Efficacy and safety of ramucirumab plus carboplatin and paclitaxel in untreated metastatic thymic carcinoma: RELEVENT phase II trial (NCT03921671).

BACKGROUND: Thymic carcinoma (TC) is a rare tumor with aggressive behavior. Chemotherapy with carboplatin plus paclitaxel represents the treatment of choice for advanced disease. Antiangiogenic drugs, including ramucirumab, have shown activity in previously treated patients. RELEVENT trial was designed to evaluate the activity and safety of ramucirumab plus chemotherapy as first-line treatment in advanced TC. PATIENTS AND METHODS: This phase II trial was conducted within the Italian TYME network. Eligible patients had treatment naive advanced TC. They received ramucirumab, carboplatin and paclitaxel for 6 cycles, followed by ramucirumab maintenance until disease progression or intolerable toxicity. Primary endpoint was ORR according to RECIST v1.1 as assessed by the investigator. Secondary endpoints were PFS, OS and safety. Centralized radiologic review was performed. RESULTS: From 11/2018 to 06/2023, 52 patients were screened, 35 were enrolled. Median age was 60.8 years, 71.4% of patients were male and 85.7% had Masaoka-Koga stage IVB. ECOG PS was 0 in 68.5%, 1 in 31.4% patients. At the present analysis carried out some months later the interim analysis (earlier than expected) on 35 patients, ORR was 80.0% [95%CI 63.1-91.6]. At the centralized radiological review of 33/35 evaluable patients, ORR was 57.6% [95%CI 39.2-74.5]. After a median follow-up of 31.6 months, median PFS was 18.1 [95%CI 10.8-52.3] and median OS 43.8 [95%CI 31.9-NR] months. Thirty-two out of 35 patients (91.4%) experienced at least one treatment-related adverse event (AE), of which 48.6% were AE≥G3. CONCLUSIONS: In previously untreated advanced TC, the addition of ramucirumab to carboplatin and paclitaxel showed the highest activity compared to historical controls, with a manageable safety profile. Despite the small number of patients, given the rarity of the disease, the trial results support the consideration of this combination as first-line treatment in TC.

Athlete External Load Measures Across a Competitive Season in High School Basketball.

ABSTRACT: Askow, AT, Jennings, W, Jagim, AR, Fields, JB, Beaudoin, RG, Sanchez, GM, Weeks, JE, Oliver, JM, and Jones, MT. Athlete external load measures across a competitive season in high school basketball. J Strength Cond Res 37(11): 2206-2212, 2023-The purpose of this retrospective analysis was to quantify in-season external load and to determine if relationships existed between load metrics and basketball performance. Eleven male high school varsity basketball athletes (n = 11; mass 80.5 ± 9.6 kg, height 190.2 ± 9.4 cm, age 17.6 ± 0.7 years) were monitored across a season. PlayerLoad (PL), PL per minute (PL·min -1 ), total jumps, and explosive movements (EMs) were quantified using a commercially available local positioning unit. Basketball-specific performance metrics, including points scored, points allowed, point differentials, and shooting percentages for each quarter and game, were compiled. Data were analyzed using repeated-measure analysis of variance to evaluate differences in load by starting status, session type, game outcome, and game type. Pearson's correlation coefficients were used to assess relationships between load metrics and basketball performance. Statistical significance was set at p < 0.05. The mean values across 23 games for PL, PL·min -1 , total jumps, and EMs were 457 ± 104 AU, 10.9 ± 1.6 AU, 42.6 ± 9.6, and 46.7 ± 7.2, respectively. Relationships were observed ( p < 0.05) between PL and points scored ( r = 0.38) and free throw percentage ( r = 0.21). Further relationships were observed between PL·min -1 and free throw shooting percentage ( r = -0.27), and between points scored and total jumps ( r = 0.28), and EMs ( r = 0.26). Notable differences in game demands were observed for playing status. Meaningful differences in measures of external load were observed between each quarter of play, with the highest measures evident in quarters 1 and 3. Guards and forwards experienced minimal differences in external load during gameplay, and game outcome did not result in differences. Higher point totals corresponded with higher PL, total jumps, and EM.

Potential antimicrobial effects of photocatalytic nanothecnologies in hospital settings.

BACKGROUND: Recently, several advanced technologies have been considered to reduce the microbial load in hospital environments and control Healthcare Associated Infections (HAIs) incidence. New strategies for preventing HAIs have continuously evolved, including enforcement of hygiene procedures by novel liquid biocides or no-touch technologies, self-disinfecting surfaces coated by heavy metals or light-activated photosensitizers such as Titanium Dioxide (TiO2) nanoparticles. STUDY DESIGN: Review publications concerning the use of photocatalytic systems in hospital setting, focusing on products based on TiO2. METHODS: Specific keywords combinations were analitically searched in PubMed and Scopus databases. RESULTS: Starting 80s-90s, over 2000 papers report "in vitro" studies on antimicrobial activity of TiO2 photocatalysis on several microorganisms including bacteria, viruses, fungi, yeasts, and antibiotic resistant strains. Besides, at least 4 selected papers addressed the potentials of this approach by "in field" studies, showing a widespread pool of applications in hospital and healthcare settings. However, the low number of available experiences and their heterogeneity represent major limitations to achieve a comprehensive final overview on effectiveness and feasibility of these technologies. CONCLUSIONS: Photocatalytic systems based on TiO2 represent a promising strategy for hospital hygiene and HAI prevention. Additional "in field" studies are desirable in a next future to further evaluate and exploit this novel and interesting health technology.

Imaging tests in staging and surveillance of non-metastatic breast cancer: changes in routine clinical practice and cost implications.

BACKGROUND: Although guidelines do not recommend computerised tomography (CT), positron emission tomography (PET) or magnetic resonance imaging (MRI) for the staging or follow-up of asymptomatic patients with non-metastatic breast cancer, they are often requested in routine clinical practice. The aim of this study was to determine the staging and follow-up patterns, and relative costs in a large population of breast cancer patients living and treated in a Southern Italian region. METHODS: We analysed the clinical computerised information recorded by 567 primary-care physicians assisting about 650 000 inhabitants in the Campania region. Patients with non-metastatic breast cancer were identified and divided into calendar years from 2001 to 2010. The number of diagnostic tests prescribed per 100 patients (N/Pts) and the mean cost per patient was determined 3 months before diagnosis and up to 1 year after diagnosis. Costs are expressed in constant 2011 euros. RESULTS: We identified 4680 newly diagnosed cases of asymptomatic non-metastatic breast cancer. N/Pts increased significantly (P<0.0001) from 2001 to 2010. The mean number of prescribed mammograms, bone scans, abdominal ultrasound and chest X-rays ('routine tests'), and costs was unchanged. However, the number of CT, PET scans and MRI ('new tests')prescriptions almost quadrupled and the mean cost per patient related to these procedures significantly increased from [euro ]357 in 2001 to [euro ]830 in 2010 (P<0.0001). CONCLUSIONS: New test prescriptions and relative costs significantly and steadily increased throughout the study period. At present there is no evidence that the delivery of new tests to asymptomatic patients improves breast cancer outcome. Well-designed clinical trials are urgently needed to shed light on the impact of these tests on clinical outcome and overall survival.

GRPR/PI3Kγ: Partners in Central Transmission of Itch.

The gastrin-releasing peptide (GRP) and its receptor (GRPR) are important components of itch transmission. Upstream, but not downstream, aspects of GRPR signaling have been investigated extensively. We hypothesize that GRPR signals in part through the PI3Kγ/Akt pathway. We used pharmacological, electrophysiological, and behavioral approaches to further evaluate GRPR downstream signaling pathways. Our data show that GRP directly activates small-size capsaicin-sensitive DRG neurons, an effect that translates into transient calcium flux and membrane depolarization (∼ 20 mV). GRPR activation also induces Akt phosphorylation, a proxy for PI3Kγ activity, in ex vivo naive mouse spinal cords and in GRPR transiently expressing HEK293 cells. The intrathecal injection of GRP led to intense scratching, an effect largely reduced by either GRPR antagonists or PI3Kγ inhibitor. Scratching behavior was also induced by the intrathecal injection of an Akt activator. In a dry skin model of itch, we show that GRPR blockade or PI3Kγ inhibition reversed the scratching behavior. Altogether, these findings are highly suggestive that GRPR is expressed by the central terminals of DRG nociceptive afferents, which transmit itch via the PI3Kγ/Akt pathway. SIGNIFICANCE STATEMENT: Itch is the most common symptom of the skin and is related to noncutaneous diseases. It severely impairs patients' quality of life when it becomes chronic and there is no specific or effective available therapy, mainly because itch pathophysiology is not completely elucidated. Our findings indicate that the enzyme PI3Kγ is a key central mediator of itch transmission. Therefore, we suggest PI3Kγ as an attractive target for the development of new anti-pruritic drugs. With this study, we take a step forward in our understanding of the mechanisms underlying the central transmission of itch sensation.

Tumor characteristics and prognosis in familial breast cancer.

BACKGROUND: Approximately 5-10% of breast cancers are hereditary and their biology and prognosis appear to differ from those of sporadic breast cancers. In this study we compared the biological features and clinical characteristics of non metastatic breast cancer in patients with BRCA mutations versus patients with a family history suggesting hereditary breast cancer but without BRCA mutations (BRCA wild type) versus patients with sporadic disease, and correlated these findings with clinical outcome. METHODS: We retrieved the clinical and biological data of 33 BRCA-positive, 66 BRCA-wild type and 1826 sporadic breast cancer patients contained in a single institution clinical database between 1980 and 2012. Specifically, we recorded age, tumor size, nodal status, treatment type, pattern of relapse, second primary incidence, outcome (disease-free survival and overall survival), and biological features (estrogen receptor [ER], progesterone receptor [PgR], tumor grade, proliferation and c-erbB2 status). Median follow-up was 70 months. RESULTS: BRCA-positive patients were significantly younger than sporadic breast cancer patients, and less likely to be ER-, PgR- or c-erbB2-positive than women with BRCA-wild type or sporadic breast cancer. Tumor size and grade, nodal status and proliferation did not differ among the three groups. Rates of radical mastectomy were 58, 42 and 37%, and those of conservative surgery were 42, 58 and 63% in women with BRCA-positive, BRCA-wild type and sporadic breast cancer (p = 0.03), respectively. The incidence of contralateral breast cancer was 12, 14 and 0% (p <0.0001) and the incidence of second primary tumors (non breast) was 9, 1 and 2% (p <0.0001) in BRCA-positive, BRCA-wild type and sporadic breast cancer, respectively. Median disease-free survival in years was 29 in BRCA-wild type, 19 in BRCA-positive and 14 in sporadic breast cancer patients (log-rank = 0.007). Median overall survival in years was not reached for BRCA-wild type, 19 for BRCA-positive and 13 for sporadic breast cancer patients (log-rank <0.0001). At multivariate analyses only BRCA-wild type status was related to a significant improvement in overall survival versus the sporadic breast cancer group (HR = 0,51; 95% CI (0,28-0,93) p = 0.028). CONCLUSIONS: The biology and outcome of breast cancer differ between patients with BRCA mutations, patients with a family history but no BRCA mutations and patients with sporadic breast cancer.

Accuracy of frozen section, imprint cytology, and permanent histology of sub-nipple tissue for predicting occult nipple involvement in patients with breast carcinoma.

The sub-nipple tissue (SNT) examination has been used by surgeons to preserve, or not, the nipple in nipple-sparing mastectomy. However, it is uncertain whether SNT evaluation can predict nipple involvement. The aim of this study was to evaluate the accuracy, sensitivity, specificity, PPV, and NPV of the intraoperative frozen section and imprint cytology, and permanent histology of SNT to predict the involvement of the nipple in breast carcinoma and to compare the three exams. A prospective study was performed with 68 consecutive breast carcinoma women who had undergone mastectomy or central segmentectomy (removing nipple-areolar complex). After surgery, the nipple-areolar complex was dissected simulating a nipple-sparing flap (ex vivo). The SNT was subsequently removed and submitted to frozen section, imprint cytology, and permanent histology. The nipple was examined separately by paraffin histopathology and was considered the gold standard. The occult nipple involvement rate was 11.7 %. The frozen section, cytology, and permanent histology of SNT presented accuracy 86.8, 76.5, and 86.8 %; sensitivity 50, 37.5, and 62.5 %; specificity 91.7, 81.7, and 90 %; PPV 44.4, 21.4, and 45.5 %; and NPV 93.2, 90.7, and 94.7 %, respectively. The accuracy of the frozen section was similar to that of permanent histology (p = 0.77) and both were better than cytology (p = 0.01). False negative rates were 6.8 % for frozen section, 9.3 % for cytology and 5.3 % for paraffin. SNT evaluation is a good method for predicting occult nipple involvement; the outcomes showed a good accuracy and low false negative rate for the frozen section, cytology, and permanent histology exams. When we compared the exams, the frozen section was similar to permanent histology and more accurate than imprint cytology.

Hepatitis B virus mother-to-child transmission among HIV-infected women receiving lamivudine-containing antiretroviral regimens during pregnancy and breastfeeding.

The study included 309 HIV-infected pregnant women receiving a lamivudine-containing antiretroviral regimen from week 25 of gestational age until 6 months postpartum, during breastfeeding. Twenty-seven of them (8.7%) were hepatitis B virus surface antigen (HBsAg) positive; at baseline, hepatitis B virus (HBV) DNA levels >3 log(10) IU/mL (with a median level of 6.2 log(10) IU/mL) were found in 10 women, who at one, three and six months postpartum had median levels of 5.2 log(10) IU/mL, 4.5 log(10) IU/mL and 2.8 log(10) IU/mL, respectively. Twenty-four of the 30 breast milk samples evaluated had undetectable HBV DNA and the other six had values between 15 and 155 IU/mL. Median lamivudine concentrations were 1070 ng/mL in serum and 684 ng/mL in breast milk. Among the 24 HBV-exposed children with available samples, 16 always tested negative, four had a transient infection, one had an undetermined status and three (12.5%) first tested positive at Month 12 or Month 24. Among the children born to the HBV-uninfected mothers of the same cohort, the rate of HBsAg positivity at 12-24 months was 2% (4/196). Our finding of the absence of significative levels of HBV DNA in the breast milk of co-infected mothers supports the present recommendations for breastfeeding in HBV-infected women. Horizontal transmission can be hypothesized for the infections detected in children at 12-24 months. Children born to HBV-positive mothers remained at higher risk of postnatal HBV acquisition compared to those born to HBV-negative women.

HIV-1 coreceptor switch during 2 years of structured treatment interruptions.

The purpose of this investigation was to determine the impact on human immunodeficiency virus (HIV) tropism of uncontrolled virus exposure during 2 years of intermittent highly active antiretroviral therapy (HAART). The Istituto Superiore di Sanità-Pulsed Antiretroviral Therapy (ISS-PART) randomized study compared the outcome of 2 years of structured treatment interruptions (STIs) versus standard continuous treatment in first-line HAART responder subjects. The STI schedule consisted of five STIs of 1, 1, 2, 2, and 3 months, respectively, separated by four periods of 3-month therapy. In the present study, coreceptor tropism was assessed in 12 patients of the STI arm at different time points over a period of 2 years. Tropism was determined on DNA and RNA by V3 loop region sequencing. The Geno2pheno algorithm (false-positive rate, FPR: 20%) was used for data interpretation. At baseline, 9/12 subjects (75.0%) had CCR5-tropic viruses in their HIV. Three had a CXCR4-tropic virus. Ten patients maintained the same coreceptor in DNA after 2 years, whereas in two patients, a shift occurred (one R5-X4, one X4-R5). In a patient with an R5 virus at baseline, a transient change to X4 tropism was seen in the rebounding virus during STI. Changes in tropism were not associated with the amplitude and duration of virus exposure during STIs, residual viremia at baseline, or the development of resistance mutations in the RT region. Our preliminary results suggest that viral replication, observed after short periods of treatment interruption, is not enough to drive the evolution of HIV tropism.

Salso-sulphide thermal water in the prevention of recurrent respiratory infections in children.

Recurrent respiratory infections (RRI) represent a social problem for both the pharmaco-economic impact and the burden on the family. Thermal water is popularly well accepted. However, there is no scientific evidence of its preventive activity on recurrent respiratory tract infections (RRI). Therefore, the purpose of this study was to evaluate the effects of Agnano thermal water nasal irrigation on RRI prevention in children.A total of 107 children (70 males, mean age 4.5 plus minus1.2 years) with RRI were enrolled in the study. At baseline, children were randomly assigned to the treatment with: A) inhaled crenotherapy with salso-sulphide water or B) isotonic saline (NaCl 0.9 percent). Inhaled therapy was performed using nasal washing by Rino-jet (ASEMA srl, Milan, Italy) b.i.d. for 12 days. Nasal washing lasted 2 minutes per nostril. Immediately before washing, children inhaled 1 l of water by stream inhalation per 2 minutes. Crenotherapy was capable of significantly reducing: the number of respiratory infections, nasal symptoms, neutrophil and bacteria count, turbinate and adenoidal hypertrophy, presence of biofilm, and blockage of ostiomeatal complex (OCM). In conclusion, this study provides the first evidence that Agnano crenotherapy may be capable of preventing RRI in children as it exerts some positive effects, such as reduction of nasal obstruction, OCM blockage, biofilm, and inflammatory events.

Discontinuation rate and serious adverse events of chemoimmunotherapy as neoadjuvant treatment for triple-negative breast cancer: a systematic review and meta-analysis.

BACKGROUND: The use of combination of chemotherapy with immune checkpoint inhibitors (ICIs) has shown efficacy in triple-negative breast cancer (TNBC), and chemoimmunotherapy has been introduced in clinical practice. However, limited data are available on the discontinuation rate and serious adverse events of these treatments, particularly in the neoadjuvant setting. Herein, we carried out a comprehensive systematic review and meta-analysis to assess discontinuation rate and serious adverse events of chemoimmunotherapy compared to chemotherapy alone in phase II and III neoadjuvant clinical trials in TNBC. MATERIALS AND METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, EMBASE, Cochrane Library, and PubMed/Medline were searched for articles published from June 2008 to May 2023. The outcomes of interest were the discontinuation rate, serious adverse events, and grade 3-4 adverse events. RESULTS: Four studies were included in the analysis. The pooled odds ratios (ORs) for discontinuation rate and serious adverse events were 1.26 [95% confidence interval (CI) 0.78-2.06] and 1.79 (95% CI 1.4-2.28), respectively, in patients receiving chemoimmunotherapy compared to chemotherapy alone as neoadjuvant treatment for TNBC. The chemoimmunotherapy group had a higher risk of grade 3-4 adverse events (OR 1.30, 95% CI 1.07-1.59). The analysis showed substantial heterogeneity, and the risk of discontinuation rate was heavily influenced by the KEYNOTE-522 trial. CONCLUSIONS: Our findings highlight the need for clinical trials specifically focused on safety, quality of life, and treatment adherence in TNBC patients receiving neoadjuvant treatment. Close monitoring of tolerability remains crucial in this clinical setting.

Circulating tumor cells in immunohistochemical subtypes of metastatic breast cancer: lack of prediction in HER2-positive disease treated with targeted therapy.

BACKGROUND: Circulating tumor cells (CTCs) are associated with inferior prognosis in metastatic breast cancer (MBC). We hypothesized that the relationship between CTCs and disease subtype would provide a better understanding of the clinical and biologic behavior of MBC. PATIENTS AND METHODS: We retrospectively analyzed 517 MBC patients treated at a single institution. Subtypes of primary tumors were analyzed by immunohistochemical (IHC) or fluorescent in situ hybridization analyses and CTCs were enumerated by CellSearch(®) at starting a new therapy. Overall survival (OS) and progression-free survival durations for each IHC subtype were determined. RESULTS: At a median follow-up of 24.6 months, 276 of 517 (53%) patients had died. The median OS for patients with <5 and ≥ 5 CTCs were 32.4 and 18.3 months, respectively (P < 0.001). Except in HER2+ patients, the prognostic value of CTCs was independent of disease subtype and disease site. CONCLUSIONS: In this large retrospective study, CTCs were strongly predictive of survival in all MBC subtypes except HER2+ patients who had been treated with targeted therapy. Our results clearly demonstrate the value of enumerating CTCs in MBC and strongly suggest an interesting biological implication in the HER2+ subset of patients that need to be further explored.

How I treat HER2-positive early breast cancer: how long adjuvant trastuzumab is needed?

Since its first approval in 2006, 1 year of adjuvant trastuzumab has been the standard of care for early-stage HER2-positive breast cancer. Nevertheless, the optimal duration of adjuvant trastuzumab was uncertain, and the standard 12-month duration has been questioned by a number of different trials. Although most of these studies were formally negative, a patient-level meta-analysis presented at the 2021 European Society for Medical Oncology (ESMO) meeting first showed the non-inferiority of 6-month trastuzumab. Through this review, we sought to take a closer look at the meta-analysis and the included trials to explain why we believe that non-inferiority should be interpreted with caution. Indeed, here we underline how the meta-analysis' results were mainly driven by the PERSEPHONE study, an old trial that tested non-standard chemo-trastuzumab regimens in a relatively low-risk population with doubtful endpoints. In summary, considering all the limitations of this analysis and the increasing use of effective anthracycline-free de-escalation strategies, we are convinced that 1-year trastuzumab should remain the standard of care.

Health-related quality of life in breast cancer patients treated with CDK4/6 inhibitors: a systematic review.

BACKGROUND: Evaluation of health-related quality of life (HR-QoL) among cancer patients has gained an increasing importance and is now a key determinant of anticancer treatments' value. HR-QoL has been assessed in trials testing cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in breast cancer (BC), using various questionnaires at different timepoints. HR-QoL reports from BC patients treated with CDK4/6i in the real-world setting are also available. METHODS: We systematically reviewed the literature, searching for full-length articles, and selected conference abstracts reporting data on HR-QoL in BC patients at any stage and of any molecular subtype treated with abemaciclib, palbociclib or ribociclib. RESULTS: A total of 533 full-length articles and 143 abstracts were retrieved. After screening for eligibility, 38 records were included (31 clinical trials; 7 real-world reports). Assessment methods were heterogeneous across studies in terms of questionnaires, evaluation timepoints and endpoints. Overall, adding CDK4/6i to endocrine therapy did not worsen patients' HR-QoL, with a positive trend towards pain improvement. Gastrointestinal scores (diarrhea, nausea and appetite loss) statistically favored the control arm among metastatic BC patients receiving abemaciclib, whereas they were superimposable in the early setting. The combination of palbociclib and endocrine therapy showed similar HR-QoL outcomes compared with endocrine therapy alone, but determined better scores compared with chemotherapy. HR-QoL was specifically assessed in premenopausal patients treated with ribociclib, showing similar scores compared with postmenopausal patients. CONCLUSIONS: Despite methodological heterogeneity does not allow a proper comparison, HR-QoL was generally maintained with CDK4/6i. However, differences between abemaciclib, palbociclib and ribociclib exist and mainly rely on the distinct safety profiles of the compounds. These differences should be acknowledged and taken into account in the clinical practice.

Simian virus-40 large-T antigen binds p53 in human mesotheliomas.

We found that simian virus 40 (SV40) induces mesotheliomas in hamsters and that 60% of human mesotheliomas contain and express SV40 sequences, results now confirmed by others [ref. 3-5, and presentations by D. Griffiths & R. Weiss, F. Galateau-SallE, and H.I.P. at "Simian virus 40: A possible human polyoma virus," NIH workshop, 27-28 January 1997, Bethesda, MD (transcript available through SAG Corp., Washington, DC 20008)]. Mesothelioma, an aggressive malignancy resistant to therapy, originates from the serosal lining of the pleural, pericardial and peritoneal cavities. The incidence of mesothelioma continues to increase worldwide because of exposure to crocidolite asbestos. However, at least 20% of mesotheliomas in the United States are not associated with asbestos exposure, and only a minority of people exposed to high concentrations of asbestos develop mesothelioma. Thus, other carcinogens may induce mesothelioma in individuals not exposed to asbestos, and/or may render particular individuals more susceptible to the carcinogenic effect of asbestos. We investigated whether the expression of the SV40 large T-antigen (Tag) interferes with the normal expression of the tumor suppressor gene p53 in human mesotheliomas. We found that SV40 Tag retains its ability to bind and to inactivate p53, a cellular protein that when normally expressed plays an important role in suppressing tumor growth and in inducing sensitivity to therapy. Our findings do not establish a cause-and-effect relation, but indicate that the possibility that SV40 contributes to the development of human mesotheliomas should be carefully investigated.

Designing a Graphene Coating-Based Supercapacitor with Lithium Ion Electrolyte: An Experimental and Computational Study via Multiscale Modeling.

Graphene electrodes are investigated for electrochemical double layer capacitors (EDLCs) with lithium ion electrolyte, the focus being the effect of the pore size distribution (PSD) of electrode with respect to the solvated and desolvated electrolyte ions. Two graphene electrode coatings are examined: a low specific surface area (SSA) xGNP-750 coating and a high SSA coating based on a-MWGO (activated microwave expanded graphene oxide). The study comprises an experimental and a computer modeling part. The experimental part includes fabrication, material characterization and electrochemical testing of an EDLC with xGNP-750 coating electrodes and electrolyte 1M LiPF6 in EC:DMC. The computational part includes simulations of the galvanostatic charge-discharge of each EDLC type, based on a continuum ion transport model taking into account the PSD of electrodes, as well as molecular modeling to determine the parameters of the solvated and desolvated electrolyte ions and their adsorption energies with each type of electrode pore surface material. Predictions, in agreement with the experimental data, yield a specific electrode capacitance of 110 F g-1 for xGNP-750 coating electrodes in electrolyte 1M LiPF6 in EC:DMC, which is three times higher than that of the high SSA a-MWGO coating electrodes in the same lithium ion electrolyte.

Anatomical Evaluation of Rat and Mouse Simulators for Laboratory Animal Science Courses.

According to the European Directive 63/2010/EU, education and training involving living rats and mice are classified as an animal experiment and demands the implementation of the 3Rs. Therefore, as a method of refinement, rat and mouse simulators were developed to serve as an initial training device for various techniques, prior to working on living animals. Nevertheless, little is known about the implementation, anatomical correctness, learning efficiency and practical suitability of these simulators. With this in mind, a collaborative research project called "SimulRATor" was initiated to systematically evaluate the existing rat and mouse simulators in a multi-perspective approach. The objective of the study presented here was to identify the anatomical strengths and weaknesses of the available rat and mouse simulators and to determine anatomical requirements for a new anatomically correct rat simulator, specifically adapted to the needs of Laboratory Animal Science (LAS) training courses. Consequently, experts of Veterinary Anatomy and LAS evaluated the anatomy of all currently available rat and mouse simulators. The evaluation showed that compared to the anatomy of living rats and mice, the tails were perceived as the most anatomically realistic body part, followed by the general exterior and the limbs. The heads were rated as the least favored body part.

Alternatives in Education-Evaluation of Rat Simulators in Laboratory Animal Training Courses from Participants' Perspective.

In laboratory animal science (LAS) education and training, five simulators are available for exercises on handling and routine procedures on the rat, which is-beside mice-the most commonly used species in LAS. Since these simulators may have high potential in protecting laboratory rats, the aim of this study is to investigate the simulators' impact on the 3R (replace, reduce, refine) principle in LAS education and training. Therefore, the simulators were evaluated by 332 course participants in 27 different LAS courses via a practical simulator training workshop and a paper-based two-part questionnaire-both integrated in the official LAS course schedule. The results showed a high positive resonance for simulator training and it was considered especially useful for the inexperienced. However, the current simulators may not completely replace exercises on live animals and improvements regarding more realistic simulators are demanded. In accordance with literature data on simulator-use also in other fields of education, more research on simulators and new developments are needed, particularly with the aim for a broad implementation in LAS education and training benefiting all 3Rs.

Alternatives in Education-Rat and Mouse Simulators Evaluated from Course Trainers' and Supervisors' Perspective.

Simulators allow the inexperienced to practice their skills prior to exercise on live animals. Therefore, they bear great potential in overcoming the dilemma between the present demand for high-quality practical training involving live animals whilst implementing the 3R principle according to the Directive 2010/63/EU. Currently, one mouse and six rat simulators are commercially available. As data on their impact are lacking, this project aimed at providing an overview of the awareness, implementation, and methodical and practical satisfaction provided by 35 course trainers and supervisors of laboratory animal training courses for mice and rats regarding the simulators available. Although simulators facilitate training of relevant techniques and relatively high awareness of them seemed to be present, their implementation is currently very low, possibly due to lack of meeting the respondents' demands. Thus, this study revealed the overall approval of simulator training and general demand for user-optimized, realistic, and financially affordable simulators and, hence, indicates a strong impulse for new developments strengthening the 3Rs as a benefit to all animals used in research.