IL-10–producing Tfh cells accumulate with age and link inflammation with age-related immune suppression

Aging results in profound immune dysfunction, resulting in the decline of vaccine responsiveness previously attributed to irreversible defects in the immune system. In addition to increased interleukin-6 (IL-6), we found aged mice exhibit increased systemic IL-10 that requires forkhead box P3–negative (FoxP3−), but not FoxP3+, CD4+T cells. Most IL-10–producing cells manifested a T follicular helper (Tfh) phenotype and required the Tfh cytokines IL-6 and IL-21 for their accrual, so we refer to them as Tfh10 cells. IL-21 was also required to maintain normal serum levels of IL-6 and IL-10. Notably, antigen-specific Tfh10 cells arose after immunization of aged mice, and neutralization of IL-10 receptor signaling significantly restored Tfh-dependent antibody responses, whereas depletion of FoxP3+ regulatory and follicular regulatory cells did not. Thus, these data demonstrate that immune suppression with age is reversible and implicate Tfh10 cells as an intriguing link between “inflammaging” and impaired immune responses with age

DNA methylome analysis in Burkitt and follicular lymphomas identifies differentially methylated regions linked to somatic mutation and transcriptional control

Although Burkitt lymphomas and follicular lymphomas both have features of germinal center B cells, they are biologically and clinically quite distinct. Here we performed whole-genome bisulfite, genome and transcriptome sequencing in 13 IG-MYC translocation-positive Burkitt lymphoma, nine BCL2 translocation-positive follicular lymphoma and four normal germinal center B cell samples. Comparison of Burkitt and follicular lymphoma samples showed differential methylation of intragenic regions that strongly correlated with expression of associated genes, for example, genes active in germinal center dark-zone and light-zone B cells. Integrative pathway analyses of regions differentially methylated in Burkitt and follicular lymphomas implicated DNA methylation as cooperating with somatic mutation of sphingosine phosphate signaling, as well as the TCF3-ID3 and SWI/SNF complexes, in a large fraction of Burkitt lymphomas. Taken together, our results demonstrate a tight connection between somatic mutation, DNA methylation and transcriptional control in key B cell pathways deregulated differentially in Burkitt lymphoma and other germinal center B cell lymphomas

Clinical and virological characteristics of hospitalised COVID-19 patients in a German tertiary care centre during the first wave of the SARS-CoV-2 pandemic: a prospective observational study

Purpose: Adequate patient allocation is pivotal for optimal resource management in strained healthcare systems, and requires detailed knowledge of clinical and virological disease trajectories. The purpose of this work was to identify risk factors associated with need for invasive mechanical ventilation (IMV), to analyse viral kinetics in patients with and without IMV and to provide a comprehensive description of clinical course. Methods: A cohort of 168 hospitalised adult COVID-19 patients enrolled in a prospective observational study at a large European tertiary care centre was analysed. Results: Forty-four per cent (71/161) of patients required invasive mechanical ventilation (IMV). Shorter duration of symptoms before admission (aOR 1.22 per day less, 95% CI 1.10-1.37, p < 0.01) and history of hypertension (aOR 5.55, 95% CI 2.00-16.82, p < 0.01) were associated with need for IMV. Patients on IMV had higher maximal concentrations, slower decline rates, and longer shedding of SARS-CoV-2 than non-IMV patients (33 days, IQR 26-46.75, vs 18 days, IQR 16-46.75, respectively, p < 0.01). Median duration of hospitalisation was 9 days (IQR 6-15.5) for non-IMV and 49.5 days (IQR 36.8-82.5) for IMV patients. Conclusions: Our results indicate a short duration of symptoms before admission as a risk factor for severe disease that merits further investigation and different viral load kinetics in severely affected patients. Median duration of hospitalisation of IMV patients was longer than described for acute respiratory distress syndrome unrelated to COVID-19

Human Cytomegalovirus IE1 Protein Elicits a Type II Interferon-Like Host Cell Response That Depends on Activated STAT1 but Not Interferon-γ

Human cytomegalovirus (hCMV) is a highly prevalent pathogen that, upon primary infection, establishes life-long persistence in all infected individuals. Acute hCMV infections cause a variety of diseases in humans with developmental or acquired immune deficits. In addition, persistent hCMV infection may contribute to various chronic disease conditions even in immunologically normal people. The pathogenesis of hCMV disease has been frequently linked to inflammatory host immune responses triggered by virus-infected cells. Moreover, hCMV infection activates numerous host genes many of which encode pro-inflammatory proteins. However, little is known about the relative contributions of individual viral gene products to these changes in cellular transcription. We systematically analyzed the effects of the hCMV 72-kDa immediate-early 1 (IE1) protein, a major transcriptional activator and antagonist of type I interferon (IFN) signaling, on the human transcriptome. Following expression under conditions closely mimicking the situation during productive infection, IE1 elicits a global type II IFN-like host cell response. This response is dominated by the selective up-regulation of immune stimulatory genes normally controlled by IFN-γ and includes the synthesis and secretion of pro-inflammatory chemokines. IE1-mediated induction of IFN-stimulated genes strictly depends on tyrosine-phosphorylated signal transducer and activator of transcription 1 (STAT1) and correlates with the nuclear accumulation and sequence-specific binding of STAT1 to IFN-γ-responsive promoters. However, neither synthesis nor secretion of IFN-γ or other IFNs seems to be required for the IE1-dependent effects on cellular gene expression. Our results demonstrate that a single hCMV protein can trigger a pro-inflammatory host transcriptional response via an unexpected STAT1-dependent but IFN-independent mechanism and identify IE1 as a candidate determinant of hCMV pathogenicity

Design of experiments as a tool to guide the preparation of tailor-made activated carbons

Activated carbon produced from biomass exhibits a high specific surface area due to the natural hierarchical porous structure of the precursor material. To reduce production costs of activated carbon, bio-waste materials receive more and more attention, which has led to a steep increase in the number of publications over the past decade. However, the characteristics of activated carbon are highly dependent on the properties of the precursor material used, making it difficult to draw assumptions about activation conditions for new precursor materials based on published work. Here, we introduce a Design of Experiment methodology with a Central Composite Design to better predict the properties of activated carbons from biomass. As a model precursor, we employ well-defined regenerated cellulose-based fibers which contain 25 wt.% chitosan as intrinsic dehydration catalyst and nitrogen donor. The use of the DoE methodology opens up the possibility to better identify the crucial dependencies between activation temperature and impregnation ratio on the yield, surface morphology, porosity and chemical composition of the activated carbon, independent of the used biomass. The use of DoE yields contour plots, which allows for more facile analysis on correlations between activation conditions and activated carbon properties, thus enabling its tailor-made manufacturing.</p

Interest in Birds and its Relationship with Attitudes and Myths: A Cross-cultural Study in Countries with Different Levels of Economic Development

WOS: 000353305900020Birds are one of the most important species that can help protect biodiversity. Although birds are important beings for biodiversity and human existence, there is a relatively less quantity of research that has investigated the interest in and attitudes toward birds. This study aims to investigate the knowledge level of and attitudes toward birds among students in countries at different levels of economic development. To collect the data, a Bird Knowledge Questionnaire and a Bird Attitude Questionnaire were developed and used by the researchers in this study. These questionnaires were administered to a total of 852 students from different countries, including Colombia, Germany, Slovakia, and Turkey. The results obtained in this study showed that Colombian students had the highest interest in birds as compared to students in Slovakia, Turkey, and Germany. Girls had consistently higher interest in birds than boys in all countries, but there were no gender differences in the cognitive domain. Our research suggests that factual knowledge about birds is not a necessary prerequisite for interest in birds, but animal-related activities show strong associations with an interest in birds

Effects of Body Condition and Concentrate Proportion of the Ration on Mobilization of Fat Depots and Energetic Condition in Dairy Cows during Early Lactation Based on Ultrasonic Measurements

The aim of this study was to evaluate energy metabolism and lipid mobilization via ultrasonic measurements (USM), considering inner fat depots, in lactating dairy cows differing in body condition score (BCS) and fed rations with low (35% at dry matter basis; C35) or high (60% at dry matter basis; C60) concentrate feed proportions postpartum. Sixty pluriparous German Holstein cows were arranged in a 2 &#215; 2 factorial design from d 42 antepartum (relative to calculated calving) until d 120 postpartum. Animals were divided into a group with a lower (initial BCS = 3.1 &#177; 0.38 SD; BCSL) and a group with a higher (initial BCS = 3.83 &#177; 0.41 SD; BCSH) BCS. Due to higher dry matter intake C60 groups reached the positive energy balance earlier, whereas C35 groups had a more pronounced negative energy balance. Although this would suggest a more pronounced mobilization of C35 groups the USM revealed no differences between feeding groups. Differences in BCS between both BCS groups remained almost the same over the trial. This was not reflected in ultrasonic data, as lipid mobilization was higher in higher conditioned cows. These findings demonstrate the extended possibilities of USM to depict metabolic processes

Profiling of patients in a specialized geriatric outpatient clinic

Background In Germany geriatric outpatient care is predominantly done by family doctors and general practitioners (GP). There are regionally different concepts for additional specialized geriatric outpatient care but they have not yet been validated and established. Still, it remains unclear whether a geriatric patient has to be diagnosed rather in a specialized outpatient or inpatient setting. The aim of the present study is the profiling of geriatric outpatients to find key distinctions from geriatric patients that have to be admitted to hospital. Methods Retrospective data analysis of patients sent to a specialized geriatric outpatient clinic by their GP, compared with data of geriatric inpatients sent to hospital by their GP during the same time period. Study parameters comprised elements of the comprehensive geriatric assessment as well as results of routinely applied laboratory tests. Results Patients sent to the specialized geriatric outpatient clinic showed better results of functional assessments. Regression analysis: improvement of Barthel Index, GFR and total protein increased the chance of outpatient treatment. Conclusion Early identification of geriatric patients who can be treated in a specialized outpatient setting would ease the burden for GPs by interdisciplinary cooperation and prevent cost-intensive readmissions to hospital

Psychological insulin resistance in geriatric patients with diabetes mellitus

Objective To determine the extent to which geriatric patients with diabetes mellitus experience psychological insulin resistance (PIR). Methods A total of 67 unselected geriatric patients with diabetes (mean age 82.8 ± 6.7 years, diabetes duration 12.2 [0.04–47.2] years, 70.1% female) were recruited in a geriatric care center of a university hospital. A comprehensive geriatric assessment (CGA) was performed including WHO-5, Hospital Anxiety and Depression Scale (HADS), Mini Mental State Examination (MMSE) and Barthel-Index. We assessed PIR using the Barriers of Insulin Treatment Questionnaire (BIT) and the Insulin Treatment Appraisal Scale in a face-to-face interview. Results Insulin-naïve patients (INP) showed higher PIR scores than patients already on insulin therapy (BIT-sum score: 4.3 ± 1.4 vs. 3.2 ± 1.0; p < 0.001). INP reported in the BIT increased fear of injection and self-testing (2.4 ± 2.4 vs. 1.3 ± 0.8; p = 0.016), expect disadvantages from insulin treatment (2.7 ± 1.6 vs. 1.9 ± 1.4; p = 0.04), and fear of stigmatization by insulin injection (5.2 ± 2.3 vs. 3.6 ± 2.6; p = 0.008). Fear of hypoglycemia, however, did not differ significantly (6.3 ± 2.8 vs. 5.1 ± 3.1; p = 0.11). Depression was not shown to be a barrier to insulin therapy. Conclusion INP with diabetes have a significantly more negative attitude toward insulin therapy in comparison to patients already on insulin. Practice implications Systematic assessment of barriers of insulin therapy, individualized diabetes treatment plans and information of patients may help to overcome such negative attitudes, leading to quicker initiation of therapy, improved adherence to treatment and a better quality of life