Sustainability initiatives in inpatient psychiatry: tackling food waste.

Background: Food plays a dual role in promoting human health and environmental sustainability. Yet, current food systems jeopardize both. Food waste poses a major global challenge due to its significant economic, social, and environmental impacts. Healthcare facilities generate the largest amounts of food waste compared to other forms of catering provision. Food waste correlates with environmental unsustainability and diminished patient satisfaction, compounding the prevalent challenge of hospital malnutrition and contributing to suboptimal patient outcomes. Materials and methods: In a three-year interventional study (2020-2022) at a psychiatric tertiary care center, we assessed and mitigated food waste using evidence-based measures. We conducted systematic food wastage audits over three years (2020-2022) in May and June, each lasting four weeks. Costs were analyzed comprehensively, covering food, staff, infrastructure, and disposal. Environmental impact was assessed using Umweltbelastungspunkte (UBP) and CO2e/kg emissions, alongside water usage (H2O - l/kg). Results: Economic losses due to food wastage were substantial, primarily from untouched plates and partially consumed dinners, prompting meal planning adjustments. Despite a >3% increase in meals served, both food waste mass and costs decreased by nearly 6%. Environmental impact indicators showed a reduction >20%. Vegetables, salad, and fruits constituted a significant portion of waste. Overproduction minimally contributed to waste, validating portion control efficacy. Conclusion: Our study highlights significant economic and environmental losses due to hospital food waste, emphasizing the importance of resource efficiency. The strategies outlined offer promising avenues for enhanced efficiency. The decrease in food waste observed over the three-year period underscores the potential for improvement.

Structural basis of tRNA recognition by the m3C RNA methyltransferase METTL6 in complex with SerRS seryl-tRNA synthetase.

Methylation of cytosine 32 in the anticodon loop of tRNAs to 3-methylcytosine (m3C) is crucial for cellular translation fidelity. Misregulation of the RNA methyltransferases setting this modification can cause aggressive cancers and metabolic disturbances. Here, we report the cryo-electron microscopy structure of the human m3C tRNA methyltransferase METTL6 in complex with seryl-tRNA synthetase (SerRS) and their common substrate tRNASer. Through the complex structure, we identify the tRNA-binding domain of METTL6. We show that SerRS acts as the tRNASer substrate selection factor for METTL6. We demonstrate that SerRS augments the methylation activity of METTL6 and that direct contacts between METTL6 and SerRS are necessary for efficient tRNASer methylation. Finally, on the basis of the structure of METTL6 in complex with SerRS and tRNASer, we postulate a universal tRNA-binding mode for m3C RNA methyltransferases, including METTL2 and METTL8, suggesting that these mammalian paralogs use similar ways to engage their respective tRNA substrates and cofactors.

Concerted structural rearrangements enable RNA channeling into the cytoplasmic Ski238-Ski7-exosome assembly.

The Ski2-Ski3-Ski8 (Ski238) helicase complex directs cytoplasmic mRNAs toward the nucleolytic exosome complex for degradation. In yeast, the interaction between Ski238 and exosome requires the adaptor protein Ski7. We determined different cryo-EM structures of the Ski238 complex depicting the transition from a rigid autoinhibited closed conformation to a flexible active open conformation in which the Ski2 helicase module has detached from the rest of Ski238. The open conformation favors the interaction of the Ski3 subunit with exosome-bound Ski7, leading to the recruitment of the exosome. In the Ski238-Ski7-exosome holocomplex, the Ski2 helicase module binds the exosome cap, enabling the RNA to traverse from the helicase through the internal exosome channel to the Rrp44 exoribonuclease. Our study pinpoints how conformational changes within the Ski238 complex regulate exosome recruitment for RNA degradation. We also reveal the remarkable conservation of helicase-exosome RNA channeling mechanisms throughout eukaryotic nuclear and cytoplasmic exosome complexes.

Structural basis for guide RNA selection by the RESC1-RESC2 complex.

Kinetoplastid parasites, such as trypanosomes or leishmania, rely on RNA-templated RNA editing to mature mitochondrial cryptic pre-mRNAs into functional protein-coding transcripts. Processive pan-editing of multiple editing blocks within a single transcript is dependent on the 20-subunit RNA editing substrate binding complex (RESC) that serves as a platform to orchestrate the interactions between pre-mRNA, guide RNAs (gRNAs), the catalytic RNA editing complex (RECC), and a set of RNA helicases. Due to the lack of molecular structures and biochemical studies with purified components, neither the spacio-temporal interplay of these factors nor the selection mechanism for the different RNA components is understood. Here we report the cryo-EM structure of Trypanosoma brucei RESC1-RESC2, a central hub module of the RESC complex. The structure reveals that RESC1 and RESC2 form an obligatory domain-swapped dimer. Although the tertiary structures of both subunits closely resemble each other, only RESC2 selectively binds 5'-triphosphate-nucleosides, a defining characteristic of gRNAs. We therefore propose RESC2 as the protective 5'-end binding site for gRNAs within the RESC complex. Overall, our structure provides a starting point for the study of the assembly and function of larger RNA-bound kinetoplast RNA editing modules and might aid in the design of anti-parasite drugs.

Structural basis for sequence-independent substrate selection by eukaryotic wobble base tRNA deaminase ADAT2/3.

The essential deamination of adenosine A34 to inosine at the wobble base is the individual tRNA modification with the greatest effects on mRNA decoding, empowering a single tRNA to translate three different codons. To date, many aspects of how eukaryotic deaminases specifically select their multiple substrates remain unclear. Here, using cryo-EM, we present the structure of a eukaryotic ADAT2/3 deaminase bound to a full-length tRNA, revealing that the enzyme distorts the anticodon loop, but in contrast to the bacterial enzymes, selects its substrate via sequence-independent contacts of eukaryote-acquired flexible or intrinsically unfolded motifs distal from the conserved catalytic core. A gating mechanism for substrate entry to the active site is identified. Our multi-step tRNA recognition model yields insights into how RNA editing by A34 deamination evolved, shaped the genetic code, and directly impacts the eukaryotic proteome.

Physician assisted-dying in mentally and somatically ill individuals in Switzerland: Protocol for survey-based study.

Background: Article 115 of the Swiss Penal Code (StGB) permits physician-assisted dying (PAD), provided it is not performed for "selfish reasons," and thus, occupies a special role in international comparison. However, the Swiss federal law does not regulate who exactly is entitled to access PAD, and there is no universal agreement in the concerned professional societies. Additional uncertainty arises when assessing the wish for PAD of a mentally ill person compared to a somatically ill person. Objectives: This study aims to contribute to the discussion of PAD among the mentally ill and to provide insight into the current situation in Switzerland. Methods: This is a monocentric prospective observational survey-based study. We will conduct an exploratory online/telephone survey about PAD in somatic vs. mental illness in Switzerland. The survey sample will comprise 10,000 Swiss residents of the general population from all three language regions (German, Italian, and French) as well as 10,000 medical professionals working in the seven states ("cantons") of Basel-Stadt, Basel-Landschaft, Aargau, Lucerne, Graubünden, Ticino, and Vaud. Opinions on PAD in mentally and somatically ill patients will be assessed using 48 different case vignettes. Each participant will be randomly assigned a somatic terminal, a somatic non-terminal, and a mental non-terminal case vignette. Furthermore, the attitude toward the ethical guidelines of the Swiss Medical Association of 2004, 2018, and 2022, as well as the stigmatization of mentally ill people will be assessed. Discussion: Physician-assisted dying in mentally ill persons is a highly relevant yet controversial topic. On the one hand, mentally ill persons must not be discriminated against in their desire for PAD compared to somatically ill persons while at the same time, their vulnerability must be considered. On the other hand, treating physicians must be protected in their ethical integrity and need security when judging PAD requests. Despite its relevance, data on PAD in the mentally ill is sparse. To regulate PAD for the mentally ill, it is therefore important for Switzerland-but also internationally-to gain more insight into the ongoing debate. Clinical trial registration: ClinicalTrials.gov, identifier: NCT05492461.

METTLing in the right place: METTL8 is a mitochondrial tRNA-specific methyltransferase.

Schöller et al. (2021) discovered that METTL8, thought of as an mRNA modifier, is a tRNA-specific mitochondrial enzyme important for mitochondrial translation and function. Paradoxically, increased expression of METTL8 is associated with high respiratory rates in pancreatic cancers.

[Six years of open-door policy at the University Psychiatric Hospital Basel]. / Sechs Jahre "offene Türen" an den Universitären Psychiatrischen Kliniken Basel.

BACKGROUND: Coercive measures in psychiatry have well-known negative consequences for the patients and their treatment. They are considered ethically problematic and must only be used as a last resort. Locked wards may promote a threatening atmosphere leading to more aggression and a subsequent higher use of coercive measures. The aim of this was to investigate the frequency of seclusion and forced medication during clinic-wide implementation of an open-door policy. MATERIAL AND METHODS: In this 6­year longitudinal observational study (2010-2015) the frequencies of seclusion and forced medication were investigated on the basis of 17,359 cases treated in the University Psychiatric Hospital Basel. During the observational period, six formerly permanently locked wards were opened. RESULTS: The examined data showed a clinically relevant decrease in the frequency of seclusion (from 8.2% to 3.5%) and forced medication (from 2.4% to 1.2%) during the observational period. CONCLUSION: These results underline the potential of a less restrictive policy in psychiatry to reduce the frequency of coercive measures.

Reliability of Paper-Based Routine Documentation in Psychiatric Inpatient Care and Recommendations for Further Improvement.

Background: Health services research is of increasing importance in current psychiatry. Therefore, large datasets and aggregation of data generated by electronic routine documentation due to legal, financial, or administrative purposes play an important role. However, paper-based routine documentation is still of interest. It remains relevant in less developed health care systems, in emergency settings, and in long-term retrospective and historical studies. Whereas studies examining the reliability of electronic routine documentation support the application of routine data for research purposes, our knowledge regarding reliability of paper-based routine documentation is still very sparse. Methods: Basic documentation (BADO) was completed on paper forms and digitalized manually for all inpatients of the Department of Psychiatry and Psychotherapy, University Hospital Hamburg-Eppendorf, Germany, treated within the time period from 1998 to 2006. Four hundred twelve cases of first-episode psychosis patients were chosen for comparison with clinical data from paper-based patient files. The percentage of missing information, the percentage of correct classifications, sensitivity, and positive predictive value were calculated for all applicable variables. Results: In eight cases (1.9%), a BADO form was available, but was not filled in. In 37 cases (7.0%), the patient files were lost and could not be obtained from the centralized archive. Routine data were available for all other cases in 20 (58.8%) of the examined 34 variables, and the percentage of missing data for the remaining variables ranged between 0.3% and 22.9%, with only the variables education and suicidality during treatment having more than 5% missing data. In general, the overall rate of correct classifications was high, with a median percentage of 86.4% to 99.7% for the examined variables. Sensitivity was above 75% for eight and <75% but above 50% for six of the examined 17 variables. Values for the positive predictive value were above 75% for nine and <75% but above 50% for three variables. Conclusion: In summary, paper-based routine documentation reaches acceptable reliability, but this is dependent on the chosen documentation categories and variables. Based on the present findings, paper-based routine documentation can indeed be used for quality management, organizational development, and health services research. Its limitations, however, have to be kept in mind.

Molecular mechanism of influenza A NS1-mediated TRIM25 recognition and inhibition.

RIG-I is a viral RNA sensor that induces the production of type I interferon (IFN) in response to infection with a variety of viruses. Modification of RIG-I with K63-linked poly-ubiquitin chains, synthesised by TRIM25, is crucial for activation of the RIG-I/MAVS signalling pathway. TRIM25 activity is targeted by influenza A virus non-structural protein 1 (NS1) to suppress IFN production and prevent an efficient host immune response. Here we present structures of the human TRIM25 coiled-coil-PRYSPRY module and of complexes between the TRIM25 coiled-coil domain and NS1. These structures show that binding of NS1 interferes with the correct positioning of the PRYSPRY domain of TRIM25 required for substrate ubiquitination and provide a mechanistic explanation for how NS1 suppresses RIG-I ubiquitination and hence downstream signalling. In contrast, the formation of unanchored K63-linked poly-ubiquitin chains is unchanged by NS1 binding, indicating that RING dimerisation of TRIM25 is not affected by NS1.

Aggression and violence in psychiatric hospitals with and without open door policies: A 15-year naturalistic observational study.

Aggressive behavior and violence in psychiatric patients have often been quoted to justify more restrictive settings in psychiatric facilities. However, the effects of open vs. locked door policies on aggressive incidents remain unclear. This study had a naturalistic observational design and analyzed the occurrence of aggressive behavior as well as the use of seclusion or restraint in 21 German hospitals. The analysis included data from 1998 to 2012 and contained a total of n = 314,330 cases, either treated in one of 17 hospitals with (n = 68,135) or in one of 4 hospitals without an open door policy (n = 246,195). We also analyzed the data according to participants' stay on open, partially open, or locked wards. To compare hospital and ward types, we used generalized linear mixed-effects models on a propensity score matched subset (n = 126,268) and on the total dataset. The effect of open vs. locked door policy was non-significant in all analyses of aggressive behavior during treatment. Restraint or seclusion during treatment was less likely in hospitals with an open door policy. On open wards, any aggressive behavior and restraint or seclusion were less likely, whereas bodily harm was more likely than on closed wards. Hospitals with open door policies did not differ from hospitals with locked wards regarding different forms of aggression. Other restrictive interventions used to control aggression were significantly reduced in open settings. Open wards seem to have a positive effect on reducing aggression. Future research should focus on mental health care policies targeted at empowering treatment approaches, respecting the patient's autonomy and promoting reductions of institutional coercion.

The cryo-EM structure of a ribosome-Ski2-Ski3-Ski8 helicase complex.

Ski2-Ski3-Ski8 (Ski) is a helicase complex functioning with the RNA-degrading exosome to mediate the 3'-5' messenger RNA (mRNA) decay in turnover and quality-control pathways. We report that the Ski complex directly associates with 80S ribosomes presenting a short mRNA 3' overhang. We determined the structure of an endogenous ribosome-Ski complex using cryo-electron microscopy (EM) with a local resolution of the Ski complex ranging from 4 angstroms (Å) in the core to about 10 Å for intrinsically flexible regions. Ribosome binding displaces the autoinhibitory domain of the Ski2 helicase, positioning it in an open conformation near the ribosomal mRNA entry tunnel. We observe that the mRNA 3' overhang is threaded directly from the small ribosomal subunit to the helicase channel of Ski2, primed for ongoing exosome-mediated 3'-5' degradation.

Suicide risk and absconding in psychiatric hospitals with and without open door policies: a 15 year, observational study.

BACKGROUND: Inpatient suicide and absconding of inpatients at risk of self-endangering behaviour are important challenges for all medical disciplines, particularly psychiatry. Patients at risk are often admitted to locked wards in psychiatric hospitals to prevent absconding, suicide attempts, and death by suicide. However, there is insufficient evidence that treatment on locked wards can effectively prevent these outcomes. We did this study to compare hospitals without locked wards and hospitals with locked wards and to establish whether hospital type has an effect on these outcomes. METHODS: In this 15 year, naturalistic observational study, we examined 349 574 admissions to 21 German psychiatric inpatient hospitals from Jan 1, 1998, to Dec 31, 2012. We used propensity score matching to select 145 738 cases for an analysis, which allowed for causal inference on the effect of ward type (ie, locked, partly locked, open, and day clinic wards) and hospital type (ie, hospitals with and without locked wards) on suicide, suicide attempts, and absconding (with and without return), despite the absence of an experimental design. We used generalised linear mixed-effects models to analyse the data. FINDINGS: In the 145 738 propensity score-matched cases, suicide (OR 1·326, 95% CI 0·803-2·113; p=0·24), suicide attempts (1·057, 0·787-1·412; p=0·71), and absconding with return (1·288, 0·874-1·929; p=0·21) and without return (1·090, 0·722-1·659; p=0·69) were not increased in hospitals with an open door policy. Compared with treatment on locked wards, treatment on open wards was associated with a decreased probability of suicide attempts (OR 0·658, 95% CI 0·504-0·864; p=0·003), absconding with return (0·629, 0·524-0·764; p<0·0001), and absconding without return (0·707, 0·546-0·925; p=0·01), but not completed suicide (0·823, 0·376-1·766; p=0·63). INTERPRETATION: Locked doors might not be able to prevent suicide and absconding. FUNDING: None.

Structure of a Cytoplasmic 11-Subunit RNA Exosome Complex.

The RNA exosome complex associates with nuclear and cytoplasmic cofactors to mediate the decay, surveillance, or processing of a wide variety of transcripts. In the cytoplasm, the conserved core of the exosome (Exo10) functions together with the conserved Ski complex. The interaction of S. cerevisiae Exo10 and Ski is not direct but requires a bridging cofactor, Ski7. Here, we report the 2.65 Å resolution structure of S. cerevisiae Exo10 bound to the interacting domain of Ski7. Extensive hydrophobic interactions rationalize the high affinity and stability of this complex, pointing to Ski7 as a constitutive component of the cytosolic exosome. Despite the absence of sequence homology, cytoplasmic Ski7 and nuclear Rrp6 bind Exo10 using similar surfaces and recognition motifs. Knowledge of the interacting residues in the yeast complexes allowed us to identify a splice variant of human HBS1-Like as a Ski7-like exosome-binding protein, revealing the evolutionary conservation of this cytoplasmic cofactor.

Saccharomyces cerevisiae Ski7 Is a GTP-Binding Protein Adopting the Characteristic Conformation of Active Translational GTPases.

Ski7 is a cofactor of the cytoplasmic exosome in budding yeast, functioning in both mRNA turnover and non-stop decay (NSD), a surveillance pathway that degrades faulty mRNAs lacking a stop codon. The C-terminal region of Ski7 (Ski7C) shares overall sequence similarity with the translational GTPase (trGTPase) Hbs1, but whether Ski7 has retained the properties of a trGTPase is unclear. Here, we report the high-resolution structures of Ski7C bound to either intact guanosine triphosphate (GTP) or guanosine diphosphate-Pi. The individual domains of Ski7C adopt the conformation characteristic of active trGTPases. Furthermore, the nucleotide-binding site of Ski7C shares similar features compared with active trGTPases, notably the presence of a characteristic monovalent cation. However, a suboptimal polar residue at the putative catalytic site and an unusual polar residue that interacts with the γ-phosphate of GTP distinguish Ski7 from other trGTPases, suggesting it might function rather as a GTP-binding protein than as a GTP-hydrolyzing enzyme.

RIG-I self-oligomerization is either dispensable or very transient for signal transduction.

Effective host defence against viruses depends on the rapid triggering of innate immunity through the induction of a type I interferon (IFN) response. To this end, microbe-associated molecular patterns are detected by dedicated receptors. Among them, the RIG-I-like receptors RIG-I and MDA5 activate IFN gene expression upon sensing viral RNA in the cytoplasm. While MDA5 forms long filaments in vitro upon activation, RIG-I is believed to oligomerize after RNA binding in order to transduce a signal. Here, we show that in vitro binding of synthetic RNA mimicking that of Mononegavirales (Ebola, rabies and measles viruses) leader sequences to purified RIG-I does not induce RIG-I oligomerization. Furthermore, in cells devoid of endogenous functional RIG-I-like receptors, after activation of exogenous Flag-RIG-I by a 62-mer-5'ppp-dsRNA or by polyinosinic:polycytidylic acid, a dsRNA analogue, or by measles virus infection, anti-Flag immunoprecipitation and specific elution with Flag peptide indicated a monomeric form of RIG-I. Accordingly, when using the Gaussia Luciferase-Based Protein Complementation Assay (PCA), a more sensitive in cellula assay, no RIG-I oligomerization could be detected upon RNA stimulation. Altogether our data indicate that the need for self-oligomerization of RIG-I for signal transduction is either dispensable or very transient.

A structure-based model of RIG-I activation.

A series of high-resolution crystal structures of RIG-I and RIG-I:dsRNA cocrystals has recently been reported. Comparison of these structures provides considerable insight into how this innate immune pattern recognition receptor is activated upon detecting and binding a certain class of viral RNAs.

Structural analysis of specific metal chelating inhibitor binding to the endonuclease domain of influenza pH1N1 (2009) polymerase.

It is generally recognised that novel antiviral drugs, less prone to resistance, would be a desirable alternative to current drug options in order to be able to treat potentially serious influenza infections. The viral polymerase, which performs transcription and replication of the RNA genome, is an attractive target for antiviral drugs since potent polymerase inhibitors could directly stop viral replication at an early stage. Recent structural studies on functional domains of the heterotrimeric polymerase, which comprises subunits PA, PB1 and PB2, open the way to a structure based approach to optimise inhibitors of viral replication. In particular, the unique cap-snatching mechanism of viral transcription can be inhibited by targeting either the PB2 cap-binding or PA endonuclease domains. Here we describe high resolution X-ray co-crystal structures of the 2009 pandemic H1N1 (pH1N1) PA endonuclease domain with a series of specific inhibitors, including four diketo compounds and a green tea catechin, all of which chelate the two critical manganese ions in the active site of the enzyme. Comparison of the binding mode of the different compounds and that of a mononucleotide phosphate highlights, firstly, how different substituent groups on the basic metal binding scaffold can be orientated to bind in distinct sub-pockets within the active site cavity, and secondly, the plasticity of certain structural elements of the active site cavity, which result in induced fit binding. These results will be important in optimising the design of more potent inhibitors targeting the cap-snatching endonuclease activity of influenza virus polymerase.