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Hintergrund: Die Produktion von Lebensmitteln ist für ca. 30 % der globalen Treibhausgasemissionen verantwortlich. Die 2019 von der EAT-Lancet-Kommission entwickelte Planetary Health Diet (PHD) ist der Versuch, mit einem global anwendbaren Ernährungskonzept den Anforderungen der individuellen und der planetaren Gesundheit gerecht zu werden. Die Diät ist reich an vollwertigen Lebensmitteln und arm an tierischen und verarbeiteten Produkten. In Deutschland sind viele Menschen an Typ-2-Diabetes erkrankt, die Prävalenz steigt. Auch Lebensstilinterventionen im Bereich der Ernährung, die in vielem der PHD ähneln, können Auftreten und Verlauf der Erkrankung auf individueller und auf Public-Health-Ebene beeinflussen. Ziel der Arbeit: Geprüft wurde, ob die PHD als Ernährungsempfehlung bei Typ-2-Diabetes geeignet sein könnte. Material und Methoden: Für die pragmatische Übersichtsarbeit wurde in PubMed und Google Scholar fokussiert nach Ernährungsempfehlungen bei Typ-2-Diabetes und genauer Zusammensetzung der PHD recherchiert. Auf Basis dieser Literatur wurde die PHD hinsichtlich der aktuellen Empfehlungen zur Ernährung bei Typ-2-Diabetes abgeglichen. Ergebnisse: Die PHD erscheint unter Beachtung möglicher Fallstricke, wie etwa einem Protein- oder Kalziummangel, für an Typ-2-Diabetes erkrankte Menschen geeignet. Schlussfolgerung: Eine pflanzenbasierte, ausgewogene Ernährung ist gut für die individuelle und die planetare Gesundheit. Bei der Umsetzung einer Ernährungsumstellung von an Typ-2-Diabetes Erkrankten kann die PHD eine Orientierung bieten. Dabei können Hausärzt:innen eine wichtige Multiplikator:innenrolle innehaben, ergänzend kann eine strukturierte Ernährungsberatung sinnvoll sein. Für die konkrete Anwendung innerhalb der Patient:innengruppe besteht weiterer Forschungsbedarf.

We present a novel, straightforward, and reproducible one-pot heating up technique to synthesize core/crown SnSe/SnS nanosheets by a careful adjustment of the sulfur and selenium precursor reactivity. Here, the SnSe nanosheets are prepared via a wet-chemical route using SnCl2and selenium phosphines. By adding a highly reactive S-oleylamine complex during the growth of the SnSe sheets at 240 °C, SnS crowns were formed within the SnSe sheets. The number of SnS crowns can be tailored upon repeated addition of S-oleylamine. A combination of transmission electron microscopy, high-resolution transmission electron microscopy, atomic force microscopy, scanning transmission electron microscopy, and energy-dispersive X-ray spectroscopy proves the formation of highly crystalline core/crown structures.

Cation exchange is a versatile method for modifying the material composition and properties of nanostructures. However, control of the degree of exchange and material properties is difficult at the single-particle level. Successive cation exchange from CdSe to Ag2Se has been utilized here on the same individual nanowires to monitor the change of electronic properties in field-effect transistor devices. The transistors were fabricated by direct synthesis of CdSe nanowires on prepatterned substrates followed by optical lithography. The devices were then subjected to cation exchange by submerging them in an exchange solution containing silver nitrate. By removal of the devices from solution and probing the electrical transport properties at different times, the change in electronic properties of individual nanowires could be monitored throughout the entire exchange reaction from CdSe to Ag2Se. Transistor characterization revealed that the electrical conductivity can be tuned by up to 8 orders of magnitude and the charge-carrier mobility by 7 orders of magnitude. While analysis of the material composition by energy dispersive X-ray spectroscopy confirmed successful cation exchange from CdSe to Ag2Se, X-ray fluorescence spectroscopy proved that cation exchange also took place below the contacts. The method presented here demonstrates an efficient way to tune the material composition and access the resulting properties nondestructively at the single-particle level. This approach can be readily applied to many other material systems and can be used to study the electrical properties of nanostructures as a function of material composition or to optimize nanostructure-based devices after fabrication.

ABSTRACTThis paper explores multi-method community engagement activities used to quickly and effectively produce an action plan based on city stakeholders’ perceptions and wishes. A UN-Habitat Urban Thinkers Campus (UTC), focused on promoting urban liveability, adopted a methodology aimed to effectively engage participants through the completion of urban diaries prior to the event. Engagement with participants was further enhanced through urban labs and discussions culminating in a Design Sprint, producing meaningful action statements. The methodology was aimed at capturing impressions, concerns and roles of each stakeholder group in producing human-centred urban environments. Results suggest the adopted methodology was successful in producing a clear set of tangible action statements, identified as potentially generating high impact and requiring low effort to be implemented. These readily applicable actions were compiled by the end of a single but intense workday.

Understanding the transcriptional changes that are engaged in stress resilience may reveal novel antidepressant targets. Here we use gene co-expression analysis of RNA-sequencing data from brains of resilient mice to identify a gene network that is unique to resilience. Zfp189, which encodes a previously unstudied zinc finger protein, is the highest-ranked key driver gene in the network, and overexpression of Zfp189in prefrontal cortical neurons preferentially activates this network and promotes behavioral resilience. The transcription factor CREB is a predicted upstream regulator of this network and binds to the Zfp189promoter. To probe CREB–Zfp189interactions, we employ CRISPR-mediated locus-specific transcriptional reprogramming to direct CREB or G9a (a repressive histone methyltransferase) to the Zfp189promoter in prefrontal cortex neurons. Induction of Zfp189with site-specific CREB is pro-resilient, whereas suppressing Zfp189expression with G9a increases susceptibility. These findings reveal an essential role for Zfp189and CREB–Zfp189interactions in mediating a central transcriptional network of resilience. Researchers identify a transcriptional network engaged in stress-resilient mice that is regulated by a previously unstudied transcription factor, Zfp189, and elucidate molecular mechanisms controlling this network and resilience behavior.

Die negativen Auswirkungen des Klimawandels auf die Gesundheit werden zunehmend spürbar. Zudem liegt im Klimaschutz großes Potenzial für die Gesundheitsförderung. Im Praxisalltag können Themen zu Klimawandel und Gesundheit in die Beratung von Patient:innen integriert werden. Ziele sind der Schutz und die Förderung der individuellen und öffentlichen Gesundheit sowie weitere klima- und gesundheitsrelevante Aspekte. Inhalte einer solchen „klimasensiblen Gesundheitsberatung“ (KSGB) können Informationen über gesundheitliche Auswirkungen des Klimawandels und entsprechende Schutzmaßnahmen, Aufklärung zu gesunden und klimafreundlichen Lebensstilen oder seltener auch gesellschaftliche Aspekte sein. Bei der Integration von KSGB in Sprechstunde und Praxisabläufe finden bekannte Strategien aus der Gesundheits- und Klimawandelkommunikation Anwendung, v. a. patient:innenzentrierte Kommunikation, motivierende Gesprächsführung oder der differenzierte und offene Umgang mit klimabezogenen Gefühlen.

Cation exchange is known to occur during the synthesis of colloidal semiconductor heteronanoparticles, affecting their band gap and thus altering their optoelectronic properties. It is often neglected, especially when anisotropic heterostructures are discussed. We present a study on the role of cation exchange inevitably occurring during the growth of anisotropic dot-in-rod structures consisting of a spherical ZnSe core enclosed by a rod-shaped CdS shell. The material combination exhibits a type-II band alignment. Two reactions are compared: the shell-growth reaction of CdS on ZnSe and an exchange-only reaction of ZnSe cores to CdSe. Transmission electron microscopy and a comprehensive set of optical spectroscopy data, including linear and time-resolved absorption and fluorescence data, prove that cation exchange from ZnSe to CdSe is the dominant process in the initial stages of the shell-growth reaction. The degree of cation exchange before significant shell growth starts was determined to be about 50%, highlighting the importance of cation exchange during the heteronanostructure growth.

Major depressive disorder (MDD) is the leading cause of disability worldwide. There is an urgent need for objective biomarkers to diagnose this highly heterogeneous syndrome, assign treatment, and evaluate treatment response and prognosis. MicroRNAs (miRNAs) are short non-coding RNAs, which are detected in body fluids that have emerged as potential biomarkers of many disease conditions. The present study explored the potential use of miRNAs as biomarkers for MDD and its treatment. We profiled the expression levels of circulating blood miRNAs from mice that were collected before and after exposure to chronic social defeat stress (CSDS), an extensively validated mouse model used to study depression, as well as after either repeated imipramine or single-dose ketamine treatment. We observed robust differences in blood miRNA signatures between stress-resilient and stress-susceptible mice after an incubation period, but not immediately after exposure to the stress. Furthermore, ketamine treatment was more effective than imipramine at re-establishing baseline miRNA expression levels, but only in mice that responded behaviorally to the drug. We identified the red blood cell-specific miR-144-3p as a candidate biomarker to aid depression diagnosis and predict ketamine treatment response in stress-susceptible mice and MDD patients. Lastly, we demonstrate that systemic knockdown of miR-144-3p, via subcutaneous administration of a specific antagomir, is sufficient to reduce the depression-related phenotype in stress-susceptible mice. RNA-sequencing analysis of blood after such miR-144-3p knockdown revealed a blunted transcriptional stress signature as well. These findings identify miR-144-3p as a novel target for diagnosis of MDD as well as for antidepressant treatment, and enhance our understanding of epigenetic processes associated with depression.

Few therapeutic options have been made available for treating central nervous system tumors, especially upon recurrence. Recurrent medulloblastoma is uniformly lethal with no approved therapies. Recent preclinical studies have shown promising results for eradicating various solid tumors by targeting the overexpressed immune checkpoint molecule, B7-H3. However, due to several therapy-related toxicities and reports of tumor escape, the full potential of targeting this pan-cancer antigen has yet to be realized. Here, we designed and characterized bispecific chemically self-assembling nanorings (CSANs) that target the T cell receptor, CD3ε, and tumor associated antigen, B7-H3, derived from the humanized 8H9 single chain variable fragment. We show that the αB7-H3-αCD3 CSANs increase T cell infiltration and facilitate selective cytotoxicity of B7-H3+medulloblastoma spheroids and that activity is independent of target cell MHC class I expression. Importantly, nonspecific T cell activation against the ONS 2303 medulloblastoma cell line can be reduced by tuning the valency of the αCD3 targeted monomer in the oligomerized CSAN. Intraperitoneal injections of αB7-H3-αCD3 bispecific CSANs were found to effectively cross the blood–tumor barrier into the brain and elicit significant antitumor T cell activity intracranially as well as systemically in an orthotopic medulloblastoma model. Moreover, following treatment with αB7-H3-αCD3 CSANs, intratumoral T cells were found to primarily have a central memory phenotype that displayed significant levels of characteristic activation markers. Collectively, these results demonstrate the ability of our multivalent, bispecific CSANs to direct potent antitumor T cell responses and indicate its potential utility as an alternative or complementary therapy for immune cell targeting of B7-H3+brain tumors.

Nanomaterials with a defined composition and structure can be synthesized by exploiting natural templates or biomolecular matrices. In the present work, we use protein nanocages derived from human ferritin as a nanoscale building block for the assembly of gold nanoparticles and fluorescent molecules in the solid state. As a generalizable strategy, we show that prior to material synthesis, the cargo can be encapsulated into the protein nanocages using a dis- and reassembly approach. Toward this end, a new ligand system for gold nanoparticles enables efficient encapsulation of these particles into the nanocages. The gold nanoparticle-loaded protein nanocages are co-assembled with fluorophore-loaded protein nanocages. Binary superlattices are formed because two oppositely charged ferritin nanocages are used as templates for the assembly. The binary crystals show strong exciton–plasmon coupling between the encapsulated fluorophores and gold nanoparticles, which was spatially resolved with fluorescence lifetime imaging. The strategy outlined here offers a modular approach toward binary nanomaterials with highly ordered building blocks.

This paper situates the De XII abusivis saeculi [DDAS] within the evolution of scriptural exegesis in seventh-century Ireland, paying particular attention to the De mirabilibus sacrae scripturae, the anonymous commentary on the catholic Epistles, and Cummian’s Penitential as well as to the Turonensis, an early version of Hibernensis as a legal code.

ABSTRACTIn a time of unprecedented change and uncertainty due to the ongoing COVID-19 pandemic, cities worldwide became the epicentre of the unfolding health drama. Questions related to the contemporary human condition, rate of urbanization and alternative socioeconomic frameworks that started to emerge over the course of the past decade, now seem to be more relevant than ever. Urban typologies such as public spaces are under pressure, as the measure of “social distancing” rapidly became a novel narrative. Within this narrative, children – while seemingly less affected medically – may actually be influenced more than expected, both physically and mentally, since their social and spatial developmental needs are different to those of adults. The Urban Health Community of Practice of ISOCARP offers a series of questions and critical reflections accompanied by a wide geographical, cultural and disciplinary array of examples from around the world regarding the spatial, social and physical effects of the current crisis on children and how this could provide valuable feedback on updating future urban planning policies. This is a first step towards a commonly expressed paradigm shift that embraces human and planetary health resilience, a new equilibrium for cities and natural systems and a new, more inclusive social model.

A ligand exchange strategy has been employed to understand the role of ligands on the structural and optical properties of atomically precise 29 atom silver nanoclusters (NCs). By ligand optimization, ∼44-fold quantum yield (QY) enhancement of Ag29(BDT)12–x(DHLA)xNCs (x= 1–6) was achieved, where BDT and DHLA refer to 1,3-benzene-dithiol and dihydrolipoic acid, respectively. High-resolution mass spectrometry was used to monitor ligand exchange, and structures of the different NCs were obtained through density functional theory (DFT). The DFT results from Ag29(BDT)11(DHLA) NCs were further experimentally verified through collisional cross-section (CCS) analysis using ion mobility mass spectrometry (IM MS). An excellent match in predicted CCS values and optical properties with the respective experimental data led to a likely structure of Ag29(DHLA)12NCs consisting of an icosahedral core with an Ag16S24shell. Combining the experimental observation with DFT structural analysis of a series of atomically precise NCs, Ag29–yAuy(BDT)12–x(DHLA)x(where y, x= 0,0; 0,1; 0,12 and 1,12; respectively), it was found that while the metal core is responsible for the origin of photoluminescence (PL), ligands play vital roles in determining their resultant PLQY.

Cocaine use disorder (CUD) is a chronic neuropsychiatric condition that results from enduring cellular and molecular adaptations. Among substance use disorders, CUD is notable for its rising prevalence and the lack of approved pharmacotherapies. The nucleus accumbens (NAc), a region that is integral to the brain’s reward circuitry, plays a crucial role in the initiation and continuation of maladaptive behaviors that are intrinsic to CUD. Leveraging advancements in neuroproteomics, we undertook a proteomic analysis that spanned membrane, cytosolic, nuclear, and chromatin compartments of the NAc in a mouse model. The results unveiled immediate and sustained proteomic modifications after cocaine exposure and during prolonged withdrawal. We identified congruent protein regulatory patterns during initial cocaine exposure and reexposure after withdrawal, which contrasted with distinct patterns during withdrawal. Pronounced proteomic shifts within the membrane compartment indicated adaptive and long-lasting molecular responses prompted by cocaine withdrawal. In addition, we identified potential protein translocation events between soluble-nuclear and chromatin-bound compartments, thus providing insight into intracellular protein dynamics after cocaine exposure. Together, our findings illuminate the intricate proteomic landscape that is altered in the NAc by cocaine use and provide a dataset for future research toward potential therapeutics.

Animals susceptible to chronic social defeat stress (CSDS) exhibit depression-related behaviors, with aberrant transcription across several limbic brain regions, most notably in the nucleus accumbens (NAc). Early life stress (ELS) promotes susceptibility to CSDS in adulthood, but associated enduring changes in transcriptional control mechanisms in the NAc have not yet been investigated. In this study, we examined long-lasting changes to histone modifications in the NAc of male and female mice exposed to ELS. Dimethylation of lysine 79 of histone H3 (H3K79me2) and the enzymes (DOT1L and KDM2B) that control this modification are enriched in D2-type medium spiny neurons and are shown to be crucial for the expression of ELS-induced stress susceptibility. We mapped the site-specific regulation of this histone mark genome wide to reveal the transcriptional networks it modulates. Finally, systemic delivery of a small molecule inhibitor of DOT1L reversed ELS-induced behavioral deficits, indicating the clinical relevance of this epigenetic mechanism.

We present a detailed powder X-ray diffraction (p-XRD) and transmission electron microscopy (TEM) study to explore the structural properties of CdS, CdSe, and CdTe semiconductor nanowires (NWs) grown by the solution-liquid-solid (SLS) method. The SLS method yields easily dispersible NWs with a controllable diameter and polytypic crystal structure. The different samples exhibit different wurtzite (WZ) and zincblende (ZB) fractions, which are investigated by high-resolution TEM of selected wires with distinct crystallographic orientations, and also by p-XRD of a large amount of NWs. In combination with atomistic models containing up to one million atoms, we calculate diffraction patterns based on the kinematic theory of diffraction. We show that the ZB-rate in WZ-rich NWs can be directly determined from relative reflex intensities in the experimental p-XRD data.

Manganese (Mn)-doped ZnS nanocrystals (NCs) have been extensively explored for optical applications with the advantages of low toxicity, large Stokes shifts, and enhanced thermal and environmental stability. Although numerous studies on Mn-doped ZnS dots, rods, and wires have been reported, the literature related to Mn-doped ZnS nanoplatelets (ZnS:Mn NPLs) is scarce. Here, we present the first example of direct doping of Mn2+ions into ZnS NPLs via the nucleation-doping strategy. The resulting ZnS:Mn NPLs exhibit Mn luminescence, indicative for successful doping of the host ZnS NPLs with Mn2+ions. The energy transfer from the ZnS NPLs to the Mn2+ions was observed by employing spectroscopic methods. Furthermore, the impact of the Mn concentration on the optical properties of ZnS:Mn NPLs was systematically investigated. As a result of Mn–Mn interaction, tunable Mn emission and shortened photoluminescence (PL) lifetime decay were observed and rationalized by means of electron paramagnetic resonance (EPR) and X-ray photoelectron spectroscopy (XPS). Finally, we show that the initially low dopant PL quantum yield (QY) of ZnS:Mn NPLs can be dramatically enhanced by passivating the surface trap states of the samples. The presented synthetic strategy of ZnS:Mn NPLs opens a new way to synthesize further doped systems of two-dimensional (2D) NPLs.

Background: Solid Dispersions (SDs) have been extensively used to increase the dissolution of poorly water-soluble drugs. However, there are few studies exploring SDs properties that must be considered during tablet development, like tabletability. Poorly water-soluble drugs with poor compression properties and high therapeutic doses, like gemfibrozil, are an additional challenge in the production of SDs-based tablets. Objective: This study evaluates the applicability of SDs to improve both tabletability and dissolution rate of gemfibrozil. A SD-based tablet formulation was also proposed. Methods: SDs were prepared by ball milling, using hydroxypropyl methylcellulose (HPMC) as a carrier, according to a 23 factorial design. The formulation variables were gemfibrozil:HPMC ratio, milling speed, and milling time. The response in the factorial analysis was the tensile strength of the compacted SDs. Dissolution rate and solid-state characterization of SDs were also performed. Results: SDs showed simultaneous drug dissolution enhancement and improved tabletability when compared to corresponding physical mixtures and gemfibrozil. The main variable influencing drug dissolution and tabletability was the gemfibrozil:HPMC ratio. Tablets containing gemfibrozil- HPMC-SD (1:0.250 w/w) and croscarmellose sodium showed fast and complete drug release, while those containing the same SD and sodium starch glycolate exhibited poor drug release due to their prolonged disintegration time. Conclusion: SDs proved to be effective for simultaneously improving tabletability and dissolution profile of gemfibrozil. Tablets containing gemfibrozil-HPMC-SD and croscarmellose sodium as disintegrating agent showed improved drug release and good mechanical strength, demonstrating the potential of HPMC-based SDs to simultaneously overcome the poor dissolution and tabletability properties of this drug.

The rational combination of tetracene (Tc) with crystalline silicon (c-Si) could greatly enhance c-Si solar cell efficiencies via singlet fission. The Tc/c-Si energy-level alignment (ELA) is thought to be central to controlling the required interface transfer processes. We modified hydrogen-terminated c-Si (H–Si) with 2,2′-(perfluoronaphthalene-2,6-diylidene)dimalononitrile (F6TCNNQ), C60, or NF3and probed the effect on the c-Si surface chemistry, the Tc/c-Si ELA, the Tc morphology, and solar cell characteristics using ultraviolet and X-ray photoelectron spectroscopy, atomic force microscopy, X-ray diffraction, photoluminescence transients, device measurements, and transfer matrix-optical modeling. Submonolayer interlayers of F6TCNNQ shifted the Tc/H–Si(111) ELA by up to 0.55 eV. C60showed no notable effect on the ELA and proved detrimental for the Tc film morphology and solar cell performance. Neither F6TCNNQ nor C60improved the Tc-related photocurrent significantly. NF3CVD substituted the H-termination of H–Si(100) with more electronegative species and resulted in work functions as high as 6 eV. This changed the Tc/H–Si(100) ELA by up to 0.45 eV. NF3plasma from a remote source caused pronounced c-Si oxidation and a diminished c-Si photoluminescence lifetime, which was not observed for NF3plasma created in close proximity to the c-Si surface or neutral NF3. We discuss possible reasons for why the improved ELA does not lead to an improved singlet fission harvest.

To assess long term graft and patient survival after donor liver retransplantation in children in Australia and New Zealand during 1986–2017; to determine the factors that influence survival. Retrospective cohort analysis (registry data). Australia and New Zealand Liver Transplant Registry data for all liver retransplantations in children (under 18 years of age), 1986–2017, in all four paediatric and six adult liver transplantation centres in the two countries. Graft and patient survival at one, 5, 10 and 15 years. 142 liver retransplantations were undertaken in children (59 during 1986–2000, 83 during 2001–2017). Kaplan–Meier survival analysis indicated that survival was significantly greater during 2001–2017 than 1986–2000 (P< 0.001). During 2001–2017, graft survival one year after retransplantation was 84%, at 5 years 75%, at 10 years 70%, and at 15 years 54%; patient survival was 89% at one year, 87% at 5 years, 87% at 10 years, and 71% at 15 years. Median time between transplantations was 0.2 years (IQR, 0.03–1.4 years) during 1986–2000, and 1.8 years (IQR, 0.1–6.8 years) during 2001–2017 (P= 0.002). The proportion of graft failures that involved split grafts was larger during 2001–2017 (35 of 83, 42%) than 1986–2000 (10 of 59, 17%). Graft type, cause of graft failure, and number of transplants did not influence survival following retransplantation. Survival for children following retransplantation is excellent. Graft survival is similar for split and whole grafts. Children on the liver waiting list requiring retransplantation should have the same access to donor grafts as children requiring a first transplant.

Bei einer Erkrankung an Diabetes mellitus ist die Schulung ein wesentlicher Therapiebaustein. Es mangelt an empirischen Daten zu Erfahrungen mit den anerkannten Schulungsprogrammen in der Schulung von Menschen mit einem (türkeistämmigen) Migrationshintergrund und geringen schriftsprachlichen Kompetenzen. Ziel der Untersuchung war die Erhebung der Erfahrungen von Praxen mit der Schulung dieser Personengruppe.

Coeliac disease (CD) diagnosis is based on clinical assessment, detection of specific autoantibodies and histological examination of small intestinal biopsies. The European Society of Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines have recently been updated and recommend CD may be diagnosed without a biopsy or HLA typing in symptomatic patients with high titre IgA tissue transglutaminase antibodies (aTTG) and positive endomysial antibodies (EMA). However, the need for EMA in patients with high level aTTG has been questioned. We aimed to determine the diagnostic benefit of HLA typing, EMA and IgG antibodies to deamidated gliadin (DGP) in children with high level aTTG.