Intraoperative Anesthetic Strategies to Mitigate Early Allograft Dysfunction After Orthotopic Liver Transplantation: A Narrative Review.

Orthotopic liver transplantation (OLT) is the most effective treatment for patients with end-stage liver disease (ESLD). Hepatic insufficiency within a week of OLT, termed early allograft dysfunction (EAD), occurs in 20% to 25% of deceased donor OLT recipients and is associated with morbidity and mortality. Primary nonfunction (PNF), the most severe form of EAD, leads to death or retransplantation within 7 days. The etiology of EAD is multifactorial, including donor, recipient, and surgery-related factors, and largely driven by ischemia-reperfusion injury (IRI). IRI is an immunologic phenomenon characterized by dysregulation of cellular oxygen homeostasis and innate immune defenses in the allograft after temporary cessation (ischemia) and later restoration (reperfusion) of oxygen-rich blood flow. The rising global demand for OLT may lead to the use of marginal allografts, which are more susceptible to IRI, and thus lead to an increased incidence of EAD. It is thus imperative the anesthesiologist is knowledgeable about EAD, namely its pathophysiology and intraoperative strategies to mitigate its impact. Intraoperative strategies can be classified by 3 phases, specifically donor allograft procurement, storage, and recipient reperfusion. During procurement, the anesthesiologist can use pharmacologic preconditioning with volatile anesthetics, consider preharvest hyperoxemia, and attenuate the use of norepinephrine as able. The anesthesiologist can advocate for normothermic regional perfusion (NRP) and machine perfusion during allograft storage at their institution. During recipient reperfusion, the anesthesiologist can optimize oxygen exposure, consider adjunct anesthetics with antioxidant-like properties, and administer supplemental magnesium. Unfortunately, there is either mixed, little, or no data to support the routine use of many free radical scavengers. Given the sparse, limited, or at times conflicting evidence supporting some of these strategies, there are ample opportunities for more research to find intraoperative anesthetic strategies to mitigate the impact of EAD and improve postoperative outcomes in OLT recipients.

A novel theta-controlled vibrotactile brain-computer interface to treat chronic pain: a pilot study.

Limitations in chronic pain therapies necessitate novel interventions that are effective, accessible, and safe. Brain-computer interfaces (BCIs) provide a promising modality for targeting neuropathology underlying chronic pain by converting recorded neural activity into perceivable outputs. Recent evidence suggests that increased frontal theta power (4-7 Hz) reflects pain relief from chronic and acute pain. Further studies have suggested that vibrotactile stimulation decreases pain intensity in experimental and clinical models. This longitudinal, non-randomized, open-label pilot study's objective was to reinforce frontal theta activity in six patients with chronic upper extremity pain using a novel vibrotactile neurofeedback BCI system. Patients increased their BCI performance, reflecting thought-driven control of neurofeedback, and showed a significant decrease in pain severity (1.29 ± 0.25 MAD, p = 0.03, q = 0.05) and pain interference (1.79 ± 1.10 MAD p = 0.03, q = 0.05) scores without any adverse events. Pain relief significantly correlated with frontal theta modulation. These findings highlight the potential of BCI-mediated cortico-sensory coupling of frontal theta with vibrotactile stimulation for alleviating chronic pain.

Interventions Targeting Bottle and Formula Feeding in the Prevention and Treatment of Early Childhood Caries, Overweight and Obesity: An Integrative Review.

Overweight, obesity and early childhood caries (ECC) are preventable conditions affecting infants and young children, with increased prevalence in those formula-fed. Previous research has focused on distinct outcomes for oral health and healthy weight gain. However, the aetiology may be linked through overlapping obesogenic and cariogenic feeding behaviours, such as increased sugar exposure through bottle propping and overfeeding. Best-practice bottle feeding and transition to cup use may concurrently reduce overweight, obesity and ECC. This integrative review aimed to identify interventions supporting best-practice formula feeding or bottle cessation and examine the intervention effects on feeding, oral health and weight outcomes. The reviewers searched nine databases and found 27 studies that met the predetermined inclusion criteria. Eighteen studies focused on populations vulnerable to ECC or unhealthy weight gain. All studies focused on carer education; however, only 10 studies utilised behaviour change techniques or theories addressing antecedents to obesogenic or cariogenic behaviours. The outcomes varied: 16 studies reported mixed outcomes, and eight reported worsened post-intervention outcomes. While some studies reported improvements, these were not maintained long-term. Many study designs were at risk of bias. Effective intervention strategies for preventing ECC and child obesity require the holistic use of interdisciplinary approaches, consumer co-design and the use of behavioural change theory.

Novel Solutions to Student Problems: A Phenomenological Exploration of a Single Session Approach to Art Therapy With Creative Arts University Students.

Within the Australian university context, research has uncovered increasing levels of psychological distress, in the form of stress, anxiety and depression. Higher rates of psychological distress have been reported in undergraduate students specifically enrolled in creative arts programs. Despite these increasing levels of psychological distress, university students are reluctant to engage with mental health and wellbeing supports. To explore ways to meet the mental health and wellbeing needs of creative arts university students, the Creative Arts and Music Therapy Research Unit at The University of Melbourne commenced a project exploring the benefits and pitfalls of a brief creative arts therapies approach for students attending a campus based wellbeing clinic. This exploratory research study formed the art therapy component of this much broader research endeavor. Creative arts students in this research study were invited to participate in a single session art therapy encounter that involved the visual exploration of the miracle question, asking students to visually depict "what the problem looks like and how it will look when the problem is resolved or you feel like you can cope with it better?" The descriptive findings of this exploratory research study revealed how the combination of art therapy used within a single session framework was able to afford students a novel means to externalize problems, leading students to forming a less internalized view of the self.

Assessing drug efficacy against Plasmodium falciparum liver stages in vivo.

Malaria eradication necessitates new tools to fight the evolving and complex Plasmodium pathogens. These tools include prophylactic drugs that eliminate Plasmodium liver stages and consequently prevent clinical disease, decrease transmission, and reduce the propensity for resistance development. Currently, the identification of these drugs relies on in vitro P. falciparum liver stage assays or in vivo causal prophylaxis assays using rodent malaria parasites; there is no method to directly test in vivo liver stage activity of candidate antimalarials against the human malaria-causing parasite P. falciparum. Here, we use a liver-chimeric humanized mouse (FRG huHep) to demonstrate in vivo P. falciparum liver stage development and describe the efficacy of clinically used and candidate antimalarials with prophylactic activity. We show that daily administration of atovaquone-proguanil (ATQ-PG; ATQ, 30 mg/kg, and PG, 10 mg/kg) protects 5 of 5 mice from liver stage infection, consistent with the use in humans as a causal prophylactic drug. Single-dose primaquine (60 mg/kg) has similar activity to that observed in humans, demonstrating the activity of this drug (and its active metabolites) in FRG huHep mice. We also show that DSM265, a selective Plasmodial dihydroorotate dehydrogenase inhibitor with causal prophylactic activity in humans, reduces liver stage burden in FRG huHep mice. Finally, we measured liver stage-to-blood stage transition of the parasite, the ultimate readout of prophylactic activity and measurement of infective capacity of parasites in the liver, to show that ATQ-PG reduces blood stage patency to below the limit of quantitation by quantitative PCR (qPCR). The FRG huHep model, thus, provides a platform for preclinical evaluation of drug candidates for liver stage causal prophylactic activity, pharmacokinetic/pharmacodynamics studies, and biological studies to investigate the mechanism of action of liver stage active antimalarials.

Combined theoretical and mass spectrometry study of the formation-fragmentation of small polyoxomolybdates.

We investigate the assembly of small polyoxomolybdates using Car-Parrinello molecular dynamics simulations which show that there is an expansion of the coordination sphere of the Mo center from four to six in molybdate anions when the acidity of the solution is increased. With the help of complementary static density functional theory (DFT) calculations and electrospray ionization mass spectrometry experiments, we are able to postulate tentative mechanisms, with energy-cascade profiles, for the formation of the Lindqvist [Mo(6)O(19)](2-) anion. Similar to the family of isopolytungstates, it can be proposed that the [Mo(6)O(19)](2-) is formed by the aggregation of one molybdenum unit at a time; however, significant differences with respect to isopolytungstates are also found. The different behavior of chromates with respect to molybdates and tungstates is also considered.

Costs of managing conditions associated with obesity among Australian teenagers.

AIM: To determine the health-care charges associated with monitoring and managing, over 1 year, the cases of elevated insulin concentration, elevated alanine aminotransferase concentration and dyslipidaemia due to overweight or obesity among 15-19-year-old Australian males and females. METHODS: Fasting blood samples (n= 500) were collected in 2004 from a representative population sample of adolescents (n= 496; mean age 15.3 years) attending schools in Sydney, Australia. Full service charges and Medicare expenditures for specialist medical and dietary consultations, pathology tests and radiological investigations, over 1 year, under efficient and inefficient health-care delivery models, including and excluding participants in the healthy body mass index (BMI) category. RESULTS: Under an inefficient delivery model and including all participants with elevated risk factors, the Medicare expenditure was $A305.1 million per annum (M pa). Exclusion of participants in the healthy BMI category resulted in an annual Medicare expenditure of $A170.0M pa. Under an efficient delivery model and including all participants with elevated risk factors, the Medicare expenditure was $A295.5M pa. Exclusion of participants in the healthy BMI category reduced annual Medicare expenditure to $A164.8M pa. Medicare expenditure for 15-19-year-olds would increase by 48% if only cases among overweight and obese adolescents were treated and by 85% if all cases were identified and treated. CONCLUSIONS: Short-term management of the health consequences of overweight and obesity among adolescents will increase Medicare expenditure on this group by at least 48%. Failure to treat will delay, but compound, health-care expenditure.

Asthma 1-2-3: a low literacy multimedia tool to educate African American adults about asthma.

Asthma 1-2-3 is a newly-developed low-literacy multimedia education tool designed to promote asthma self-care concepts among African American adults. An expert panel (n = 10) informed content development for the tool. The video script and storyboard imagery were shown to 30 African Americans recruited from the American Lung Association, whose reactions and comments guided further revisions. The final version was pilot tested in three diverse community settings in Chicago to determine the efficacy of Asthma 1-2-3 at improving patient understanding of asthma and its symptoms. In all, 130 adults participated in the pilot test. Knowledge scores significantly improved from pretest to posttest following presentation of the developed tool for subjects across all literacy levels (Pretest: Mean = 4.2 [SD = 1.6]; Posttest: M = 6.8 [SD = 2.0], P < 0.001). Symptom pathophysiology concepts were the least understood. Individuals with low literacy had less total knowledge score gains compared to those with marginal and adequate literacy (1.8, 2.6, and 3.2 respectively; P = 0.002). The multimedia tool significantly improved understanding of asthma. Individuals with limited literacy may require additional instruction, repeated viewing, or added tangible cues (i.e. supplementary print materials) to support knowledge retention. In general, feedback from the target population was particularly helpful in the development of the tool and its initial evaluation, and should be considered as a necessary step in the creation of other patient education materials.

Naturally occurring progesterone in loblolly pine (Pinus taeda L.): a major steroid precursor of environmental androgens.

Progesterone, androstenedione, and androstadienedione were previously identified in the water and sediment of the Fenholloway River (Taylor County, FL, USA), a river that contains populations of masculinized female mosquitofish downstream of a paper mill, at levels higher than those in the nearby Spring Creek. Plant sterols, such as beta-sitosterol in mill effluent derived from pine tree pulp, were suggested to be metabolized by bacteria to progesterone and androgens to account for the masculinization phenomenon. The current study made use of standard solid-phase methanol extraction procedures, high-performance liquid chromatography, liquid chromatography-mass spectrometry, and a cell-based, androgen-receptor transcription assay to determine naturally occurring progesterone levels in mature pine trees. Progesterone concentrations in the loblolly pine (Pinus taeda L.) were 49.34 +/- 4.1 nmol/g dry mature wood (15.5 +/- 1.29 microg/g), 12.26 +/- 1.78 nmol/g pine needles (3.85 +/- 0.56 microg/g), and 3.81 +/- 0.36 nmol/g pine bark (1.19 +/- 0.11 mug/g). The results suggest that naturally occurring progesterone from pine wood pulp contributes to increased progesterone levels downstream of paper mill effluent discharges and may serve as the natural steroid precursor for environmental androgen production that causes masculinization of female mosquitofish.

Tertiary paediatric obesity services in Australia.

AIM: To examine the nature and availability of paediatric obesity services in tertiary care settings across the states/territories of Australia. METHODS: Surveys were sent to all clinicians identified as offering obesity services to children and adolescents. Respondents were asked to identify other service providers in their area, who were also asked to complete the survey. RESULTS: Sixteen clinicians responded to the survey, from 20 requests. The clinicians who responded identified nine services in three of the eight states/territories of Australia. Existing services are limited to children and adolescents with severe obesity, with an average of 12 new referrals per service each month and an average waiting time of 5 months for an appointment. Most services involve a multidisciplinary approach, although the mix of staff varies considerably and emphasises nutrition rather than physical activity approaches. CONCLUSIONS: Despite the public attention devoted to paediatric obesity, tertiary services in Australia are inadequate to meet the increasing incidence and prevalence of this complex condition. The development of tertiary services as part of service delivery arrangements for paediatric obesity and its associated morbidities must become a priority within the health system.

The risks of underwater birth.

OBJECTIVE: We performed a retrospective review of the literature on the complications that could be associated potentially with water birth. STUDY DESIGN: We performed an extensive review of the medical literature using the Pub Med search engine, which is available through the National Library of Medicine. We also examined the Cochrane review on immersion in pregnancy, labor and birth. RESULTS: Our review revealed 74 articles regarding water births. We found 16 citations that described complications that were associated with underwater birth. Possible complications that were associated with water birth included fresh water drowning, neonatal hyponatremia, neonatal waterborne infectious disease, cord rupture with neonatal hemorrhage, hypoxic ischemic encephalopathy, and death. Our systematic review did not identify an adequately controlled trial of delivery underwater (second stage of labor underwater) compared with delivery in air. CONCLUSION: Water birth may be associated with potential complications that are not seen with land-based birth. The rates of these complications are likely to be low but are not well defined.

Raltitrexed (Tomudex): an alternative choice in patients intolerant to 5-fluorouracil.

Raltitrexed (Tomudex), a classical folate antagonist, is a selective inhibitor of thymidylate synthase (TS). It has significant single-agent activity in metastatic colorectal cancer. Severe life-threatening toxicity related to the administration of 5-fluorouracil and leucovorin is described in two patients, both of whom were not deficient in dihydropyrimidine dehydrogenase. Raltitrexed was administered to both patients with clinically acceptable side effects and allowed a TS inhibitor to be administered as part of an adjuvant program.