Fluorescence microscopy is a broadly used technique within a variety of different fields, including life sciences and medical research, and its quantitative aspects are becoming emphasized. The ...challenge now lies in improving the accuracy and precision of the measurements obtained from fluorescence microscopy. Improving these will facilitate the comparison of results between different instruments/institutions and therefore ensure the reproducibility of results. In this review, recent standardization procedures, including the benchmarking of the instrument performance and the standardization of the image itself, as well as the reference materials for calibration are summarized, and an overview of the advances in fluorescence microscopy standardization and the current limitations are presented. A procedure for the comparison of the image data obtained using different instruments, by different analysts and/or at different times, should be developed to improve the standardization of this data. The standardization of image data would lead to the development of new applications of fluorescence microscopy not only in academic research but also in regulatory science.
The repeated emergence of SARS-CoV-2 escape mutants from host immunity has obstructed the containment of the current pandemic and poses a serious threat to humanity. Prolonged infection in ...immunocompromised patients has received increasing attention as a driver of immune escape, and accumulating evidence suggests that viral genomic diversity and emergence of immune-escape mutants are promoted in immunocompromised patients. However, because immunocompromised patients comprise a small proportion of the host population, whether they have a significant impact on antigenic evolution at the population level is unknown. We consider an evolutionary epidemiological model that combines antigenic evolution and epidemiological dynamics. Applying this model to a heterogeneous host population, we study the impact of immunocompromised hosts on the evolutionary dynamics of pathogen antigenic escape from host immunity. We derived analytical formulae of the speed of antigenic evolution in heterogeneous host populations and found that even a small number of immunocompromised hosts in the population significantly accelerates antigenic evolution. Our results demonstrate that immunocompromised hosts play a key role in viral adaptation at the population level and emphasize the importance of critical care and surveillance of immunocompromised hosts.
Tubeworms and sulfur-oxidizing bacteria mutualism, an essential part of the chemosynthetic ecosystem in the deep sea, has several puzzling features. After acquiring sulfur-oxidizing bacteria from the ...environment, tubeworms become fully dependent on their symbiont bacteria for nutrient intake. Once ingested by the tubeworm larva, no additional symbionts join from the environment, and no symbionts are released until the host tubeworm dies. Despite this very narrow window to acquire symbionts, some tubeworm species can live for >200 years. Such a restricted release of symbionts could lead to a shortage of symbiont bacteria in the environment without which tubeworms could not survive. In our study, we examine the conditions under which this mutualism can persist and whether the host mortality rate evolves toward a low value using a mathematical model for the tubeworm–symbiont bacteria system. Our model reveals that mutualism can persist only when the host mortality rate is within an intermediate range. With cohabitation of multiple symbionts strains in the same host, host mortality rate evolves toward a low value without driving either host or symbiont to extinction when competition among symbionts is weak and their growth within a host is slow. We also find the parameter conditions that lead to unlimited evolutionary escalation of host mortality rate toward coextinction of both tubeworms and symbionts populations (evolutionary double suicide). The generality of this evolutionary fragility in obligate mutualistic systems as well as the contrasting evolutionary robustness in host-parasite systems are discussed.
Background
Extending the clinical indications for laparoscopic liver resection (LLR) should be carefully considered based on a surgeon’s experience and skill. However, objective indexes to help ...surgeons assess the estimated difficulty of LLR are scarce. The aim of our study was to develop the first objective numerical rating scale to predict the surgical difficulty of various LLR procedures.
Methods
We performed a retrospective review of the operative outcomes of 187 patients who underwent a pure LLR. First, the value of preoperative factors for predicting surgical time was evaluated by multivariate linear regression analyses, and a scoring system was constructed. Next, the integrity of our predictive linear model was evaluated against the documented operative outcomes for patients forming our study group.
Results
Four predictive factors were identified and scored based on the weighted contribution of each factor predicting surgical time: extent of resection (scored 0, 2, or 3); location of tumor (scored 0, 1, or 2); obesity (scored 0 or 1); and platelet count (scored 0 or 1). The scores were summed to classify surgical difficulty into three levels: low (total score ≤1); medium (total score 2–3); and high (total score ≥4). Operative outcomes, including surgical time, volume of blood loss, length of hospital stay, and rate of morbidity, were significantly different between the three surgical difficulty levels.
Conclusion
Our novel model will be useful for surgeons to predict the difficulty of an LLR procedure relative to their own experience and skill.
Our understanding of the evolution of quantitative traits in nature is still limited by the challenge of including realistic trait distributions in the context of frequency-dependent selection and ...ecological feedbacks. We extend to class-structured populations a recently introduced “oligomorphic approximation,” which bridges the gap between adaptive dynamics and quantitative genetics approaches and allows for the joint description of the dynamics of ecological variables and of the moments of multimodal trait distributions. Our theoretical framework allows us to analyze the dynamics of populations composed of several morphs and structured into distinct classes (e.g., age, size, habitats, infection status, and species). We also introduce a new approximation to simplify the eco-evolutionary dynamics using reproductive values. We illustrate the effectiveness of this approach by applying it to the important conceptual case of two-habitat migration-selection models. In particular, we show that our approach allows us to predict both the long-term evolutionary end points and the short-term transient dynamics of the eco-evolutionary process, including fast evolution regimes. We discuss the theoretical and practical implications of our results and sketch perspectives for future work.
Abstract
Nonalcoholic steatohepatitis (NASH) and glucose intolerance are associated with an increased risk of mortality in patients with severe obesity; however, whether histological findings of the ...liver are related to glucose intolerance in these patients remain unknown. Sixty-nine consecutive patients who underwent metabolic surgery between June 2008 and February 2020 were included; histological findings of the liver and laboratory data were analyzed. Twenty patients with biopsy-proven NASH were chronologically evaluated using sequential biopsies; data before metabolic surgery was considered as the baseline. Glucose intolerance—demonstrated by an increased area under the curve (AUC) for blood sugar (BS) during the 75-g oral glucose tolerance test—and increased homeostatic model assessment for insulin resistance (HOMA-IR) correlated with the grade of hepatocyte ballooning in patients. Patients with persistent ballooning at the follow-up biopsy had a higher HOMA-IR, high AUC for BS, and lower adiponectin level than those in patients in whom ballooning was eliminated, while there was no significant difference in body weight. We concluded that glucose intolerance was associated with the grade of hepatocyte ballooning; additionally, persistent hepatocyte ballooning sustained glucose intolerance, while elimination of hepatocyte ballooning improved the condition. Glucose intolerance may, thus, mediate balloon formation of the hepatocyte.
Purpose This study investigated whether liver damage severity relates to the mobilization of multilineage-differentiating stress-enduring (Muse) cells, which are endogenous reparative pluripotent ...stem cells, into the peripheral blood (PB) and whether the degree of mobilization relates to the recovery of liver volume following human liver surgery. Methods Forty-seven patients who underwent liver surgery were included in the present study. PB-Muse cells were counted before surgery, on postoperative days (PODs) 3 and on POD 7. Liver volume was measured using computed tomography before and after surgery. Results The PB-Muse cell count increased after surgery. The number of PB-Muse cells before surgery was higher, but without statistical significance in the group with neoplasms than in the healthy group that included liver donors (p = 0.065). Forty-seven patients who underwent liver surgery were divided into major hepatic resection (MHR; hepatectomy of three or more segments according to the Couinaud classification, n = 22) and minor hepatic resection (mhr; hepatectomy of two segments or less according to the Couinaud classification, n = 25) groups. PB-Muse cells increased at high rates among MHR patients (p = 0.033). Except for complication cases, PB-Muse cells increased at higher rates in the group with advanced liver volume recovery (p = 0.043). The predictive impact of the rate of increase in PB-Muse cells on the recovery of liver volume was demonstrated by multivariate analysis (OR 11.0, p = 0.014). Conclusions PB-Muse cell mobilization correlated with the volume of liver resection, suggesting that the PB-Muse cell number reflects the degree of liver injury. Given that the degree of PB-Muse cell mobilization was related to liver volume recovery, PB-Muse cells were suggested to contribute to liver regeneration, although this mechanism remains unclear.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
The prevalence of non-alcoholic steatohepatitis (NASH) in Japanese patients with severe obesity is extremely high. The aim of the present study was to evaluate the metabolic and ...histological effects of laparoscopic sleeve gastrectomy (LSG) on NASH and liver fibrosis in Japanese patients with severe obesity.
Methods
Between June 2008 and March 2019, all 79 patients with severe obesity who underwent LSG were included in the study. Sixty-eight patients had an intraoperative liver biopsy performed at the time of LSG. Ultrasound-guided liver biopsies were performed in patients with fibrosis at 12 months after LSG.
Results
NASH was present in 43 patients (63.2%), and 10 patients had a unique feature in which their fibrosis were observed without steatosis at the time of LSG. Of the 28 patients with NASH, 25 showed improvement and no longer met the diagnostic criteria of NASH at 12 months after LSG. Mean pericellular fibrosis scores showed significant improvement from 1.62 at baseline, to 1.50, 1.00, and 0.78, respectively (
p
< 0.001). Univariate analysis of the preoperative predictors in the improvement of fibrosis showed significant effects in preoperative weight (
p
= 0.037), HbA1c (
p
= 0.037), and serum insulin (
p
= 0.037). Multivariate analysis revealed HbA1c to be the only preoperative predictor of improvement in fibrosis (
p
= 0.004; odds ratio 0.440, 95% CI 0.229–0.842).
Conclusions
LSG has great potential as an effective treatment for patients with NASH.
Despite the propensity for complex and non-equilibrium dynamics in nature, eco-evolutionary analytical theory typically assumes that populations are at equilibria. In particular, pathogens often show ...antigenic escape from host immune defences, leading to repeated epidemics, fluctuating selection and diversification, but we do not understand how this impacts the evolution of virulence. We model the impact of antigenic drift and escape on the evolution of virulence in a generalized pathogen and apply a recently introduced oligomorphic methodology that captures the dynamics of the mean and variance of traits, to show analytically that these non-equilibrium dynamics select for the long-term persistence of more acute pathogens with higher virulence. Our analysis predicts both the timings and outcomes of antigenic shifts leading to repeated epidemics and predicts the increase in variation in both antigenicity and virulence before antigenic escape. There is considerable variation in the degree of antigenic escape that occurs across pathogens and our results may help to explain the difference in virulence between related pathogens including, potentially, human influenzas. Furthermore, it follows that these pathogens will have a lower R
, with clear implications for epidemic behaviour, endemic behaviour and control. More generally, our results show the importance of examining the evolutionary consequences of non-equilibrium dynamics.
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