Perioperative visual loss (POVL), a rare, but devastating complication, can follow non-ocular surgery. Highest rates of visual loss are with cardiac and spine surgery. The main causes of visual loss ...after non-ocular surgery are retinal vascular occlusion and ischaemic optic neuropathy. This review updates readers on the incidence, suspected risk factors, diagnosis, and treatment of POVL due to these conditions.
At the moment of the diagnosis of hepatocellular carcinoma (HCC), 70% of patients have only access to palliative treatments, with very few therapeutic options. Liver immunology is very specific, and ...liver immunotolerance is particularly developed because of the constant and massive influx of antigens. Deregulation of hepatic immunotolerance is implicated in chronic liver diseases development and particularly in liver carcinogenesis. For these reasons, HCC may be an excellent candidate for anticancer immunotherapies such as immune checkpoint inhibitors targeting CTLA-4 and PD-L1/PD-1. Nonetheless, because of the specific immune environment of the liver and the frequent association of HCC with hepatocellular insufficiency, the safety and the efficacy of these new treatments have to be properly studied in this situation. Thus, multiple phase II and III studies are in progress studying immune checkpoint inhibitor monotherapies, combination of different immunotherapies or local strategies such as transarterial chemoembolization combined with immune checkpoint inhibitors. Currently, only the final results of the tremelimumab phase II and the Nivolumab phase I/II study (CheckMate-040) are available. The latter is promising but need to be confirmed by the ongoing phase III studies to confirm the place of immunotherapy in the treatment of HCC. With many new molecular targets and therapeutic combination, immunotherapy represents a new hope in treating HCC patients although serious evaluation is still needed to confirm its interest.
•Liver immunotolerance is particularly developed due to a permanent and massive antigen influx.•Immunotolerance deregulation is involved in chronic liver diseases and hepatocellular carcinoma (HCC) carcinogenesis.•Multiple immunotherapies as vaccines, cytokines, adoptive cell transfer have been evaluated in HCC with heterogenous results.•Immune checkpoints as CTLA-4 and PD-1 are essential in liver immunotolerance.•Immune checkpoints inhibitors are promising in HCC treatment with multiple ongoing phase II and III clinical trials.
The potential of bispecific T cell-engaging antibodies is hindered by manufacturing challenges and short serum half-life. We circumvented these limitations by treating mice with in vitro-transcribed ...pharmacologically optimized, nucleoside-modified mRNA encoding the antibody. We achieved sustained endogenous synthesis of the antibody, which eliminated advanced tumors as effectively as the corresponding purified bispecific antibody. Because manufacturing of pharmaceutical mRNA is fast, this approach could accelerate the clinical development of novel bispecific antibodies.
A systematic study of the magnetic properties and both the temperature- and magnetic-field-induced structural transformations in the Ni50−xCoxMn39Sn11 (0⩽x⩽10) multifunctional alloys over a large ...temperature range from 500K down to 10K was performed. It is revealed that, with increasing x, the martensitic transformation temperatures first decrease slowly when 0⩽x⩽4 and then decrease rapidly when 5⩽x⩽8; no martensitic transformation was observed in the alloys with 9⩽x⩽10. The magnetic properties of these alloys are very sensitive to their chemical composition. The austenite in the alloys with 0⩽x⩽4 shows paramagnetic behavior and the martensite exhibits paramagnetic, superparamagnetic (SPM), and superspin glass (SSG) behaviors in different temperature ranges during cooling. In contrast, the austenite in the alloys with 5⩽x⩽8 is paramagnetic above its Curie temperature TC and ferromagnetic below TC, and the martensite shows SPM and SSG behaviors in different temperature ranges. The austenite in the alloys with 9⩽x⩽10, which remains stable down to 10K, shows paramagnetic and ferromagnetic behaviors above and below TC, respectively. The complete phase diagram for the Ni50−xCoxMn39Sn11 (0⩽x⩽10) alloy system, from high temperature down to 10K, is established. A significant magnetic-field-induced decrease of martensitic transformation temperatures and almost fully reversible magnetic-field-induced structural transformation are achieved across a broad temperature range in the alloys with 5⩽x⩽8. These results are important for understanding the composition and temperature-dependent functional properties, as well as their underlying mechanisms, in the Ni–(Co)–Mn–X (X=In, Sn, Sb) multifunctional alloys.
Previously, we found that dogs belonging to the herding breed group, selected for human cooperation, synchronise their long-term stress levels with their owners. The aim of the current study was to ...investigate features that could influence long-term stress levels in ancient dog breeds, genetically closer to wolves, and dogs specifically selected to work independently of their owner. Twenty-four ancient breed dogs and 18 solitary hunting dogs were recruited and hair samples were obtained from both dogs and owners from which hair cortisol concentration (HCC) was analysed. Additionally, the owners completed lifestyle surveys, the Monash Dog Owner Relationship Scale (MDORS) on human-dog relationship, and both dog and owner personality questionnaires (Dog Personality questionnaire and Big Five Inventory survey). The results from the MDORS indicate that the subscale Perceived cost correlated to the dog HCC of tested breed groups: solitary hunting breeds (χ
= 4.95, P = 0.026, β = 0.055), ancient breeds (χ
= 2.74, P = 0.098, β = 0.027), and herding dogs included from a previous study (χ
= 6.82, P = 0.009, β = - 0.061). The HCC of the solitary hunting dogs was also related to the owner personality traits Agreeableness (χ
= 12.30, P < 0.001, β = - 0.060) and Openness (χ
= 9.56, P = 0.002, β = 0.048) suggesting a more substantial influence of the owner on the solitary hunting dog's HCC compared to the ancient breeds. No effect of owner HCC on dog HCC was found in either ancient or in solitary hunting breeds. Hence, the long-term stress synchronisation is likely to be a trait in breeds selected for human cooperation. In conclusion, dog HCC is often related to the owners' personality, but is primarily influenced by the owner-dog relationship.
Caloric restriction (CR) without malnutrition extends lifespan and delays the onset of age-related disorders in most species but its impact in nonhuman primates has been controversial. In the late ...1980s two parallel studies were initiated to determine the effect of CR in rhesus monkeys. The University of Wisconsin study reported a significant positive impact of CR on survival, but the National Institute on Aging study detected no significant survival effect. Here we present a direct comparison of longitudinal data from both studies including survival, bodyweight, food intake, fasting glucose levels and age-related morbidity. We describe differences in study design that could contribute to differences in outcomes, and we report species specificity in the impact of CR in terms of optimal onset and diet. Taken together these data confirm that health benefits of CR are conserved in monkeys and suggest that CR mechanisms are likely translatable to human health.
The global pandemic of SARS-CoV-2, the causative viral pathogen of COVID-19, has driven the biomedical community to actionto uncover and develop antiviral interventions. One potential therapeutic ...approach currently being evaluated in numerous clinical trials is the agent remdesivir, which has endured a long and winding developmental path. Remdesivir is a nucleotide analogue prodrug that perturbs viral replication, originally evaluated in clinical trials to thwart the Ebola outbreak in 2014. Subsequent evaluation by numerous virology laboratories demonstrated the ability of remdesivir to inhibit coronavirus replication, including SARS-CoV-2. Here, we provide an overview of remdesivir’s discovery, mechanism of action, and the current studies exploring its clinical effectiveness.
Dogs have previously been shown to synchronise their behaviour with their owner and the aim of this study was to test the effect of immediate interactions, breed, and the effects of domestication. ...The behavioural synchronisation test was conducted in outdoor enclosures and consisted of 30 s where the owner/handler was walking and 30 s of standing still. Three studies were conducted to explore the effect of immediate interaction (study A), the effect of breed group (study B), and the effect of domestication (study C). In study A, a group of twenty companion dogs of various breeds were tested after three different human interaction treatments: Ignore, Pet, and Play. The results showed that dogs adjusted their movement pattern to align with their owner's actions regardless of treatment. Furthermore, exploration, eye contact, and movement were all influenced by the owners moving pattern, and exploration also decreased after the Play treatment. In study B, the synchronisation test was performed after the Ignore treatment on three groups: 24 dogs of ancient dog breeds, 17 solitary hunting dogs, and 20 companion dogs (data from study A). Irrespective of the group, all dogs synchronised their moving behaviour with their owner. In addition, human walking positively influenced eye contact behaviour while simultaneously decreasing exploration behaviour. In study C, a group of six socialised pack-living wolves and six similarly socialised pack-living dogs were tested after the Ignore treatment. Interestingly, these animals did not alter their moving behaviour in response to their handler. In conclusion, dogs living together with humans synchronise with their owner's moving behaviour, while wolves and dogs living in packs do not. Hence, the degree of interspecies behavioural synchronisation may be influenced by the extent to which the dogs are immersed in everyday life with humans.
Acute brain ischemia induces a local neuroinflammatory reaction and alters peripheral immune homeostasis at the same time. Recent evidence has suggested a key role of the gut microbiota in autoimmune ...diseases by modulating immune homeostasis. Therefore, we investigated the mechanistic link among acute brain ischemia, microbiota alterations, and the immune response after brain injury. Using two distinct models of acute middle cerebral artery occlusion, we show by next-generation sequencing that large stroke lesions cause gut microbiota dysbiosis, which in turn affects stroke outcome via immune-mediated mechanisms. Reduced species diversity and bacterial overgrowth of bacteroidetes were identified as hallmarks of poststroke dysbiosis, which was associated with intestinal barrier dysfunction and reduced intestinal motility as determined by in vivo intestinal bolus tracking. Recolonizing germ-free mice with dysbiotic poststroke microbiota exacerbates lesion volume and functional deficits after experimental stroke compared with the recolonization with a normal control microbiota. In addition, recolonization of mice with a dysbiotic microbiome induces a proinflammatory T-cell polarization in the intestinal immune compartment and in the ischemic brain. Using in vivo cell-tracking studies, we demonstrate the migration of intestinal lymphocytes to the ischemic brain. Therapeutic transplantation of fecal microbiota normalizes brain lesion-induced dysbiosis and improves stroke outcome. These results support a novel mechanism in which the gut microbiome is a target of stroke-induced systemic alterations and an effector with substantial impact on stroke outcome.
We have identified a bidirectional communication along the brain-gut microbiota-immune axis and show that the gut microbiota is a central regulator of immune homeostasis. Acute brain lesions induced dysbiosis of the microbiome and, in turn, changes in the gut microbiota affected neuroinflammatory and functional outcome after brain injury. The microbiota impact on immunity and stroke outcome was transmissible by microbiota transplantation. Our findings support an emerging concept in which the gut microbiota is a key regulator in priming the neuroinflammatory response to brain injury. These findings highlight the key role of microbiota as a potential therapeutic target to protect brain function after injury.
The urobiome in men and women: a clinical review Roth, Romain S.; Liden, Mia; Huttner, Angela
Clinical microbiology and infection,
October 2023, 2023-10-00, 20231001, Letnik:
29, Številka:
10
Journal Article
Recenzirano
Antibiotic therapy alone is unable to control recurrent urinary tract infection (UTI); uropathogens have become multiresistant, and alternative strategies are needed. Far from sterile, the urinary ...tract contains various low-biomass microbiota, some of whose members appear to protect against clinical UTI.
This narrative review summarizes (a) the current knowledge of male and female urobiomes in healthy and diseased states, as well as their interplay among sexual partners and (b) clinical trials to date assessing probiotic and other nonantibiotic measures to reduce UTI.
We used the PubMed interface to search Ovid Medline for articles describing urogenital flora, UTI, UTI dysbiosis, the effects of sexual intercourse on urogenital flora, and clinical trials of probiotics as UTI prophylaxis.
The healthy urobiome of women contains several Lactobacillus species, some of which may impede Escherichia coli growth in the urinary tract. Although Lactobacilli have been found in male urethral microbiota, their presence in male bladder microbiota is less certain. Distal male urethral and vaginal microbiomes of male and sexual female partners influence one another, but more research is needed on the direct interplay of their full urobiomes. Clinical trials assessing the therapeutic potential of Lactobacilli have been largely underpowered and highly varied in tested formulations and routes and frequencies of administration; as such, they have failed to show a clear benefit. Faecal microbiota transplantation for recurrent Clostridium difficile infection was shown, in a retrospective study of seven patients, to reduce recurrent UTI as a side effect.
The urobiome in men and women is complex, variable, and still understudied. Although there is hope that Lactobacilli and faecal microbial transplantation could be future nonantibiotic options for recurrent UTI, both require more pharmacologic and clinical research to identify optimal preparations and routes of administration.
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