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The purine adenosine 5′-triphosphate (ATP) is not only a universal intracellular energy carrier but plays also an important role as extracellular signaling molecule. Purinergic signaling is involved in many physiological and pathological processes like coagulation, inflammation, or sepsis in mammals. ATP is well-known as a messenger for intercellular communications in multicellular organisms, but phylogenetically much older unicellular organisms like yeast or bacteria use ATP as an extracellular signaling molecule as well. However, the mechanisms of ATP secretion by bacteria and its extracellular implications still have to be elucidated. This review will provide an overview of the current knowledge about bacterial extracellular ATP (eATP) under homeostatic conditions and during growth. Possible secretion mechanisms of ATP by bacteria will be discussed and implications of bacterial ATP are shown, with a focus on bacteria–host interactions.

Extracellular nucleotides (e.g., ATP, ADP, UTP, UDP) released by inflammatory cells interact with specific purinergic P2 type receptors to modulate their recruitment and activation. The focus of this review is on stimuli and mechanisms of extracellular nucleotide release and its consequences during inflammation. Necrosis leads to non-specific release of nucleotides, whereas specific release mechanisms include vesicular exocytosis and channel-mediated release via connexin or pannexin hemichannels. These release mechanisms allow stimulated inflammatory cells such as macrophages, neutrophils, and endothelial cells to fine-tune autocrine/paracrine responses during acute and chronic inflammation. Key effector functions of inflammatory cells are therefore regulated by purinergic signaling in acute and chronic diseases, making extracellular nucleotide release a promising target for the development of new therapies.

Surgical skills are associated with clinical outcomes. To improve surgical skills and thereby reduce adverse outcomes, continuous surgical training and feedback is required. Currently, assessment of surgical skills is a manual and time-consuming process which is prone to subjective interpretation. This study aims to automate surgical skill assessment in laparoscopic cholecystectomy videos using machine learning algorithms. To address this, a three-stage machine learning method is proposed: first, a Convolutional Neural Network was trained to identify and localize surgical instruments. Second, motion features were extracted from the detected instrument localizations throughout time. Third, a linear regression model was trained based on the extracted motion features to predict surgical skills. This three-stage modeling approach achieved an accuracy of 87 ± 0.2% in distinguishing good versus poor surgical skill. While the technique cannot reliably quantify the degree of surgical skill yet it represents an important advance towards automation of surgical skill assessment.

Speech analysis offers a non-invasive method for assessing emotional and cognitive states through acoustic correlates, including spectral, prosodic, and voice quality features. Despite growing interest, research remains inconsistent in identifying reliable acoustic markers, providing limited guidance for researchers and practitioners in the field. This review identifies key acoustic correlates for detecting negative emotions, stress, and cognitive load in speech. A systematic search was conducted across four electronic databases: PubMed, PsycInfo, Web of Science, and Scopus. Peer-reviewed articles reporting studies conducted with healthy adult participants were included. Thirty-eight articles were reviewed, encompassing 39 studies, as one article reported on two studies. Among all features, prosodic features were the most investigated and showed the greatest accuracy in detecting negative emotions, stress, and cognitive load. Specifically, anger was associated with elevated fundamental frequency (F0), increased speech volume, and faster speech rate. Stress was associated with increased F0 and intensity, and reduced speech duration. Cognitive load was linked to increased F0 and intensity, although the results for F0 were overall less clear than those for negative emotions and stress. No consistent acoustic patterns were identified for fear or anxiety. The findings support speech analysis as a useful tool for researchers and practitioners aiming to assess negative emotions, stress, and cognitive load in experimental and field studies.

Bacterial spillage into a sterile environment following intestinal hollow-organ perforation leads to peritonitis and fulminant sepsis. Outcome of sepsis critically depends on macrophage activation by extracellular ATP-release and associated autocrine signalling via purinergic receptors. ATP-release mechanisms, however, are poorly understood. Here, we show that TLR-2 and −4 agonists trigger ATP-release via Connexin-43 hemichannels in macrophages leading to poor sepsis survival. In humans, Connexin-43 was upregulated on macrophages isolated from the peritoneal cavity in patients with peritonitis but not in healthy controls. Using a murine peritonitis/sepsis model, we identified increased Connexin-43 expression in peritoneal and hepatic macrophages. Conditional Lyz2cre/creGja1flox/flox mice were developed to specifically assess Connexin-43 impact in macrophages. Both macrophage-specific Connexin-43 deletion and pharmacological Connexin-43 blockade were associated with reduced cytokine secretion by macrophages in response to LPS and CLP, ultimately resulting in increased survival. In conclusion, inhibition of autocrine Connexin-43-dependent ATP signalling on macrophages improves sepsis outcome.

Recent studies have helped to increase the understanding of the function of Connexin-43 (Cx43) in macrophages (Mφ). The various roles of Cx43 in Mφs range from migration, antigen-presentation and some forms of intercellular communication to more delicate processes, such as electrochemical support in the propagation of the heartbeat, immunomodulatory regulation in the lungs and in macrophage-differentiation. Its relevance in pathophysiology becomes evident in inflammatory bowel disease (IBD), tumours and HIV, in which aberrant functioning of Cx43 has been described. However, the involvement of Cx43 in other Mφ functions, such as phagocytosis and polarisation, and its involvement in other types of local and systemic inflammation, are still unclear and need further research.

Surgical site infections (SSIs) continue to pose a significant healthcare challenge by contributing to longer post-surgical recovery times, greater healthcare costs and higher patient mortality. The traditional understanding of SSIs has focused on the impact of various external origins of contamination or on the importance of intestinal spillage during surgical procedures. However, recent studies highlight the significant contribution of the patient's intestinal microbiota in the onset of SSIs. One possible pathway of infection is translocation of bacteria from the intestines to organs that are typically sterile, such as the mesenteric lymph nodes (MLNs). These secondary lymphoid organs are then potential reservoirs for SSIs. This review summarizes the current data on the incidence and mechanisms of bacterial translocation (BT) to MLNs in the context of a surgical insult and its association with postoperative infectious complications. Data from animal studies discuss how BT to MLNs is driven by factors such as dysbiosis and surgical interventions and is strongly linked to infectious outcomes. Potential translocation pathways including intracellular transit and carrier-independent mechanisms are explored. Similarly, human studies provide evidence that BT to MLNs is a frequent occurrence during abdominal surgery and significantly increases the risk of infectious complications. We further discuss the limitations of current methodologies for studying BT and SSIs and highlight how advanced techniques can provide novel insights into these processes. This review identifies key areas for future research and potential targets for preventative strategies to increase our understanding of the role of the intestinal microbiota in BT to MLNs and its contribution to SSIs.

Sepsis causes millions of deaths per year worldwide and is a current global health priority declared by the WHO. Sepsis-related deaths are a result of dysregulated inflammatory immune responses indicating the need to develop strategies to target inflammation. An important mediator of inflammation is extracellular adenosine triphosphate (ATP) that is released by inflamed host cells and tissues, and also by bacteria in a strain-specific and growth-dependent manner. Here, we investigated the mechanisms by which bacteria release ATP. Using genetic mutant strains of Escherichia coli ( E. coli ), we demonstrate that ATP release is dependent on ATP synthase within the inner bacterial membrane. In addition, impaired integrity of the outer bacterial membrane notably contributes to ATP release and is associated with bacterial death. In a mouse model of abdominal sepsis, local effects of bacterial ATP were analyzed using a transformed E. coli bearing an arabinose-inducible periplasmic apyrase hydrolyzing ATP to be released. Abrogating bacterial ATP release shows that bacterial ATP suppresses local immune responses, resulting in reduced neutrophil counts and impaired survival. In addition, bacterial ATP has systemic effects via its transport in outer membrane vesicles (OMV). ATP-loaded OMV are quickly distributed throughout the body and upregulated expression of genes activating degranulation in neutrophils, potentially contributing to the exacerbation of sepsis severity. This study reveals mechanisms of bacterial ATP release and its local and systemic roles in sepsis pathogenesis. Sepsis is a severe condition often caused by the body’s immune system overreacting to bacterial infections. This can lead to excessive inflammation which damages organs and requires urgent medical care. With sepsis claiming millions of lives each year, new and improved ways to treat this condition are urgently needed. One potential strategy for treating sepsis is to target the underlying mechanisms controlling inflammation. Inflamed and dying cells release molecules called ATP (the energy carrier of all living cells), which strongly influence the immune system, including during sepsis. In the early stages of an infection, ATP acts as a danger signal warning the body that something is wrong. However, over time, it can worsen infections by disturbing the immune response. Similar to human cells, bacteria release their own ATP, which can have different impacts depending on the type of bacteria and where they are located in the body. However, it is not well understood how bacterial ATP influences severe infections like sepsis. To investigate this question, Spari et al analysed how ATP is released from Escherichia coli , a type of bacteria that causes severe infections . This revealed that the bacteria secrete ATP directly in to their environment and via small membrane-bound structures called vesicles. Spari et al. then probed a mouse model of abdominal sepsis which had been infected with E. coli that release either normal or low levels of ATP. They found that the ATP released from E. coli impaired the mice’s survival and lowered the number of neutrophils (immune cells which are important for defending against bacteria) at the site of the infection. The ATP secreted via vesicles also altered the role of neutrophils but in more distant regions, and it is possible that these changes may be contributing to the severity of sepsis. These findings provide a better understanding of how ATP released from bacteria impacts the immune system during sepsis. While further investigation is needed, these findings may offer new therapeutic targets for treating sepsis.

Background Noise pollution in operation rooms may distract the surgical team members. In particular during phases of high task complexity, noise can jeopardize concentration. Phases of high complexity are related to task specificities and may thus be different for different members of the surgical team. Study design Noise exposure was measured during 110 open abdominal surgeries. Distinguishing three phases (opening, main phase, and closing), noise was related to self-report of distraction levels by main and secondary surgeons, scrub nurses and anesthetists. Results Noise pollution was higher than recommended levels for concentrated work. Adjusted for duration, surgical type, and difficulty of the surgery, results showed that second surgeons are more likely distracted when noise pollution was high in the main phase; and anesthetists are more likely distracted when noise pollution was high during the closing phase. Main surgeons’ and scrub nurses’ concentration was not impaired by measured noise levels. Conclusions In phases with higher concentration demands, noise pollution was particularly distracting for second surgeons and anesthetist, corresponding to their specific task demands (anesthetists) and experience (second surgeons). Reducing noise levels particularly in the main and closing phase of the surgery may reduce concentration impairments.

Echinococcus multilocularis causes alveolar echinococcosis (AE), a rising zoonotic disease in the northern hemisphere. Treatment of this fatal disease is limited to chemotherapy using benzimidazoles and surgical intervention, with frequent disease recurrence in cases without radical surgery. Elucidating the molecular mechanisms underlying E. multilocularis infections and host-parasite interactions ultimately aids developing novel therapeutic options. This study explored an involvement of unfolded protein response (UPR) and endoplasmic reticulum-stress (ERS) during E. multilocularis infection in mice. E. multilocularis- and mock-infected C57BL/6 mice were subdivided into vehicle, albendazole (ABZ) and anti-programmed death ligand 1 (αPD-L1) treated groups. To mimic a chronic infection, treatments of mice started six weeks post i.p. infection and continued for another eight weeks. Liver tissue was then collected to examine inflammatory cytokines and the expression of UPR- and ERS-related genes. E. multilocularis infection led to an upregulation of UPR- and ERS-related proteins in the liver, including ATF6, CHOP, GRP78, ERp72, H6PD and calreticulin, whilst PERK and its target eIF2α were not affected, and IRE1α and ATF4 were downregulated. ABZ treatment in E. multilocularis infected mice reversed, or at least tended to reverse, these protein expression changes to levels seen in mock-infected mice. Furthermore, ABZ treatment reversed the elevated levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in the liver of infected mice. Similar to ABZ, αPD-L1 immune-treatment tended to reverse the increased CHOP and decreased ATF4 and IRE1α expression levels. AE caused chronic inflammation, UPR activation and ERS in mice. The E. multilocularis-induced inflammation and consecutive ERS was ameliorated by ABZ and αPD-L1 treatment, indicating their effectiveness to inhibit parasite proliferation and downregulate its activity status. Neither ABZ nor αPD-L1 themselves affected UPR in control mice. Further research is needed to elucidate the link between inflammation, UPR and ERS, and if these pathways offer potential for improved therapies of patients with AE.