Supporting strong families and capable communities through cross-national research

Background Mental and behavioral ill-health are growing global problems and while there are promising evidence-based approaches aimed at reducing their impact, availability of services varies greatly, not only across nations, but also between urban, regional, and remote locations. Rural areas face accessibility and acceptability challenges related to mental health services that are similar to barriers experienced in developing countries. Initiatives to address mental health challenges in under-served rural areas can inform global mental health strategies. Methods Using a public health approach, we illustrate how innovations in rural communities build community capacity and capability in areas that are currently, and are likely to remain, under-served by specialist mental health services. We provide examples of initiatives and key principles of action from three locations in Nebraska, United States of American and New South Wales, Australia to highlight similarities of context and practice. Results While each of the initiatives was developed independently, there are striking similarities across them. Similarities in initiatives include: a) recognition that solutions developed in urban settings are not necessarily the most effective in under- served rural areas, b) engagement of community members is needed to ensure acceptance of initiatives in target communities, c) each initiative involved community members acting on their own behalf with an emphasis on prevention and early intervention, and d) research is a key aspect that informs practice and has local relevance. Commonalities of contexts and environments may have played an important role in the similarities. Conclusions Linking initiatives within and between countries can expand local, national, and global reach and impacts. If we are to meet lofty global goals related to health and wellbeing, cross-national collaborations are needed to share resources, expand expertise, and stimulate ideas necessary to develop and enhance local and global initiatives. High-income country partnerships addressing mental health in under-served areas, such as rural communities, can play a vital role in contributing to global mental health solutions

Prevalence and pattern of brown adpose tissue distribution of 18F-FDG in patients undergoing PET-CT in a subtropical climatic zone

BACKGROUND The uptake of 18F-FDG in brown adipose tissue (BAT) may have important implications in understanding the pathophysiology of BAT and obesity. Because of the thermal implications of BAT uptake of 18F-FDG, this study aimed to contribute to existing knowledge by assessing patients scanned in a subtropical environment with particular reference to ethnicity. PATIENTS AND METHODS A retrospective study was carried out to determine the prevalence and pattern of BAT uptake in patients undergoing 18F-FDG PET-CT imaging in a PET facility located in a subtropical climatic zone. Standardized uptake values were obtained for regions of BAT uptake of 18F-FDG, and the distribution pattern was assessed according to anatomical region, sex, age, BMI and ethnicity. RESULTS Following a reveiw of a total of 386 scans, 38 patients showed BAT uptake of 18F-FDG (9.85%), with the mass and activity of BAT being greater in women than in men (11.95 and 6.88%, respectively). BAT uptake of 18F-FDG in the neck/supraclavicular, axillary and mediastinal regions was greater in adults whose BMI was less than 18kg/m2. However, perirenal BAT activity was shown to be greater in obese individuals. The frequency of BAT uptake of 18F-FDG was 55% in winter as against 45% during summer (P<0.012). There was no statistical difference in BAT uptake between black and white patients. CONCLUSION This study shows the pattern and prevalence of BAT in patients in a subtropical environment. Although the average seasonal temperatures are higher in a subtropical climate, a seasonal variation in BAT expression was observed, although there were no differences with respect to patient ethnicity.http://www.lww.comhb201

Simultaneous measurement of gastric emptying of a soup test meal using MRI and gamma scintigraphy

Measurement of gastric emptying is of clinical value for a range of conditions. Gamma scintigraphy (GS) has an established role, but the use of magnetic resonance imaging (MRI) has recently increased. Previous comparison studies between MRI and GS showed good correlation, but were performed on separate study days. In this study, the modalities were alternated rapidly allowing direct comparison with no intra-individual variability confounds. Twelve healthy participants consumed 400 g of Technetium-99m (99mTc)-labelled soup test meal (204 kcal) and were imaged at intervals for 150 min, alternating between MRI and GS. The time to empty half of the stomach contents (T1/2) and retention rate (RR) were calculated and data correlated. The average T1/2 was similar for MRI (44 ± 6 min) and GS (35 ± 4 min) with a moderate but significant difference between the two modalities (p ≤0.004). The individual T1/2 values were measured, and MRI and GS showed a good positive correlation (r = 0.95, p ≤ 0.0001), as well as all the RRs at each time point up to 120 min. Gastric emptying was measured for the first time by MRI and GS on the same day. This may help with translating the use of this simple meal, known to elicit reliable, physiological, and pathological gastrointestinal motor, peptide, and appetite response

A Multimodality Hybrid Gamma-Optical Camera for Intraoperative Imaging

The development of low profile gamma-ray detectors has encouraged the production of small field of view (SFOV) hand-held imaging devices for use at the patient bedside and in operating theatres. Early development of these SFOV cameras was focussed on a single modality-gamma ray imaging. Recently, a hybrid system-gamma plus optical imaging-has been developed. This combination of optical and gamma cameras enables high spatial resolution multi-modal imaging, giving a superimposed scintigraphic and optical image. Hybrid imaging offers new possibilities for assisting clinicians and surgeons in localising the site of uptake in procedures such as sentinel node detection. The hybrid camera concept can be extended to a multimodal detector design which can offer stereoscopic images, depth estimation of gamma-emitting sources, and simultaneous gamma and fluorescence imaging. Recent improvements to the hybrid camera have been used to produce dual-modality images in both laboratory simulations and in the clinic. Hybrid imaging of a patient who underwent thyroid scintigraphy is reported. In addition, we present data which shows that the hybrid camera concept can be extended to estimate the position and depth of radionuclide distribution within an object and also report the first combined gamma and Near-Infrared (NIR) fluorescence images.Peer-reviewedPublisher Versio

Synthesis, in vitro evaluation, and radiolabeling of fluorinated puromycin analogues: potential candidates for PET imaging of protein synthesis

There is currently no ideal radiotracer for imaging protein synthesis rate (PSR) by positron emission tomography (PET). Existing fluorine-18 labelled amino acid-based radiotracers predominantly visualize amino acid transporter processes, and in many cases they are not incorporated into nascent proteins at all. Others are radiolabelled with the short half-life positron emitter carbon-11 which is rather impractical for many PET centers. Based on the puromycin (6) structural manifold, a series of 10 novel derivatives of 6 was prepared via Williamson ether synthesis from a common intermediate. A bioluminescence assay was employed to study their inhibitory action on protein synthesis which identified fluoroethyl analogue (7b) as a lead compound. The fluorine-18 analogue was prepared via nucleophilic substitution of the corresponding tosylate precursor in modest radiochemical yield 2±0.6% and excellent radiochemical purity (>99%) and showed complete stability over 3 h at ambient temperature

Nasal Administration and Plasma Pharmacokinetics of Parathyroid Hormone Peptide PTH 1-34 for the Treatment of Osteoporosis

Nasal delivery of large peptides such as parathyroid 1-34 (PTH 1-34) can benefit from a permeation enhancer to promote absorption across the nasal mucosa into the bloodstream. Previously, we have published an encouraging bioavailability (78%), relative to subbcutaneous injection in a small animal preclinical model, for a liquid nasal spray formulation containing the permeation enhancer polyethylene glycol (15)-hydroxystearate (Solutol® HS15). We report here the plasma pharmacokinetics of PTH 1-34 in healthy human volunteers receiving the liquid nasal spray formulation containing Solutol® HS15. For comparison, data for a commercially manufactured teriparatide formulation delivered via subcutaneous injection pen are also presented. Tc-99m-DTPA gamma scintigraphy monitored the deposition of the nasal spray in the nasal cavity and clearance via the inferior meatus and nasopharynx. The 50% clearance time was 17.8 min (minimum 10.9, maximum 74.3 min). For PTH 1-34, mean plasma Cmax of 5 pg/mL and 253 pg/mL were obtained for the nasal spray and subcutaneous injection respectively; relative bioavailability of the nasal spray was 1%. Subsequently, we investigated the pharmacokinetics of the liquid nasal spray formulation as well as a dry powder nasal formulation also containing Solutol® HS15 in a crossover study in an established ovine model. In this preclinical model, the relative bioavailability of liquid and powder nasal formulations was 1.4% and 1.0% respectively. The absolute bioavailability of subcutaneously administered PTH 1-34 (mean 77%, range 55–108%) in sheep was in agreement with published human data for teriparatide (up to 95%). These findings have important implications in the search for alternative routes of administration of peptides for the treatment of osteoporosis, and in terms of improving translation from animal models to humans

Whole-body and adipose tissue-specific mechanisms underlying the metabolic effects of fibroblast growth factor 21 in the Siberian hamster.

OBJECTIVE: Fibroblast growth factor 21 (FGF21) has been shown to rapidly lower body weight in the Siberian hamster, a preclinical model of adiposity. This induced negative energy balance mediated by FGF21 is associated with both lowered caloric intake and increased energy expenditure. Previous research demonstrated that adipose tissue (AT) is one of the primary sites of FGF21 action and may be responsible for its ability to increase the whole-body metabolic rate. The present study sought to determine the relative importance of white (subcutaneous AT [sWAT] and visceral AT [vWAT]), and brown (interscapular brown AT [iBAT]) in governing FGF21-mediated metabolic improvements using the tissue-specific uptake of glucose and lipids as a proxy for metabolic activity. METHODS: We used positron emission tomography-computed tomography (PET-CT) imaging in combination with both glucose (18F-fluorodeoxyglucose) and lipid (18F-4-thiapalmitate) tracers to assess the effect of FGF21 on the tissue-specific uptake of these metabolites and compared responses to a control group pair-fed to match the food intake of the FGF21-treated group. In vivo imaging was combined with ex vivo tissue-specific functional, biochemical, and molecular analyses of the nutrient uptake and signaling pathways. RESULTS: Consistent with previous findings, FGF21 reduced body weight via reduced caloric intake and increased energy expenditure in the Siberian hamster. PET-CT studies demonstrated that FGF21 increased the uptake of glucose in BAT and WAT independently of reduced food intake and body weight as demonstrated by imaging of the pair-fed group. Furthermore, FGF21 increased glucose uptake in the primary adipocytes, confirming that these in vivo effects may be due to a direct action of FGF21 at the level of the adipocytes. Mechanistically, the effects of FGF21 are associated with activation of the ERK signaling pathway and upregulation of GLUT4 protein content in all fat depots. In response to treatment with FGF21, we observed an increase in the markers of lipolysis and lipogenesis in both the subcutaneous and visceral WAT depots. In contrast, FGF21 was only able to directly increase the uptake of lipid into BAT. CONCLUSIONS: These data identify brown and white fat depots as primary peripheral sites of action of FGF21 in promoting glucose uptake and also indicate that FGF21 selectively stimulates lipid uptake in brown fat, which may fuel thermogenesis

Hypoxia imaging with [18F]HX4 PET in squamous cell head and neck cancer: a pilot study for integration into treatment planning

Background: Radical chemoradiotherapy is the primary treatment for head and neck cancers in many hospitals. Tumour hypoxia causes radiotherapy resistance, and is an indicator of poor prognosis for patients. Identifying hypoxia to select patients for intensified or hypoxia-modified treatment regimens is therefore of high clinical importance. Patients and Methods: We evaluated hypoxia in a group of patients with newly diagnosed squamous cell head and neck cancer using the hypoxia-selective radiotracer [18F]HX4. Patients underwent a single [18F]HX4 PET/CT scan prior to beginning chemoradiotherapy.Results: Three out of eight patients recruited were scanned with [18F]HX4. Two out of three had pre-treatment [18F]FDGPET/CT scans available for review. [18F]HX4 tumour uptake varied between patients, with tumour to mediastinal ratios ranging from1 to3.5. Conclusions: The spectrum of [18F]HX4 uptake in this small series of patients exemplifies the difference in oxygenation profiles between histologically similar tumours. Performing an additional PET scan with [18F]HX4 prior to chemoradiotherapy treatment was logistically challenging in a routine setting, and therefore validation of its clinical impact should be the focus of future studies

Black Box 2019

The Black Box is a student based creative publication serving the Embry-Riddle Prescott campus. It is our goal to provide a showcase for the creativity and talent of the Embry-Riddle students. Creative works by members of Embry-Riddle\u27s faculty and staff are included