The Jak/Stat pathway mediates disease tolerance during systemic bacterial infection in Drosophila

Disease tolerance describes a hosts ability to maintain health independently of the ability to clear microbe loads. However, we currently know little about the mechanisms that underlie disease tolerance or how known mechanisms of tissue damage signalling and repair may contribute to variation in tolerance. The Jak/Stat pathway plays a pivotal role in Drosophila humoral innate immunity, signalling tissue damage and triggering cellular renewal, making it a potential mechanism underlying the disease tolerance phenotype. Here, we show that disrupting the Jak/Stat pathway in Drosophila melanogaster alters disease tolerance during Pseudomonas entomophila systemic infection. Overall, flies with disrupted Jak/Stat show variation in survival that is not explained by variation in pathogen loads. For instance, mutations disrupting the function of ROS producing dual oxidase (duox) or the negative regulator of Jak/Stat, Socs36E render males less tolerant to systemic bacterial infection but not females. We also investigated whether the negative regulator of Jak/Stat, G9a which has previously been associated with tolerance of viral infections is also implicated in tolerance of bacterial infection. While female flies lacking G9a showed higher mortality and reduced bacterial clearance, disease tolerance did not differ between G9a mutants and the wildtype. This suggests that G9a does not affect tolerance during systemic bacterial infection as it appears to do with viral infection. Overall, our findings highlight that Jak/Stat signalling mediates disease tolerance during systemic bacterial infection and that this response differs between males and females. Our work therefore suggests that differences in Jak/Stat mediated disease tolerance may be a potential source of sexually dimorphic response to infection in Drosophila.

Negative regulation of IMD contributes to disease tolerance during systemic bacterial infection in Drosophila

Disease tolerance is an infection phenotype where hosts show relatively high health despite harbouring elevated pathogen loads. Compared to the mechanisms of immune clearance our knowledge of the mechanisms underlying increased tolerance remains incomplete. Variation in the ability to reduce immunopathology may explain why some hosts can tolerate higher pathogen burdens with reduced pathology. Negative immune regulation would therefore appear to be a clear candidate for a mechanism underlying disease tolerance but this has not been tested directly for bacterial infections. Here, we examined how the negative regulation of the immune deficiency (IMD) pathway affects disease tolerance in Drosophila melanogaster when infected with the gram-negative bacterial pathogen Pseudomonas entomophila. We find that UASRNAi-mediated reduced expression of the negative regulators of IMD (pirk & caudal) severely reduced the ability to tolerate infection in both males and females across a wide range of infectious doses. While flies unable to regulate the IMD response exhibited higher expression of antimicrobial peptides and lower bacterial loads as expected, this was not accompanied by a proportional reduction in mortality. Instead, tolerance (measured as fly survival relative to its microbe load) was drastically reduced, likely due to the combination of increased immunopathology and cytotoxicity of elevated AMP expression. Our results therefore highlight that in addition to regulating an efficient pathogen clearance response, negative regulators of IMD also contribute to disease tolerance.

Ceftriaxone-Induced Gallbladder Stones in Children

Gallbladder stones in children is one complication that is mostly seen in diseases such as hemolytic diseases, liver disease, and obesity. It can also be a secondary complication of long-duration use of antibiotics like ceftriaxone. However, gallbladder stone, together with sludge themselves, is unusual within the children's population. We observed three children with gallbladder stones who were on along course of intravenous ceftriaxone. In this study, we present the three cases of children aged between eleven months to seven years who were treated with high doses and for an extended period (more than two weeks) of intravenous ceftriaxone for a complicated systemic bacterial infection. The goal of this study is to raise awareness about the possibility of developing gallbladder stones in pediatric patients who receive a long course of intravenous ceftriaxone.

Serious infectious events and ibuprofen administration in pediatrics: a narrative review in the era of COVID-19 pandemic

Purpose of review Despite its recognized efficacy and tolerability profile, during the last decade a rise of adverse events following ibuprofen administration in children has been reported, including a possible role in worsening the clinical course of infections. Our aim was to critically evaluate the safety of ibuprofen during the course of pediatric infectious disease in order to promote its appropriate use in children. Recent findings Ibuprofen is associated with severe necrotizing soft tissue infections (NSTI) during chickenpox course. Pre-hospital use of ibuprofen seems to increase the risk of complicated pneumonia in children. Conflicting data have been published in septic children, while ibuprofen in the setting of Cystic Fibrosis (CF) exacerbations is safe and efficacious. No data is yet available for ibuprofen use during COVID-19 course. Summary Ibuprofen should not be recommended for chickenpox management. Due to possible higher risks of complicated pneumonia, we suggest caution on its use in children with respiratory symptoms. While it remains unclear whether ibuprofen may have harmful effects during systemic bacterial infection, its administration is recommended in CF course. Despite the lack of data, it is seems cautious to prefer the use of paracetamol during COVID-19 acute respiratory distress syndrome in children.

Hemodynamic Changes of Hepatic & Renal Vessels in Systemic Bacterial Infection with Fever in HCV Related Cirrhosis

Objective: To study the hemodynamic changes of hepatic & renal vessels in systemic bacterial infection with fever in HCV related cirrhosis with possible complications. Methods: Three groups of patients with systemic bacterial infection with fever were included in the study; group І included 15 patients with decompensated cirrhosis, group ІІ included 15 patients with compensated cirrhosis and group ІІІ included 10 patients without liver affection. Laboratory parameters and Doppler US of hepatic and renal vessels were evaluated during and after subsidence of fever in all patients. Results: Forty patients were enrolled in this prospective study. There were 22 male and 18 female patients. We found that the direction of blood flow in the portal and splenic veins was hepatopetal and the veins were non pulsatile in all cases with no change during and after subsidence of infection. There was no significant difference in portal or splenic vein diameters during and after subsidence of infection in the three studied groups. However, the mean values of portal and splenic veins peak velocities were significantly lower during infection in cirrhotic groups. The mean value of hepatic artery resistive index during fever was significantly higher than after fever in cirrhotic groups. Renal resistive and pulsatility indices were significantly higher during fever in cirrhotic groups. Conclusion: Systemic bacterial infection with fever can affect hepatic haemodynamics leading to aggravation of portal hypertension and increasing the risk of complications as variceal bleeding and hepatic encephalopathy and can also affect renal haemodynamics with increased risk of renal impairment.

Stroke and the immune system: A review of the new strategies

The immunology of stroke can be approached in several ways. By viewing stroke from an immunological standpoint, we are trying to achieve new insights in its pathogenesis and reach new therapeutic options. To review and summarize the findings from publications on immunology of stroke. Infections are a well-known risk factor for stroke. This is due to activated immune cells interacting with throm-bocytes and releasing coagulation factors, which affect the formation of the thrombus. Aseptic inflammation in the ischemic lesion leads to cellular invasion of the area and triggers a pro-inflammatory response, which has an impact on further destruction of ischemic brain tissue. Another aspect of stroke is systemic immune suppression, which is a predisposing factor towards a systemic bacterial infection. Infection itself is also an independent risk factor for negative clinical outcomes and increased mortality. The immunological approach to the topic of ischemic stroke holds significant value for future research.

Pathologic findings and causes of death in bottlenose dolphins Tursiops truncatus stranded along the Georgia coast, USA (2007-2013)

Between 2007 and 2013, before the 2013 cetacean morbillivirus outbreak, 26 fresh bottlenose dolphin carcasses were necropsied on the coast of Georgia, USA. Here, we present the pathological and microbiological findings associated with their most likely causes of death. The primary cause of death was determined in 25 individuals and included systemic bacterial infection (n = 7), verminous and bacterial bronchopneumonia (n = 5), drowning/entanglement (n = 5), disseminated histoplasmosis (n = 1), intestinal intussusception (n = 1), vegetative endocarditis (n = 1), meningitis (n = 1), necrotizing dermatitis (n = 1), disseminated angiomatosis (n = 1), emaciation (n = 1) and stingray spine trauma (n = 1). Histiocytic and eosinophilic bronchopneumonia associated with Halocerchus sp. infection was observed in 69% of the animals (18/26) and eosinophilic gastritis due to Anisakidae nematodes was found in 36% of the examined stomachs (8/22). Moderate to severe eosinophilic pancreatitis with fibrosis was observed in 4 animals infected with Brachycladiidae trematodes. Proliferative and ulcerative lymphoplasmacytic dermatitis was found in 5 animals and was considered to contribute to deteriorated health status in 2 calves. Pulmonary and lymph node angiomatosis were observed in 15 and 10 animals, respectively. In at least 2 animals, the concentration of polychlorinated biphenyls (PCBs) in the blubber exceeded 1500 µg g-1 of lipid. Bottlenose dolphins stranded on the Georgia coast have a wide range of inflammatory lesions associated with a variety of helminth, bacterial, and fungal pathogens. Some resident animals have also been exposed to high levels of PCB contamination, which could reduce host immunocompetence. Higher exposure to these or other pathogens could result in further decline in the health of resident and migrant dolphin populations in this region.