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Background Psycho-oncological services (POS) are an integral and widely recommended part of comprehensive cancer care. However, their utilisation appears to fall short of the perceived need. This study aimed to explore barriers and facilitators for the uptake of POS in the context of existing clinical structures and pathways to POS. Methods A mixed-methods study was conducted, drawing on elements of a Delphi approach, including an iterative two-round feedback process and an expert panel. The expert panel consisted of healthcare professionals in cancer care ( n  = 27) and cancer patients ( n  = 14). The first round comprised open-ended questions to explore different perspectives related to the research question. The resulting material was analysed qualitatively and grouped into themes, which were rated according to their perceived importance by the expert panel in the second survey-round ( N  = 27). Results The expert panel identified 69 aspects influencing the uptake of POS; 81% were rated as relevant in the second round. They were grouped into structural factors at hospital level, aspects related to internal processes, and factors at patient level. Central aspects were recommendations of POS by the clinical staff, personal introduction of the psycho-oncologist, integration and acceptance of POS within the hospital organisation, information dissemination about POS to both patients and clinical staff, and the possibility of flexible access routes to POS since patients’ preferences differed. Patient-groups more difficult to reach with a POS-offer were also identified. Conclusion The results can be used to review implemented clinical pathways to POS in diverse hospital contexts, helping to identify and improve critical aspects accordingly, and thus improve service accessibility. Trial registration This study was pre-registered at the German Clinical Trials Register (DRKS-ID: DRKS00025105; registration date: 26-05-2021).

Hantaviruses cause the acute zoonotic diseases hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Infected patients show strong systemic inflammation and immune cell activation. NK cells are highly activated in HFRS, suggesting that also other innate lymphoid cells (ILCs) might be responding to infection. Here, we characterized peripheral ILC responses, and measured plasma levels of soluble factors and plasma viral load, in 17 Puumala virus (PUUV)-infected HFRS patients. This revealed an increased frequency of ILC2 in patients, in particular the ILC2 lineage-committed c-Kit lo ILC2 subset. Patients’ ILCs showed an activated profile with increased proliferation and displayed altered expression of several homing markers. How ILCs are activated during viral infection is largely unknown. When analyzing PUUV-mediated activation of ILCs in vitro we observed that this was dependent on type I interferons, suggesting a role for type I interferons—produced in response to virus infection–in the activation of ILCs. Further, stimulation of naïve ILC2s with IFN-β affected ILC2 cytokine responses in vitro , causing decreased IL-5 and IL-13, and increased IL-10, CXCL10, and GM-CSF secretion. These results show that ILCs are activated in HFRS patients and suggest that the classical antiviral type I IFNs are involved in shaping ILC functions.

A considerable body of research has recently emerged around nonmotor symptoms in Parkinson’s disease (PD) and their substantial impact on patients’ well-being. A prominent example is constipation which occurs in up to two thirds of all PD-patients thereby effecting psychological and social distress and consequently reducing quality of life. Despite the significant clinical relevance of constipation, unfortunately little knowledge exists on effective treatments. Therefore this systematic review aims at providing a synopsis on clinical effects and safety of available treatment options for constipation in PD. For this purpose, three electronic databases (MEDLINE, EMBASE, PsycINFO) were searched for experimental and quasi-experimental studies investigating the efficacy/effectiveness of interventions in the management of PD-associated constipation. Besides, adverse events were analyzed as secondary outcome. In total, 18 publications were identified involving 15 different interventions, of which none can be attributed sufficient evidence to derive strong recommendations. Nevertheless, some evidence indicates that dietetic interventions with probiotics and prebiotics may reduce symptom burden while providing a very favorable side-effects profile. Furthermore, the use of lubiprostone, macrogol and in the specific case of isolated or prominent outlet obstruction constipation injections of botulinum neurotoxin A into the puborectal muscles may as well be moderately supported. In summary, too little attention has been paid to treatment options for constipation in PD leaving abundant room for further research addressing this topic.

ILCs and T helper cells have been shown to exert bi-directional regulation in mice. However, how crosstalk between ILCs and CD4 + T cells influences immune function in humans is unknown. Here we show that human intestinal ILCs co-localize with T cells in healthy and colorectal cancer tissue and display elevated HLA-DR expression in tumor and tumor-adjacent areas. Although mostly lacking co-stimulatory molecules ex vivo, intestinal and peripheral blood (PB) ILCs acquire antigen-presenting characteristics triggered by inflammasome-associated cytokines IL-1β and IL-18. IL-1β drives the expression of HLA-DR and co-stimulatory molecules on PB ILCs in an NF-κB-dependent manner, priming them as efficient inducers of cytomegalovirus-specific memory CD4 + T-cell responses. This effect is strongly inhibited by the anti-inflammatory cytokine TGF-β. Our results suggest that circulating and tissue-resident ILCs have the intrinsic capacity to respond to the immediate cytokine milieu and regulate local CD4 + T-cell responses, with potential implications for anti-tumor immunity and inflammation. Murine ILCs can modulate T cell responses in MHCII-dependent manner. Here the authors show that human ILCs process and present antigens and induce T-cell responses upon exposure to IL-1-family cytokines; along with the article by Lehmann et al, this work elucidates how cytokines set context specificity of ILC-T cell crosstalk by regulating ILC antigen presentation.

Triphenyl phosphate (TPHP) is one of the most highly utilized organophosphorus flame retardants, and has been frequently detected in various environmental matrices, including soil. So far, limited information is known regarding the potential toxicity of TPHP to the earthworm-soil ecosystem. We investigated the metabolism of TPHP and the perturbation of the endogenous metabolome in the earthworm, Perionyx excavatus , using gas chromatography mass spectrometry (GC-MS) and liquid chromatography quadrupole time-of-flight (LC-QTOF)-based untargeted metabolomics approach after acute exposure to TPHP for one and two days through a filter paper contact test, as well as after chronic exposure for 28 days in a soil microcosm experiment. TPHP showed low bioaccumulation potential in the earthworm-soil ecosystem at concentrations of 10 mg/kg and 50 mg/kg. Identified phase I metabolites include diphenyl phosphate, mono-hydroxylated and di-hydroxylated TPHP. Two groups of phase II metabolites, thiol conjugates (including mercaptolactic acid, cysteine, cysteinylglycine, and mercaptoethanol conjugates) and glucoside conjugates (including glucoside, glucoside-phosphate, and C 14 H 19 O 10 P conjugates), were putatively identified. Only acute TPHP exposure caused significant perturbations of the endogenous metabolome in earthworms, featuring fluctuations in amino acids, glucose, inosine and phospholipids. These results reveal novel phase II metabolism and toxicity of TPHP in P. excavatus .

The implementation of successful strategies to achieve an HIV cure has become a priority in HIV research. However, the current location and size of HIV reservoirs is still unknown since there are limited tools to evaluate HIV latency in viral sanctuaries such as gut-associated lymphoid tissue (GALT). As reported in the so called \"Boston Patients\", despite undetectable levels of proviral HIV-1 DNA in blood and GALT, viral rebound happens in just few months after ART interruption. This fact might imply that current methods are not sensitive enough to detect residual reservoirs. Showing that, it is imperative to improve the detection and quantification of HIV-1 reservoir in tissue samples. Herein, we propose a novel non-enzymatic protocol for purification of Lamina Propria Leukocytes (LPL) from gut biopsies combined to viral HIV DNA (vDNA) quantification by droplet digital PCR (ddPCR) to improve the sensitivity and accuracy of viral reservoir measurements (LPL-vDNA assay). Endoscopic ileum biopsies were sampled from 12 HIV-1-infected cART-suppressed subjects. We performed a DTT/EDTA-based treatment for epithelial layer removal followed by non-enzymatic disruption of the tissue to obtain lamina propria cell suspension (LP). CD45+ cells were subsequently purified by flow sorting and vDNA was determined by ddPCR. vDNA quantification levels were significantly higher in purified LPLs (CD45+) than in bulk LPs (p<0.01). The levels of vDNA were higher in ileum samples than in concurrent PBMC from the same individuals (p = 0.002). As a result of the increased sensitivity of this purification method, the Poisson 95% confidence intervals of the vDNA quantification data from LPLs were narrower than that from bulk LPs. Of note, vDNA was unambiguously quantified above the detection limit in 100% of LPL samples, while only in 58% of bulk LPs. We propose an innovative combined protocol for a more sensitive detection of the HIV reservoir in gut-associated viral sanctuaries, which might be used to evaluate any proposed eradication strategy.

Nowadays, there is a growing awareness of the great environmental impact caused by the enormous amounts of carbon dioxide emitted. Several alternatives exist to solve this problem, and one of them is the hydrogenation of carbon dioxide into methanol by using nanomaterials as catalysts. The aim of this alternative is to produce a value-added chemical, such as methanol, which is a cheaply available feedstock. The development of improved materials for this conversion reaction and a deeper study of the existing ones are important for obtaining higher efficiencies in terms of yield, conversion, and methanol selectivity, in addition to allowing milder reaction conditions in terms of pressure and temperature. In this work, the performance of copper, zinc, and zinc oxide nanoparticles in supported and unsupported bimetallic systems is evaluated in order to establish a comparison among the different materials according to their efficiency. For that, a packed bed reactor operating with a continuous gas flow is used. The obtained results indicate that the use of bimetallic systems combined with porous supports, such as zeolite and activated carbon, is beneficial, thus improving the performance of unsupported materials by four times.

IntroductionIdiopathic Parkinson syndrome (iPS) is one of the most common neurodegenerative disorders characterised by the triad of bradykinesia, rigidity and tremor. Tremor at rest predominantly at one side is often perceived by patients as severely disabling and yet ranges among the most difficult symptoms to treat. In medically refractory cases, lesional approaches have proven to be effective alternatives. However, to date, there is no comprehensive analysis of non-surgical therapies to manage iPS-patients’ tremor. We therefore present a detailed study protocol for a systematic literature review assessing efficacy/effectiveness and safety of non-lesional treatments for tremor in iPS.Methods and analysisWe will search three electronic databases (MEDLINE, EMBASE and PsycINFO) using a combination of title/abstract keywords. Additionally, hand-searched reference and citation lists of key reviews identified through the search strategy will be screened. Eligible studies should investigate the efficacy/effectiveness and safety of therapeutic options for tremor in iPS excluding lesional interventions. Publications will be independently assessed for inclusion criteria by two investigators and study information summarised using a standardised template including quality assessment according to the QualSyst tool. We will provide a narrative synthesis of results and conduct a meta-analysis whenever possible.Ethics and disseminationWe commit to present contemporary evidence on the efficacy/effectiveness and safety of non-lesional interventions for tremor in iPS in a future publication. We aim to compile rich data of published studies to inform healthcare professionals in order to ultimately improve patient outcomes.PROSPERO registration numberCRD42020202911).

Objectives The role of innate lymphoid cells (ILCs) in coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is unknown. Understanding the immune response in COVID‐19 could contribute to unravel the pathogenesis and identification of treatment targets. Here, we describe the phenotypic landscape of circulating ILCs in COVID‐19 patients and identified ILC phenotypes correlated to serum biomarkers, clinical markers and laboratory parameters relevant in COVID‐19. Methods Blood samples collected from moderately (n = 11) and severely ill (n = 12) COVID‐19 patients, as well as healthy control donors (n = 16), were analysed with 18‐parameter flow cytometry. Using supervised and unsupervised approaches, we examined the ILC activation status and homing profile. Clinical and laboratory parameters were obtained from all COVID‐19 patients, and serum biomarkers were analysed with multiplex immunoassays. Results Innate lymphoid cells were largely depleted from the circulation of COVID‐19 patients compared with healthy controls. Remaining circulating ILCs revealed decreased frequencies of ILC2 in severe COVID‐19, with a concomitant decrease of ILC precursors (ILCp) in all patients, compared with controls. ILC2 and ILCp showed an activated phenotype with increased CD69 expression, whereas expression levels of the chemokine receptors CXCR3 and CCR4 were significantly altered in ILC2 and ILCp, and ILC1, respectively. The activated ILC profile of COVID‐19 patients was associated with soluble inflammatory markers, while frequencies of ILC subsets were correlated with laboratory parameters that reflect the disease severity. Conclusion This study provides insights into the potential role of ILCs in immune responses against SARS‐CoV‐2, particularly linked to the severity of COVID‐19. In this study, we found that circulating innate lymphoid cells (ILCs) are reduced in COVID‐19 patients. Severely diseased patients display decreased frequencies of ILC2 compared to moderate COVID‐19 patients and healthy donors, whereas ILC precursors are found decreased in all patients. The remaining circulating ILCs in COVID‐19 patients show a dysregulated expression of activation and migration markers, with an activated profile that associates with soluble inflammatory markers. Moreover, frequencies of ILC subsets correlate with laboratory parameters that reflect the disease severity.

Tonsil hyperplasia is the most common cause of pediatric obstructive sleep apnea (OSA). Despite the growing knowledge in tissue immunology of tonsils, the immunopathology driving tonsil hyperplasia and OSA remains unknown. Here we used multi-parametric flow cytometry to analyze the composition and phenotype of tonsillar innate lymphoid cells (ILCs), T cells, and B cells from pediatric patients with OSA, who had previous polysomnography. Unbiased clustering analysis was used to delineate and compare lymphocyte heterogeneity between two patient groups: children with small tonsils and moderate OSA (n = 6) or large tonsils and very severe OSA (n = 13). We detected disturbed ILC and B cell proportions in patients with large tonsils, characterized by an increase in the frequency of naïve CD27 - CD21 hi B cells and a relative reduction of ILCs. The enrichment of naïve B cells was not commensurate with elevated Ki67 expression, suggesting defective differentiation and/or migration rather than cellular proliferation to be the causative mechanism. Finally, yet importantly, we provide the flow cytometry data to be used as a resource for additional translational studies aimed at investigating the immunological mechanisms of pediatric tonsil hyperplasia and OSA.