Differences in Discounting Behavior and Brain Responses for Food and Money Reward.

Most neuroeconomic research seeks to understand how value influences decision-making. The influence of reward type is less well understood. We used functional magnetic resonance imaging (fMRI) to investigate delay discounting of primary (i.e., food) and secondary rewards (i.e., money) in 28 healthy, normal-weighted participants (mean age = 26.77; 18 females). To decipher differences in discounting behavior between reward types, we compared how well-different option-based statistical models (exponential, hyperbolic discounting) and attribute-wise heuristic choice models (intertemporal choice heuristic, dual reasoning and implicit framework theory, trade-off model) captured the reward-specific discounting behavior. Contrary to our hypothesis of different strategies for different rewards, we observed comparable discounting behavior for money and food (i.e., exponential discounting). Higher k values for food discounting suggest that individuals decide more impulsive if confronted with food. The fMRI revealed that money discounting was associated with enhanced activity in the right dorsolateral prefrontal cortex, involved in executive control; the right dorsal striatum, associated with reward processing; and the left hippocampus, involved in memory encoding/retrieval. Food discounting, instead, was associated with higher activity in the left temporoparietal junction suggesting social reinforcement of food decisions. Although our findings do not confirm our hypothesis of different discounting strategies for different reward types, they are in line with the notion that reward types have a significant influence on impulsivity with primary rewards leading to more impulsive choices.

Opening up a tailored tutor qualification program for medical students to other healthcare students - a mixed-method study.

BACKGROUND: Peer-led tutorials are widely used in medical education to promote practical skills acquisition and support faculty staff. Typically, student tutors are custom trained for this specific task. We investigated whether opening up an existing medical tutor qualification program to other degree programs is successful in terms of acceptance among students, acquisition of tutor-specific and interprofessional competencies, and which factors contribute to success or failure. METHODS: We developed a two-day tutor qualification program and conducted it annually from 2016 to 2020 with medical and other healthcare students. At the end of each course, we administered a written survey in which the participants rated the following items: their attitudes towards interprofessional learning (using the UWE-IP-D Interprofessional Learning Scale), the interprofessional learning setting, the teaching approach, and their competency acquisition (each on a five-point Likert scale; 1 = strongly agree, 5 = strongly disagree). Furthermore, we assessed participants' qualitative feedback in free-text fields and performed inductive content analyses. RESULTS: The study participation rate was high (response rate 97%; medical students: n = 75; healthcare students: n = 22). Participants stated high levels of competency acquisition (total M = 1.59, individual items' M's ranging from 1.20 to 2.05) and even higher satisfaction with the teaching approach (total M = 1.28, individual items' M's ranging from 1.43 to 1.05). Overall satisfaction with the training was M = 1.22; SD = 0.58. No significant differences in ratings were found between the student groups. The qualitative results showed that students appreciated the interprofessional setting and experienced it as enriching. The most positive feedback was found in didactics/teaching methods on role-plays and group work; most suggestions for improvement were found in the area of structure and organisation on breaks and time management. CONCLUSIONS: Opening up an existing medical tutor qualification program to other student groups can be seen as fruitful to teach not only tutor-related aspects but also interprofessional competencies. The results demonstrate the importance of detailed planning that considers group composition and contextual conditions and provides interactive teaching methods to promote interprofessional experiences. This study offers important information about prerequisites and methodological implementation that could be important for the interprofessional redesign of existing training programs.

Metabolic engineering of Rhodotorula toruloides IFO0880 improves C16 and C18 fatty alcohol production from synthetic media.

BACKGROUND: The oleaginous, carotenogenic yeast Rhodotorula toruloides has been increasingly explored as a platform organism for the production of terpenoids and fatty acid derivatives. Fatty alcohols, a fatty acid derivative widely used in the production of detergents and surfactants, can be produced microbially with the expression of a heterologous fatty acyl-CoA reductase. Due to its high lipid production, R. toruloides has high potential for fatty alcohol production, and in this study several metabolic engineering approaches were investigated to improve the titer of this product. RESULTS: Fatty acyl-CoA reductase from Marinobacter aqueolei was co-expressed with SpCas9 in R. toruloides IFO0880 and a panel of gene overexpressions and Cas9-mediated gene deletions were explored to increase the fatty alcohol production. Two overexpression targets (ACL1 and ACC1, improving cytosolic acetyl-CoA and malonyl-CoA production, respectively) and two deletion targets (the acyltransferases DGA1 and LRO1) resulted in significant (1.8 to 4.4-fold) increases to the fatty alcohol titer in culture tubes. Combinatorial exploration of these modifications in bioreactor fermentation culminated in a 3.7 g/L fatty alcohol titer in the LRO1Δ mutant. As LRO1 deletion was not found to be beneficial for fatty alcohol production in other yeasts, a lipidomic comparison of the DGA1 and LRO1 knockout mutants was performed, finding that DGA1 is the primary acyltransferase responsible for triacylglyceride production in R. toruloides, while LRO1 disruption simultaneously improved fatty alcohol production, increased diacylglyceride and triacylglyceride production, and increased glucose consumption. CONCLUSIONS: The fatty alcohol titer of fatty acyl-CoA reductase-expressing R. toruloides was significantly improved through the deletion of LRO1, or the deletion of DGA1 combined with overexpression of ACC1 and ACL1. Disruption of LRO1 surprisingly increased both lipid and fatty alcohol production, creating a possible avenue for future study of the lipid metabolism of this yeast.

CUT&RUN identifies centromeric DNA regions of Rhodotorula toruloides IFO0880.

Rhodotorula toruloides has been increasingly explored as a host for bioproduction of lipids, fatty acid derivatives and terpenoids. Various genetic tools have been developed, but neither a centromere nor an autonomously replicating sequence (ARS), both necessary elements for stable episomal plasmid maintenance, has yet been reported. In this study, cleavage under targets and release using nuclease (CUT&RUN), a method used for genome-wide mapping of DNA-protein interactions, was used to identify R. toruloides IFO0880 genomic regions associated with the centromeric histone H3 protein Cse4, a marker of centromeric DNA. Fifteen putative centromeres ranging from 8 to 19 kb in length were identified and analyzed, and four were tested for, but did not show, ARS activity. These centromeric sequences contained below average GC content, corresponded to transcriptional cold spots, were primarily nonrepetitive and shared some vestigial transposon-related sequences but otherwise did not show significant sequence conservation. Future efforts to identify an ARS in this yeast can utilize these centromeric DNA sequences to improve the stability of episomal plasmids derived from putative ARS elements.

Changing Paradigms in the Management of Acute Uncomplicated Diverticulitis.

Left-sided colonic diverticulitis is a common condition with significant morbidity and health care costs in Western countries. Acute uncomplicated diverticulitis which is characterized by the absence of organ dysfunction, abscesses, fistula, or perforations accounts for around 80% of the cases. In the last decades, several traditional paradigms in the management of acute uncomplicated diverticulitis have been replaced by evidence-based routines. This review provides a comprehensive evidence-based and clinical-oriented overview of up-to-date diagnostics with computer tomography, non-antibiotic treatment, outpatient treatment, and surgical strategies as well as follow-up of patients with acute uncomplicated diverticulitis.

Identification of novel metabolic engineering targets for S-adenosyl-L-methionine production in Saccharomyces cerevisiae via genome-scale engineering.

S-Adenosyl-L-methionine (SAM) is an important intracellular metabolite and widely used for treatment of various diseases. Although high level production of SAM had been achieved in yeast, novel metabolic engineering strategies are needed to further enhance SAM production for industrial applications. Here genome-scale engineering (GSE) was performed to identify new targets for SAM overproduction using the multi-functional genome-wide CRISPR (MAGIC) system, and the effects of these newly identified targets were further validated in industrial yeast strains. After 3 rounds of FACS screening and characterization, numerous novel targets for enhancing SAM production were identified. In addition, transcriptomic and metabolomic analyses were performed to investigate the molecular mechanisms for enhanced SAM accumulation. The best combination (upregulation of SNZ3, RFC4, and RPS18B) improved SAM productivity by 2.2-fold and 1.6-fold in laboratory and industrial yeast strains, respectively. Using GSE of laboratory yeast strains to guide industrial yeast strain engineering presents an effective approach to design microbial cell factories for industrial applications.

European Society of Coloproctology: guidelines for the management of diverticular disease of the colon.

AIM: The goal of this European Society of Coloproctology (ESCP) guideline project is to give an overview of the existing evidence on the management of diverticular disease, primarily as a guidance to surgeons. METHODS: The guideline was developed during several working phases including three voting rounds and one consensus meeting. The two project leads (JKS and EA) appointed by the ESCP guideline committee together with one member of the guideline committee (WB) agreed on the methodology, decided on six themes for working groups (WGs) and drafted a list of research questions. Senior WG members, mostly colorectal surgeons within the ESCP, were invited based on publication records and geographical aspects. Other specialties were included in the WGs where relevant. In addition, one trainee or PhD fellow was invited in each WG. All six WGs revised the research questions if necessary, did a literature search, created evidence tables where feasible, and drafted supporting text to each research question and statement. The text and statement proposals from each WG were arranged as one document by the first and last authors before online voting by all authors in two rounds. For the second voting ESCP national representatives were also invited. More than 90% agreement was considered a consensus. The final phrasing of the statements with < 90% agreement was discussed in a consensus meeting at the ESCP annual meeting in Vienna in September 2019. Thereafter, the first and the last author drafted the final text of the guideline and circulated it for final approval and for a third and final online voting of rephrased statements. RESULTS: This guideline contains 38 evidence based consensus statements on the management of diverticular disease. CONCLUSION: This international, multidisciplinary guideline provides an up to date summary of the current knowledge of the management of diverticular disease as a guidance for clinicians and patients.

[Painful orbital swelling in a 61-year-old female patient]. / Schmerzhafte Schwellung der Orbita bei einer 61-jährigen Patientin.

Adenocarcinoma of the esophagus is the oncologic entity with the most progressive incidence in western countries over the last 30 years. This is caused by, among other factors, a growing rate of obesity and the associated gastroesophageal reflux disease. Typical sites of metastasis include the liver, lymph nodes and peritoneum. Adrenal glands and thoraco-abdominal skeleton can also be affected. Cerebral metastasis is infrequent and there are only a handful cases described in the literature. The case presented here relates to a 61-year-old woman with osteolytic metastasis that was infiltrating the orbital cavity and was initially diagnosed as a dacryoadenitis.

Warming and acidification threaten glass sponge Aphrocallistes vastus pumping and reef formation.

The glass sponge Aphrocallistes vastus contributes to the formation of large reefs unique to the Northeast Pacific Ocean. These habitats have tremendous filtration capacity that facilitates flow of carbon between trophic levels. Their sensitivity and resilience to climate change, and thus persistence in the Anthropocene, is unknown. Here we show that ocean acidification and warming, alone and in combination have significant adverse effects on pumping capacity, contribute to irreversible tissue withdrawal, and weaken skeletal strength and stiffness of A. vastus. Within one month sponges exposed to warming (including combined treatment) ceased pumping (50-60%) and exhibited tissue withdrawal (10-25%). Thermal and acidification stress significantly reduced skeletal stiffness, and warming weakened it, potentially curtailing reef formation. Environmental data suggests conditions causing irreversible damage are possible in the field at +0.5 °C above current conditions, indicating that ongoing climate change is a serious and immediate threat to A. vastus, reef dependent communities, and potentially other glass sponges.

Recent advances in domesticating non-model microorganisms.

Non-model microorganisms have been increasingly explored as microbial cell factories for production of chemicals, fuels, and materials owing to their unique physiology and metabolic capabilities. However, these microorganisms often lack facile genetic tools for strain development, which hinders their adoption as production hosts. In this review, we describe recent advances in domestication of non-model microorganisms, including bacteria, actinobacteria, cyanobacteria, yeast, and fungi, with a focus on the development of genetic tools. In addition, we highlight some successful applications of non-model microorganisms as microbial cell factories.

Risk of colorectal cancer following CT-verified acute diverticulitis: a nationwide population-based cohort study.

AIM: Routine colonoscopy to exclude colorectal cancer (CRC) after CT-verified acute diverticulitis is controversial. This study aimed to compare the incidence of CRC in patients with acute diverticulitis with that in the general population. METHOD: Patients with an emergency admission for diverticular disease to any Norwegian hospital between 1 January 2008 and 31 December 2010 were included through identification in the Norwegian Patient Registry using International Classification of Diseases (ICD-10) codes K57.1-9. To estimate the age-specific distribution of CT-verified acute uncomplicated diverticulitis (AUD) and acute complicated diverticulitis (ACD) in this nationwide study population, numbers from the largest Norwegian emergency hospital were used. Patients diagnosed with CRC within 1 year following their admission for acute diverticulitis were detected through cross-matching with the Cancer Registry of Norway. Based on both Norwegian age-specific incidence of CRC and estimated age-specific distribution of CT-verified diverticulitis, standard morbidity ratios (SMRs) were calculated. RESULTS: A total of 7473 patients with emergency admissions for diverticular disease were identified (estimated CT-verified AUD n = 3523, ACD n = 1206); of these 155 patients were diagnosed with CRC within 1 year. Eighty had a CT-verified diverticulitis at index admission [41 AUD (51.3%); 39 ACD (49.7%)]. Compared with the general population, the SMR was 6.6 following CT-verified AUD and 16.3 following ACD, respectively. CONCLUSION: In the first year after CT-verified acute diverticulitis, especially after ACD, the risk of CRC is higher than in the general population. This probably represents misdiagnosis of CRC as acute diverticulitis. Follow-up colonoscopy should be recommended to all patients admitted with acute diverticulitis.

Development of a CRISPR/Cas9 system for high efficiency multiplexed gene deletion in Rhodosporidium toruloides.

The oleaginous yeast Rhodosporidium toruloides is considered a promising candidate for production of chemicals and biofuels thanks to its ability to grow on lignocellulosic biomass, and its high production of lipids and carotenoids. However, efforts to engineer this organism are hindered by a lack of suitable genetic tools. Here we report the development of a CRISPR/Cas9 system for genome editing in R. toruloides based on a fusion 5S rRNA-tRNA promoter for guide RNA (gRNA) expression, capable of greater than 95% gene knockout for various genetic targets. Additionally, multiplexed double-gene knockout mutants were obtained using this method with an efficiency of 78%. This tool can be used to accelerate future metabolic engineering work in this yeast.

Demographic histories and genetic diversity across pinnipeds are shaped by human exploitation, ecology and life-history.

A central paradigm in conservation biology is that population bottlenecks reduce genetic diversity and population viability. In an era of biodiversity loss and climate change, understanding the determinants and consequences of bottlenecks is therefore an important challenge. However, as most studies focus on single species, the multitude of potential drivers and the consequences of bottlenecks remain elusive. Here, we combined genetic data from over 11,000 individuals of 30 pinniped species with demographic, ecological and life history data to evaluate the consequences of commercial exploitation by 18th and 19th century sealers. We show that around one third of these species exhibit strong signatures of recent population declines. Bottleneck strength is associated with breeding habitat and mating system variation, and together with global abundance explains much of the variation in genetic diversity across species. Overall, bottleneck intensity is unrelated to IUCN status, although the three most heavily bottlenecked species are endangered. Our study reveals an unforeseen interplay between human exploitation, animal biology, demographic declines and genetic diversity.

The prevalence of community programmes and policies to prevent childhood obesity in a diverse sample of US communities: the Healthy Communities Study.

INTRODUCTION: This manuscript describes the prevalence and attributes of community programmes and policies (CPPs) to address childhood obesity documented as occurring in 130 diverse US communities. METHODS: Key informant interviews (N = 1420) and document abstraction were used to identify and characterize CPPs to promote physical activity and healthy nutrition occurring during a 10-year retrospective study period. Data were collected in 2013-2015 and analysed in 2016. RESULTS: Across all 130 communities, 9681 distinct CPPs were reported as occurring by key informants. Of these, 5574 (58%) focused on increasing physical activity, 2596 (27%) on improving nutrition and 1511 (16%) on both behaviours. The mean number of CPPs per community was 74.0, with a range of 25 to 295 across all communities. Most CPPs occurred more than once (63%) and on average lasted 6.1 years. The greatest number of reported CPPs occurred in school settings (44%). CONCLUSIONS: Communities showed a wide range of investment in the amount of CPPs occurring in settings that affect opportunities for children to engage in physical activity and healthy nutrition. The pattern of implementation of CPPs showed variation over time, with an increase in more recent years. This observational study provides new and valuable information about what US communities are doing to prevent childhood obesity.

Spectral field mapping in plasmonic nanostructures with nanometer resolution.

Plasmonic nanostructures and -devices are rapidly transforming light manipulation technology by allowing to modify and enhance optical fields on sub-wavelength scales. Advances in this field rely heavily on the development of new characterization methods for the fundamental nanoscale interactions. However, the direct and quantitative mapping of transient electric and magnetic fields characterizing the plasmonic coupling has been proven elusive to date. Here we demonstrate how to directly measure the inelastic momentum transfer of surface plasmon modes via the energy-loss filtered deflection of a focused electron beam in a transmission electron microscope. By scanning the beam over the sample we obtain a spatially and spectrally resolved deflection map and we further show how this deflection is related quantitatively to the spectral component of the induced electric and magnetic fields pertaining to the mode. In some regards this technique is an extension to the established differential phase contrast into the dynamic regime.

Community characteristics modify the relationship between obesity prevention efforts and dietary intake in children: the Healthy Communities Study.

BACKGROUND: The influence of community characteristics on the effectiveness of childhood obesity prevention efforts is not well understood. OBJECTIVE: Examine the interaction of community characteristics with the relationship between community programmes and policies (CPPs) and dietary intake. METHODS: An observational study of 5138 children in grades K-8 in 130 US communities was conducted in 2013-2015. Key informant interviews identified and characterized CPPs. CPP scores were generated for the number of target behaviours (CPP-Behav) and the number of behaviour change strategies (CPP-Strat) addressed by all CPPs and CPPs with nutrition goals over the prior 6 years in each community. Dietary intake was assessed by dietary screener and included intake of sugar from sugar-sweetened beverages; energy-dense foods; fruits and vegetables; whole grains; and fibre. Multivariate statistical models assessed the interactions between US region, urbanicity, community-level income, and community-level race/ethnicity and CPP scores in relation to dietary intake. RESULTS: CPP-Strat was positively associated with healthier dietary intakes in the Northeast and West, and in high Hispanic communities; the reverse was true in the South, and in high African-American and low-income communities. The CPP-Behav was positively associated with healthier dietary intakes in the South and rural areas, and the reverse was true in the West. CONCLUSION: The relationships between CPP index scores and dietary intake were most strongly influenced by region and urbanicity and to a lesser extent by community-level race/ethnicity and income. Findings suggest that different considerations may be needed for childhood obesity prevention efforts in communities with different characteristics.

Etiology-dependent impairment of relaxation kinetics in right ventricular end-stage failing human myocardium.

BACKGROUND: In patients with end-stage heart failure, the primary etiology often originates in the left ventricle, and eventually the contractile function of the right ventricle (RV) also becomes compromised. RV tissue-level deficits in contractile force and/or kinetics need quantification to understand involvement in ischemic and non-ischemic failing human myocardium. METHODS AND RESULTS: The human population suffering from heart failure is diverse, requiring many subjects to be studied in order to perform an adequately powered statistical analysis. From 2009-present we assessed live tissue-level contractile force and kinetics in isolated myocardial RV trabeculae from 44 non-failing and 41 failing human hearts. At 1 Hz stimulation rate (in vivo resting state) the developed active force was not different in non-failing compared to failing ischemic nor non-ischemic failing trabeculae. In sharp contrast, the kinetics of relaxation were significantly impacted by disease, with 50% relaxation time being significantly shorter in non-failing vs. non-ischemic failing, while the latter was still significantly shorter than ischemic failing. Gender did not significantly impact kinetics. Length-dependent activation was not impacted. Although baseline force was not impacted, contractile reserve was critically blunted. The force-frequency relation was positive in non-failing myocardium, but negative in both ischemic and non-ischemic myocardium, while the ß-adrenergic response to isoproterenol was depressed in both pathologies. CONCLUSIONS: Force development at resting heart rate is not impacted by cardiac pathology, but kinetics are impaired and the magnitude of the impairment depends on the underlying etiology. Focusing on restoration of myocardial kinetics will likely have greater therapeutic potential than targeting force of contraction.

Association between community characteristics and implementation of community programmes and policies addressing childhood obesity: the Healthy Communities Study.

BACKGROUND: Little is known about whether characteristics of communities are associated with differential implementation of community programmes and policies to promote physical activity and healthy eating. This study examines associations between community characteristics (e.g. region and race/ethnicity) and the intensity of community programmes and policies implemented to prevent childhood obesity. It explores whether community characteristics moderate the intensity of community efforts to prevent childhood obesity. OBJECTIVE: The objective of this study is to investigate associations between community characteristics and the intensity of community policies and programmes to prevent childhood obesity documented in the Healthy Communities Study that engaged a diverse sample of US communities. METHOD: Programmes and policies were documented in 130 communities across the USA, reporting over 9000 different community programmes and policies to prevent obesity among children ages 4-15. We examined associations between community characteristics and the intensity of community programmes and policies implemented (i.e. their amount and reach, duration and strength of change strategy). CONCLUSION: Community characteristics explain 25% of the variability in the intensity of community programmes and policies implemented in communities. Particular characteristics - urbanicity, region, being a large county and the per cent of African-Americans in a community - contributed to more (over 18% of the 25%) of the observed variability.

Measuring the intensity of community programs and policies for preventing childhood obesity in a diverse sample of US communities: the Healthy Communities Study.

INTRODUCTION: Efforts to address the critical public health problem of childhood obesity are occurring across the USA; however, little is known about how to characterize the intensity of these efforts. OBJECTIVES: The purposes of this study are to describe the intensity of community programs and policies (CPPs) to address childhood obesity in 130 US communities and to examine the extent to which observed CPPs targeted multiple behaviours and employed a comprehensive array of strategies. METHODS: To document CPPs occurring over a 10-year period, key informants were interviewed using a semi-structured interview protocol. Staff coded CPPs for key characteristics related to intensity, including reach, duration and strategy. Three types of CPP scores were calculated for intensity of CPPs, targeting of CPPs towards multiple behaviours and strategies used. RESULTS: Nine thousand six hundred eighty-one CPPs were identified. On average, communities had 74 different CPPs in place (standard deviation 30), with variation in documented CPPs (range 25-295). Most communities experienced a steady, modest increase in intensity scores over 10 years. CPP targeting scores suggested that communities expanded the focus of their efforts over time to include more behaviours and strategies. CONCLUSIONS: Findings of this large-scale study indicate that great variation exists across communities in the intensity and focus of community interventions being implemented to address childhood obesity.

Associations between community programmes and policies and children's physical activity: the Healthy Communities Study.

BACKGROUND: Community initiatives to promote physical activity in children are common, but evidence supporting their effectiveness is limited. OBJECTIVES: The objective of this study is to examine the relationships between community programmes and policies and children's physical activity in a large and diverse sample of US communities. METHODS: Programmes and policies to promote children's physical activity were assessed in 130 communities by key informant interviews, and physical activity behaviours were measured by self-report and parental report in samples of children in each community (total n = 5138). Associations between composite indices of community programmes and policies and indicators of total and moderate-to-vigorous physical activity were examined without and with adjustment for demographic factors. RESULTS: An index reflecting the 6-year history of the number of behaviour change strategies used in community programmes and policies was positively associated with children's moderate-to-vigorous physical activity. This association was attenuated with adjustment for demographic factors. Effect modification analyses found that the association was positive among non-Hispanic children but was negative for Hispanic children. CONCLUSIONS: Community initiatives to promote physical activity in children were positively associated with children's physical activity in non-Hispanic children. Such initiatives were negatively associated with physical activity in Hispanic children, suggesting that future research should consider unique cultural factors when designing community initiatives to promote activity in this population sub-group.