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Quorum sensing peptides (QSPs) are bacterial peptides produced by Gram-positive bacteria to communicate with their peers in a cell-density dependent manner. These peptides do not only act as interbacterial communication signals, but can also have effects on the host. Compelling evidence demonstrates the presence of a gut-brain axis and more specifically, the role of the gut microbiota in microglial functioning. The aim of this study is to investigate microglial activating properties of a selected QSP (PapRIV) which is produced by Bacillus cereus species. PapRIV showed in vitro activating properties of BV-2 microglia cells and was able to cross the in vitro Caco-2 cell model and reach the brain. In vivo peptide presence was also demonstrated in mouse plasma. The peptide caused induction of IL-6, TNFα and ROS expression and increased the fraction of ameboid BV-2 microglia cells in an NF-κB dependent manner. Different metabolites were identified in serum, of which the main metabolite still remained active. PapRIV is thus able to cross the gastro-intestinal tract and the blood-brain barrier and shows in vitro activating properties in BV-2 microglia cells, hereby indicating a potential role of this quorum sensing peptide in gut-brain interaction.

Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein, was shown to be expressed 100–1000 fold higher in prostate adenocarcinoma as compared to normal prostate epithelium. Given the enzymatic function of PSMA with the presence of an internalization triggering motif, various Glu-urea-Lys-based inhibitors have been developed and, amongst others, radiolabeled with positron emitters for targeted positron emission tomography imaging such as 68Ga-PSMA-HBED-CC Glu-urea-Lys(Ahx) as well as with beta and alpha-emitting radioisotopes for targeted therapy, e.g., 177Lu-PSMA-617. In this paper, we review and discuss the potential implications for targeted imaging and therapy of altered PSMA-glycosylation, of PSMA-driven activation of the P13K/Akt/mTOR, of the evolution over time and the relationship with androgen signaling and changes in DNA methylation of PSMA, and of androgen deprivation therapy (ADT) in prostate carcinoma. [ABSTRACT FROM AUTHOR]

Quorum-sensing peptides (QSPs) are bacterial peptides traditionally considered only as inter-bacterial communication molecules. Recently, their involvement in microbiome–host interactions influencing host diseases such as cancer and sarcopenia were explored. However, it is still unknown to what extent these peptides have the potential to modulate the immune system. In this proof-of-concept study, we screened 89 QSPs for their potential to induce IL-6 and TNFα in murine splenocytes and J774 macrophages. Confirmatory experiments on the positive screening-hits were conducted using murine splenocytes and human PBMCs of different ages. Finally, to investigate the biological relevance of immunomodulatory QSPs, we analysed plasma in a human cohort for the presence of the immunomodulatory QSP Q010. To do this, we used a newly developed UHPLC-MS/MS method. Our findings indicated that specific QSPs activate immune cells in vitro, with Q007, Q010, Q017 and Q212 being the top four screening hits. Q007 and Q010 were affirmed in subsequent confirmatory experiments using murine splenocytes and human PBMCs. Finally, Q010 was detected in human plasma, demonstrating for the first time the presence of an immunomodulatory QSP in human circulation. In conclusion, our data are the first evidence indicating the potential of biologically relevant quorum-sensing peptides to modulate the immune system. [ABSTRACT FROM AUTHOR]

(C) iAM373 concentrations in faeces and plasma of germ-free mice untreated (untreated), gavaged with wild-type E. coli (placebo) or gavaged with E. coli expressing iAM373 (iAM373). Dear Editor, Sarcopenia - the accelerated loss of muscle mass, strength and function with ageing - represents an important health challenge with reduced quality of life and increased mortality.1 Gut microbiota has been suggested to contribute to this age-associated muscle wasting but the underlying mechanisms are still unclear.2 Here, we uncover the quorum sensing peptide iAM373 as a hitherto unknown contributor to sarcopenia. [Extracted from the article]

Background: Statins are progressively accepted as being associated with reduced mortality. However, few real-world statin studies have been conducted on statin use in older people and especially the most frail, that is, the nursing home residents. Objective: The aim of this study was to evaluate the impact of statin intake in nursing home residents on all-cause mortality. Method: This is a cross-sectional study of 1,094 older people residing in 6 nursing homes in Flanders (Belgium) between March 1, 2020 and May 30, 2020. We considered all residents who were taking statins for at least 5 days as statin users. All-cause mortality during the 3 months of data collection was the primary outcome. Propensity score overlap-weighted logistic regression models were applied with age, sex, functional status, diabetes, and cardiac failure/ischemia as potential confounders. Results: 185 out of 1,094 residents were on statin therapy (17%). The statin intake was associated with decreased all-cause mortality: 4% absolute risk reduction; adjusted odds ratio 0.50; CI 0.31–0.81, p = 0.005. Conclusions: The statin intake was associated with decreased all-cause mortality in older people residing in nursing homes. More in-depth studies investigating the potential geroprotector effect of statins in this population are needed. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia, defined as the pathological decline in muscle mass, muscle strength and physical performance with aging, has become one of the geriatric giants because of its increasing prevalence and devastating health effects. The Belgian Society of Gerontology and Geriatrics (BSGG) is currently developing evidence-based guidelines for the prevention and therapy of sarcopenia for use in broad clinical practice. This systematic review summarizes the results of the Working Group on Pharmacology.Objective: Our objective was to provide an evidence-based overview of the possible pharmacological interventions for sarcopenia with a focus on interventions that have already been studied in systematic reviews or meta-analyses.Methods: We conducted a systematic umbrella review. Using the electronic databases PubMed and Web of Science, we identified systematic reviews and meta-analyses that assessed the effect of pharmacological interventions on criteria for sarcopenia in subjects aged ≥ 65 years. Study selection, quality assessment and data extraction were performed by two independent reviewers.Results: We identified seven systematic reviews or meta-analyses, encompassing ten pharmacological interventions: vitamin D, combined estrogen-progesterone, dehydroepiandrosterone, growth hormone, growth hormone-releasing hormone, combined testosterone-growth hormone, insulin-like growth factor-1, pioglitazone, testosterone and angiotensin-converting enzyme inhibitors. Importantly, very few systematic reviews or meta-analyses clearly mentioned baseline sarcopenia status. Therefore, our recommendations are generalised to older people, without specifying whether the muscle effect is more effective in healthy, pre-sarcopenic or sarcopenic older people. Vitamin D had a significant effect on muscle strength and physical performance, especially in women with low baseline values (< 25 nmol/l). Adverse events were rare. Testosterone had a strong effect on muscle mass and a modest to minimal effect on muscle strength and physical performance, respectively, when supplementing men with low serum levels (< 200-300 ng/dl). The adverse events were rare and mild. Insufficient evidence was available to recommend other pharmacological interventions.Conclusion: Only vitamin D, especially in older women, and testosterone in older men with clinical muscle weakness and low testosterone serum levels can be justified in daily clinical practice to improve muscle mass, muscle strength and/or physical performance. [ABSTRACT FROM AUTHOR]

Background Chlamydia psittaci is a gram-negative, obligate intracellular organism. Birds are the main reservoir, but also non-avian domestic animals and humans can be infected. In humans it mostly causes respiratory infections due to occupational exposure with varying severity. Sensitive and specific diagnostic tests are needed to define psittacosis in humans as these tests also allow rapid tracing of the animal source. However, diagnosis in humans is often based on time-consuming culture techniques and antibody detection assays as in many countries, the existing molecular diagnostic tests for psittacosis are not reimbursed by the public health insurance. Case presentation An 82-year old female was referred to the hospital with a non-productive cough since four weeks and since one week fever up to 39 °C, myalgia, generalized skin rash, acral edema and generalized weakness under treatment with moxifloxacin. Blood analysis showed signs of inflammation with mild eosinophilia. Chest CT showed multiple peripheral ground glass opacities with consolidation in both lungs. Pulmonary function testing only showed a mild decrease in diffusion capacity. Viral and bacterial serology were negative. As the patient kept a pet parakeet for over ten years, a nested PCR for C. psittaci was performed on a nasopharyngeal swab of the patient and on feces of the parakeet. Both returned positive for the same genotype. Genotyping was performed by a genotype-specific real-time PCR. The patient fully recovered after a ten-day course of azithromycin. Conclusion Due to non-specific signs during psittacosis, early detection of the infection and differentiation from hypersensitivity pneumonitis can be challenging. Culture and antibody titers for C. psittaci have a lower sensitivity than PCR-testing due to several factors. We present a case of human psittacosis (presenting as pneumonia) with diagnosis based on clinical findings confirmed by means of nested PCR. This case suggests the added value of PCR in suspect cases despite negative serology. Our current paper underlines the need for a broader implementation of PCR for early diagnosis of human psittacosis and thus early initiation of correct antibiotic treatment with reduction of morbidity and mortality. [ABSTRACT FROM AUTHOR]

Many analogues of the glycolipid alpha-galactosylceramide (α-GalCer) are known to activate iNKT cells through their interaction with CD1d-expressing antigen-presenting cells, inducing the release of Th1 and Th2 cytokines. Because of iNKT cell involvement and associated Th1/Th2 cytokine changes in a broad spectrum of human diseases, the design of iNKT cell ligands with selective Th1 and Th2 properties has been the subject of extensive research. This search for novel iNKT cell ligands requires refined structural insights. Here we will visualize the chemical space of 333 currently known iNKT cell activators, including several newly tested analogues, by more than 3000 chemical descriptors which were calculated for each individual analogue. To evaluate the immunological responses we analyzed five different cytokines in five different test-systems. We linked the chemical space to the immunological space using a system biology computational approach resulting in highly sensitive and specific predictive models. Moreover, these models correspond with the current insights of iNKT cell activation by α-GalCer analogues, explaining the Th1 and Th2 biased responses, downstream of iNKT cell activation. We anticipate that such models will be of great value for the future design of iNKT cell agonists. [ABSTRACT FROM AUTHOR]

Introduction: Hospitalization is associated with acute changes in sarcopenia status in older people, but the influencing factors are not fully understood. Pre-admission care dependency level as a risk factor has not yet been investigated., Objective: Evaluate if pre-admission care dependency level is an independent predictor of sarcopenia changes following hospitalization., Setting and Subjects: Data came from the Sarcopenia 9+ EAMA Project, a European prospective multi-centre study. For this study, 227 hospitalised older people were included from four different hospitals in Belgium, Spain and Poland, between 18 February 2019 and 5 September 2020., Methods: Sarcopenia status at admission and discharge were calculated using a combined score (desirability value) based on muscle mass (calf circumference), strength (grip) and function (walking speed). Ratio of admission to discharge status was the outcome (desirability ratio; 1.00 meaning no difference). Predictor variable was the pre-admission care dependency level, classified into three groups: independent older people living at home, dependent older people living at home and older people living in a care home. Linear regression models were applied, considering potential confounders., Results: Mean desirability ratio for dependent older people living at home ('middle dependent group') was lower (0.89) compared to independent older people (0.98; regression coefficient -0.09 [95% CI -0.16, -0.02]) and care home patients (1.05; -0.16 [95% CI -0.01, -0.31]). Adjusting for potential confounders or using another statistical approach did not affect the main results., Conclusion: Dependent older people living at home were at higher risk of deterioration in sarcopenia status following hospitalization. In-depth studies investigating causes and potential interventions of these findings are needed., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Sarcopenia - or the loss of muscle mass, strength and function with ageing - represents an important health issue of the twenty-first century because of its devastating effects in addition to an increased prevalence of aged people. The devastating health effects of sarcopenia are multiple: an increased falls risk, a decreased physical ability and quality of life and an independent increase of all-cause mortality. Although the ultimate remedy for sarcopenia yet has to be found, some interventions have proven their merit and might be of practical use in clinical practice, especially for geriatricians, who deal most with sarcopenia. This review intends to summarize the current therapeutic interventions, their proposed mechanism of action as well as their clinical value. The results of our review highlight the importance of exercise (50% resistance training, 50% endurance training), nutrition (25-30 g proteins with essential amino acids every meal and long-chain ω-3 fatty acids) and limitation of alcohol and smoking. In addition, studies also suggest a place for vitamin D (aim serum levels >30 ng/L), testosterone (aim serum levels >300 ng/dL) and creatine (15-20 g/d for five days, thereafter 3-5 g/d). In conclusion, although more studies are needed to elucidate the exact effectiveness and safety of many sarcopenia interventions, the current evidence already provides clinically useful information, which might benefit the patient with (pre-)sarcopenia.