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Venous congestion is an under-recognized contributor to mortality in critically ill patients. Unfortunately, venous congestion is difficult to measure, and right heart catheterization (RHC) remains the gold standard. Recently, a novel “Venous Excess Ultrasound (VExUS)” score was developed to noninvasively quantify venous congestion using inferior vena cava (IVC) diameter and doppler flow through the hepatic, portal, and renal veins. A preliminary retrospective study of post-cardiac surgery patients showed promising results, including a high positive-likelihood ratio of high VExUS grade for acute kidney injury. However, further validation studies have not been reported in broader patient populations, and validity of VExUS as compared to other measures of venous congestion such as IVC diameter is unknown. To address this gap, the authors prospectively validated the VExUS against right atrial pressure (RAP), with comparison to inferior vena cava (IVC) diameter. Patients undergoing RHC at the Denver Health Medical Center underwent VExUS examination before their procedure. VExUS grades were assigned before RHC, blinding ultrasonographers to RHC outcomes. After controlling for age, sex, and common comorbidities, there was a significant positive linear association between RAP and VExUS grade (p 2 = .68). VExUS had a favorable AUC for prediction of a RAP ≥ 12 mmHg (0.99, 95% CI 0.96-1) compared to IVC diameter (0.79, 95% CI 0.65–0.92). These results suggest a strong physiologic correlation between VExUS and RAP in a diverse patient population, and support future studies of VExUS as a tool to assess venous congestion and guide management in a variety of critical illnesses.

The personal care industry is focused on developing safe, more efficacious, and increasingly milder products, that are routinely undergoing preclinical and clinical testing before becoming available for consumer use on skin. In vitro systems based on skin reconstructed equivalents are now established for the preclinical assessment of product irritation potential and as alternative testing methods to the classic Draize rabbit skin irritation test. We have used the 3-D EpiDerm™ model system to evaluate tissue viability and primary cytokine interleukin-1α release as a way to evaluate the potential dermal irritation of 224 non-ionic, amphoteric and/or anionic surfactant-containing formulations, or individual raw materials. As part of our testing programme, two representative benchmark materials with known clinical skin irritation potential were qualified through repeated testing, for use as references for the skin irritation evaluation of formulations containing new surfactant ingredients. We have established a correlation between the in vitro screening approach and clinical testing, and are continually expanding our database to enhance this correlation. This testing programme integrates the efforts of global manufacturers of personal care products that focus on the development of increasingly milder formulations to be applied to the skin, without the use of animal testing.

Background/Objective Epidermal structure, function, and composition are different in white infants and adults. We investigated whether ethnicity and location contribute to differences in functional and clinical measurements of skin barrier function during the first years of life and in adults. Methods Children (n = 397, ages 3–49 mos) and women (n = 117, mean age 31 yrs) were enrolled at independent centers in Beijing, China (ethnic Chinese), Skillman, New Jersey (white, African American), and Mumbai, India (ethnic South Asian). Water barrier properties of the stratum corneum were assessed using high-frequency conductance and transepidermal water loss (TEWL) on the dorsal forearm and upper inner arm. Digital imaging was used to evaluate facial erythema and scaling. Results Despite differences in local climate, TEWL was similar in adults. In children, conductance and TEWL decreased monotonically from age 3 months to 4 years. In children from Beijing, TEWL values were higher in both arm locations than in children in Mumbai and Skillman. No significant differences were observed in TEWL or conductance between the white and African American groups. Conclusion In general, TEWL and conductance were greater on the upper inner arm than the dorsal forearm. Erythema and scaling were observed most often in subjects from Beijing and most infrequently in subjects from Mumbai. Stratum corneum water barrier properties were different in children and adults. Although there may be differences in these properties between ethnic groups in childhood, TEWL values were similar in adults across the three geographic locations and four ethnicities.

Domiciliary NIV has been shown to improve admission-free survival in COPD patients with persistent hypercapnia. European teaching hospitals tend to setup their domiciliary NIV patients as inpatients. With increasing bed pressures, our district general hospital has had to find innovative ways achieve good outcomes for our hypercapnic COPD patients by setting them up on domiciliary NIV as outpatients. Aim: We compared our inpatient to outpatient setups to determine which was more cost- efficient and clinically effective. Our domiciliary NIV machines have modems which allow us to monitor patients’ compliance via Encore Anywhere. Method: We examined the records of COPD patients commenced on domiciliary NIV (24 inpatient, 15 outpatient) and obtained arterial blood gas results and rates of compliance, amount of air leak and frequency of exacerbations resulting in hospital admissions. Results: Mean pCO2 prior to commencing NIV was higher in the inpatient cohort (9.54 vs 8.47), and there was a greater drop in pCO2 (36.5% vs 33.3%) during follow up. However, the average pCO2 after commencement of NIV was lower in the outpatient group (5.65 vs 6.06). Compliance (71.2% vs 67.7%), frequency of air leak (4.1% vs 4%,) and hospital admissions for exacerbations (63.9% vs 61.2%) were similar in both groups. Discussion: Patients set up as outpatients had similar clinical outcomes compared to those set up as inpatients. An outpatient set up saves at least £759 per patient compared to inpatient setup and would be a cost-effective way of managing the increasing number of hypercapnic COPD patients.

Although there has been substantial research and reform in Vocational Education and Training (VET) over the past 30 years, it is argued that this has ostensibly had limited effectiveness on practices in TAFE colleges. Many policy changes during this period have not resulted in the requisite changed practices by TAFE teachers. This paper reports on an investigation of the concerns for TAFE teachers in Western Australia when carrying out their work functions in a changing VET environment. Using semi-structured interviews with 55 TAFE teachers from three colleges the study explored the everyday lives of this workforce, also known as VET practitioners. The issues which emerged were categorised in four broad themes: college administration systems, financial constraints, pedagogical skills and college management. In addition, TAFE teachers indicated that they were adopting an unofficial code of professional conduct using practices which may not necessarily align with organisational objectives.

The transient receptor potential vanilloid type 1 (TRPV1) channel is one of the most well-characterized pain-inducing receptors. The purpose of this study was to predict human eye stinging of 19 baby bath and shampoo formulations by studying TRPV1 activity, as measured by increase in intracellular free Ca(2+). The NociOcular test, a novel recombinant neuronal in vitro model with high expression of functional TRPV1 channels, was used to test formulations containing a variety of surfactants, preservatives, and fragrances. TRPV1-specific Ca(2+) influx was abolished when the TRPV1 channel antagonist capsazepine was applied to the cells prior to shampoo samples. The positive control, an adult shampoo that contains cocamide monoethanolamine (CMEA), a known stinging ingredient, was the most active sample tested in the NociOcular test. The negative control, a marketed baby shampoo, was negative in the NociOcular and human tests. Seven of the formulations induced stinging in the human test, and of those six were positive in the NociOcular test. Twelve formulations were classified as nonstinging in the human test, and of those ten were negative in the NociOcular test. There was no correlation between the clinical stinging results for the baby formulations and the data generated from other in vitro eye irritation assays (cytosensor microphysiometer, neutral red uptake, EpiOcular, transepithelial permeability). Our data support that the TRPV1 channel is a principal mediator of eye-stinging sensation induced by baby bath and shampoo formulations and that the NociOcular test may be a valuable in vitro tool to predict human eye-stinging sensation.

The presence of irritants from feces and urine with the concurrent mechanical friction and occlusion creates an environment in the diapered area that renders the skin prone to diaper dermatitis. Besides being a source of discomfort to the infant, these skin irritations pose a risk of secondary infections. In this study, we used noninvasive in vivo techniques to define measurable parameters that correlate with diaper dermatitis pathophysiology. In 35 infants (16 with mild or moderate and 19 without diaper dermatitis) we compared skin of diapered areas afflicted with diaper dermatitis to lesion-free diapered sites and to skin outside the diapered area (thigh). Our findings show significantly elevated cutaneous erythema, pH, and hydration, with significantly compromised water barrier function in involved areas compared to nonlesional sites both within and outside the diapered area. Furthermore, skin pH in nonlesional diapered skin for the diaper dermatitis cohort was significantly higher compared to the nondiapered sites. These observations are consistent with the current understanding of pathological skin changes in diaper dermatitis. In this study, we demonstrate that noninvasive methods can document relevant parameters to diaper dermatitis in vivo.

Background This study investigates nutritional behavior among adolescents and young adults with bipolar disorder (BP) in comparison to those without history of major psychiatric disorder. Methods 131 participants (82 BP, 49 controls) with a mean age of 16.11±1.61 years were included. The self-reported Quick Weight, Activity, Variety & Excess (WAVE) Screener was used to assess dietary habits, yielding a total nutritional score as well as Excess, Variety, and Household Food Insecurity subscale scores. Specifically, the Variety subscale was used to measure daily consumption of essential nutrients; the Excess subscale measured unhealthy eating behaviors such as binge eating and excessive intake of fat and sugar; and the Household Food Insecurity subscale was used to detect food insecurity. Within-group analysis was conducted on participants with BP to identify correlates of unhealthy diet. Results BP participants scored significantly lower than controls on the WAVE (t=2.62, p=0.010), specifically the Excess subscale (t=3.26, p=0.001). This was related to higher prevalence of binge eating and emotional eating behaviors among participants with BP compared to controls. Within-group analyses showed that self-reported emotional dysregulation/impulsivity was associated with maladaptive nutritional behaviors (t=3.38, p=0.035). Limitations Cross-sectional design. Within-group analyses were underpowered. Diet quality was measured using a brief self-report screener. Conclusion Adolescents and young adults with BP have poorer nutritional behaviors compared to controls, and this difference is related to stress-induced eating. This demonstrates the need to screen for stress-induced eating and to intervene when needed in order to optimize nutritional behaviors among adolescents and young adults with BP.

The availability of an in vitro test system to replace animal testing of potential irritants is becoming more and more urgent especially in Europe as a consequence of the European Community Cosmetics Directive. To evaluate the ability of Advanced Tissue Sciences' (ATS) ZK1301 skin model to predict the skin irritation potential of surfactants, we performed a pilot validation study utilizing four different laboratories. The in vitro protocol was designed as a quantitative pre-screen for the clinical patch studies. Sixteen substances, representing various surfactant categories and ranges of irritation potential, were tested. The 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay was used to quantitate viability in vitro. We documented the viability of tissues exposed to unknown substances for specific periods. The in vitro results were calculated as percent distilled water controls (DWC). The time required to reduce the viability of each tissue to 50% of the distilled water controls (T50) was compared to mean erythema and edema scores from the clinical studies by Pearson's correlation. The individual laboratories demonstrated coefficients of 0.72. The results indicated that the 30 min percent untreated control values best predicted the 24 h clinical patch scores. No statistically significant interlab variability was found. Only one false negative was seen when non/mild and moderate/severe irritant categories were assigned according to the in vitro scores. These results demonstrate that the skin2 in vitro test system may serve as a good screening method prior to clinical patch studies.

Extracts of Tanacetum parthenium (L.) Sch. Bip., a plant known under the common name "Feverfew", contains the sesquiterpene lactone parthenolide, a potent skin sensitizer. To eliminate the risk of skin sensitization from Feverfew, we developed a parthenolide-depleted extract of Feverfew (PD-Feverfew) and determined its effectiveness as an anti-inflammatory agent. We confirmed that PD-Feverfew was sufficiently depleted of parthenolide since PD-Feverfew did not inhibit TNF-alpha induced-NF-kappaB activity unlike parthenolide containing whole Feverfew. PD-Feverfew directly inhibited the activity of pro-inflammatory enzymes 5-lipoxygenase, phosphodiesterase-3 and phosphodiesterase-4. PD-Feverfew inhibited the release of pro-inflammatory mediators nitric oxide, PGE(2) and TNF-alpha from macrophages and TNF-alpha, IL-2, IFN-gamma and IL-4 from human peripheral blood mononuclear cells. Additionally, PD-Feverfew inhibited TPA-induced release of PGE(2) from human skin equivalents. In vivo, PD-Feverfew inhibited oxazolone-induced dermatitis, and was more potent than whole Feverfew in reducing TPA-induced dermatitis. Finally the efficacy of PD-Feverfew was confirmed clinically by a reduction in erythema in a methyl nicotinate-induced vasodilation model. In conclusion, our results indicate that PD-Feverfew extracts have potent anti-inflammatory activity suggesting that this botanical would be efficacious in relieving inflammation without inducing immune sensitization.

A number of diverse in vitro model systems have been employed for the prediction of irritation potential of test articles. Monolayer systems have proven to be useful for preliminary screening but are not always capable of distinguishing mild effects or adaptable to fully formulated product. Three-dimensional reconstructed skin equivalents integrate cellular toxicity with the kinetics of exposure and absorption, serving as more realistic models; however, it is not obvious which of the three-dimensional models will give the most predictive response, and which biomarker should be used for an endpoint measurement for different groups of irritants. While evaluating these variables, we have shown that different irritants modulate various cytokine mRNA levels and secretion patterns in a time- and concentration-dependent manner that is unique to each product category. These profiles are also dependent on keratinocyte–fibroblast interactions. The most predictive combinations of model systems and biomarkers for each product category were identified following comparison to preclinical data and human in vivo skin responses. Using a panel of representative consumer products, we identified IL-1α, IL-1ra, IL-8 and GM-CSF release from skin equivalents as being the best indicators of irritation.

The Transient Receptor Potential Vanilloid type 1 (TRPV1) receptor is one of the most well characterized pain-inducing receptors. The purpose of this study was to predict human eye stinging of 19 b ...