Promotion of cell death or neurite outgrowth in PC-12 and N2a cells by the fungal alkaloid militarinone A depends on basal expression of p53

The fungal alkaloid militarinone A (MiliA) was recently found to stimulate neuronal outgrowth in PC-12 cells by persistant activation of pathways that are also involved in NGF-mediated differentiation, namely the PI3-K/PKB and the MEK/ERK pathways. Application of equal concentrations of MiliA to other cells such as the murine neuroblastoma cell line N2a resulted in immediate onset of apoptosis by nuclear translocation of apoptosis inducing factor (AIF), activation of caspases and c-Jun/AP-1 transcription factor without an intermediate differentiated phenotype, although minor transient phosphorylation of PKB and MAPK as well as activation of NF-κB were also observed. Translocation of AIF was preceded by p53 phosphorylation at Ser15 and blocked by pifithrin α, a known inhibitor of p53-transcriptional activity. We here show that both cell types activate the same pathways albeit in different time scales. This is mainly due to contrasting basal expression levels of p53, which in turn regulates expression of AIF. In PC-12 cells, continuous activation of these pathways after prolonged treatment with 40μM MiliA first led to up-regulation of p53, phosphorylation of p53, release of AIF from mitochondria and its translocation into the nucleus. Additionally, also activation of the c-Jun/AP-1 transcription factor was observed, and PC-12 cells subsequently underwent apoptosis 48-72h post-treatment. We report that similar pathways working on different levels are able to initially shape very divergent cellular response

Nutritional status of Tajik children and women: transition towards a double burden of malnutrition

The double burden of malnutrition, an emerging concern in developing countries, can exist at various levels: individual, household, and population. Here, we explore the nutritional status of Tajik women (15-49 years) and children (5-59 months) focusing on overweight/obesity along with undernutrition (underweight, stunting, and micronutrient deficiencies). For this, nutritional markers (haemoglobin (Hb), transferrin receptor (TfR), serum ferritin (Sf), retinol binding protein (RBP), vitamin D, serum folate, and urinary iodine), height, and weight were assessed from 2,145 women and 2,149 children. Dietary intake, weaning, and breastfeeding habits were recorded using a 24-hr recall and a questionnaire. Overweight (24.5%) and obesity (13.0%) are increasing among Tajik women compared with previous national surveys (2003 and 2009). Prevalence of iron deficiency and anaemia was 38.0% and 25.8%, respectively; 64.5% of women were iodine deficient, 46.5% vitamin A deficient, and 20.5% had insufficient folate levels. Women in rural areas had significantly lower iron status and body mass index and higher iodine intake compared with urban areas; 20.9% of children were stunted, 2.8% wasted, 6.2% underweight, 52.4% iron deficient, and 25.8% anaemic; all more prominent in rural areas. Dietary diversity was higher among urban women. Intraindividual or household double burden was not seen. In summary, double burden of malnutrition constituted an increase in overweight among women, especially in urban areas, and persisting levels of undernutrition (stunting, iron, and vitamin A deficiency), predominately in rural areas. A holistic, innovative approach is needed to improve infant and young children feeding and advise mothers to maintain an adequate diet

Volumetric Prefrontal Cortex Alterations in Patients With Alcohol Dependence and the Involvement of Self‐Control

Background: Aspects of self-control such as sensation seeking and impaired impulse control have been implicated in alcohol dependence (ALC). Conversely, sensation seeking has been ascribed a possible protective role in stress-related psychopathologies. We therefore examined gray matter (GM) morphology in individuals with ALC, focusing on differences in prefrontal regions that have been associated with self-control. Additionally, we accounted for differences in lifetime alcohol intake regarding self-control measures and cortical structures in ALC patients. Methods: With voxel-based morphometry (VBM) focusing on prefrontal a priori defined regions of interest, we assessed a group of 62 detoxified ALC patients and 62 healthy controls (HC). ALC patients were subsequently divided into high (n = 9) and low consumers (n = 53). Self-control was assessed by use of the Barratt Impulsiveness Scale and the Sensation Seeking Scale. Results: Compared to HC, ALC had significantly less GM volume in bilateral middle frontal gyrus (MFG) and right medial prefrontal cortex as well as in the right anterior cingulate. High-consuming ALC showed smaller GM in right orbitofrontal cortex as well as lower sensation seeking scores than low consumers. In low-consuming ALC, right MFG-GM was positively associated with magnitude of sensation seeking; particularly, larger MFG-GM correlated with greater thrill and adventure seeking. Conclusion: Thus, our findings (i) indicate deficient GM volume in prefrontal areas related to self-control and (ii) might accentuate the phenotypic divergence of ALC patients and emphasize the importance of the development of individual treatment options

Biology of Plasmopara viticola - Approach to a biological control of grapevine downy mildew

Plasmopara viticola, the causai agent of grapevine downy mildew is very well adapted to its host pianI. Therefore it is very difficult to develop methods for the biological control which meet the requests of ecological viticulture. One of the possibilities for a biological control of grapevine downy mildew is the usage of the natural resistance potential of the European cultivars of Vitis vinifera, more exactly the induced resistance. Another way is the use of specific inhibitors which either stop the infection process or have an effect on the interaction of the pathogen with the host pianI. Whereas generai information about the resistance reactions in plants is available and the first results were also won for vine, the knowledge about inhibitors is very scanty. The basic prerequisite to develop methods and strategies for the biological control of grapevine downy mildew is a comprehensive knowledge about the biology of P. viticola, especially so with respect to the interaction between pathogen and host. Since P. viticola is well adapted to the host plant, the development of biological methods is a scientific and technical challenge. P. viticola is indigenous in the south-eastern part of North America with a damp warm climate where it can be found on different autochtonous Vitis species. Due to the coevolution of the pathogen and the host a balanced relationship exists between the pathogen's virulence and the host's resistance. In contrast the European Vitis vinifera cultivars are highly susceptible for P. viticola; they have got in contact with the pathogen only 120 years ago and no adaptation has been developed in this short period of time. According to our hypothesis, a lack of a fast recognition of the pathogen results in a delayed resistance response of V. vinifera cultivars. The growth and development of P. viticola is \.ery fast on the host plant and reproduction as well as propagation potential is high. In addition, the growing conditions of grapevine, e.g. regional coverage of viticulture, dense canopy and humid climate, promote epidemic

THE ASSOCIATION OF PINEAL GLAND VOLUME AND BODY MASS IN OBESE AND NORMAL WEIGHT INDIVIDUALS: A PILOT STUDY

Background: In obese individuals impaired sleep and neuroendocrine alterations such as melatonin deficits are associated with circadian rhythm disruption, altered circadian clock gene expression, and bright light at night. While the relation of pineal gland volume (PGV) and melatonin levels has recently been documented in humans, surprisingly little is known about the possible interference of the PGV and the pathophysiology of obesity in humans. Subjects and methods: We therefore compared the PGV of obese with non-obese individuals; both groups were matched by age and gender. Volumetric analyses were performed on the basis of 3 Tesla high resolution Magnetic Resonance Imaging (MRI). Results: We found, that the PGV was significantly smaller in obese individuals than in lean controls (P=0.036). Moreover, PGV and waist-hip ratio showed a significant negative association in controls (P=0.018, rS=-0.602) whereas no association of both variables was found in obese individuals (P=0.856, rS=-0.051). Conclusions: Thus, the current pilot investigation suggests that pineal gland function, reflected by PGV might be involved in the energy homeostasis and pathophysiological mechanisms that contribute to the development and the maintenance of obesity in humans. Moreover, our data supports the notion that the replacement of melatonin deficits might be a novel strategy in the treatment of obesity

The links between healthy, problematic, and addicted Internet use regarding comorbidities and self-concept-related characteristics

Background: Addicted Internet users present with higher rates of comorbidities, e.g., attention-deficit hyperactivity disorder (ADHD), depressive, and anxiety disorders. In addition, deficits in self-concept-related characteristics were found in addicted Internet gamers and social network users. The aim of this study was to examine the links between healthy, problematic, and addicted Internet use regarding comorbidities and self-concept-related characteristics. The association between recently developed ADHD-like symptoms without an underlying diagnosis and addictive Internet use was also examined. Methods: n = 79 healthy controls, n = 35 problematic, and n = 93 addicted Internet users were assessed for comorbidities, social and emotional competencies, body image, self-esteem, and perceived stress. Apart from an ADHD-diagnosis, recently developed ADHD-like symptoms were also assessed. Results: Addicted users showed more self-concept-related deficits and higher rates of comorbidities with ADHD, depressive, and anxiety disorders. Addicted and problematic users showed similarities in the prevalence of cluster B personality disorders and decreased levels of characteristics related to emotional intelligence. Participants with recently developed ADHD-like symptoms scored higher in lifetime and current severity of Internet use compared with those without ADHD symptoms. Addicted participants with recently developed ADHD symptoms showed higher lifetime Internet use severity compared with those without any symptoms. Conclusions: Our findings indicate that cluster B personality disorders and premorbid problems in emotional intelligence might present a link between problematic and addictive Internet use. Furthermore, the findings provide a first indication that addictive Internet use is related to ADHD-like symptoms. Symptoms of ADHD should therefore be assessed against the background of possible addicted Internet use

Zweinutzungshuhn – was ist das? Umfrage unter Landwirt*innen und Geflügelhalter*innen in Deutschland 2022

Um das seit Januar 2022 geltende Verbot des Kükentötens einzuhalten, schlägt das Bundesministerium für Ernährung und Landwirtschaft drei Alternativen vor, darunter das Ausbrüten von Zweinutzungshühnern. Neben züchterischen und wirtschaftlichen Herausforderungen, Zweinutzungstiere in der Wertschöpfungskette zu etablieren, werden das uneinheitliche Verständnis was überhaupt ein Zweinutzungshuhn ist und wie dessen Besonderheiten gegenüber Verbraucher*innen erfolgreich kommuniziert werden können, als Herausforderungen angesehen Dazulegen, was ein Zweinutzungshuhn ist bzw. welches Verständnis darüber aus Sicht von Landwirt*innen vorliegt, ist Ziel dieses Arbeitsberichts. Die deutschlandweite Online-Umfrage unter Landwirt*innen und Geflügelhalter*innen zum Verständnis und der Zukunft von Zweinutzungshühnern wurde im Herbst 2022 im Rahmen des EIP-Agri Projekts „ZweiWert“ durchgeführt. Das EIP-Projekt mit dem Titel „Aufbau von Wertschöpfungsketten für Zweinutzungshühner in Baden-Württemberg“ (ZweiWert) wird vom Ministerium für Ernährung, ländliche Räume und Verbraucherschutz Baden-Württemberg von 01/2022 bis 12/2024 gefördert. Projektpartner sind der Naturlandverband Baden-Württemberg, mehrere Fachgebiete der Universität Hohenheim und viele Partner aus der landwirtschaftlichen Erzeugung und Vermarktung

Status-Quo und Perspektiven von Zweinutzungshühnern in Baden-Württemberg: Ergebnisse eines World-Cafés im Rahmen des 1. Dialogforums des Projektes „ZweiWert“ am 2.3.2023.

Die Hintergründe für das wachsende Interesse an Zweinutzungshühnern sind vielschichtig und reichen vom Verbot der Tötung männlicher Küken aus Legelinien über Wünsche zur allgemeinen Verbesserung des Tierwohls, der Erhaltung der genetischen Biodiversität bis hin zu einer verbesserten Nachhaltigkeit der Produktion. Das Projekt "ZweiWert" hat zum Ziel, ein regionales Netzwerk von Akteur*innen zu schaffen, um die Wertschöpfungskette für Zweinutzungshühner in Baden-Württemberg zu etablieren. Im Anschluss an eine Status-Quo- und Potenzialanalyse der landwirtschaftlichen Erzeugung von Zweinutzungshühnern soll ein Netzwerk entlang der Wertschöpfungskette aufgebaut und langfristig ein Clusterstelle geschafft werden, sodass eine nachhaltige Produktion sowie eine regelmäßige Abnahme der Erzeugnisse sichergestellt werden kann. Um den Austausch zwischen den Akteur*innen zu fördern und politische Handlungsoptionen und Empfehlungen entwickeln zu können, werden im Rahmen des Projektes Dialogforen veranstaltet. Das erste Dialogforum fand im März 2023 statt und brachte Vertreter*innen aus verschiedenen Sektoren zusammen. Im Anschluss an verschiedene Fachbeiträge konnten sich die Teilnehmenden in einem World Café über verschiedene Bereiche der Wertschöpfungskette austauschen. Im Rahmen des Forums wurden insbesondere die Themen Vernetzung und wirtschaftliche Effizienz, Kooperationen, rechtliche/politische Rahmenbedingungen sowie Transparenz und Kommunikation diskutiert

MRI texture-based radiomics analysis for the identification of altered functional networks in alcoholic patients and animal models

[EN] Alcohol use disorder (AUD) is a complex condition representing a leading risk factor for death, disease and disability. Its high prevalence and severe health consequences make necessary a better understanding of the brain network alterations to improve diagnosis and treatment. The purpose of this study was to evaluate the potential of resting-state fMRI 3D texture features as a novel source of biomarkers to identify AUD brain network alterations following a radiomics approach. A longitudinal study was conducted in Marchigian Sardinian alcoholpreferring msP rats (N = 36) who underwent resting-state functional and structural MRI before and after 30 days of alcohol or water consumption. A cross-sectional human study was also conducted among 33 healthy controls and 35 AUD patients. The preprocessed functional data corresponding to control and alcohol conditions were used to perform a probabilistic independent component analysis, identifying seven independent components as resting-state networks. Forty-three radiomic features extracted from each network were compared using a Wilcoxon signed-rank test with Holm correction to identify the network most affected by alcohol consumption. Features extracted from this network were then used in the machine learning process, evaluating two feature selection methods and six predictive models within a nested cross-validation structure. The classification was evaluated by computing the area under the ROC curve. Images were quantized using different numbers of graylevels to test their influence on the results. The influence of ageing, data preprocessing, and brain iron accumulation were also analyzed. The methodology was validated using structural scans. The striatal network in alcohol-exposed msP rats presented the most significant number of altered features. The radiomics approach supported this result achieving good classification performance in animals (AUC = 0.915 +/- 0.100, with 12 features) and humans (AUC = 0.724 +/- 0.117, with 9 features) using a random forest model. Using the structural scans, high accuracy was achieved with a multilayer perceptron in both species (animals: AUC > 0.95 with 2 features, humans: AUC > 0.82 with 18 features). The best results were obtained using a feature selection method based on the p-value. The proposed radiomics approach is able to identify AUD patients and alcohol-exposed rats with good accuracy, employing a subset of 3D features extracted from fMRI. Furthermore, it can help identify relevant networks in drug addiction.This work was supported by the European Union's Horizon 2020 research and innovation program (668863-SyBil-AA) and the ERA-NET NEURON program (FKZ 01EW1112-TRANSALC and PIM2010ERN-00679), as well as the Spanish State Research Agency through the Severo Ochoa Program for Centres of Excellence in R & D (SEV-2017-0723). S. C. acknowledges financial support from the Ministerio de Economia y Competitividad (MINECO) under grant PGC2018-101055-B-I00. D.M. and S.C. acknowledge financial support from the Generalitat Valenciana through the Prometeo Program (PROMETEO/2019/015). Additional support was given to W.H.S by the Deutsche Forschungsgemeinschaft Center grant TRR 265 (Heinz et al., 2020) and the Bundesministerium fur Bildung und Forschung (BMBF; FKZ: 031L0190A, 01ZX1909CA). We thank Dr. Begona Fernandez for excellent technical assistance and Dr. Cecile Bordier for helping with the human data preprocessing.Ruiz-España, S.; Ortiz-Ramón, R.; Pérez-Ramírez, MÚ.; Díaz-Parra, A.; Ciccocioppo, R.; Bach, P.; Vollstädt-Klein, S.... (2023). MRI texture-based radiomics analysis for the identification of altered functional networks in alcoholic patients and animal models. Computerized Medical Imaging and Graphics. 104. https://doi.org/10.1016/j.compmedimag.2023.10218710

Understanding private sector antimalarial distribution chains: a cross-sectional mixed methods study in six malaria-endemic countries.

BACKGROUND: Private for-profit outlets are important treatment sources for malaria in most endemic countries. However, these outlets constitute only the last link in a chain of businesses that includes manufacturers, importers and wholesalers, all of which influence the availability, price and quality of antimalarials patients can access. We present evidence on the composition, characteristics and operation of these distribution chains and of the businesses that comprise them in six endemic countries (Benin, Cambodia, Democratic Republic of Congo, Nigeria, Uganda and Zambia). METHODS AND FINDINGS: We conducted nationally representative surveys of antimalarial wholesalers during 2009-2010 using an innovative sampling approach that captured registered and unregistered distribution channels, complemented by in-depth interviews with a range of stakeholders. Antimalarial distribution chains were pyramidal in shape, with antimalarials passing through a maximum of 4-6 steps between manufacturer and retailer; however, most likely pass through 2-3 steps. Less efficacious non-artemisinin therapies (e.g. chloroquine) dominated weekly sales volumes among African wholesalers, while volumes for more efficacious artemisinin-based combination therapies (ACTs) were many times smaller. ACT sales predominated only in Cambodia. In all countries, consumer demand was the principal consideration when selecting products to stock. Selling prices and reputation were key considerations regarding supplier choice. Business practices varied across countries, with large differences in the proportions of wholesalers offering credit and delivery services to customers, and the types of distribution models adopted by businesses. Regulatory compliance also varied across countries, particularly with respect to licensing. The proportion of wholesalers possessing any up-to-date licence from national regulators was lowest in Benin and Nigeria, where vendors in traditional markets are important antimalarial supply sources. CONCLUSIONS: The structure and characteristics of antimalarial distribution chains vary across countries; therefore, understanding the wholesalers that comprise them should inform efforts aiming to improve access to quality treatment through the private sector