scholarly journals Route of Injection Affects the Impact of InlB Internalin Domain Variants on Severity ofListeria monocytogenesInfection in Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Konstantin A. Sobyanin ◽  
Elena V. Sysolyatina ◽  
Yaroslava M. Chalenko ◽  
Egor V. Kalinin ◽  
Svetlana A. Ermolaeva

The facultative intracellular pathogenListeria monocytogenescauses a severe food-borne infection in humans and animals.L. monocytogenesinvasion factor InlB interacts with the tyrosine kinase c-Met via the N-terminal internalin domain. Previously, distinct variants of the InlB internalin domain (idInlB) have been described inL. monocytogenesfield isolates. Three variants were used to restore full-length InlB expression in theL. monocytogenesstrain EGDeΔinlB. Obtained isogenicL. monocytogenesstrains were tested in the invasion assay and intravenous, intraperitoneal, and intragastric models of infection in mice. All idInlBs were functional, restored InlB activity as an invasion factor, and improved invasion of the parental strain EGDeΔinlB into human kidney HEK23 cells. Meanwhile, distinct idInlBs provided different mortality rates and bacterial loads in internal organs. When recombinant strains were compared, the variant designated idInlB14 decreased severity of disease caused by intravenous and intraperitoneal bacterial administration, whereas this variant improved intestine colonization and stimulated intragastric infection. Obtained results demonstrated that naturally occurring idInlBs differed in their impact on severity ofL. monocytogenesinfection in mice in dependence on the infection route.

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Matthias Unterberg ◽  
Tim Rahmel ◽  
Katharina Rump ◽  
Alexander Wolf ◽  
Helge Haberl ◽  
...  

Abstract Background The COVID-19 pandemic has taken a toll on health care systems worldwide, which has led to increased mortality of different diseases like myocardial infarction. This is most likely due to three factors. First, an increased workload per nurse ratio, a factor associated with mortality. Second, patients presenting with COVID-19-like symptoms are isolated, which also decreases survival in cases of emergency. And third, patients hesitate to see a doctor or present themselves at a hospital. To assess if this is also true for sepsis patients, we asked whether non-COVID-19 sepsis patients had an increased 30-day mortality during the COVID-19 pandemic. Methods This is a post hoc analysis of the SepsisDataNet.NRW study, a multicentric, prospective study that includes septic patients fulfilling the SEPSIS-3 criteria. Within this study, we compared the 30-day mortality and disease severity of patients recruited pre-pandemic (recruited from March 2018 until February 2020) with non-COVID-19 septic patients recruited during the pandemic (recruited from March 2020 till December 2020). Results Comparing septic patients recruited before the pandemic to those recruited during the pandemic, we found an increased raw 30-day mortality in sepsis-patients recruited during the pandemic (33% vs. 52%, p = 0.004). We also found a significant difference in the severity of disease at recruitment (SOFA score pre-pandemic: 8 (5 - 11) vs. pandemic: 10 (8 - 13); p < 0.001). When adjusted for this, the 30-day mortality rates were not significantly different between the two groups (52% vs. 52% pre-pandemic and pandemic, p = 0.798). Conclusions This led us to believe that the higher mortality of non-COVID19 sepsis patients during the pandemic might be attributed to a more severe septic disease at the time of recruitment. We note that patients may experience a delayed admission, as indicated by elevated SOFA scores. This could explain the higher mortality during the pandemic and we found no evidence for a diminished quality of care for critically ill sepsis patients in German intensive care units.


Author(s):  
Michel Paul Johan Teuben ◽  
Carsten Mand ◽  
Laura Moosdorf ◽  
Kai Sprengel ◽  
Alba Shehu ◽  
...  

Abstract Background Simultaneous trauma admissions expose medical professionals to increased workload. The impact of simultaneous trauma admissions on hospital allocation, therapy, and outcome is currently unclear. We hypothesized that multiple admission-scenarios impact the diagnostic pathway and outcome. Methods The TraumaRegister DGU® was utilized. Patients admitted between 2002–2015 with an ISS ≥ 9, treated with ATLS®- algorithms were included. Group ´IND´ included individual admissions, two individuals that were admitted within 60 min of each other were selected for group ´MULT´. Patients admitted within 10 min were considered as simultaneous (´SIM´) admissions. We compared patient and trauma characteristics, treatment, and outcomes between both groups. Results 132,382 admissions were included, and 4,462/3.4% MULTiple admissions were found. The SIM-group contained 1,686/1.3% patients. The overall median injury severity score was 17 and a mean age of 48 years was found. MULT patients were more frequently admitted to level-one trauma centers (68%) than individual trauma admissions were (58%, p < 0.001). Mean time to CT-scanning (24 vs. 26/28 min) was longer in MULT / SIM patients compared to individual admissions. No differences in utilization of damage control principles were seen. Moreover, mortality rates did not differ between the groups (13.1% in regular admissions and 11.4%/10,6% in MULT/SIM patients). Conclusion This study demonstrates that simultaneous treatment of injured patients is rare. Individuals treated in parallel with other patients were more often admitted to level-one trauma centers compared with individual patients. Although diagnostics take longer, treatment principles and mortality are equal in individual admissions and simultaneously admitted patients. More studies are required to optimize health care under these conditions.


Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 848
Author(s):  
Benjamin Eid ◽  
David Beggs ◽  
Peter Mansell

In 2019–2020, a particularly bad bushfire season in Australia resulted in cattle being exposed to prolonged periods of smoke haze and reduced air quality. Bushfire smoke contains many harmful pollutants, and impacts on regions far from the fire front, with smoke haze persisting for weeks. Particulate matter (PM) is one of the major components of bushfire smoke known to have a negative impact on human health. However, little has been reported about the potential effects that bushfire smoke has on cattle exposed to smoke haze for extended periods. We explored the current literature to investigate evidence for likely effects on cattle from prolonged exposure to smoke generated from bushfires in Australia. We conducted a search for papers related to the impacts of smoke on cattle. Initial searching returned no relevant articles through either CAB Direct or PubMed databases, whilst Google Scholar provided a small number of results. The search was then expanded to look at two sub-questions: the type of pollution that is found in bushfire smoke, and the reported effects of both humans and cattle being exposed to these types of pollutants. The primary mechanism for damage due to bushfire smoke is due to small airborne particulate matter (PM). Although evidence demonstrates that PM from bushfire smoke has a measurable impact on both human mortality and cardiorespiratory morbidities, there is little evidence regarding the impact of chronic bushfire smoke exposure in cattle. We hypothesize that cattle are not severely affected by chronic exposure to smoke haze, as evidenced by the lack of reports. This may be because cattle do not tend to suffer from the co-morbidities that, in the human population, seem to be made worse by smoke and pollution. Further, small changes to background mortality rates or transient morbidity may also go unreported.


Biology ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 471
Author(s):  
Camino Gutiérrez-Corbo ◽  
Bárbara Domínguez-Asenjo ◽  
María Martínez-Valladares ◽  
Yolanda Pérez-Pertejo ◽  
Carlos García-Estrada ◽  
...  

Diseases caused by trypanosomatids (Sleeping sickness, Chagas disease, and leishmaniasis) are a serious public health concern in low-income endemic countries. These diseases are produced by single-celled parasites with a diploid genome (although aneuploidy is frequent) organized in pairs of non-condensable chromosomes. To explain the way they reproduce through the analysis of natural populations, the theory of strict clonal propagation of these microorganisms was taken as a rule at the beginning of the studies, since it partially justified their genomic stability. However, numerous experimental works provide evidence of sexual reproduction, thus explaining certain naturally occurring events that link the number of meiosis per mitosis and the frequency of mating. Recent techniques have demonstrated genetic exchange between individuals of the same species under laboratory conditions, as well as the expression of meiosis specific genes. The current debate focuses on the frequency of genomic recombination events and its impact on the natural parasite population structure. This paper reviews the results and techniques used to demonstrate the existence of sex in trypanosomatids, the inheritance of kinetoplast DNA (maxi- and minicircles), the impact of genetic exchange in these parasites, and how it can contribute to the phenotypic diversity of natural populations.


Marine Drugs ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 196
Author(s):  
Muhammad Bilal ◽  
Leonardo Vieira Nunes ◽  
Marco Thúlio Saviatto Duarte ◽  
Luiz Fernando Romanholo Ferreira ◽  
Renato Nery Soriano ◽  
...  

Naturally occurring biological entities with extractable and tunable structural and functional characteristics, along with therapeutic attributes, are of supreme interest for strengthening the twenty-first-century biomedical settings. Irrespective of ongoing technological and clinical advancement, traditional medicinal practices to address and manage inflammatory bowel disease (IBD) are inefficient and the effect of the administered therapeutic cues is limited. The reasonable immune response or invasion should also be circumvented for successful clinical translation of engineered cues as highly efficient and robust bioactive entities. In this context, research is underway worldwide, and researchers have redirected or regained their interests in valorizing the naturally occurring biological entities/resources, for example, algal biome so-called “treasure of untouched or underexploited sources”. Algal biome from the marine environment is an immense source of excellence that has also been demonstrated as a source of bioactive compounds with unique chemical, structural, and functional features. Moreover, the molecular modeling and synthesis of new drugs based on marine-derived therapeutic and biological cues can show greater efficacy and specificity for the therapeutics. Herein, an effort has been made to cover the existing literature gap on the exploitation of naturally occurring biological entities/resources to address and efficiently manage IBD. Following a brief background study, a focus was given to design characteristics, performance evaluation of engineered cues, and point-of-care IBD therapeutics of diverse bioactive compounds from the algal biome. Noteworthy potentialities of marine-derived biologically active compounds have also been spotlighted to underlying the impact role of bio-active elements with the related pathways. The current review is also focused on the applied standpoint and clinical translation of marine-derived bioactive compounds. Furthermore, a detailed overview of clinical applications and future perspectives are also given in this review.


Author(s):  
Alessandro Marcon ◽  
Elena Schievano ◽  
Ugo Fedeli

Mortality from idiopathic pulmonary fibrosis (IPF) is increasing in most European countries, but there are no data for Italy. We analysed the registry data from a region in northeastern Italy to assess the trends in IPF-related mortality during 2008–2019, to compare results of underlying vs. multiple cause of death analyses, and to describe the impact of the COVID-19 epidemic in 2020. We identified IPF (ICD-10 code J84.1) among the causes of death registered in 557,932 certificates in the Veneto region. We assessed time trends in annual age-standardized mortality rates by gender and age (40–74, 75–84, and ≥85 years). IPF was the underlying cause of 1310 deaths in the 2251 certificates mentioning IPF. For all age groups combined, the age-standardized mortality rate from IPF identified as the underlying cause of death was close to the European median (males and females: 3.1 and 1.3 per 100,000/year, respectively). During 2008–2019, mortality rates increased in men aged ≥85 years (annual percent change of 6.5%, 95% CI: 2.0, 11.2%), but not among women or for the younger age groups. A 72% excess of IPF-related deaths was registered in March–April 2020 (mortality ratio 1.72, 95% CI: 1.29, 2.24). IPF mortality was increasing among older men in northeastern Italy. The burden of IPF was heavier than assessed by routine statistics, since less than two out of three IPF-related deaths were directly attributed to this condition. COVID-19 was accompanied by a remarkable increase in IPF-related mortality.


Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 942
Author(s):  
Yuanbin Zhang ◽  
Dongfang Liu ◽  
Fan Xue ◽  
Hongli Yu ◽  
Hao Wu ◽  
...  

This study evaluated the anti-ascites effect of total diterpenoids extracted from Euphorbiae ebracteolatae Radix (TDEE) on malignant ascitic mice and elucidated its underlying mechanism. TDEE was extracted by dichloromethane and subjected to column chromatography. The purity of six diterpenoids isolated from TDEE was determined to be 77.18% by HPLC. TDEE (3 and 0.6 g raw herbs/kg, p.o.) reduced ascites and increased urine output. Meanwhile, analysis of tumor cell viability, cycle and apoptosis indicated that TDEE had no antitumor activity. In addition, the expression levels of aquaporins (AQPs) and the membrane translocation levels of protein kinase C (PKC) α and PKCβ in kidney and cells were measured. TDEE reduced the levels of AQP1–4, and inhibited PKCβ expression in membrane fraction. Four main diterpenoids, except compound 2, reduced AQP1 level in human kidney-2 cells. Compounds 4 and 5 inhibited AQP2–4 expression in murine inner medullary collecting duct cells. The diterpenoid-induced inhibition of AQP1–4 expression was blocked by phorbol-12-myristate-13-acetate (PMA; agonist of PKC). The diterpenoids from TDEE are the main anti-ascites components. The anti-ascites effect of diterpenoids may be associated with alterations in AQPs in the kidneys to promote diuresis. The inhibition of AQP1–4 expression by TDEE is related to the inhibition of PKCβ activation.


2010 ◽  
Vol 28 (15) ◽  
pp. 2625-2634 ◽  
Author(s):  
Malcolm A. Smith ◽  
Nita L. Seibel ◽  
Sean F. Altekruse ◽  
Lynn A.G. Ries ◽  
Danielle L. Melbert ◽  
...  

Purpose This report provides an overview of current childhood cancer statistics to facilitate analysis of the impact of past research discoveries on outcome and provide essential information for prioritizing future research directions. Methods Incidence and survival data for childhood cancers came from the Surveillance, Epidemiology, and End Results 9 (SEER 9) registries, and mortality data were based on deaths in the United States that were reported by states to the Centers for Disease Control and Prevention by underlying cause. Results Childhood cancer incidence rates increased significantly from 1975 through 2006, with increasing rates for acute lymphoblastic leukemia being most notable. Childhood cancer mortality rates declined by more than 50% between 1975 and 2006. For leukemias and lymphomas, significantly decreasing mortality rates were observed throughout the 32-year period, though the rate of decline slowed somewhat after 1998. For remaining childhood cancers, significantly decreasing mortality rates were observed from 1975 to 1996, with stable rates from 1996 through 2006. Increased survival rates were observed for all categories of childhood cancers studied, with the extent and temporal pace of the increases varying by diagnosis. Conclusion When 1975 age-specific death rates for children are used as a baseline, approximately 38,000 childhood malignant cancer deaths were averted in the United States from 1975 through 2006 as a result of more effective treatments identified and applied during this period. Continued success in reducing childhood cancer mortality will require new treatment paradigms building on an increased understanding of the molecular processes that promote growth and survival of specific childhood cancers.


Author(s):  
Wouter C. Rottier ◽  
Mette Pinholt ◽  
Akke K. van der Bij ◽  
Magnus Arpi ◽  
Sybrandus N. Blank ◽  
...  

Abstract Objective: To study whether replacement of nosocomial ampicillin-resistant Enterococcus faecium (ARE) clones by vancomycin-resistant E. faecium (VRE), belonging to the same genetic lineages, increases mortality in patients with E. faecium bacteremia, and to evaluate whether any such increase is mediated by a delay in appropriate antibiotic therapy. Design: Retrospective, matched-cohort study. Setting: The study included 20 Dutch and Danish hospitals from 2009 to 2014. Patients: Within the study period, 63 patients with VRE bacteremia (36 Dutch and 27 Danish) were identified and subsequently matched to 234 patients with ARE bacteremia (130 Dutch and 104 Danish) for hospital, ward, length of hospital stay prior to bacteremia, and age. For all patients, 30-day mortality after bacteremia onset was assessed. Methods: The risk ratio (RR) reflecting the impact of vancomycin resistance on 30-day mortality was estimated using Cox regression with further analytic control for confounding factors. Results: The 30-day mortality rates were 27% and 38% for ARE in the Netherlands and Denmark, respectively, and the 30-day mortality rates were 33% and 48% for VRE in these respective countries. The adjusted RR for 30-day mortality for VRE was 1.54 (95% confidence interval, 1.06–2.25). Although appropriate antibiotic therapy was initiated later for VRE than for ARE bacteremia, further analysis did not reveal mediation of the increased mortality risk. Conclusions: Compared to ARE bacteremia, VRE bacteremia was associated with higher 30-day mortality. One explanation for this association would be increased virulence of VRE, although both phenotypes belong to the same well-characterized core genomic lineage. Alternatively, it may be the result of unmeasured confounding.


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