468 research outputs found
Π‘ΡΠ°Π²Π½ΠΈΡΠ΅Π»ΡΠ½Π°Ρ ΠΌΠΎΡΡΠΎΡΡΠ½ΠΊΡΠΈΠΎΠ½Π°Π»ΡΠ½Π°Ρ ΠΎΡΠ΅Π½ΠΊΠ° ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ ΡΠΏΠΎΡΠΎΠ±ΠΎΠ² Π΄ΠΈΡΡΠ΅ΠΊΡΠΈΠΈ ΠΏΠ΅ΡΠ΅Π½ΠΎΡΠ½ΠΎΠΉ ΠΏΠ°ΡΠ΅Π½Ρ ΠΈΠΌΡ
ΠΡΠΎΠ²Π΅Π΄Π΅Π½Π° ΠΎΡΠ΅Π½ΠΊΠ° ΠΌΠΎΡΡΠΎΡΡΠ½ΠΊΡΠΈΠΎΠ½Π°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠΎΡΡΠΎΡΠ½ΠΈΡ ΠΏΠ΅ΡΠ΅Π½ΠΈ Π΄ΠΎ ΠΈ ΠΏΠΎΡΠ»Π΅ ΡΠ΅Π·Π΅ΠΊΡΠΈΠΈ Ρ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ΠΌ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² Π΄ΠΈΡΡΠ΅ΠΊΡΠΈΠΈ ΠΏΠ΅ΡΠ΅Π½ΠΎΡΠ½ΠΎΠΉ ΠΏΠ°ΡΠ΅Π½Ρ
ΠΈΠΌΡ. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ ΠΏΡΠΈ Π²ΡΠΏΠΎΠ»Π½Π΅Π½ΠΈΠΈ ΠΎΠ±ΡΠΈΡΠ½ΡΡ
ΡΠ΅Π·Π΅ΠΊΡΠΈΠΉ ΠΏΠ΅ΡΠ΅Π½ΠΈ ΡΠ΅Π»Π΅ΡΠΎΠΎΠ±ΡΠ°Π·Π½ΠΎ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊ ΡΠ»ΡΡΡΠ°Π·Π²ΡΠΊΠΎΠ²ΠΎΠΉ, ΡΡΡΡΠΉΠ½ΠΎΠΉ Π΄ΠΈΡΡΠ΅ΠΊΡΠΈΠΈ ΠΈΠ»ΠΈ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠΈ "clamp crushing".ΠΡΠΎΠ²Π΅Π΄Π΅Π½ΠΎ ΠΎΡΡΠ½ΠΊΡ ΠΌΠΎΡΡΠΎΡΡΠ½ΠΊΡΡΠΎΠ½Π°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΡΠ°Π½Ρ ΠΏΠ΅ΡΡΠ½ΠΊΠΈ Π΄ΠΎ Ρ ΠΏΡΡΠ»Ρ ΡΠ΅Π·Π΅ΠΊΡΡΡ ΡΠ· Π·Π°ΡΡΠΎΡΡΠ²Π°Π½Π½ΡΠΌ ΡΡΠ·Π½ΠΈΡ
ΠΌΠ΅ΡΠΎΠ΄ΡΠ² Π΄ΠΈΡΠ΅ΠΊΡΡΡ ΠΏΠ΅ΡΡΠ½ΠΊΠΎΠ²ΠΎΡ ΠΏΠ°ΡΠ΅Π½Ρ
ΡΠΌΠΈ. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΠΎ ΠΏΡΠ΄ ΡΠ°Ρ Π²ΠΈΠΊΠΎΠ½Π°Π½Π½Ρ ΠΎΠ±ΡΠΈΡΠ½ΠΈΡ
ΡΠ΅Π·Π΅ΠΊΡΡΠΉ ΠΏΠ΅ΡΡΠ½ΠΊΠΈ Π΄ΠΎΡΡΠ»ΡΠ½ΠΈΠΌ Ρ Π²ΠΈΠΊΠΎΡΠΈΡΡΠ°Π½Π½Ρ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠΈ ΡΠ»ΡΡΡΠ°Π·Π²ΡΠΊΠΎΠ²ΠΎΡ, ΡΡΡΡΠΌΠ΅Π½Π΅Π²ΠΎΡ Π΄ΠΈΡΠ΅ΠΊΡΡΡ Π°Π±ΠΎ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠΈ "clamp crushing".The morphofunctional state of the liver before and after resection using different methods of dissection of liver parenchyma are assessed. It is shown that at large resections of the liver it is reasonable to use the methods of ultrasound, stream dissection or "clamp crushing" technique
The small protein CydX is required for function of cytochrome bd oxidase in Brucella abortus.
A large number of hypothetical genes potentially encoding small proteins of unknown function are annotated in the Brucella abortus genome. Individual deletion of 30 of these genes identified four mutants, in BAB1_0355, BAB2_0726, BAB2_0470, and BAB2_0450 that were highly attenuated for infection. BAB2_0726, an YbgT-family protein located at the 3' end of the cydAB genes encoding cytochrome bd ubiquinal oxidase, was designated cydX. A B. abortus cydX mutant lacked cytochrome bd oxidase activity, as shown by increased sensitivity to H(2)O(2), decreased acid tolerance and increased resistance to killing by respiratory inhibitors. The C terminus, but not the N terminus, of CydX was located in the periplasm, suggesting that CydX is an integral cytoplasmic membrane protein. Phenotypic analysis of the cydX mutant, therefore, suggested that CydX is required for full function of cytochrome bd oxidase, possibly via regulation of its assembly or activity
Screen-and-Treat Strategies for Albuminuria to Prevent Cardiovascular and Renal Disease:Cost-Effectiveness of Nationwide and Targeted Interventions Based on Analysis of Cohort Data From the Netherlands
Background: Albuminuria is a marker for renal and cardiovascular (CV) risk, allowing early diagnosis of subjects with elevated renal and CV risk. Objective: This study aimed to estimate the cost-effectiveness and budget impact of various population-based screen-and-treat scenarios for elevated albuminuria levels (ie, microalbuminuria) in the Netherlands. Methods: A multistate transition Markov model was developed to simulate the natural course of albuminuria-based disease progression to dialysis and occurrence of CV events. Several population-based strategies directed at screening for elevated albuminuria were evaluated. These strategies depended on urinary albumin concentration (UAC), urinary albumin excretion (UAE), and age. Transition probabilities were derived from the observational community-based Prevention of Renal and Vascular End Stage Disease (PREVEND) cohort study. Health care costs (in year-2008 euros) and life-years gained were calculated over an 8-year period. In the base-case analysis, we analyzed screening for and treatment of microalbuminuria. Screening for microalbuminuria involved prescreening for UAC >= 20 mg/L, followed by a confirmation test for UAE >= 30 mg/d. Other options based on combinations of albuminuria for UAC prescreening (no prescreening, and >= 10, >= 20, >= 100, and >= 200 mg/L) and UAE confirmation test (>= 15, >= 30, and 300 mg/d) for treatment were investigated in scenario analyses. Furthermore, these various strategies based on UAC and UAE values were analyzed in different subgroups based on age (all ages, aged >= 50 years, and aged >= 60 years). Results: The PREVEND study included 8592 Dutch residents aged 28 to 75 years at the time of initial screening. Among a hypothetical cohort of 1000 subjects identified and treated in the base-case analysis, it was estimated (based on PREVEND follow-up data) that, in the screening/treatment and no-screening scenarios, 76 versus 124 CV events occurred, 16 versus 27 CV deaths, and 3 versus 5 dialysis cases, respectively. The per-person difference in net costs for screening was calculated at (sic)926 ((sic)2003 vs (sic)1077), and prevention of CV deaths was estimated to gain 0.0421 discounted life-year per person. Correspondingly, the cost-effectiveness was estimated at (sic)22,000 per life-year gained. In the base-case analysis, probabilistic sensitivity analysis indicated that the likelihood of cost-effectiveness of a screen-and-treat strategy was 54%, 90%, and 95% for a maximum acceptable cost-effectiveness threshold of (sic)20,000, (sic)50,000, and (sic)80,000 per life-year gained, respectively. Higher albuminuria thresholds for screening and start of treatment further improved the cost-effectiveness but reduced the overall health gains achieved. Limiting screening to those subjects aged >= 50 and >= 60 years resulted in more favorable cost-effectiveness compared with population-based screening without age restriction. Conclusions: Our analyses suggest the potentially favorable cost-effectiveness of population-based screen
Erythropoietin, Fibroblast Growth Factor 23, and Death After Kidney Transplantation
Elevated levels of erythropoietin (EPO) are associated with an increased risk of death in renal transplant recipients (RTRs), but the underlying mechanisms remain unclear. Emerging data suggest that EPO stimulates production of the phosphaturic hormone fibroblast growth factor 23 (FGF23), another strong risk factor for death in RTRs. We hypothesized that the hitherto unexplained association between EPO levels and adverse outcomes may be attributable to increased levels of FGF23. We included 579 RTRs (age 51 Β± 12 years, 55% males) from the TransplantLines Insulin Resistance and Inflammation Cohort study (NCT03272854). During a follow-up of 7.0 years, 121 RTRs died, of which 62 were due to cardiovascular cause. In multivariable Cox regression analysis, EPO was independently associated with all-cause (HR, 1.66; 95% CI 1.16-2.36; P = 0.005) and cardiovascular death (HR, 1.87; 95% CI 1.14-3.06; P = 0.01). However, the associations were abrogated following adjustment for FGF23 (HR, 1.28; 95% CI 0.87-1.88; P = 0.20, and HR, 1.45; 95% CI 0.84-2.48; P = 0.18, respectively). In subsequent mediation analysis, FGF23 mediated 72% and 50% of the association between EPO and all-cause and cardiovascular death, respectively. Our results underline the strong relationship between EPO and FGF23 physiology, and provide a potential mechanism underlying the relationship between increased EPO levels and adverse outcomes in RTRs
From the wound to the bench:exoproteome interplay between wound-colonizing Staphylococcus aureus strains and co-existing bacteria
Wound-colonizing microorganisms can form complex and dynamic polymicrobial communities where pathogens and commensals may co-exist, cooperate or compete with each other. The present study was aimed at identifying possible interactions between different bacteria isolated from the same chronic wound of a patient with the genetic blistering disease epidermolysis bullosa (EB). Specifically, this involved two different isolates of the human pathogen Staphylococcus aureus, and isolates of Bacillus thuringiensis and Klebsiella oxytoca. Particular focus was attributed to interactions of S. aureus with the two other species, because of the high staphylococcal prevalence among chronic wounds. Intriguingly, upon co-cultivation, none of the wound isolates inhibited each other's growth. Since the extracellular proteome of bacterial pathogens is a reservoir of virulence factors, the exoproteomes of the staphylococcal isolates in monoculture and co-culture with B. thuringiensis and K. oxytoca were characterized by Mass Spectrometry to explore the inherent relationships between these co-exisiting bacteria. This revealed a massive reduction in the number of staphylococcal exoproteins upon co-culturing with K. oxytoca or B. thuringiensis. Interestingly, this decrease was particularly evident for extracellular proteins with a predicted cytoplasmic localization, which were recently implicated in staphylococcal virulence and epidemiology. Furthermore, our exoproteome analysis uncovered potential cooperativity between the two different S. aureus isolates. Altogether, the observed exoproteome variations upon co-culturing are indicative of unprecedented adaptive mechanisms that set limits to the production of secreted staphylococcal virulence factors
Brucella abortus Infection of Placental Trophoblasts Triggers Endoplasmic Reticulum Stress-Mediated Cell Death and Fetal Loss via Type IV Secretion System-Dependent Activation of CHOP.
Subversion of endoplasmic reticulum (ER) function is a feature shared by multiple intracellular bacteria and viruses, and in many cases this disruption of cellular function activates pathways of the unfolded protein response (UPR). In the case of infection with Brucella abortus, the etiologic agent of brucellosis, the unfolded protein response in the infected placenta contributes to placentitis and abortion, leading to pathogen transmission. Here we show that B. abortus infection of pregnant mice led to death of infected placental trophoblasts in a manner that depended on the VirB type IV secretion system (T4SS) and its effector VceC. The trophoblast death program required the ER stress-induced transcription factor CHOP. While NOD1/NOD2 expression in macrophages contributed to ER stress-induced inflammation, these receptors did not play a role in trophoblast death. Both placentitis and abortion were independent of apoptosis-associated Speck-like protein containing a caspase activation and recruitment domain (ASC). These studies show that B. abortus uses its T4SS to induce cell-type-specific responses to ER stress in trophoblasts that trigger placental inflammation and abortion. Our results suggest further that in B. abortus the T4SS and its effectors are under selection as bacterial transmission factors.IMPORTANCE Brucella abortus infects the placenta of pregnant cows, where it replicates to high levels and triggers abortion of the calf. The aborted material is highly infectious and transmits infection to both cows and humans, but very little is known about how B. abortus causes abortion. By studying this infection in pregnant mice, we discovered that B. abortus kills trophoblasts, which are important cells for maintaining pregnancy. This killing required an injected bacterial protein (VceC) that triggered an endoplasmic reticulum (ER) stress response in the trophoblast. By inhibiting ER stress or infecting mice that lack CHOP, a protein induced by ER stress, we could prevent death of trophoblasts, reduce inflammation, and increase the viability of the pups. Our results suggest that B. abortus injects VceC into placental trophoblasts to promote its transmission by abortion
Liver Resection for Hepatic Metastases from Soft Tissue Sarcoma:A Nationwide Study
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209467pub.pdf (publisher's version ) (Open Access
Fibroblast growth factor 23 and new-onset chronic kidney disease in the general population:the Prevention of Renal and Vascular Endstage Disease (PREVEND) study
Background. Fibroblast growth factor 23 (FGF23), a phosphate-regulating hormone that increases early in the course of chronic kidney disease (CKD), is associated with disease progression in patients with established CKD. Here we aimed to investigate the association between plasma FGF23 and new-onset CKD in the general population.Methods. We included 5253 individuals without CKD who participated in the Prevention of Renal and Vascular Endstage Disease study, a prospective, population-based cohort. Multi-variable Cox regression was used to study the association of plasma C-terminal FGF23 with new-onset CKD, defined as a combined endpoint of estimated glomerular filtration rate (eGFR) 30 mg/24 h or both, or with all-cause mortality.Results. The median baseline FGF23 was 68 [interquartile range (IQR) 56-85]RU/mL, eGFR was 9513mL/min/1.73m(2) and UAE was 7.8 (IQR 5.8-11.5) mg/24h. After follow-up of 7.5 (IQR 7.2-8.0) years, 586 participants developed CKD and 214 participants died. A higher FGF23 level was associated with new-onset CKD, independent of risk factors for kidney disease and parameters of bone and mineral homoeostasis {fully adjusted hazard ratio (HR) 1.25 [95% confidence interval (CI) 1.10-1.44] per doubling of FGF23; P=0.001}. In secondary analyses, FGF23 was independently associated with new-onset eGFR 30mg/24h [adjusted HR 1.24 (95% CI 1.06-1.45); P=0.01] individually. A higher FGF23 level was also associated with an increased risk of all-cause mortality [fully adjusted HR 1.30 (95% CI 1.03-1.63); P=0.03].Conclusions. High FGF23 levels are associated with an increased risk of new-onset CKD and all-cause mortality in this prospective population-based cohort, independent of established CKD risk factors.</p
Prevalence of pulmonary hypertension in the general population : the Rotterdam study
Background: Pulmonary hypertension is characterized by increased pulmonary artery pressure and carries an increased mortality. Population-based studies into pulmonary hypertension are scarce and little is known about its prevalence in the general population. We aimed to describe the distribution of echocardiographically-assessed pulmonary artery systolic pressure (ePASP) in the general population, to estimate the prevalence of pulmonary hypertension, and to identify associated factors.
Methods: Participants (n = 3381, mean age 76.4 years, 59% women) from the Rotterdam Study, a population-based cohort, underwent echocardiography. Echocardiographic pulmonary hypertension was defined as ePASP>40 mmHg.
Results: Mean ePASP was 26.3 mmHg (SD 7.0). Prevalence of echocardiographic pulmonary hypertension was 2.6% (95%CI: 2.0; 3.2). Prevalence was higher in older participants compared to younger ones (8.3% in those over 85 years versus 0.8% in those between 65 and 70), and in those with underlying disorders versus those without (5.9% in subjects with COPD versus 2.3%; 9.2% in those with left ventricular systolic dysfunction versus 2.3%; 23.1% in stages 3 or 4 left ventricular diastolic dysfunction versus 1.9% in normal or stage 1). Factors independently associated with higher ePASP were older age, higher BMI, left ventricular diastolic dysfunction, COPD and systemic hypertension.
Conclusion: In this large population-based study, we show that pulmonary hypertension as measured by echocardiography has a low prevalence in the overall general population in the Netherlands, but estimates may be higher in specific subgroups, especially in those with underlying diseases. Increased pulmonary arterial pressure is likely to gain importance in the near future due to population aging and the accompanying prevalences of underlying disorders
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