To determine whether clinical and patient-reported outcomes differ in children receiving blenderized diets compared with conventional formula.
We conducted a prospective cohort study of 70 children ...aged 1-18 years receiving blenderized diets vs conventional formula via feeding tube. We assessed rates of hospitalization and visits to the emergency department (ED) at Boston Children's Hospital in 2017 and Likert scale addressing satisfaction with feeding regimen; Pediatric Gastroesophageal Reflux Disease Symptom and Quality of Life Questionnaire; Pediatric Quality of Life Inventory; and Pediatric Quality of Life Inventory Gastrointestinal Symptoms Scale.
Participants receiving blenderized diets (n = 42, 60%) did not differ in demographics or comorbid diagnoses from those receiving conventional formula (n = 28, 40%). Rates of total visits to the ED (0.8 ± 1.5 vs 1.4 ± 2.7, P = .05), total admissions (0.8 ± 1.2 vs 1.7 ± 2.3, P = .01), and respiratory-related admissions (0.2 ± 0.5 vs 0.6 ± 0.8, P = .04) per year were significantly lower in participants receiving blenderized diets, and respiratory-related visits to the ED trended toward significance (0.1 ± 0.4 vs 0.4 ± 0.8, P = .08). Compared with those receiving conventional formula, participants on blenderized diets reported greater satisfaction ratings (Likert scale 4.3 ± 1.0 vs 3.3 ± 1.2, P = .001), lower symptom (0.7 ± 0.8 vs 1.2 ± 1.1, P = .03), and total (0.8 ± 0.8 vs 1.2 ± 1.0, P = .02) scores on Pediatric Gastroesophageal Reflux Disease Symptom and Quality of Life Questionnaire and greater scores on the Pediatric Quality of Life Inventory Gastrointestinal Symptoms Scale, indicating less nausea and vomiting (64.0 ± 22.6 vs 49.0 ± 37.9, P = .02), abdominal pain (65.0 ± 26.8 vs 56.4 ± 33.9, P = .04), diarrhea (87.9 ± 15.5 vs 73.6 ± 26.3, P = .004), and fewer total symptoms (70.2 ± 16.3 vs 62.3 ± 19.6, P = .03).
Blenderized diets are associated with decreased healthcare use, improved symptom scores, and increased patient satisfaction compared with conventional formulas.
Define incidence and risk factors of osteonecrosis of the jaw (ONJ) and explore oral microbial signatures and host immune response as reflected by cytokine changes in saliva and serum in multiple ...myeloma (MM) patients on bisphosphate (BP) therapy.
A single center observational prospective study of MM patients (n = 110) on >2 years of BP, none had ONJ at enrollment. Patients were followed every 3 months for 18 months with clinical/dental examination and serial measurements of inflammatory cytokines, bone turnover markers, and angiogenic growth factors. Oral microbiota was characterized by sequencing of 16S rRNA gene from saliva.
Over the study period 14 patients (13%) developed BRONJ, at a median of 5.7 years (95% CI: 1.9-12.0) from MM diagnosis. Chronic periodontal disease was the main clinically observed risk factor. Oral microbial profiling revealed lower bacterial richness/diversity in BRONJ.
,
, and
were abundant in controls;
and
were prevalent in BRONJ. In the saliva, at baseline patients who developed BRONJ had higher levels of MIP-1β; TNF-α and IL-6 compared to those without BRONJ, cytokine profile consistent with M-1 macrophage activation. In the serum, patients with BRONJ have significantly lower levels of TGF beta and VEGF over the study period.
Periodontal disease associated with low microbial diversity and predominance of invasive species with a proinflammatory cytokine profile leading to tissue damage and alteration of immunity seems to be the main culprit in pathogenesis of BRONJ.
The Visionary Art of C.G Jung Hester, Lisa
The international journal of Jungian studies,
05/2022, Letnik:
15, Številka:
2
Journal Article
Recenzirano
Abstract This article considers how visionary art expresses itself within paintings and pictorial configurations by using Neumann’s work to expand on Jung’s notion of the ‘visionary mode of ...creativity.’ The first part is a comparative study of Neumann’s ‘four stages of psychological development’ discussed in ‘The Origins and History of Consciousness’ (1949) and his ‘four stages of art in relation to its epoch’ discussed in his essay ‘Art and Time’ (1959). This comparison aims to establish a selection of categories that considers the role of art on the micro-level (the individual) and the macro-level (society). Additionally, it is suggested that these four categories offer an interesting framework for identifying and understanding visionary artworks. Subsequently, the second part uses Neumann’s framework to examine a selection of paintings from ‘Liber Novus’ (2009).
The Visionary Art of C.G Jung Hester, Lisa
The international journal of Jungian studies,
05/2022, Letnik:
15, Številka:
2
Journal Article
Recenzirano
Abstract
This article considers how visionary art expresses itself within paintings and pictorial configurations by using Neumann's work to expand on Jung's notion of the 'visionary mode of ...creativity.' The first part is a comparative study of Neumann's 'four stages of psychological development' discussed in 'The Origins and History of Consciousness' (1949) and his 'four stages of art in relation to its epoch' discussed in his essay 'Art and Time' (1959). This comparison aims to establish a selection of categories that considers the role of art on the micro-level (the individual) and the macro-level (society). Additionally, it is suggested that these four categories offer an interesting framework for identifying and understanding visionary artworks. Subsequently, the second part uses Neumann's framework to examine a selection of paintings from 'Liber Novus' (2009).
Increasing evidence suggests that development of heart failure involves activation of stress-response inflammatory cytokines, including tumor necrosis factor-alpha and interleukin-6. Yet, the myocyte ...contribution to their induction in failing hearts and the underlying regulatory mechanism in stressed myocardium remain unclear.
In cultured cardiac myocytes, specific activation of stress-activated mitogen-activated protein kinase, p38, by upstream activator MKK6bE led to significant induction of tumor necrosis factor-alpha and interleukin-6 secretion, whereas treating cells with a selective p38 inhibitor (SB239068) significantly blocked the cytokine secretion from myocytes and increased their intracellular accumulation. Targeted expression of MKK6bE in transgenic hearts also resulted in a marked elevation in plasma tumor necrosis factor-alpha and interleukin-6; oral administration of SB239068 resulted in a significant reduction in their plasma levels but an increase in intracardiac accumulation of both cytokines. MKK6bE transgenic hearts developed marked interstitial fibrosis with increased matrix metalloproteinase abundance and selective induction of tissue inhibitor of matrix metalloproteinase-1; this extracellular matrix remodeling was also significantly attenuated by p38 inhibition. Along with cytokine induction and extracellular remodeling, MKK6bE transgenic animals displayed impaired hemodynamic function, whereas p38 inhibition improved the cardiac performance and prolonged the survival of the animals.
Stress-activated p38 kinase is a critical regulator of inflammatory response in cardiomyocytes with significant contribution to pathological remodeling in stressed myocardium. Inhibition of p38 may represent a useful therapeutic avenue to ameliorate cardiac pathology and heart failure evolution.
Heat Shock Co-Activates Interleukin-8 Transcription Singh, Ishwar S; Gupta, Aditi; Nagarsekar, Ashish ...
American journal of respiratory cell and molecular biology,
08/2008, Letnik:
39, Številka:
2
Journal Article
Recenzirano
Odprti dostop
The heat shock (HS) response is a phylogenetically ancient cellular response to stress, including heat, that shifts gene expression to a set of conserved HS protein (HSP) genes. In our earlier ...studies, febrile-range hyperthermia (FRH) not only activated HSP gene expression, but also increased expression of CXC chemokines in mice, leading us to hypothesize that the CXC chemokine family of genes might be HS-responsive. To address this hypothesis we analyzed the effect of HS on the expression of IL-8/CXCL-8, a member of the human CXC family of ELR(+) chemokines. HS markedly enhanced TNF-alpha-induced IL-8 secretion in human A549 respiratory epithelial-like cells and in primary human small airway epithelial cells. IL-8 mRNA was also up-regulated by HS, but the stability of IL-8 mRNA was not affected. TNF-alpha-induced reporter activity of an IL-8 promoter construct IL8(-1471/+44)-luc stably transfected in A549 cells was also enhanced by HS. Electrophoretic mobility and chromatin immunoprecipitation assays showed that the stress-activated transcription factor heat shock factor-1 (HSF-1) binds to at least two putative heat shock response elements (HSE) present in the IL-8 promoter. Deletional reporter constructs lacking either one or both of these sites showed reduced HS responsiveness. Furthermore, depletion of HSF-1 using siRNA also reduced the effects HS on TNF-alpha-induced IL-8 expression, demonstrating that HSF-1 could also act to regulate IL-8 gene transcription. We speculate that during evolution the CXC chemokine genes may have co-opted elements of the HS response to amplify their expression and enhance neutrophil delivery during febrile illnesses.
We have shown previously that febrile range temperatures modify cytokine production by adult macrophages. In this study, we compared the effects of moderate hyperthermia and hypothermia on the ...kinetics of lipopolysaccharide (LPS)-induced cytokine expression in monocytes and macrophages of newborns and adults. During culture at 40 degrees C, the initial rates of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) secretion were preserved, but the duration of secretion was shorter than the duration at 37 degrees C. TNF-alpha and IL1-beta concentrations in 24-h 40 degrees C culture supernatants were reduced 18%-50%. IL-6 concentration in 24-h 40 degrees C cultures was reduced 26%-29% in all cells except adult macrophages. At 32 degrees C, changes in early (2 h) and sustained (24 h) cytokine expression were reversed compared with those caused by hyperthermia. Culturing adult macrophages at 32 degrees C blunted early secretion of TNF-alpha and IL-6 by 69% and 65%, respectively, and increased TNF-alpha concentration at 24 h by 48% compared with levels at 37 degrees C. In adult monocytes cultured at 32 degrees C, early IL-6 and IL-1 beta secretion was decreased 64% and 51%, respectively. We speculate that the burst/suppression cytokine profile at febrile temperatures might enhance early activation of host defenses and prevent prolonged exposure to potentially cytotoxic cytokines. Hypothermia, on the other hand, may worsen outcome in infections by delaying and prolonging cytokine production.
Background
Immune‐checkpoint inhibitors (ICIs) are an effective therapeutic strategy, improving the survival of patients with lung cancer compared with conventional treatments. However, novel ...predictive biomarkers are needed to stratify which patients derive clinical benefit because the currently used and highly heterogenic histological PD‐L1 has shown low accuracy. Liquid biopsy is the analysis of biomarkers in body fluids and represents a minimally invasive tool that can be used to monitor tumor evolution and treatment effects, potentially reducing biases associated with tumor heterogeneity associated with tissue biopsies. In this context, cytokines, such as transforming growth factor‐β (TGF‐β), can be found free in circulation in the blood and packaged into extracellular vesicles (EVs), which have a specific delivery tropism and can affect in tumor/immune system interaction. TGF‐β is an immunosuppressive cytokine that plays a crucial role in tumor immune escape, treatment resistance, and metastasis. Thus, we aimed to evaluate the predictive value of circulating and EV TGF‐β in patients with non–small‐cell lung cancer receiving ICIs.
Methods
Plasma samples were collected in 33 patients with advanced non–small‐cell lung cancer before and during treatment with ICIs. EV were isolated from plasma by serial ultracentrifugation methods and circulating and EV TGF‐β expression levels were evaluated by enzyme‐linked immunosorbent assay.
Results
Baseline high expression of TGF‐β in EVs was associated with nonresponse to ICIs as well as shorter progression‐free survival and overall survival, outperforming circulating TGF‐β levels and tissue PD‐L1 as a predictive biomarker.
Conclusion
If validated, EV TGF‐β could be used to improve patient stratification, increasing the effectiveness of treatment with ICIs and potentially informing combinatory treatments with TGF‐β blockade.
Plain language summary
Treatment with immune‐checkpoint inhibitors (ICIs) has improved the survival of some patients with lung cancer. However, the majority of patients do not benefit from this treatment, making it essential to develop more reliable biomarkers to identify patients most likely to benefit.
In this pilot study, the expression of transforming growth factor‐β (TGF‐β) in blood circulation and in extracellular vesicles was analyzed.
The levels of extracellular vesicle TGF‐β before treatment were able to determine which patients would benefit from treatment with ICIs and have a longer survival with higher accuracy than circulating TGF‐β and tissue PD‐L1, which is the currently used biomarker in clinical practice.
Extracellular vesicle transforming growth factor‐β (TGF‐β) outperformed circulating TGF‐β and standard tissue PD‐L1 characterization for predicting treatment response and survival of patients with non–small cell lung cancer undergoing treatment with immune checkpoint inhibitors.
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