Dissection in biology education compared to alternative methods in terms of their influence on students' emotional experience.

Introduction: Dissecting animal organs is a method of biology teaching that offers a direct and authentic view into morphological structures and enables hands-on activity and multisensory experiences. However, the dissection process is often associated with certain (negative) emotions that might hinder successful learning. One such emotion that is particularly common during dissection is disgust. Experiencing disgust can negatively affect emotional experiences. Consequently, alternatives for dissection in biology lessons are being sought. Methods: In this study, the method of dissection is compared with two common methods of teaching the anatomy of the mammalian eye: watching a video and working with an anatomical model. The focus of the comparison is on the influence on the following emotional qualities of experience: perceived disgust, perceived interest, well-being and boredom. Two hundred and eighteen students (Mage = 14.19, SDage = 1.02 years, 52% female) from secondary schools in Germany participated in a two-hour lesson on the anatomy of the mammalian eye using one of the three aforementioned teaching methods. Findings: Our results show that perceived disgust was higher for the dissection group than in the ones that worked with a video or a model. We found that dissecting and watching a video led to a similar level of interest, well-being, and boredom. The anatomical model was perceived as less disgusting but more boring than the dissection. The detailed videos of a dissection seem to offer similar positive emotional experiences when compared to dissecting in class and may be an alternative approach when teachers have concerns about performing a real dissection.

Comparing POD and MOD ENDS Users' Product Characteristics, Use Behaviors, and Nicotine Exposure.

INTRODUCTION: POD electronic nicotine delivery systems (ENDS), often containing high concentrations of nicotine salts, have replaced MODs (ie, open/modifiable devices) as the most popular devices. The purpose of this study was to compare device/liquid characteristics, use behavior, and nicotine exposure between POD and MOD users. METHODS: Data from the initial visit of a prospective observational study of exclusive ENDS users compared MOD (n = 48) and POD (n = 37) users. Participants completed questionnaires on demographic characteristics, patterns of ENDS use, and ENDS features. A urine sample was collected to test for cotinine and an ENDS liquid sample was collected to test for nicotine and salts. Puff topography was captured during an ad libitum bout at the end of the session. RESULTS: MOD and POD users did not differ on demographic characteristics. MOD users reported purchasing more liquid in the past month than POD users (180.4 ±â€…28.0 vs. 50.9 ±â€…9.0 ml, p < .001). Differences in characteristics of devices used by MOD and POD users included flavor type (p = .029), nicotine concentration (liquids used by MOD users contained less nicotine than those used by POD users: 8.9 ±â€…2.0 vs. 41.6 ±â€…3.2 mg/ml, p < .001), and presence of the nicotine salt (fewer MOD liquids had salts present than POD liquids: 11.9% vs. 77.4%, p < .001). User groups did not differ on urinary cotinine levels or puff topography (ps > .05). CONCLUSIONS: Despite different characteristics of MOD and POD ENDS, users of those products are exposed to similar amounts of nicotine, likely due to using more liquid among MOD users. IMPLICATIONS: This study directly compares ENDS product characteristics, user behavior, and nicotine exposure between MOD and POD ENDS users. Although POD products contained higher nicotine concentrations compared to MOD products, users of PODs reported consuming less liquid than MOD users. Ultimately, MOD and POD users were exposed to similar levels of nicotine, suggesting users behaviorally compensate for differences in product characteristics.

Changes in product labelling practices and the use of flavouring chemical additives in vaping products after enactment of statewide flavour legislation.

INTRODUCTION: On 18 May 2020, New York State enacted legislation banning the sale of vaping products with distinguishable flavours (other than tobacco). According to this new statute, vaping products are deemed flavoured if they include a statement, whether expressed or implied, that have distinguishable tastes or aromas other than tobacco. This study aimed to determine how manufacturers responded. METHODS: We collected 555 vaping products from daily vapers (238 preban and 317 postban). We compared preban and postban labelling of products for expressed and implied flavour descriptions, graphics and colours. Flavouring chemicals and concentrations were identified using chromatography methods and were compared preban and postban. RESULTS: Analysis of the labels preban and postban did not reveal a change in products with expressed flavoured descriptors (45.8% vs 44.2%) and a minimal decrease in implied descriptors (22.3% vs 14.5%). An increase in products without any descriptors was observed (28.2% vs 37.2%) notably within products from a popular pod brand. The average concentration of eight popular flavourings identified preban was 1.4±2.7 compared with 2.3±3.5 mg/mL (p<0.001) postban. No significant changes between individual flavouring concentrations in the most popular refill solutions and pods were found. CONCLUSION: While a majority of products appeared to remain non-compliant, this study suggests that enactment of legislation on vaping products making expressed or implied flavour claims may result in some manufacturer changes to product labelling including removal of flavour descriptors. However, use of flavouring additives in vaping products appeared not to be impacted by the ban.

A phase II study of the PI3K inhibitor copanlisib in combination with the anti-CD20 monoclonal antibody rituximab for patients with marginal zone lymphoma: treatment rationale and protocol design of the COUP-1 trial.

BACKGROUND: Advanced stage marginal zone lymphoma (MZL) is an incurable indolent B-cell lymphoma, for which a wide variety of treatments ranging from single agent rituximab to more dose intense immunochemotherapy exists. One of the major goals in this palliative setting is to develop chemotherapy-free treatments, which approach the efficacy of immunochemotherapies, but avoid chemotherapy associated toxicity in this often elderly patient population. The PI3K inhibitor copanlisib has recently shown remarkable clinical activity in refractory or relapsed indolent B-cell lymphomas, among them MZL. Based on these data, copanlisib monotherapy was granted breakthrough designation by the FDA for the treatment of adult patients with relapsed marginal zone lymphoma who have received at least two prior therapies. However, data are still limited in particular for MZL. Based on this, the COUP-1 trial aims at testing the toxicity and efficacy of copanlisib in combination with rituximab in treatment naive and relapsed MZL. METHODS: COUP-1 is a prospective, multicenter, single-arm, open-label, non-randomized phase II trial of 6 cycles (28 days cycle) of copanlisib (60 mg intravenous day 1, 8, 15) and rituximab (375 mg/m2 intravenous day 1) in the induction phase followed by a maintenance phase of copanlisib (d1, d15 every 4 weeks for a maximum of 12 cycles) and rituximab (d1 every 8 weeks for a maximum of 12 cycles) in patients aged ≥18 years with previously untreated or relapsed MZL in need of treatment. A total of 56 patients are to be enrolled. Primary endpoint is the complete response (CR) rate determined 12 months after start of induction therapy. Secondary endpoints include the overall response (OR) rate, progression free survival (PFS), overall survival (OS), safety and patient related outcome with quality of life. The study includes a translational bio-sampling program with the prospect to measure minimal residual disease. The study was initiated in November 2019. DISCUSSION: The COUP-1 trial evaluates the efficacy and toxicity of the treatment of copanlisib in combination with rituximab in patients with MZL and additionally offers the chance for translational research in this heterogenous type of lymphoma. TRIAL REGISTRATION: ClinicalTrials.gov : NCT03474744 . Registration date: 03/23/2018.

Targeting of CXCR4 by the Naturally Occurring CXCR4 Antagonist EPI-X4 in Waldenström's Macroglobulinemia.

CXCR4 expression and downstream signaling have been identified as key factors in malignant hematopoiesis. Thus, up to 40% of all patients with Waldenström's macroglobulinemia (WM) carry an activating mutation of CXCR4 that leads to a more aggressive clinical course and inferior outcome upon treatment with the Bruton's tyrosine kinase inhibitor ibrutinib. Nevertheless, little is known about physiological mechanisms counteracting CXCR4 signaling in hematopoietic neoplasms. Recently, the endogenous human peptide EPI-X4 was identified as a natural CXCR4 antagonist that effectively blocks CXCL12-mediated receptor internalization and suppresses the migration and invasion of cancer cells towards a CXCL12 gradient. Here, we demonstrate that EPI-X4 efficiently binds to CXCR4 of WM cells and decreases their migration towards CXCL12. The CXCR4 inhibitory activity of EPI-X4 is accompanied by reduced expression of genes involved in MAPK signaling and energy metabolism. Notably, the anti-WM activity of EPI-X4 could be further augmented by the rational design of EPI-X4 derivatives showing higher binding affinity to CXCR4. In summary, these data demonstrate that a naturally occurring anti-CXCR4 peptide is able to interfere with WM cell behaviour, and that optimized derivatives of EPI-X4 may represent a promising approach in suppressing growth promoting CXCR4 signaling in WM.

CXCR4 in Waldenström's Macroglobulinema: chances and challenges.

It is one of the major aims in cancer research to improve our understanding of the underlying mechanisms which initiate and maintain tumor growth and to translate these findings into novel clinical diagnostic and therapeutic concepts with the ultimate goal to improve patient care. One of the greater success stories in this respect has been Waldenström's Macroglobulinemia (WM), which is an incurable B-cell neoplasm characterized by serum monoclonal immunoglobulin M (IgM) and clonal lymphoplasmacytic cells infiltrating the bone marrow. Recent years have succeeded to describe the molecular landscape of WM in detail, highlighting two recurrently mutated genes, the MYD88 and the CXCR4 genes: MYD88 with an almost constant and recurrent point mutation present in over 90% of patients and CXCR4 with over 40 different mutations in the coding region affecting up to 40% of patients. Intriguingly, both mutations are activating mutations leading in the case of CXCR4 to an indelible activation and perpetual signaling of the chemokine receptor. These data have shed light on the essential role of CXCR4 in this disease and have paved the way to use these findings for predicting treatment response to the Bruton tyrosine kinase (BTK) inhibitor ibrutinib and novel therapeutic approaches in WM, which might be transferable to other related CXCR4 positive diseases. Well known for its central role in cancer progression and distribution, CXCR4 is highlighted in this review with regard to its biology, prognostic and predictive relevance and therapeutic implications in WM.

Phase II trial evaluating the efficacy and safety of the anti-CD20 monoclonal antibody obinutuzumab in patients with marginal zone lymphoma.

Marginal zone lymphoma (MZL) belongs to the group of indolent B-cell non-Hodgkin's lymphomas, which is characterized by an indolent course. In this mostly elderly patient population, the development of chemotherapy-free approaches is of particular interest. In this situation, single-agent treatment with the next-generation anti-CD20 antibody obinutuzumab is an attractive approach, which promises high efficacy without major toxicity. We describe here an open-label, multicentric Phase II trial evaluating the efficacy and safety of obinutuzumab in de novo MZL patients, who are treatment naive for systemic therapy and not eligible for or failed local treatment. ClinicalTrials.gov identifier NCT03322865.

Effect of e-cigarette flavors on nicotine delivery and puffing topography: results from a randomized clinical trial of daily smokers.

RATIONALE: There is limited understanding regarding how various e-cigarette flavorings may influence the behavior of non-regular e-cigarette users who are regular cigarette smokers. OBJECTIVES: To assess differences in nicotine delivery, puffing topography, subjective effects, and user satisfaction from different flavored e-liquids. METHODS: Eighteen daily smokers (average age, 44.1 ± 7.0; 9 males; average CPD, 13.0 ± 5.8) smoked their tobacco cigarettes during an initial visit and returned five times to try an e-cigarette (eGo type) refilled with a nicotine solution (24 mg/ml) of five different flavors: cherry, tobacco, espresso, menthol, and vanilla (randomized order). Assessments at each visit included puffing topography, blood samples for nicotine analysis, and subjective reports of nicotine effects and flavor satisfaction. RESULTS: Vaping different flavors resulted in different levels of plasma nicotine. The flavor producing the highest plasma nicotine concentration (Cmax) was cherry (median 21.2 ng/ml), which was not significantly different than nicotine delivery from a combustible cigarette (29.2 ng/ml, p > .05). Vanilla e-liquid produced the lowest Cmax (9.7 ng/ml), and participants tended to puff less frequently on vanilla compared to tobacco flavor (p = .013). Flavors did not differ significantly in the speed of nicotine delivery (Tmax). During controlled use, puff duration for all flavors was significantly longer than a combustible cigarette (p < 0.05). After controlling for nicotine delivery, significant differences in flavor enjoyment were detected. Menthol flavored e-liquid was rated as more enjoyable than vanilla and tobacco flavored e-liquids (p < 0.05). CONCLUSIONS: Flavors tested in this study yielded different patterns of nicotine delivery and led to differences in reduction in smoking urges. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: #NCT02575885.

Randomized within-subject trial to evaluate smokers' initial perceptions, subjective effects and nicotine delivery across six vaporized nicotine products.

BACKGROUND AND AIMS: Vaporized nicotine products (VNPs) can vary in important characteristics including size, shape, flavor and nicotine yield. We examined whether complex interactions among these characteristics could affect smokers' VNP perceptions and usage patterns. DESIGN: A within-subject randomized cross-over trial. SETTING: Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA. PARTICIPANTS: Eighteen daily cigarette smokers. MEASUREMENTS: Participants attended eight weekly visits during which they sampled six different VNPs (disposable, rechargeable, eGO, mod, e-Cigar and e-Pipe) with tobacco-flavored e-liquid. Prior to device use, participants completed product-ranking questionnaires. Participants completed controlled puffing sessions during each of the six trials, after which satisfaction questionnaires were completed and blood samples were taken. FINDINGS: Initial perceptions showed that the smallest device (disposable) was ranked as safer compared with a larger device (e-Pipe) (P < 0.05). Participants rated the eGO and mod devices higher on satisfaction and enjoyment from use, taste, pleasantness, harshness ('throat hit') and speed of effect, but lower on perceived health risk and embarrassment from use (P < 0.05). All devices had a lower Cmax than the combustible cigarette (P < 0.05), but there were differences among devices (P < 0.05). The mod, e-Pipe and eGO provided the highest amount of perceived smoking urge relief, and this correlated strongly with Cmax across all devices (R2  = 0.8614, P = 0.007). The perceived speed of urge relief was not correlated with Tmax (R2  = 0.0035, P = 0.911) CONCLUSIONS: Daily cigarette smokers testing six types of vaporized nicotine products (VNPs) reported that they varied in taste, amount of withdrawal relief, harshness, embarrassment from use, perceived health risk and subjective and objective nicotine delivery. The eGO and mod models have properties that may make them most effective for cigarette substitution among smokers who intend to switch to a VNP.

Biomarkers for classification and class prediction of stress in a murine model of chronic subordination stress.

Selye defined stress as the nonspecific response of the body to any demand and thus an inherent element of all diseases. He reported that rats show adrenal hypertrophy, thymicolymphatic atrophy, and gastrointestinal ulceration, referred to as the stress triad, upon repeated exposure to nocuous agents. However, Selye's stress triad as well as its extended version including reduced body weight gain, increased plasma glucocorticoid (GC) concentrations, and GC resistance of target cells do not represent reliable discriminatory biomarkers for chronic stress. To address this, we collected multivariate biological data from male mice exposed either to the preclinically validated chronic subordinate colony housing (CSC) paradigm or to single-housed control (SHC) condition. We then used principal component analysis (PCA), top scoring pairs (tsp) and support vector machines (SVM) analyses to identify markers that discriminate between chronically stressed and non-stressed mice. PCA segregated stressed and non-stressed mice, with high loading for some of Selye's stress triad parameters. The tsp analysis, a simple and highly interpretable statistical approach, identified left adrenal weight and relative thymus weight as the pair with the highest discrimination score and prediction accuracy validated by a blinded dataset (92% p-value < 0.0001; SVM model = 83% accuracy and p-value < 0.0001). This finding clearly shows that simultaneous consideration of these two parameters can be used as a reliable biomarker of chronic stress status. Furthermore, our analysis highlights that the tsp approach is a very powerful method whose application extends beyond what has previously been reported.

Controlled stem cell amplification by HOXB4 depends on its unique proline-rich region near the N terminus.

There is high interest in understanding the mechanisms that drive self-renewal of stem cells. HOXB4 is one of the few transcription factors that can amplify long-term repopulating hematopoietic stem cells in a controlled way. Here we show in mice that this characteristic of HOXB4 depends on a proline-rich sequence near the N terminus, which is unique among HOX genes and highly conserved in higher mammals. Deletion of this domain substantially enhanced the oncogenicity of HOXB4, inducing acute leukemia in mice. Conversely, insertion of the domain into Hoxa9 impaired leukemogenicity of this homeobox gene. These results indicate that proline-rich stretches attenuate the potential of stem cell active homeobox genes to acquire oncogenic properties.

Crohn's disease and ulcerative colitis are associated with elevated standardized mortality ratios: a meta-analysis.

BACKGROUND: Evidence regarding all-cause and cause-specific mortality in inflammatory bowel disease (IBD) is conflicting, and debate exists over appropriate study design to examine these important outcomes. We conducted a comprehensive meta-analysis of all-cause and cause-specific mortality in both Crohn's disease (CD) and ulcerative colitis (UC), and additionally examined various effects of study design on this outcome. METHODS: A systematic search of PubMed and EMBASE was conducted to identify studies examining mortality rates relative to the general population. Pooled summary standardized mortality ratios (SMR) were calculated using random effect models. RESULTS: Overall, 35 original articles fulfilled the inclusion and exclusion criteria, reporting all-cause mortality SMRs varying from 0.44 to 7.14 for UC and 0.71 to 3.20 for CD. The all-cause mortality summary SMR for inception cohort and population cohort UC studies was 1.19 (95% confidence interval, 1.06-1.35). The all-cause mortality summary SMR for inception cohort and population cohort CD studies was 1.38 (95% confidence interval, 1.23-1.55). Mortality from colorectal cancer, pulmonary disease, and nonalcoholic liver disease was increased, whereas mortality from cardiovascular disease was decreased. CONCLUSIONS: Patients with UC and CD have higher rates of death from all causes, colorectal-cancer, pulmonary disease, and nonalcoholic liver disease.

Infectious causes of chronic diarrhoea.

Infections are an uncommon cause of chronic diarrhoea. Parasites are most likely, including protozoa like giardia, cryptosporidia and cyclospora. Bacteria are unlikely to cause chronic diarrhoea in immunocompetent individuals with the possible exception of Yersinia, Plesiomonas and Aeromonas. Infectious diarrhoea can trigger other causes of chronic diarrhoea, including inflammatory bowel disease, irritable bowel syndrome and "Brainerd-type" diarrhoea. A thorough evaluation should detect most infections causing chronic diarrhoea.

Presence in three interconnected contexts: considerations for nursing education in the 21st century.

Online nursing education has grown tremendously over the past decade and there is every reason to believe that this growth will continue in the 21st century. "Presence" is concept that has familiarity in nursing, education, and technology. With the convergence of these three interrelated contexts, presence holds a new level of interest for nursing education. "Connecting with," "being with," and/or "being available" to another in a virtual world poses challenges for nurse educators as they turn their focus on student satisfaction in online courses, connecting with others in ways that enhance learning, and exploring ways of "being with" or "connecting with" patients in both traditional and virtual environments of care.