Top PDF Effective chronic disease progression model

Effective chronic disease progression model

Effective chronic disease progression model

Reduce calculation forms numerous terabytes of information on a great many machines. Software engineers discover the framework simple to utilize: many Map Reduce programs have been actualized and upwards of one thousand Map Reduce employments are executed on Google's bunches each day.As a response to this multifaceted nature, we structured another deliberation that enables us to express the basic calculations we were attempting to perform yet shrouds the chaotic subtleties of parallelization, adaptation to non-critical failure, information conveyance and burden adjusting in a library. Our reflection is motivated by the guide and diminishes natives displaying Lisp and numerous other practical dialects. We understood that the majority of our calculations included applying a guide task to each legitimate "record" in our contribution to request to process a lot of moderate key/esteem sets, and afterward applying a decrease activity to every one of the qualities that common a similar key, so as to join the determined information suitably. Our utilization of an utilitarian model with client indicated guide and decrease tasks enables us to parallelize vast calculations effectively and to utilize re-execution as the essential system for adaptation to non-critical failure.
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Estimation of progression of multi-state chronic disease using the Markov model and prevalence pool concept

Estimation of progression of multi-state chronic disease using the Markov model and prevalence pool concept

Three-fixed cohorts, 1987, 1991 and 1995, were identified according to when subjects attended their first screen. Because few subjects attended the third screen in 1995 as a first screen, we excluded them from analysis. Subjects who did not take the oral glucose tolerance test (OGTT) were also excluded from the analysis. For the 1987 cohort, 66 (8.9%) of the 678 patients tested had asymptomatic Type 2 diabetes. Among 678 subjects, only 237 (35%) subjects attended the second screening (1991) with com- plete information on OGTT test. Of these, 10 had newly diagnosed asymptomatic Type 2 diabetes. For the 1991 cohort, 39 (8.2%) of the 475 subjects were detected as having asymptomatic Type 2 diabetes at the time of the first screening. Thus, a total of 105 (39 + 66) asympto- matic Type 2 diabetes cases were ascertained at first screen. To ascertain deaths from Type 2 diabetes (ICD code 250), the above 115 asymptomatic Type 2 diabetes patients were followed until Dec 1997. Of the 115 subjects, 8 had died of Type 2 diabetes. The average follow-up was 8.29 years. Table 1 summarizes the observed transitions and corresponding transition probabilities used in the three- state Markov model and the illness-and-death Markov model.
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Attenuation of inflammatory polyarthritis in TNF transgenic mice by diacerein: comparative analysis with dexamethasone, methotrexate and anti TNF protocols

Attenuation of inflammatory polyarthritis in TNF transgenic mice by diacerein: comparative analysis with dexamethasone, methotrexate and anti TNF protocols

experimental models of RA [29] but that therapy does not affect the inflammatory tissue or symptoms of the disease. Diacerein is an effective and well tolerated agent for the treatment of OA [10–12] and it is unique among current anti-OA products in that it is able to influence both the anabolism and catabolism of chondrocytes. The effect of diacerein in chronic inflammatory arthritis was investigated in the present study using an established TNF-mediated murine model of RA – the Tg197 mouse [3]. Invasive growth of a hypertrophic synovial membrane and local accumulation of inflammatory infiltrates are typical features of RA and arthritis in TNF transgenic mice, and are consid- ered to be prerequisites for cartilage destruction and bone erosion. The Tg197 model has been extensively used by various research groups in the past as a reliable tool to assess the efficacy of potent antiarthritic compounds, as well as to investigate the mechanisms that are involved in the pathogenesis of chronic inflammatory arthritis [29–31]. The results of the present study clearly demonstrate that diacerein has antiarthritic activity, preventing the onset and suppressing the progression of joint pathology, as shown by clinical and histopathologic assessment of mice treated with three different doses (2, 20, and 60 mg/kg diacerein daily). Additional studies evaluating the effects of diacerein at 4 and 40 mg/kg daily showed a beneficial response that was clearly reproduced in the present study (data not shown). Although pharmacokinetic studies were not performed, the lack of a dose effect suggests that the beneficial response can be achieved even with the low dose of 2 mg/kg daily, which is analogous to the dose used in humans with OA [10–12]. The lowest effective dose of diacerein is yet to be assessed in the TNF trans- genic model. Our findings revealed a beneficial effect of diacerein not only for cartilage protection, which is usually the target of diacerein in OA studies, but also for synovitis and bone erosion. Preservation of the joint architecture after diacerein administration appears to be mainly due to the significant suppression of the highly proliferative pannus-like tissue, which consists of synovial fibroblasts, synovial macrophages, and various infiltrating inflammatory cells. This is the first report providing evidence for anti- proliferative and anti-inflammatory effects of diacerein in an inflammatory model of arthritis.
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Immune Responses and Viral Replication in Long-Term Inapparent Carrier Ponies Inoculated with Equine Infectious Anemia Virus

Immune Responses and Viral Replication in Long-Term Inapparent Carrier Ponies Inoculated with Equine Infectious Anemia Virus

fective control of virus replication and disease. In fact, most horses infected by EIAV are inapparent carriers that will re- main asymptomatic for the remainder of their life span of up to 20 years. Thus, the EIAV system offers a uniquely dynamic model in which to examine changes in viral replication and host immune responses during the clearly demarcated progres- sion from chronic disease to a long-term inapparent infection. A number of studies indicate that the eventual control of EIAV replication and disease in horses is mediated by host immune responses that control virus infection to subclinical levels and not by the attenuation of the virus during persistent infection. For example, transfer of whole blood from long-term inapparent carriers to naive horses reproducibly causes infec- tion and disease (11), and experimental immune suppression of inapparent carriers can cause recrudescence of disease and associated viremia (19, 43). Recent analyses of EIAV infection in long-term apparent carriers by genetic (8, 40) and in situ (29) methods demonstrate persistent low levels of virus infec- tion and replication predominantly in tissue macrophages, with negligible virus detectable in plasma or peripheral blood cells. These studies indicate that the progression from chronic EIA to inapparent infection is associated with the evolution of highly effective and enduring host immune responses that are able to suppress EIAV replication, despite the array of persis- * Corresponding author. Mailing address: W1144 Biomedical Sci-
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Progression of experimental chronic Aleutian mink disease virus infection

Progression of experimental chronic Aleutian mink disease virus infection

The AMDV infection induced in this study provide a model for chronic AMDV infection in mink with a 1:10,000 dilution of an organ homogenate with the currently circulating Danish AMDV strain, Saeby/ DEN/799.1/05. Surprisingly, even with undiluted AMDV organ homogenate the mink did not become clinically affected within four weeks, indicating that the Saeby/ DEN/799.1/05 is not dose dependent. In the short time study, irrespective of the inoculation dosage, the mink developed antibodies 2–4  weeks after AMDV inocula- tion, like in the long term study [24]. Similar, all mink in the short term study excreted AMDV viral DNA in feces as shown for the long term study [24]. AMDV DNA excretion in oro-nasal secretions was detected in the mink inoculated with AMDV diluted 1:1000 and 1:100, but not undiluted and diluted 1:10,000 supporting the previously observed inconsistency in excretion [24, 25]. AMDV DNA was found in all examined organs 2 and 4  weeks after AMDV inoculation, which is consistent with another study where AMDV DNA also was found in spleen, lymph nodes, bone marrow, liver, kidney, lung and intestines 10 days after inoculation with a Canadian AMDV field strain [19]. However, the number of mink in the short term experiment was low but the apparent lack of doses dependent response in infection confirms earlier studies [7, 20] and contradicts an older study of dose dependency in AMDV infection [25]. The lowest dilution of AMDV organ homogenate was chosen for the long term experiment because the lowest dilution was enough to induce chronic infection which was the aim of the study. Using a higher dilution of the AMDV organ homogenate potentially could induce an acute infection although the short term study did not indicate it. Given the ethical considerations of an animal experiment and economic expenses no such risk were taken and the low- est AMDV organ homogenate dilution was used. Unex- pectedly, one mink delivered two kits which were kept for 3  weeks and both of these kits were subclinically infected with AMDV, i.e. the organs were PCR positive and they excreted AMDV DNA. The kits did not present symptoms in contrast to previous findings [10, 11] maybe because of their short life.
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Urinary miR 196a predicts disease progression in patients with chronic kidney disease

Urinary miR 196a predicts disease progression in patients with chronic kidney disease

of urinary miR-196a and various clinical and pathologi- cal parameters were evaluated by Spearman correlation. Cox proportional-hazards model with adjustment for age, sex, proteinuria and eGFR was used to evaluate the association of urinary miR-196a with risk for progression to ESRD modeling urinary miR-196a in tertiles as well as a continuous exposure. Renal survival rate across urinary miR-196a tertiles was analyzed and compared using the Kaplan–Meier analysis and the log-rank test. In addi- tion, to assess the goodness of fit and improved predic- tive power of urinary miR-196a, we compared Harrell concordance index (c-statistic) and akaike information criterion (AIC) by likelihood ratio tests between multi- variate Cox proportional hazards models with or without urinary miR-196a. Time-dependent receiver operating characteristic (ROC) curves were assessed using the R software module “survivalROC”. p < 0.05 was considered statistically significant.
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Role of microRNA in chronic lymphocytic leukemia onset and progression

Role of microRNA in chronic lymphocytic leukemia onset and progression

In both indolent and aggressive CLLs, miR-29 is overex- pressed when compared to normal B cells while miR- 181b is downregulated when compared to normal B cells. Although, when comparing indolent and aggressive CLLs, both mir-29 and mir-181b show higher expression levels in indolent cases [34-36]. Moreover, miR-181b ex- pression is decreased during CLL progression when se- quential samples from the same patients are compared [11]. In the same study, miR-181b is also reported to tar- get MCL1 in CLL, while in another study on human gas- tric and lung cancer cell lines, it was found able to target BCL2 and involved in the development of multi- drug resistance [37]. To clarify the role of miR-29 in CLL, we designed a transgenic mouse model and mice overexpressing miR-29 developed a disease similar to the indolent form of CLL. The role of downregulation of miR-29 and miR-181b in aggressive CLLs appears to cor- relate with Tcl1 overexpression [35]. Activation of TCL1 oncogene (T cell leukemia/lymphoma 1) is a central event in the initiation of aggressive CLL, and high Tcl1 expression correlates with aggressive phenotype [38]. We verified that coexpression of TCL1 with miR-29 and miR-181 decreased its expression and found inverse cor- relation between miR-29b , miR-181b , and Tcl1 expression in CLL samples [35].
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Metabolic acidosis and the progression of chronic kidney disease

Metabolic acidosis and the progression of chronic kidney disease

Several factors have been implicated in the effect of metabolic acidosis on the progression of kidney disease. These include ammonia-induced complement activation and increased production of endothelin and aldosterone (Figure 1). Although total ammonium excretion decreases with progressive CKD, ammonia generation per nephron actually increases [29]. This adaptive response may be deleterious for the surviving nephrons [30]. Nath et al. ex- amined the role of ammonia in the pathogenesis of tubulo- interstitial injury using the rat remnant kidney model [31]. Chronic sodium bicarbonate supplementation lowered renal vein total ammonia concentrations, reduced tubular deposition of complement components C3 and C5b-9, and ameliorated structural and functional evidence of tubulo- interstitial damage. The authors proposed that ammonia, as a nitrogen nucleophile, reacted biochemically with C3 to trigger the alternative complement pathway. Therefore, the compensatory increase in single-nephron ammoniagenesis observed in CKD could further instigate progressive kidney injury.
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Chronic Kidney Disease: Implications for Progression Using Telehealth Monitoring

Chronic Kidney Disease: Implications for Progression Using Telehealth Monitoring

This study is limited by small sample size and short follow up. In addition, cost effectiveness was not studied. This same study design is now going to be used for a larger sample using remote monitoring devices, integrating automatically with the patients’ electronic medical record, and the use of automatic feed back to the patients. This closed loop should ensure efficient, cost effective, coordinated and real time delivery of medical care.

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Hepatic Drug Metabolism, Uremic Toxins and Bacterial Composition Over Chronic Kidney Disease Progression

Hepatic Drug Metabolism, Uremic Toxins and Bacterial Composition Over Chronic Kidney Disease Progression

Models of CKD in rats include 5/6th nephrectomy, diabetic nephropathy and adenine- induced CKD. The most common 5/6th nephrectomy method surgically removes the top and bottom thirds of one kidney and the entire contralateral kidney effectively simulating the loss in kidney function although potentially inducing post-surgery stress (Ali et al., 2013). Diabetic nephropathy models of diabetes-induced kidney disease usually use the administration of streptozotocin to cause pancreatic β cell death. Additionally, the diabetic nephropathy model although most exemplary of human CKD caused by diabetes, requires a timely experimental period to successfully cause CKD that may not occur simultaneously across all animals. The newer adenine-induced model of CKD is a less invasive orally administered model suggested to provide a more consistent rate of CKD onset than the 5/6th nephrectomy (Terai et al., 2008). The adenine model of CKD also shows the best promise as a progressive CKD model suitable for temporal evaluation due to its timely onset in comparison with the diabetic model. Additionally, the adenine model has been used to study alterations in DMEs of the liver in the past, providing a clear example of severe CKD after 42 days of oral administration (Feere et al., 2015; Velenosi et al., 2016). Mechanistically, adenine and its metabolite 2,8-dihydroxyadenine precipitate when concentrated at the kidney. This mechanically damages the kidney tubules comparable to that inflicted by kidney stones and is thus a tubular model of kidney damage (Engle et al., 1996; Morishita et al., 2011; Succar et al., 2017).
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Pathogenesis and Prevention of Progression of Chronic Kidney Disease

Pathogenesis and Prevention of Progression of Chronic Kidney Disease

Generally speaking, CKD is indolent and produces no symptoms. The key to the maintenance of indolent state is frequent office visits for instance, every four to six weeks. This model of office visit is designed to evaluate pa- tients with CKD for their well-being; blood pressure control, fluid control and maintenance of acid-base status and hemoglobin. Complete exclusion of ACEI/ARB drugs is needless to emphasize to prevent rocking of renal function downhill, prevent severe metabolic acidosis, hyperkalemia and anemia. Similarly, nonsteroidal drugs as pain killer must be avoided for the same reasons as above. Further, the above drugs cause sodium and water re- tention and give rise to hypertension and CHF. Control of BP is a difficult issue in some patients despite use of safe drugs such as beta blockers, calcium channel blockers and sympathetic inhibitors. In these difficult cases, low dose diuretic such as 12.5 or 25 mg chlorthalidone every day or every other day is most appropriate to con- trol BP realizing that it may decrease renal function slightly. However, such decrease in renal function doesn’t impair well-being or alter acid-base and potassium control [17].
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Effect of oral sodium bicarbonate supplementation on progression of chronic kidney disease in patients with chronic metabolic acidosis: study protocol for a randomized controlled trial (SoBic Study)

Effect of oral sodium bicarbonate supplementation on progression of chronic kidney disease in patients with chronic metabolic acidosis: study protocol for a randomized controlled trial (SoBic Study)

patients or other reasons for dropout will be addressed by jointly modeling longitudinal eGFR and time to death using an appropriate joint model for longitudinal and time-to-event outcome [37]. In the longitudinal part of this model, a linear mixed model will be used with the repeated eGFR measurements as outcome values, and including as fixed factors treatment group, all stratifica- tion criteria (age, diabetes, severity of acidosis, previous alkali treatment), the eGFR baseline value and time since start of treatment, and a random intercept. An inter- action effect (product term) of the treatment group and the time since start of treatment will also be included. Graphical diagnostic tools (residual plots) will be used to confirm the adequacy of model assumptions. A second- ary outcome is time to death, compared between the treatment groups, which will also be estimated by the joint modeling approach. The time up to the point of need of RRT will be compared between the two treat- ment groups, accounting for death as a competing risk, by modeling the cumulative incidence function [38], in- cluding treatment group and the covariates age, diabetes, severity of acidosis and baseline eGFR. Percent change (from baseline to week 20 and baseline to week 104, respectively) in markers of bone metabolism will be ana- lyzed by analysis of covariance, to adjust for sex, age, change in renal function, and baseline values of the bone markers. The incidence of serious adverse events will be reported and compared between groups using the chi-squared test. Baseline parameters (etiology of CKD, relevant medical disease, age, gender, concomitant medi- cation, blood pressure, number of antihypertensive med- ications, and laboratory measurements) will be analyzed descriptively for the interventional and control group, respectively. SAS (Version 9.3, SAS Institute Inc., Cary, NC, USA, 2011) will be used for data management and analysis, and R 2.12.2/package JM [37] will be used for the main outcome analysis.
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Progression of chronic kidney disease: an illness-death model approach

Progression of chronic kidney disease: an illness-death model approach

Demographic data including age, gender, and body mass index (BMI) were measured at the time of diagnosis of CKD. Serum creatinine (Scr), which is standardized and calibrated every 3 months by the Department of Medical Science, Ministry of Public Health, was measured by each hospital laboratory unit. Results from the Modified Jaffe (MJ) method were converted to the Isotope Dilution Mass Spectrometry (IDMS) equivalent using the equation from the Thai SEEK study as described previously [1]. An eGFR was then calculated using the chronic kidney disease epi- demiology collaboration (CKD-EPI) equation [9]. The urine analysis (UA) was done using a urine dipstick to test for proteinuria. The results were reported as negative or normal, trace (equivalent to micro-albuminuria) or 1+ or more (equivalent to macro-albuminuria). We used the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 guideline to classify CKD [10]. GFR categories con- sisted of G1 (≥90 ml/min/1.73 m 2 ), G2 (60–89 ml/min/
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ATM germline heterozygosity does not play a role in chronic lymphocytic leukemia initiation but influences rapid disease progression through loss of the remaining ATM allele

ATM germline heterozygosity does not play a role in chronic lymphocytic leukemia initiation but influences rapid disease progression through loss of the remaining ATM allele

we propose a model whereby ATM germline mutations do not contribute to CLL initiation but rather predispose to rapid disease progression through acquired chromosome 11q deletions, loss of ATM activity and clonal expansion (Figure1). In keeping with this model, we found that most ATM mutant carriers were already high stage at diagnosis. Furthermore, although our entire CLL cohort was biased for patients with advanced disease, via selection for 11q deletion and inclusion of CLL4 trial patients, carriers of ATM mutations still demonstrated short overall survival.
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A discrete state discrete time model using indirect observation

A discrete state discrete time model using indirect observation

One diculty of developing a model of chronic disease progression from such data is that the available studies often do not include the transitions of interest. For example, in our model of diabetic nephropathy, many clinical studies did not dierentiate between patients without nephropathy and those who had microalbuminuria (a pre-clinical stage of nephropathy). Another diculty was a lack of data to directly estimate parameters of interest. We consider models which can accommodate such diculties. In this paper we consider the problem of estimating parameters of a discrete-time Markov process when longitudinal data describing the entire process are not available. First, we present a likelihood approach to estimate parameters of a discrete-time Markov model. Next, we use simulation to investigate the nite- sample behaviour of our approach. Finally, we present two examples: a model of diabetic nephropathy and a model of cardiovascular disease in diabetes. Copyright ? 2006 John Wiley & Sons, Ltd. KEY WORDS : grouped Markov chain; chronic disease; study-specic transition matrix
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The Chronic Kidney Disease Model: A General Purpose Model of Disease Progression and Treatment

The Chronic Kidney Disease Model: A General Purpose Model of Disease Progression and Treatment

Values for MI, stroke, bone disease, GFR change, and death are dependent upon the current CKD stage (Table 2), while the probabilities for disability from stroke, death from MI, and CHF from MI are not (Table 3). GFR change ranges from improvement to decline based upon a distribution adjusted for age, race, current CKD stage, hypertension, diabetes, proteinuria, and cardiovas- cular disease derived from an analysis of a primary data- set of CKD patients followed for 5 years at the Durham, NC Veteran’s Affairs Hospital[12]. Being derived from a VA dataset has potential limitations in generalizeability; however it allows a detailed analysis of the normal dis- tribution around monthly GFR changes and the specific impact of each variable, singly and combined. This level of detail is not available through other mechanisms and to explore whether the GFR change values perform appropriately we externally validate cohort GFR changes in the model against the AASK study as described in the validation section.
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Impact of chemical elements on heart failure progression in coronary heart disease patients

Impact of chemical elements on heart failure progression in coronary heart disease patients

These studies are frequently incommensurable be- cause the authors use different methods for measuring the content of chemical elements and due to the fact that blood being a common collector receives all products of organism metabolism. Therefore, relating a particular imbalance in the content of macro or trace elements in blood to the pathology of a specific organ is a challenge. Unfortunately, there are very few studies on metabolism of human organs (excluding biochemical studies) but this problem attracts considerable attention of research- ers. Of special interest is the investigation of metabolism of the heart affected by a coronary disease, because the morbidity of this pathology is rather high. With this in mind, an attempt was made to analyze the relationship of mineral metabolism with the functional state of the myocardium in CHD patients against the background of chronic heart failure progression.
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Inhibition of RAS in diabetic nephropathy

Inhibition of RAS in diabetic nephropathy

bilateral renal artery stenosis, polycystic kidney disease, and advanced kidney disease may sustain a significant decrease in GFR, and in some cases AKI. The intrarenal perfusion pressure in these cases is already reduced, and patients are highly dependent on AngII to maintain a stable intraglom- erular pressure and GFR. Similar but modest intrarenal hemodynamic changes are seen in elderly and DKD patients on RAS, increasing their risk of sustaining AKI in the setting

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Cardiovascular risk factors in chronic renal failure patient at Soavinandriana Hospital Antananarivo

Cardiovascular risk factors in chronic renal failure patient at Soavinandriana Hospital Antananarivo

study, the majority of patients (76.31%) had high cardiovascular risk factors. These patients with high cardiovascular risk factors should be received more exploration especially a cardiac and vascular auscultation, a pulse palpation, electrocardiogram records and a Doppler echocardiography to detect the CVD early. Anemia is one of the metabolic complications of chronic renal failure due to relative erythropoietin production deficiency. The less than 11 g/dl frequency of hemoglobin level in this series (77.63%) is similar with Babua’s study (71.9%), less than the one of Pancha Mbouemboue’study (94.3%) and higher than the one of El-Gamasy’s study (39.7%). 8,12,13 Anemia is also
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Relationships Between Prior Experiences, Current Teaching Contexts, and Novice Teachers' Use of Concrete Representation for Mathematics Instruction

Relationships Between Prior Experiences, Current Teaching Contexts, and Novice Teachers' Use of Concrete Representation for Mathematics Instruction

(PDTC), did not attenuate liver APR or STAT – 3 phosphorylation. But it could be argued that inability of PDTC, to suppress plasma IL – 6 could be a factor in the upregulated liver APR in these mice. But liver STAT-3 and APR were not suppressed even in the gp130 fusion protein treated mice that did suppressed plasma IL – 6 levels. As chronic inflammation induced by a chronically activated immune cell proliferation and activation, leads to cachexia onset, it is possible a yet unknown signaling intermediate sustains liver APR independent of IL – 6. Interestingly, inhibition of the energy expensive APR is detrimental to survival in endotoxemic mice due the ability of acute phase proteins to activate the anti – inflammatory MDSCs in the septic tissue (20530204). Endotoxemia in the severely cachectic mouse could thus exacerbate hepatic inflammation (via the portal vein) aggravating systemic inflammation and hypermetabolism in the Apc Min/+ mouse.
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