How Australian Health Care Services Adapted to Telehealth During the COVID-19 Pandemic: A Survey of Telehealth Professionals.

Background: In Australia, telehealth services were used as an alternative method of health care delivery during the COVID-19 pandemic. Through a realist analysis of a survey of health professionals, we have sought to identify the underlying mechanisms that have assisted Australian health services adapt to the physical separation between clinicians and patients. Methods: Using a critical realist ontology and epistemology, we undertook an online survey of health professionals subscribing to the Australian Telehealth Society newsletter. The survey had close- and open-ended questions, constructed to identify contextual changes in the operating environment for telehealth services, and assess the mechanisms which had contributed to these changes. We applied descriptive and McNemar's Chi-square analysis for the close-ended component of the survey, and a reflexive thematic analysis approach for the open-ended questions which were framed within the activity based funding system which had previously limited telehealth services to regional Australia. Results: Of the 91 respondents most (73%) reported a higher volume of telephone-based care since COVID and an increase in use of video consultations (60% of respondents). Respondents felt that the move to provide care using telehealth services had been a "forced adoption" where clinicians began to use telehealth services (often for the first time) to maintain health care. Respondents noted significant changes in managerial and medical culture which supported the legitimisation of telehealth services as a mode of access to care. The support of leaders and the use personal and organisational networks to facilitate the operation of telehealth service were felt to be particularly valuable. Access to, and reliability of, the technology were considered extremely important for services. Respondents also welcomed the increased availability of more human and financial resources. Conclusions: During the pandemic, mechanisms that legitimise practise, build confidence, support relationships and supply resources have fostered the use of telehealth. This ongoing interaction between telehealth services, contexts and mechanisms is complex. The adoption of telehealth access to enable physically separated care, may mark a "new context;" or it could be that once the pandemic passes, previous policies and practises will re-assert themselves and curb support for telehealth-enabled care.

Opposing effects of smoking in ulcerative colitis and Crohn's disease may be explained by differential effects on dendritic cells.

BACKGROUND: The mechanisms underlying the differential effects of cigarette smoking in patients with Crohn's disease (CD) and ulcerative colitis (UC) remain unknown. Smoking has been demonstrated to be protective in UC, whereas in CD it has been shown to be associated with a more severe course, more frequent relapses, and postoperative recurrence. Dendritic cells (DC) play a critical role in T-cell activation and differentiation. Thus, we examined the effects of in vitro exposure to cigarette smoke extract (CSE) on phenotype/function of DC obtained from patients with UC and CD. METHODS: Sixty-eight subjects were recruited including 30 patients with CD, 19 patients with UC, and 19 healthy controls. Peripheral blood monocytes were differentiated to DC in presence of IL-4 and granulocyte-macrophage colony-stimulating factor. The influence of CSE on Mo-DC subsets, cytokine expression, and ability to drive T cell proliferation and polarization were examined. RESULTS: CSE affected DC phenotypes including increases in class-2 major histocompatibility complex and costimulatory molecules and decreases in CXCL10 and CCL3 levels in UC compared with CD samples. Furthermore, CSE also altered DC function resulting in increasing T cell proliferation and Th1 polarization in CD, whereas it increased Foxp3+ T cells and decreased the Th1 subset in UC samples. CONCLUSIONS: CSE modulates DC phenotype and function in patients with UC leading to increased prevalence of Foxp3+ CD4 T cells, whereas in patients with CD it skews toward Th1 subsets. Differential DC responses to CSE between CD and UC may contribute to the differential effects associated with cigarette smoking status.

Increased prevalence of circulating novel IL-17 secreting Foxp3 expressing CD4+ T cells and defective suppressive function of circulating Foxp3+ regulatory cells support plasticity between Th17 and regulatory T cells in inflammatory bowel disease patients.

BACKGROUND: IL-17 and Foxp3 double-expressing (DE) CD4(+) T lymphocytes are novel crossover immune cell population, but the presence and role of these cells in human intestinal inflammation is unclear. The aim of this study was to investigate the circulating IL-17 and Foxp3 DE CD4(+) T lymphocytes in patients with inflammatory bowel disease (IBD). METHODS: The entire cohort consisted of 79 subjects: 31 patients with Crohn's disease, 28 patients with ulcerative colitis, and 20 healthy control subjects (HC). IBD patients with evidence of active disease at endoscopy were entered into the study. Peripheral blood mononuclear cells were used for ex vivo and in vitro studies to assess the characteristics and generation of these novel cells and the function of circulating Foxp3 CD4(+) regulatory T lymphocytes (Treg) in patients with IBD compared with HC. RESULTS: Patients with IBD had significantly higher prevalence of IL-17 and Foxp3 DE CD4(+) T lymphocytes compared with age- and gender-matched HC. These cells expressed RORγt. The ability of Treg cells to suppress autologous T-cell proliferation was reduced by approximately 60% in patients with IBD compared with HC. Increased generation of these DE cells was demonstrated by the modulation of cytokine environment of CD4(+) lymphocytes in vitro in patients with Crohn's disease. CONCLUSIONS: Prevalence of circulating IL-17 and Foxp3 DE CD4(+) T cells is increased in patients with IBD. Coexpression of RORγt and Foxp3 in these cells implies conversion from Treg cells to Th17 cells. This is associated with a decreased suppressive function of Foxp3 CD4(+) T lymphocytes in patients with IBD.

Regulation of neurotransmitter release from ocular tissues by isoprostanes.

Isoprostanes are prostaglandin-like compounds formed in vivo primarily by free radical-catalyzed peroxidation of arachidonic acid independent of the cyclooxygenase enzyme. In addition to being utilized as reliable indicators of oxidative stress, 8-isoprostanes exert pharmacological actions on smooth muscles from several tissues and organs, and they play a role in the release of neurotransmitters from the central and peripheral nervous systems. In the anterior uvea of the eye, 8-isoprostanes produce both excitatory and inhibitory effects on sympathetic neurotransmission in isolated mammalian iris ciliary bodies. Thromboxane (TP) receptors mediate the stimulatory action of isoprostanes on norepinephrine (NE) release from sympathetic nerves. In bovine retina, the 8-isoprostanes exhibit a biphasic regulatory effect on potassium-induced [3H]-D-aspartate release, with low concentrations being inhibitory and high concentrations causing an excitatory effect. Excitatory effects of 8-isoprostanes are mediated by TP receptors, while inhibitory responses are mediated by prostaglandin E (EP) receptors. The 8-isoprostanes produce pharmacological actions on sympathetic neurotransmission in mammalian anterior uvea, a response that is species-dependent. In the posterior segment of the eye, 8-isoprostanes elicit a complex response on the retina involving the activation of both prostanoid TP and EP receptors. An effect of isoprostanes on neurotransmitter pools provides new pharmacological target sites for the therapy of some ocular diseases.

Plasma pharmacokinetics and tissue distribution of a N-pyrrolo-[1,2-c]imidazolylphenyl sulfonamide in rats.

TY029, an N-pyrrolo[1,2-c]imidazolylphenyl sulfonamide herbicide, controls economically important weeds through inhibition of protoporphyrinogen oxygenase. As partial satisfaction of regulatory requirements to establish safety and to aid in the interpretation of toxicology bioassays, a rat metabolism study of TY029 was performed to define the pharmacokinetics and tissue distribution of this compound. Animals were exposed to single 50- and 2-mg/kg doses of [hydantoin-5-(14)C]TY029 by oral gavage. The tissue distribution studies revealed that generally greater than 5% of the oral dose was found in the carcass, gastrointestinal tract, liver, and the whole blood when plasma microgram equivalents per gram of TY029 was at maximum or at half of the maximum. However, these concentrations rapidly declined to negligible levels. By 96 h after the oral administration of [hydantoin-5-(14)C]TY029, the highest value reported for any one of the collected tissues was below 0.5% of administered dose. Therefore, neither TY029 nor its metabolites was sequestered in tissues to appreciable levels. The C(max), C(max/2), and area under the curve (AUC(INF)) obtained from the plasma pharmacokinetics suggested that in general single-dosed female rats absorbed and eliminated the test compounds faster than their male counterparts. Mass spectral evaluations of the plasma from single high- and low-dose male and female rats identified the plasma constituents related to the test compound. Although the parent molecule was present in all plasma samples, the three acidic metabolites were the predominant plasma metabolites in the high-dose groups. The overall plasma profile included TY029 and six metabolites.