patients. Additionally, CCI as well as a distinct tumor localisations in HNM were identified as important risk factors in our population-based cohort study.

AIM: To evaluate the effectiveness of complementary imaging of high-resolution ultrasound including CEUS with PET/CT for tissue characterization and tumor detection. MATERIAL AND METHODS: 100 patients were examined with PET/CT and US/CEUS between January 2018 until February 2020. All patients underwent PET/CT followed by selective US/CEUS within 4 weeks. Comparison regarding concordant or diverging findings in PET/CT and US. Analysis of the differences concerning the lesions number of found by PET/CT and US/CEUS or the possibility of a secured diagnosis following ultrasound causing therapeutic changes. RESULTS: Diverging findings regarding the number of liver lesions in PET/CT and CEUS were found in 35 out of 64 patients (54%). Regarding renal lesions, a more definite diagnosis following ultrasound, causing a change of therapeutic approach, was achieved in 89%. Concordant results in PET/CT and US were found in 83% of patients with splenic and nodal findings. In 78% of patients with increased musculoskeletal or soft tissue tracer uptake, US was able to make a secured diagnosis with therapeutic changes. CONCLUSION: The present results indicate a strong benefit of complementary imaging of PET/CT and selective, high-resolution ultrasound especially in patients with liver, renal and musculoskeletal or soft tissue findings.

International audience; BACKGROUND & AIMS: As citrulline is produced by small intestine, plasma citrulline concentration is decreased and may become essential in patients with short bowel syndrome (SBS). In a rat model of SBS, citrulline supplementation enhanced muscle protein synthesis. The aim of the study was to determine whether citrulline impacts whole body protein metabolism in patients with SBS. METHODS: Nine adults with non-malignant SBS (residual small bowel 90 ± 48 cm; mean ± SD) who were in near-normal nutritional status without any artificial nutrition, were recruited long after surgery. They received 7-day oral supplementation with citrulline (0.18 g/kg/day), or an iso-nitrogenous placebo in a randomized, double-blind, cross-over design with a 13-day wash-out between regimens, and an intravenous 5-h infusion of L-[1-13C]-leucine in the postabsorptive state to assess protein metabolism after each regimen. RESULTS: Plasma citrulline concentration rose 17-fold (25 ± 9 vs. 384 ± 95 μmol/L) and plasma arginine 3-fold after oral citrulline supplementation (both p < 4 × 10-6). Supplementation did not alter leucine appearance rate (97 ± 5 vs. 97 ± 5 μmol kg-1.h-1; p = 0.88), leucine oxidation (14 ± 1 vs. 12 ± 1 μmol kg-1.h-1; p = 0.22), or non-oxidative leucine disposal (NOLD), an index of whole-body protein synthesis (83 ± 4 vs. 85 ± 5 μmol kg-1.h-1; p = 0.36), nor insulin or IGF-1 plasma concentrations. In each of the 3 patients with baseline citrulline

The importance of physical activity has become evident since a sedentary lifestyle drives cardiovascular disease progression and is associated with increased morbidity and mortality. The favorable effects of exercise training in chronic heart failure (HF) and chronic kidney disease (CKD) are widely recognized and exercise training is recommended by European and American guidelines. However, the application of exercise intervention in HF patients hospitalized for acute decompensation or acute worsening in cardiac function has not been explored extensively and, as a result, knowledge about the effects of exercise training in the inpatient setting of acute HF is limited. Acute HF is often accompanied by signs and symptoms of congestion, termed acute decompensated heart failure (ADHF), which leads to worsening renal function (WRF) and eventually negatively affects both thoracic and abdominal organs. Therefore, we first provide a comprehensive overview of the impact of exercise training in hospitalized patients demonstrating acute decompensating HF. In the second part, we will focus on the effects of exercise training on congestion in a setting of ADHF complicated by renal dysfunction. This review suggests that exercise intervention is beneficial in the inpatient setting of acute HF, but that more clinical studies focusing on the application of exercise training to counteract venous congestion are needed.

Severe forms of anorexia nervosa are responsible for weight loss and life-threatening consequences. Refeeding represents a real psychiatric and somatic challenge. Physical activities are usually not recommended during intensive refeeding in order to avoid energy expenditure. This study assessed the interest in an early return to controlled physical activities, during a hospitalization in a Physical Medicine and Rehabilitation (PMR) department, including continuous nasogastric refeeding and psychiatric care. A total of 37 subjects aged 32 ± 11 years old performed inpatient physical activities during nasogastric refeeding initiated after intensive care. The physical activity program was adapted according to the hyperactivity of the patients. Evaluation parameters were weight, body mass index (BMI), body composition (fat, lean, and bone masses), and function (strength, balance, walking, ventilation). Patient satisfaction, re-hospitalizations, and physical activities continuation were assessed at 12 months of follow-up. Weight, BMI, and body fat increased significantly (+2.7 ± 1.7 kg; +1.0 ± 0.6 kg/m2; +1.7 ± 2.5 kg, respectively). Muscle strength increased even if the lean mass did not. Walking distance, balance, and respiratory function were significantly improved. Weight and fat mass gains did not differ according to the presence or absence of hyperactivity. At 12 months, 46% of the patients continued to be physically active, but 21% of the patients had been re-hospitalized. The early return to controlled physical activities in PMR hospitalization does not compromise the efficiency of intensive refeeding in severe anorexia nervosa patients.

Background Risks for living-liver donors are lower in case of a left liver donation, however, due to lower graft volume, the risk for small-for-size situations in the recipients increases. This study aims to prevent small-for-size situations in recipients using an auxiliary two-staged partial resection liver transplantation (LTX) of living-donated left liver lobes. Case presentation Two patients received a two-stage auxiliary LTX using living-donated left liver lobes after left lateral liver resection. The native extended right liver was removed in a second operation after sufficient hypertrophy of the left liver graft had occurred. Neither donor developed postoperative complications. In both recipients, the graft volume increased by an average of 105% (329 ml to 641 ml), from a graft-to-body-weight ratio of 0.54 to 1.08 within 11 days after LTX, so that the remnant native right liver could be removed. No recipient developed small-for-size syndrome; graft function and overall condition is good in both recipients after a follow-up time of 25 months. Conclusions Auxiliary two-staged partial resection LTX using living-donor left lobes is technically feasible and can prevent small-for-size situation. This new technique can expand the potential living-donor pool and contributes to increase donor safety.

Purpose Fluorine-18 fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG PET/CT) is the standard for staging aggressive non-Hodgkin lymphoma (NHL). Limited data from prospective studies is available to determine whether initial staging by FDG PET/CT provides treatment-relevant information of bone marrow (BM) involvement (BMI) and thus could spare BM biopsy (BMB). Methods Patients from PETAL (NCT00554164) and OPTIMAL>60 (NCT01478542) with aggressive B-cell NHL initially staged by FDG PET/CT and BMB were included in this pooled analysis. The reference standard to confirm BMI included a positive BMB and/or FDG PET/CT confirmed by targeted biopsy, complementary imaging (CT or magnetic resonance imaging), or concurrent disappearance of focal FDG-avid BM lesions with other lymphoma manifestations during immunochemotherapy. Results Among 930 patients, BMI was detected by BMB in 85 (prevalence 9%) and by FDG PET/CT in 185 (20%) cases, for a total of 221 cases (24%). All 185 PET-positive cases were true positive, and 709 of 745 PET-negative cases were true negative. For BMB and FDG PET/CT, sensitivity was 38% (95% confidence interval [CI]: 32–45%) and 84% (CI: 78–88%), specificity 100% (CI: 99–100%) and 100% (CI: 99–100%), positive predictive value 100% (CI: 96–100%) and 100% (CI: 98–100%), and negative predictive value 84% (CI: 81–86%) and 95% (CI: 93–97%), respectively. In all of the 36 PET-negative cases with confirmed BMI patients had other adverse factors according to IPI that precluded a change of standard treatment. Thus, the BMB would not have influenced the patient management. Conclusion In patients with aggressive B-cell NHL, routine BMB provides no critical staging information compared to FDG PET/CT and could therefore be omitted. Trial registration NCT00554164 and NCT01478542

Purpose Treatment of patients with laryngeal squamous cell carcinoma with radiotherapy or chemoradiation is an established alternative to laryngeal surgery in many cases, but particularly for advanced tumors without cartilage invasion. Imaging modalities face the challenge of distinguishing between posttherapeutic changes and residual disease in the complex anatomic subsite of the larynx. Guidelines concerning restaging of head and neck squamous cell carcinomas (HNSCC) are presented by the National Comprehensive Cancer Network (NCCN) and other national guidelines, but clearly defined recommendations for routine restaging particularly for laryngeal cancer are lacking. Methods A systematic search was carried out in PubMed to identify studies evaluating routine restaging methods after primary non-surgical treatment of laryngeal squamous cell carcinoma from 2009 to 2020. Results Only three studies were deemed eligible, as they included at least ≥50% patients with laryngeal squamous cell carcinoma and evaluated imaging modalities to detect residual cancer. The small number of studies in our review suggest restaging with fluoro-deoxy-glucose positron-emission tomography/computed tomography (FDG PET/CT) 3 months after initial treatment, followed by direct laryngoscopy with biopsy of the lesions identified by FDG PET/CT. Conclusion Studies evaluating restaging methods after organ-preserving non-surgical treatment of laryngeal carcinoma are limited. As radiotherapy (RT), chemoradiotherapy (CRT), systemic therapy followed by RT and radioimmunotherapy are established alternatives to surgical treatment, particularly in advanced laryngeal cancers, further studies are needed to assess and compare different imaging modalities (e.g. PET/CT, MRI, CT, ultrasound) and clinical diagnostic tools (e.g., video laryngoscopy, direct laryngoscopy) to offer patients safe and efficient restaging strategies. PET or PET/CT 3 months after initial treatment followed by direct laryngoscopy with biopsy of the identified lesions has the potential to reduce the number of unnecessary laryngoscopies.

Background Illegally manufactured potent synthetic opioids (IMPSO) like fentanyl have contributed to rises in overdose deaths in parts of North America and Europe. While many of these substances are produced in Asia, there is little evidence they have entered markets there. We consider the susceptibility to IMPSO’s encroachment in markets in the Asia-Pacific region. Methods Our analysis focuses on Australia, China, India, and Myanmar. Using a mixed-methods approach comprising interviews, literature review, and secondary data analyses, we examine factors facilitating or impeding incursion of IMPSO. Finally, we illustrate the potential for IMPSO fatalities in Australia. Results Australia reports some signs of three facilitating factors to IMPSO’s emergence: 1) existing illicit opioid markets, 2) disruption of opioid supply, and 3) user preferences. The other three countries report only existing illicit opioid markets. While diverted pharmaceutical opioids are a noted problem in Australia and India, heroin is the dominant opioid in all four countries. There are divergent trends in heroin use, with use declining in China, increasing in India, and stable in Australia and Myanmar. If IMPSO diffused in Australia as in North America from 2014 to 2018, and our assumptions generally hold, deaths from IMPSO could range from 1500–5700 over a five-year period. Conclusions This analysis and illustrative calculations serve as an early indication for policymakers. With the exception of Australia, many countries in the region fail to properly record overdose deaths or monitor changes in local drug markets. Early assessment and monitoring can give officials a better understanding of these changing threats.

It is recommended that patients with ≥50% carotid artery stenosis undergo surveillance imaging and atherosclerotic risk reduction medical therapies, regardless of whether revascularization is performed. The objective of this study was to determine rates of adherence to these recommended measures and to identify risk factors for nonadherence.A retrospective analysis was performed of all carotid duplex ultrasound (DUS) from 2016 to 2017 at a single institution. Patients with unilateral or bilateral ≥50% carotid stenosis were included. Primary outcomes were rates and timing of surveillance imaging and medication regimen. Patient and study characteristics were compared using univariate and multivariable analyses. A subgroup analysis of patients with a new finding of carotid stenosis was also performed.Carotid stenosis50% was detected in 340 patients. Overall, 182 patients (54%) had follow-up imaging (median 261 days [IQR 166-366]) and 158 patients (46%) had no imaging follow-up (NIFU). NIFU patients had similar rates of aspirin use (86% vs. 88%, P = 0.6) and tobacco cessation counseling (71% vs. 71%, P = 0.8) but had less statin use (85% vs. 94%, P = 0.01) compared to those with imaging follow-up. Subsequent carotid revascularization was more common in patients with imaging follow-up (18% vs. 3%, P0.001). NIFU patients were less likely to have Medicare or commercial insurance (54% vs. 75%, P0.001). The indication for DUS in NIFU patients, compared to those in follow up, was less commonly neurologic symptoms (11% vs. 14%), more commonly other clinical findings (35% vs. 16%), and more commonly as work up before nonvascular surgery (25% vs. 4%, P0.001), respectively. NIFU rates decreased with increasing degree of carotid stenosis. Prior carotid intervention, prior DUS, or DUS ordered by a vascular surgeon were characteristics associated with imaging follow-up (P0.05 for all). In a subgroup of 160 patients with new carotid stenosis, a majority (64%) had NIFU and statin use was lower in these patients (82% vs. 96%, P = 0.007). On multivariable analysis, preop indication was predictive of NIFU (odds ratio [OR] 8.1 [95% confidence interval, CI 2.5-26.4], P0.001) whereas protective factors included: 70-80% stenosis (OR 0.33 [95% CI 0.14-0.76], P = 0.01), study ordered by vascular surgeon (OR 0.40 [95% CI 0.19-0.83], P = 0.01), and Medicare/commercial insurance (OR 0.36 [95% CI 0.2-0.66], P = 0.001).Nearly half of patients found to have ≥50% carotid stenosis on DUS had no imaging follow-up; these patients were less likely to be on recommended statin therapy. The benefits of nonrevascularization-based treatments for carotid disease require adherence to therapy. Forgoing surveillance imaging in patients with hemodynamically significant carotid stenosis should be a shared decision between provider and patient and does not obviate the need for medical therapies.

BackgroundNeutrophils have been reported to have protumor, antitumor or neutral effects in cancer progression. The underlying causes for this functional variability are not clear.MethodsWe studied the role of neutrophils in six different mouse tumor models by intratumoral injection of antimicrobial peptides or vaccination. Changes in systemic and intratumoral immune cells were analyzed by flow-cytometry and mass-cytometry. The role of neutrophils was studied by antibody-mediated neutrophil depletion. Neutrophils from different mouse strains were compared by RNA sequencing.ResultsThe antimicrobial peptide Omiganan reduced the growth of TC-1 tumors in BL/6 mice and CT26 tumors in BALB/c mice. No significant effects were observed in B16F10, MC38 and 4T1 tumors. Growth delay was associated with increased abundance of neutrophils in TC-1 but not CT26 tumors. Systemic neutrophil depletion abrogated Omiganan efficacy in TC-1 but further reduced growth of CT26, indicating that neutrophils were required for the antitumor effect in TC-1 but suppressed tumor control in CT26. Neutrophils were also required for a therapeutic vaccine-induced T-cell mediated control of RMA tumors in BL/6 mice. Clearly, the circulating and intratumoral neutrophils differed in the expression of Ly6G and CD62L, between TC-1 and CT26 and between blood neutrophils of tumor-naïve BL/6 and BALB/c mice. RNA-sequencing revealed that neutrophils from BL/6 mice but not BALB/c mice displayed a robust profile of immune activation, matching their opposing roles in TC-1 and RMA versus CT26.ConclusionsNeutrophil functionality differs strongly between mouse strains and tumor types, with consequences for tumor progression and therapy.

Background We assessed the diagnostic value of FDG PET/CT in a real-world cohort of patients with surgically managed infective endocarditis (IE). Methods We performed a retrospective analysis of all patients hospitalized in a tertiary IE referral medical center from January 2014 to October 2018 fulfilling the following criteria: ICD-10 code for IE and OPS code for both, heart surgery and FDG PET/CT. Results Final analysis included 29 patients, whereof 28 patients had surgically proven IE. FDG PET/CT scan was true-positive in 15 patients (sensitivity (SEN) 56%) and false-negative in 12 patients. Combination of Duke criteria (DC) with FDG PET/CT scan resulted in gain of SEN for all patients with confirmed IE (SEN of DC 79% vs SEN of combination DC and FDG PET/CT 89%), driven by a relevant gain in PVE patients only (SEN of DC 78% vs SEN of combination DC and FDG PET/CT 94%). Interestingly, higher prosthesis age was observed in patients with false-negative scans. Conclusions We found a SEN of 56% for FDG PET/CT in a real-world cohort of patients with surgically proven IE which was associated with a 16% gain of IE diagnosis in patients with PVE when combined with DC.

Positron emission tomography (PET) withDie Positronen-Emissions-Tomografie (PET) mit

International audience; Background: Analysis of serum biomarkers for the assessment of atrophic gastritis (AG), considered as gastric precancerous lesion, is of growing interest and recommended by current guidelines. Our aim was to evaluate the diagnostic performance of a panel of biomarkers (GastroPanel®) for the detection of AG in France, a country of a low gastric cancer (GC) incidence. Material and Methods: In this prospective, multicenter, cross-sectional study, consecutive patients considered at increased risk of GC and undergoing upper endoscopy with gastric biopsies were included. Blood samples were collected for the analysis of GastroPanel® (association of Pepsinogens I and II, Gastrin-17, and Helicobacter pylori serology) using ELISA. The results of GastroPanel® were compared to the results of histology considered as the reference. Results: Between 2016 and 2019, 344 patients (148 cases with AG, 196 controls without AG) were included. Sensitivity, specificity, positive, and negative predictive values for the detection of AG by GastroPanel® were of 39.9% (95% CI 31.9; 48.2), 93.4% (95% CI 88.9; 96.4), 81.9 (95% CI 71.1; 90.0), and 67.3 (95% CI 61.4; 72.8), respectively. The sensitivity was significantly higher for the detection of severe AG [60.8% (95% CI 46.1; 74.6) P =.015] and corpus AG [61.0% (95% CI 49.2; 72.0), P =.004]. Diagnostic performances of GastroPanel® tended to be better than those of Pepsinogen I alone, but the difference did not reach statistical significance (P =.068). Conclusion: Serum pepsinogen and GastroPanel® tests show promising results for the detection of AG, especially of corpus AG and severe AG, in patients at high risk of GC in France.

Objectives We report on five patients with gadolinium-negative (non-enhancing magnetic resonance imaging–MRI) but 18F-fluoroethyl tyrosine positron-emission tomography (FET-PET) positive glioma (NEG) undergoing surgery under fluorescence-guidance with fluorescein sodium 10% (FL, Alkon, Germany) in combination with a dedicated light filter (YELLOW 560 nm, Carl Zeiss Meditec, Germany). Patients and method Since 2017, five patients (3 female, 2 male; mean age 45.4 years) underwent fluorescence-guided surgery for supratentorial, intracerebral lesions which showed no contrast-enhancement in the preoperative MRI but were, however, strongly suspicious for gliomas. Accordingly, all patients received a preoperative FET-PET scan and detailed histopathological workup was performed. After giving written informed consent, all patients received 5 mg/kg of FL at the induction of anesthesia. Surgery was conducted under white light and under the YELLOW 560 nm filter. We reviewed the surgical protocols, navigational storage and the image databases of our surgical microscopes for evidence of intraoperative fluorescence that corresponded to the FET-PET positive area. Results In all patients we found distinct accordances between the FET-PET positive areas and the fluorescing regions within the targeted lesions. Histopathological workup of the fluorescent tissue revealed anaplastic oligodendroglioma, IDH-mutant and 1p/19-codeleted (WHO grade III) (n = 2), anaplastic astrocytoma, IDH-mutant (WHO grade III) (n = 1), oligodendroglioma, IDH-mutant and 1p/19q-codeleted (WHO grade II) (n = 1) and pilocytic astrocytoma (WHO grade I) (n = 1). No adverse events were noted. Discussion and conclusion Despite the lack of gadolinium-enhancement in the preoperative MRI, all patients intravenously received FL to guide resection. Irrespective of the final grading, FL was extremely helpful in detecting the lesions and in identifying their border zones. In selected patients with NEG, but strong metabolic activity according to the FET-PET, FL may significantly increase the accuracy of surgery.

Background To address the overdose crisis in the United States, expert groups have been nearly unanimous in calls for increasing access to evidence-based treatment and overdose reversal drugs. In some places there have also been calls for implementing supervised consumption sites (SCSs). Some cities—primarily in coastal urban areas—have explored the feasibility and acceptability of introducing them. However, the perspectives of community stakeholders from more inland and rural areas that have also been hard hit by opioids are largely missing from the literature. Methods To examine community attitudes about implementing SCSs for people who use opioids (PWUO) in areas with acute opioid problems, the research team conducted in-depth interviews and focus groups in four counties: Ashtabula and Cuyahoga Counties in Ohio, and Carroll and Hillsborough Counties in New Hampshire, two states with high rates of opioid overdose. Participants were policy, treatment, and criminal justice professionals, frontline harm reduction and service providers, and PWUO. Results Key informants noted benefits to SCSs, but also perceived potential drawbacks such as that they may enable opioid use, and potential practical barriers, including lack of desire among PWUO to travel to an SCS after purchasing opioids and fear of arrest. Key informants generally believed their communities likely would not currently accept SCSs due to cultural, resource, and practical barriers. They viewed publication of evidence on SCSs and community education as essential for fostering acceptance. Conclusions Despite cultural and other barriers, implementation of SCSs may be more feasible in urban communities with existing (and perhaps more long-standing) harm reduction programs, greater treatment resources, and adequate transportation, particularly if there is strong evidence to support them.

For nearly a century heroin has dominated the illegal opioid trade. The global supply of heroin is estimated to generate tens of billions of dollars in revenues a year and its illegal use has long been the source of many societal harms. The arrival of inexpensive and mass-produced synthetic opioids, such as fentanyl, to parts of North America and Europe may signal the beginning of the end of heroin's dominance. Data from several places suggest that fentanyl and other synthetic opioids can quickly supplant heroin. Taking the extreme case, we calculate the estimated wholesale revenues of heroin currently and contrast that with fentanyl prospectively in the United States and in the rest of the world if fentanyl were to supplant heroin entirely. Heroin traffickers in the United States generate about $2.5 billion in revenues; the total import value of fentanyl, after replacing heroin, could be less than $100 million. For the rest of the world we project a reduction from $6.7 billion to less than $300 million. Retailer revenues on the other hand would probably rise because individuals may consume more frequently and with greater intensity due to fentanyl's shorter duration of action and so far there has been no indication of a notable reduction in retail prices. It is unlikely that heroin will entirely disappear, but very likely that globally heroin will account for a declining share of illegal opioids. Violence and corruption may decline but opioid related mortality and morbidity, as well as property crime, are likely to rise. Policy makers will face difficult challenges. Economics provides limited help in forecasting which opioid markets are likely to convert to synthetic opioids.

Duchenne muscular dystrophy (DMD) is a severe, progressive muscle wasting disorder caused by reading frame disrupting mutations in the DMD gene. Exon skipping is a therapeutic approach for DMD. It employs antisense oligonucleotides (AONs) to restore the disrupted open reading frame, allowing the production of shorter, but partly functional dystrophin protein as seen in less severely affected Becker muscular dystrophy patients. To be effective, AONs need to be delivered and effectively taken up by the target cells, which can be accomplished by the conjugation of tissue-homing peptides. We performed phage display screens using a cyclic peptide library combined with next generation sequencing analyses to identify candidate muscle-homing peptides. Conjugation of the lead peptide to 2′-O-methyl phosphorothioate AONs enabled a significant, 2-fold increase in delivery and exon skipping in all analyzed skeletal and cardiac muscle of mdx mice and appeared well tolerated. While selected as a muscle-homing peptide, uptake was increased in liver and kidney as well. The homing capacity of the peptide may have been overruled by the natural biodistribution of the AON. Nonetheless, our results suggest that the identified peptide has the potential to facilitate delivery of AONs and perhaps other compounds to skeletal and cardiac muscle., Upon systemic administration of antisense oligonucleotides (AONs), most AONs end up in liver and/or kidney and are lost for targeting other organs. Jirka et al. (2017) show a valuable approach to identify muscle-homing peptides that leads to 2-fold improvement of delivery and bioactivity of systemically administrated AONs in muscle.

Background: Goblet cell carcinoids belong to neuroendocrine tumors, according to the WHO classification. The tumors are diagnosed based on a typical histological pattern and using neuroendocrine markers. However, some tumors do not react with these markers and yet expression of proliferative markers is high. Do these tumors belong to G1 and G2 neuroendocrine tumors? Methods: The sample comprised nine cases of tumors of the appendix identified by immunohistological methods as goblet cell carcinoids or adenocarcinoma ex goblet cell carcinoid. Results: In six cases, hematoxylin and eosin staining revealed tumors completely or 90% made of characteristic large tumor cells observed in typical goblet cell carcinoids. The remaining three cases were identified as adenocarcinomas arising ex goblet cell carcinoids. Immunohistological examination revealed that in four cases of typical goblet cell carcinoids, expression of neuroendocrine markers was low or completely negative. Yet in two cases, the Ki-67 proliferative index exceeded the 20% cut-off for inclusion in the G1 and G2 category. Conclusions: Goblet cell carcinoids are a heterogeneous group of tumors that may express neuroendocrine markers in a small number of tumor cells or are negative to these markers. However, high expression of the proliferative marker Ki-67 exceeds the criteria for G1 and G2 neuroendocrine tumors. It is our opinion that these tumors may be classified as a specific type of carcinoma.

This paper investigates the interaction of human osteoblast-like Saos-2 cells with stainless steel covered by a film of densely inter-grown silicalite-1 crystals with defined outer and inner surfaces. The chemical composition of this film, labeled as SF(RT), was tuned by heat treatment at 300°C and 500°C (labeled as SF(300) and SF(500), respectively) and characterized by X-ray photoelectron spectroscopy (XPS), water drop contact angle (WCA) measurements and scanning electron microscopy (SEM). The number, the spreading area and the activity of alkaline phosphatase of human osteoblast-like Saos-2 cells in cultures on the silicalite-1 film were affected by the chemical composition of its outer surface and by its micro-porous structure. The number and the spreading area of the adhered osteoblast-like cells on day 1 was highest on the surface of SF(RT) relative to their adhesion and spreading on a glass cover slip due to the SF(RT) topology. However, SF(300) markedly supported cell growth during days 3 and 7 after seeding.

Contains fulltext : 169644.pdf (Publisher’s version ) (Closed access) BACKGROUND AND AIM: Malnutrition represents a serious health care threat, as it increases morbidity, mortality and health care cost. The effective screening and treatment with enteral (EN) or parenteral (PN) nutrition are the key elements of the policy called Optimal Nutrition Care for All (ONCA). The study tried to analyze the impact of the state's economy on the implementation of EN and PN to define its role in ONCA. MATERIAL AND METHODS: an international survey in twenty two European countries was performed between January and December 2014. An electronic questionnaire was distributed to 22 representatives of clinical nutrition (PEN) societies. The questionnaire comprised questions regarding country economy, reimbursement, education and the use EN and PN. Return rate was 90.1% (n = 20). RESULTS: EN and PN were used in all countries surveyed (100%), but to different extent. The country's income significantly influenced the reimbursement for EN and PN (p < 0.05). It was also associated with the overall use of tube feeding and PN (p = 0.05), but not with the use of oral nutritional supplements (p = 0.165). The use of both, EN and PN at hospitals was not depended on the economy (p > 0.05). Education was actively carried out in all countries, however the teaching at the pre-graduate level was the least widespread, and also correlated with the country income (p = 0.042). CONCLUSIONS: Results indicated that economic situation influences all aspects of ONCA, including education and treatment. The reimbursement for EN and PN seemed to be the key factor of effective campaign against malnutrition.

Clinical trial accrual is vital to advancing care. A single study elucidated demographic data correlating with glioma patients' clinical trial enrollment. However, it did not investigate the underlying decision-making process for non-participation. In this study, we seek to understand this key aspect of patient accrual. All notes for glioma patients seen by a single neuro-oncologist from July 2010 to May 2017 were examined for mention of clinical trial offerings. When a trial was declined, the patient's reasoning was recorded along with the following: diagnosis, KPS, extent of resection, age, gender, race, marital status, income group, religion, trial offered at initial visit versus subsequent, and distance from trial site. Of 279 consecutive glioma patients, 88 were eligible for and offered a clinical trial. Fifty-seven accepted (65%), and 31 (35%) declined participation (Fig. 1). Of those offered a clinical trial, patients with glioblastoma (GBM) were significantly more likely to accept (44 out of 57 (77%) vs. 13 out of 57 (23%), p =0.03). After we adjusted for gender and travel distance, GBM was the only significant predictor of clinical trial acceptance, with an odds ratio of 3.18 (95% CI 1.17, 8.61, p =0.02). Reasons cited for non-participation included: travel distance (39%), lack of interest (39%), visit frequency (16%), and fear of randomization (6%). This study clarified for the first time individual glioma patient rationale for non-participation and potential areas for improving enrollment. Allowing off-site treatment centers or telemedicine visits may entice rural patients to participate. Visit frequency should be carefully considered and minimized whenever possible. Further prospective study of rationale for non-participation may improve enrollment over time.

Congestion (i.e., backward failure) is an important culprit mechanism driving disease progression in heart failure. Nevertheless, congestion remains often underappreciated and clinicians underestimate the importance of congestion on the pathophysiology of decompensation in heart failure. In patients, it is however difficult to study how isolated congestion contributes to organ dysfunction, since heart failure and chronic kidney disease very often coexist in the so-called cardiorenal syndrome. Here, we review the existing relevant and suitable backward heart failure animal models to induce congestion, induced in the left- (i.e., myocardial infarction, rapid ventricular pacing) or right-sided heart (i.e., aorta-caval shunt, mitral valve regurgitation, and monocrotaline), and more specific animal models of congestion, induced by saline infusion or inferior vena cava constriction. Next, we examine critically how representative they are for the clinical situation. After all, a relevant animal model of isolated congestion offers the unique possibility of studying the effects of congestion in heart failure and the cardiorenal syndrome, separately from forward failure (i.e., impaired cardiac output). In this respect, new treatment options can be discovered. This work was funded by Bijzonder Onderzoeksfonds (BOF) from UHasselt/BIOMED to JC.

Experiencing real weightlessness in space is a dream for many of us who are interested in space research. Although space traveling fascinates us, it can cause both short-term and long-term health problems. Microgravity is the most important influence on the human organism in space. The human body undergoes dramatic changes during a long-term spaceflight. In this review, we will mainly focus on changes in calcium, sodium and bone metabolism of space travelers. Moreover, we report on the current knowledge on the mechanisms of bone loss in space, available models to simulate the effects of microgravity on bone on Earth as well as the combined effects of microgravity and cosmic radiation on bone. The available countermeasures applied in space will also be evaluated.

Background The two α-crystallins (αA- and αB-crystallin) are major components of our eye lenses. Their key function there is to preserve lens transparency which is a challenging task as the protein turnover in the lens is low necessitating the stability and longevity of the constituent proteins. α-Crystallins are members of the small heat shock protein family. αB-crystallin is also expressed in other cell types. Scope of the review The review summarizes the current concepts on the polydisperse structure of the α-crystallin oligomer and its chaperone function with a focus on the inherent complexity and highlighting gaps between in vitro and in vivo studies. Major conclusions Both α-crystallins protect proteins from irreversible aggregation in a promiscuous manner. In maintaining eye lens transparency, they reduce the formation of light scattering particles and balance the interactions between lens crystallins. Important for these functions is their structural dynamics and heterogeneity as well as the regulation of these processes which we are beginning to understand. However, currently, it still remains elusive to which extent the in vitro observed properties of α-crystallins reflect the highly crowded situation in the lens. General significance Since α-crystallins play an important role in preventing cataract in the eye lens and in the development of diverse diseases, understanding their mechanism and substrate spectra is of importance. To bridge the gap between the concepts established in vitro and the in vivo function of α-crystallins, the joining of forces between different scientific disciplines and the combination of diverse techniques in hybrid approaches are necessary. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease.

Background Some countries allow physicians to prescribe pharmaceutical-grade diamorphine to dependent users who have previously undergone treatment but are still using street-sourced heroin; this is not allowed in the US. This study provides the first nationally representative US data concerning public support for prescribing diamorphine to dependent users. We also test the hypothesis that calling it “diamorphine” instead of “heroin” increases support for this approach. Methods The RAND American Life Panel is a nationally representative, probability-based survey of US adults. Of the 3345 panel members invited to take the survey, 2530 (75.6%) provided a valid response to our question module. Respondents were randomly assigned to have the question refer to the prescribed drug as either “heroin” or “diamorphine.” The groups did not significantly differ on sex, age, race/ethnicity, or education. We compare the distribution of responses for the two groups and conduct Pearson’s chi-squared test with the Rao–Scott correction. Results For those asked whether the US should try prescribing pharmaceutical-grade “heroin,” the share answering “Yes” (20.8%) was 15 percentage points lower than those responding “No” (35.8%). When the question asked about “diamorphine,” the results were nearly reversed: the share answering “Yes” (30.6%) was almost 12 percentage points higher than those responding “No” (18.9%). The distributions of responses were significantly different (p Conclusions Support for prescribing diamorphine to dependent users is low in the US. While the results are consistent with the hypothesis that referring to heroin as diamorphine may reduce stigma associated with the substance and increase support for prescribing it, opinions may change as individuals learn they are different names for the same substance.

BACKGROUND The aim of the study was to investigate the role of von Willebrand factor (vWF), the vWF-cleaving protease, ADAMTS13, the composition of thrombus, and patient outcome following mechanical cerebral artery thrombectomy in patients with acute ischemic stroke. MATERIAL AND METHODS A prospective cohort study included 131 patients with ischemic stroke (

Zeolites are microporous tectosilicates of natural or synthetic origin, which have been extensively used in various technological applications, e.g. as catalysts and as molecular sieves, for separating and sorting various molecules, for water and air purification, including removal of radioactive contaminants, for harvesting waste heat and solar heat energy, for adsorption refrigeration, as detergents, etc. These applications of zeolites were typically related with their porous character, their high adsorption capacity, and their ion exchange properties. This review is focused on potential or already practically implemented applications of zeolites in biotechnology and medicine. Zeolites are promising for environment protection, detoxication of animal and human organisms, improvement of the nutrition status and immunity of farm animals, separation of various biomolecules and cells, construction of biosensors and detection of biomarkers of various diseases, controlled drug and gene delivery, radical scavenging, and particularly tissue engineering and biomaterial coating. As components of scaffolds for bone tissue engineering, zeolites can deliver oxygen to cells, can stimulate osteogenic cell differentiation, and can inhibit bone resorption. Zeolites can also act as oxygen reservoirs, and can improve cell performance in vascular and skin tissue engineering and wound healing. When deposited on metallic materials for bone implantation, zeolite films showed anticorrosion effects, and improved the osseointegration of these implants. In our studies, silicalite-1 films deposited on silicon or stainless steel substrates improved the adhesion, growth, viability and osteogenic differentiation of human osteoblast-like Saos-2 cells. Zeolites have been clinically used as components of haemostatics, e.g. in the Advanced Clotting Sponge, as gastroprotective drugs, e.g. Absorbatox® 2.4D, or as antioxidative agents (Klinobind®). Some zeolites are highly cytotoxic and carcinogenic, e.g. erionite. However, in other zeolites, the antiproliferative and pro-apoptotic effects can be used for tumor therapy.

The kinase/endonuclease IRE1 is the most conserved signal transducer of the unfolded protein response (UPR), an intracellular signaling network that monitors and regulates the protein folding capacity of the endoplasmic reticulum (ER). Upon sensing protein folding perturbations in the ER, IRE1 initiates the unconventional splicing of XBP1 mRNA culminating in the production of the transcription factor XBP1s, which expands the ER's protein folding capacity. We show that an RNA‐intrinsic conformational change causes the intron of XBP1 mRNA to be ejected and the exons to zipper up into an extended stem, juxtaposing the RNA ends for ligation. These conformational rearrangements are important for XBP1 mRNA splicing in vivo. The features that point to such active participation of XBP1 mRNA in the splicing reaction are highly conserved throughout metazoan evolution, supporting their importance in orchestrating XBP1 mRNA processing with efficiency and fidelity.

Antisense-mediated modulation of transcripts is a dynamic therapeutic field, especially for neuromuscular disorders.For three diseases, this approach has advanced to the clinical trial phase, that is Duchenne muscular dystrophy, spinal muscular atrophy and myotonic dystrophy. In parallel, numerous proof-of-concept studies in cell and animal models have been reported for additional neuromuscular disorders.This review discusses the most notable advances in preclinical and clinical studies in the past year. For Duchenne muscular dystrophy, spinal muscular atrophy and myotonic dystrophy trials are ongoing to assess safety and efficacy, while in parallel preclinical studies are being conducted to identify ways to improve efficiency and delivery. For other neuromuscular diseases, progress is made as well warranting future clinical trials. However, towards clinical trial readiness, it is important not only to optimize the therapy preclinically but to also develop the infrastructure that is needed to conduct trials.

Familial forms of focal segmental glomerulosclerosis (FSGS) have been linked to gain-of-function mutations in the gene encoding the transient receptor potential channel C6 (TRPC6). GPCRs coupled to Gq signaling activate TRPC6, suggesting that Gq-dependent TRPC6 activation underlies glomerular diseases. Here, we developed a murine model in which a constitutively active Gq α subunit (Gq(Q209L), referred to herein as GqQ>L) is specifically expressed in podocytes and examined the effects of this mutation in response to puromycin aminonucleoside (PAN) nephrosis. We found that compared with control animals, animals expressing GqQ>L exhibited robust albuminuria, structural features of FSGS, and reduced numbers of glomerular podocytes. Gq activation stimulated calcineurin (CN) activity, resulting in CN-dependent upregulation of TRPC6 in murine kidneys. Deletion of TRPC6 in GqQ>L-expressing mice prevented FSGS development and inhibited both tubular damage and podocyte loss induced by PAN nephrosis. Similarly, administration of the CN inhibitor FK506 reduced proteinuria and tubular injury but had more modest effects on glomerular pathology and podocyte numbers in animals with constitutive Gq activation. Moreover, these Gq-dependent effects on podocyte injury were generalizable to diabetic kidney disease, as expression of GqQ>L promoted albuminuria, mesangial expansion, and increased glomerular basement membrane width in diabetic mice. Together, these results suggest that targeting Gq/TRPC6 signaling may have therapeutic benefits for the treatment of glomerular diseases.

Real and simulated microgravity induce a variety of changes in human cells. Most importantly, changes in the cytoskeleton have been noted, and studies on microtubules have shown that they are gravisensitive. This study focuses on the effects of short-term real microgravity on gene expression, protein content, and cytoskeletal structure of human chondrocytes. We cultivated human chondrocytes, took them along a parabolic flight during the 24th Deutsches Zentrum für Luft- und Raumfahrt Parabolic (DLR) Flight Campaign, and fixed them after the 1st and the 31st parabola. Immunofluorescence microscopy revealed no changes after the 1st parabola, but disruptions of β-tubulin, vimentin, and cytokeratin networks after the 31st parabola. No F-actin stress fibers were detected even after 31 parabolas. Furthermore, mRNA and protein quantifications after the 31st parabola showed a clear up-regulation of cytoskeletal genes and proteins. The mRNAs were significantly up-regulated as follows: TUBB, 2-fold; VIM, 1.3-fold; KRT8, 1.8-fold; ACTB, 1.9-fold; ICAM1, 4.8-fold; OPN, 7-fold; ITGA10, 1.5-fold; ITGB1, 1.2-fold; TGFB1, 1.5-fold; CAV1, 2.6-fold; SOX9, 1.7-fold; BMP-2, 5.3-fold. However, SOX5 (-25%) and SOX6 (-28%) gene expression was decreased. Contrary, no significant changes in gene expression levels were observed during vibration and hypergravity experiments. These data suggest that short-term microgravity affects the gene expression of distinct proteins. In contrast to poorly differentiated follicular thyroid cancer cells or human endothelial cells, chondrocytes only exert moderate cytoskeletal alterations. The up-regulation of BMP-2, TGF-β1, and SOX9 in chondrocytes may play a key role in preventing cytoskeletal alterations.-Aleshcheva, G., Wehland, M., Sahana, J., Bauer, J., Corydon, T. J., Hemmersbach, R., Frett, T., Egli, M., Infanger, M., Grosse, J., Grimm, D. Moderate alterations of the cytoskeleton in human chondrocytes after short-term microgravity produced by parabolic flight maneuvers could be prevented by up-regulation of BMP-2 and SOX-9.

We report the case of a 40-year-old woman with a progressive right-sided hemiparesis. Standard MRI revealed a contrast-enhancing brain lesion within the left basal ganglia. Ffluoroethyl-L-tyrosine (F-FET) PET showed a distinct tracer uptake (lesion-to-brain ratio [LBR]: LBRmax = 2.03, LBRmean = 1.68) with a significant larger metabolic lesion volume than contrast-enhancement in MRI, indicating cerebral glioma. Surprisingly, histopathologic analysis demonstrated central nervous system toxoplasmosis with pronounced inflammatory reaction (reactive astrogliosis, microglia activation, macrophage, and T-lymphocyte infiltration), which was associated with strong LAT1/LAT2/CD98 expression. In conclusion, inflammatory brain lesions, such as cerebral toxoplasmosis, represent a potential pitfall of F-FET PET mimicking a brain tumor.

Background: Endothelial glycocalyx degradation has been associated with multiple pathophysiological processes in cardiovascular disease. Aims: To explore the role of glycocalyx shedding markers in pathophysiology of HFrEF. Methods: In 123 HFrEF patients, the concentration, prognostic value, and association of glycocalyx shedding markers with other disease processes were investigated. Results: Median HA levels and syndecan-1 levels in HFrEF patients were, respectively, 29.4 (10.7;61.6) ng/mL and 48.5 (33.6;80.8) ng/mL. Overall, HA-levels were significantly higher in HFrEF patients compared to healthy subjects, but only 31% of HFrEF patients had HA-levels above the cutoff of normal. There was no significant difference among HFrEF patients and healthy subjects regarding syndecan-1 levels. HFrEF patients with elevated HA-levels had a significantly worse outcome (log rank = 0.01) which remained significant after correction for established risk factors (HR 2.53 (1.13-5.69); P = .024). There was no significant relation between levels of shedding markers and neurohumoral activation (PRA, serum aldosterone, NT-proBNP), myocardial injury (HS-trop), inflammation (CRP), or other baseline characteristics. Conclusions: The glycocalyx shedding marker HA is significantly elevated in a subgroup of HFrEF patients and an independent predictor for worse clinical outcome. Glycocalyx shedding might be an additional factor in the pathophysiology of HF which warrants further investigation. P.N., F.V., P.M. and W.M. are researchers for the Limburg Clinical Research Program (LCRP) UHasselt - ZOL - Jessa, supported by the foundation Limburg Sterk Merk (LSM), Hasselt University, Ziekenhuis Oost-Limburg and Jessa Hospital. P.M. is supported by a doctoral fellowship by the Research Foundation-Flanders (FWO grant-number: 1127917N)

Differentiated thyroid cancer (DTC) is a rare malignant disease, although its incidence has increased over the last few decades. It derives from follicular thyroid cells. Generally speaking, the prognosis is excellent. If treatment according to the current guidelines is given, cases of recurrence or persistence are rare. DTC requires special expertise by the treating physician. In recent years, new therapeutic options for these patients have become available. For this article we performed a systematic literature review with special focus on the guidelines of the American Thyroid Association, the European Association of Nuclear Medicine, and the German Society of Nuclear Medicine. For DTC, surgery and radioiodine therapy followed by levothyroxine substitution remain the established therapeutic procedures. Even metastasized tumors can be cured this way. However, in rare cases of radioiodine-refractory tumors, additional options are to be discussed. These include strict suppression of thyroid-stimulating hormone (also known as thyrotropin, TSH) and external local radiotherapy. Systemic cytostatic chemotherapy does not play a significant role. Recently, multikinase or tyrosine kinase inhibitors have been approved for the treatment of radioiodine-refractory DTC. Although a benefit for overall survival has not been shown yet, these new drugs can slow down tumor progression. However, they are frequently associated with severe side effects and should be reserved for patients with threatening symptoms only.

Several years ago, we detected the formation of multicellular spheroids in experiments with human thyroid cancer cells cultured on the Random Positioning Machine (RPM), a ground-based model to simulate microgravity by continuously changing the orientation of samples. Since then, we have studied cellular mechanisms triggering the cells to leave a monolayer and aggregate to spheroids. Our work focused on spheroid-related changes in gene expression patterns, in protein concentrations, and in factors secreted to the culture supernatant during the period when growth is altered. We detected that factors inducing angiogenesis, the composition of integrins, the density of the cell monolayer exposed to microgravity, the enhanced production of caveolin-1, and the nuclear factor kappa B p65 could play a role during spheroid formation in thyroid cancer cells. In this study, we performed a deep proteome analysis on FTC-133 thyroid cancer cells cultured under conditions designed to encourage or discourage spheroid formation. The experiments revealed more than 5900 proteins. Their evaluation confirmed and explained the observations mentioned above. In addition, we learned that FTC-133 cells growing in monolayers or in spheroids after RPM-exposure incorporate vinculin, paxillin, focal adhesion kinase 1, and adenine diphosphate (ADP)-ribosylation factor 6 in different ways into the focal adhesion complex.

Sarcoidosis, a granulomatous T-cell-mediated multisystem disease with a yearly incidence of 10.9 to 35.5 cases per 100,000 in the United States, affects a variety of organ systems. Although the characteristic radiological finding of a bihilar lymphadenopathy still plays a diagnostic key role, FDG PET/CT is more sensitive in detecting and monitoring various manifestations. We present a rare case of a 37-year-old woman with bihilar, mediastinal, and abdominal lymphadenopathy in conjunction with a histologically proven cutaneous manifestation of sarcoidosis in a tattoo of the lower back exhibiting an increased uptake of FDG.

A S THE SUN-FILLED, BREEZY days of summer come to an end, it’s time for teachers and students to make their way back to school. The start of a new school year is an exciting time for students. It’s a new beginning with the promise of new friends and new experiences. And for registered dietitian nutritionists (RDNs), the new school year brings the opportunity to feed bright young minds and empower them to make healthy choices—choices that will help them grow into healthy adults and achieve the bright futures they deserve. RDNs who educate kids and teens give this gift every day, and at the US Department of Agriculture (USDA) we have a variety of resources (Figure) to hopefully make your job easier.

Background. The objective of the study was to report a rare case of primary neuroendocrine carcinoma of the right kidney in a 36 year old male. Methods. The patient was clinically assessed; CT and OctreoScan scintigraphy were performed and levels of 5-HIAA, vanillylmandelic acid and NSE were determined. The tumor and metastases were histologically and immunohistochemically examined. Results. The imaging methods showed a cystic tumor in the lower pole of the right kidney. Macroscopically, the entire tumor was sized 8x8x7 cm. Histologically, it was made up of ribbon-line or trabecular patterns of tumor cells. Occasional adenomatoid and cystic structures were present. The tumor cell nuclei were round or oval, with no irregularities and fine lumpy chromatin. The mitotic count was < 1 /10HPF and the proliferation marker Ki-67 was < 1 % of tumor cells. Immunohistochemically, the tumor cells were positive with antibodies against chromogranin A, synaptophysin, CD56 (focally), cytokeratins AE1-AE3 (focally), vimentin (most cells), glucagon (focally), and pancreatic polypeptide (PP; focally). Antibodies against serotonin, somatostatin, gastrin, vasoactive intestinal polypeptide (VIP) and calcitonin did not react with the tumor. The results of biochemical markers (5-HIAA, vanillylmandelic acid and NSE) did not correlate with development or treatment of the tumor. Conclusions. Primary neuroendocrine carcinoma of the kidney was diagnosed both histologically and immunohistochemically. The patient was clinically investigated using CT and OctreoScan scintigraphy. Within two years from nephrectomy, metastases were found in the right humerus and retrocaval lymph nodes. The metastatic lesions were surgically removed. Currently, the patient’s condition is good, with no tumor progression detected.

Background/Aims: Thyroid cancer accounts for about 1% of all cancer cases. Multikinase inhibitors like sunitinib (S) have a promising potential in thyroid cancer therapy. Therefore, the principal aim of this study was to investigate the impact of sunitinib on the secretion of cytokines of follicular thyroid cancer cells. Method: The effects of irradiation (R), S, and their combination (R+S) on cytokine secretion by the human thyroid cancer cell lines ML-1 and CGTH W-1 were evaluated after two (d2) and four days (d4) of treatment. Results: Multi-Analyte Profiling of cytokine release showed a decrease after S treatment (CGTH W-1: IFN-γ, IL-4, IL-8 d2, MIP-1a, MMP-2, TNF-α and TNF-β; ML-1: IFN-γ, IL-4, IL-6, IL-7, IL-8; MIP-1α, MMP-2, MCP-1, TNF-α and TNF-β). R elevated significantly the release of cytokines (exception ML-1: MCP-1, MMP-2; CGTH W-1: IL-4, TNF-β). In contrast, R+S treatment resulted in a reduction of IFN-γ, IL-4, and MMP-2 in both cell lines. IL-6, IL-8 and MCP-1 proteins in the supernatant correlated with the data obtained by quantitative RT-PCR. VEGFD mRNAs were significantly elevated by R+S. Conclusion: A target-based therapy with R+S changed VEGFD, IL-6 and IL-8 in follicular thyroid cancer cells. These in vitro-experiments suggest IL-6, IL-8, VEGFD and TNF-α as interesting biomarkers to be investigated in vivo. Different reactions of the cell lines under equal treatment might be due to their different origin and characteristics., OA-Komponente aus Allianzlizenz