The role of the radiographer in promoting health: A qualitative examination of diagnostic radiographer perspectives at a Scottish Major Trauma hospital.

INTRODUCTION: Publication of Government directives and initiatives have signalled a shift in healthcare priorities, with growing emphasis on prevention and early intervention. In comparison to other allied health professions, perceptions of Diagnostic Radiographers of their contribution to addressing these initiatives and role in promoting health, has not been explored. There is limited evidence on current practices, knowledge and confidence in providing health promotion advice to patients within this professional group. This study aimed to investigate the perceptions of Diagnostic Radiographers of their role in promoting health. METHODS: Semi-structured focus groups were conducted with 20 Diagnostic Radiographers recruited via convenience sampling from a Scottish Major Trauma Hospital. Focus groups were transcribed and analysed using thematic analysis. RESULTS: Findings demonstrated a lack of awareness and understanding of government initiatives and professional body recommendations surrounding health promotion. Diagnostic radiographers felt ill-equipped to provide appropriate and impactful health promotion advice and reported lack of time as a barrier to contributing to such activities. CONCLUSION: Diagnostic Radiographers noted a willingness to undertake additional training to enable them to participate and were able to identify areas where they could adopt health promotion activities in their clinical practice. Addressing the barriers to participation is essential to empower Diagnostic Radiographers to contribute to the health promotion agenda. IMPLICATIONS FOR PRACTICE: There is a need to address profession specific education at pre-registration and post-qualification levels, to ensure Diagnostic Radiographers are equipped with the knowledge, skills and confidence to promote health to their patients. Strong leadership is essential for creating a positive environment to facilitate education, training and the acceptance of health promotion as a key part of a diagnostic radiographer's role.

Transseptal puncture in the dog utilizing three-dimensional transesophageal echocardiographic guidance.

Transseptal puncture is necessary to access the left atrium and mitral valve from a transvenous approach but is poorly described in veterinary medicine. The procedure is generally regarded as difficult and dangerous, particularly given the size of most small animal patients. Precise imaging is paramount to the procedure to ensure that puncture occurs within the desired location and to monitor for potential complications. Transesophageal echocardiography, including biplanar two-dimensional and particularly three-dimensional modalities, has great potential to improve the success and safety of transseptal puncture due to superior visualization of the fossa ovalis and other intracardiac structures. Here, we describe the use of transesophageal echocardiography to guide transseptal puncture based on our experience in 159 dogs, with an emphasis on three-dimensional echocardiography. We also detail how to perform transseptal puncture from a jugular approach, which we consider preferable in most patients. Complications from transseptal puncture are discussed, along with ways to limit those complications.

Lower polyunsaturated fatty acid levels and FADS2 expression in adult compared to neonatal keratinocytes are associated with FADS2 promotor hypermethylation.

Keratinocytes produce lipids that are critical for the skin barrier, however, little is known about the impact of age on fatty acid (FA) biosynthesis in these cells. We have examined the relationship between keratinocyte FA composition, lipid biosynthetic gene expression, gene promoter methylation and age. Expression of elongase (ELOVL6 and 7) and desaturase (FADS1 and 2) genes was lower in adult versus neonatal keratinocytes, and was associated with lower concentrations of n-7, n-9 and n-10 polyunsaturated FA in adult cells. Consistent with these findings, transient FADS2 knockdown in neonatal keratinocytes mimicked the adult keratinocyte FA profile in neonatal cells. Interrogation of methylation levels across the FADS2 locus (53 genomic sites) revealed differential methylation of 15 sites in neonatal versus adult keratinocytes, of which three hypermethylated sites in adult keratinocytes overlapped with a SMARCA4 protein binding site in the FADS2 promoter.

Dominant Bacterial Phyla from the Human Gut Show Widespread Ability To Transform and Conjugate Bile Acids.

Gut bacteria influence human physiology by chemically modifying host-synthesized primary bile acids. These modified bile acids, known as secondary bile acids, can act as signaling molecules that modulate host lipid, glucose, and energy metabolism and affect gut microbiota composition via selective antimicrobial properties. However, knowledge regarding the bile acid-transforming capabilities of individual gut microbes remains limited. To help address this knowledge gap, we screened 72 bacterial isolates, spanning seven major phyla commonly found in the human gut, for their ability to chemically modify unconjugated bile acids. We found that 43 isolates, representing 41 species, were capable of in vitro modification of one or more of the three most abundant unconjugated bile acids in humans: cholic acid, chenodeoxycholic acid, and deoxycholic acid. Of these, 32 species have not been previously described as bile acid transformers. The most prevalent bile acid transformations detected were oxidation of 3α-, 7α-, or 12α-hydroxyl groups on the steroid core, a reaction catalyzed by hydroxysteroid dehydrogenases. In addition, we found 7α-dehydroxylation activity to be distributed across various bacterial genera, and we observed several other complex bile acid transformations. Finally, our screen revealed widespread bacterial conjugation of primary and secondary bile acids to glycine, a process that was thought to only occur in the liver, and to 15 other amino acids, resulting in the discovery of 44 novel microbially conjugated bile acids. IMPORTANCE Our current knowledge regarding microbial bile acid transformations comes primarily from biochemical studies on a relatively small number of species or from bioinformatic predictions that rely on homology to known bile acid-transforming enzyme sequences. Therefore, much remains to be learned regarding the variety of bile acid transformations and their representation across gut microbial species. By carrying out a systematic investigation of bacterial species commonly found in the human intestinal tract, this study helps better define the gut bacteria that impact composition of the bile acid pool, which has implications in the context of metabolic disorders and cancers of the digestive tract. Our results greatly expand upon the list of bacterial species known to perform different types of bile acid transformations. This knowledge will be vital for assessing the causal connections between the microbiome, bile acid pool composition, and human health.

The effect of statin therapy on disease-related outcomes in idiopathic pulmonary fibrosis: A systematic review and meta-analysis.

BACKGROUND: Idiopathic pulmonary fibrosis is a progressive disease and antifibrotic therapies do not reverse existing fibrosis. There has been emerging evidence of potential role for statins in idiopathic pulmonary fibrosis. The aim of this review is to synthesise the evidence on the efficacy of statins in idiopathic pulmonary fibrosis, focusing on associations with all-cause mortality, disease-specific mortality and change in pulmonary function. METHODS: Medline and Embase were reviewed to identify relevant publications. Studies were selected if they examined disease-related outcomes including mortality, pulmonary function and adverse events in people with idiopathic pulmonary fibrosis receiving statin therapy. RESULTS: Five studies with a total of 3407 people with IPF were selected and analysed. The overall risk of bias of five included studies was moderate to serious. In the fixed effect meta-analysis, statin use was associated with a reduction in mortality (RR 0.8; 95% CI 0.72-0.99). However, in the random effects model, there was no longer any significant association between statin use and all-cause mortality (RR 0.87; 95% CI 0.68-1.12). There was no statistically significant association between statin use and decline in FVC % predicted. CONCLUSION: There is currently insufficient evidence to conclude the effect of statin therapy on disease-related outcomes in idiopathic pulmonary fibrosis. Considering the limitations of available literature, we would recommend a prospective cohort study with capture of dosage and preparation of statin, statin adherence and use of concurrent antifibrotic treatment. PROSPERO REGISTRATION NUMBER: CRD42019122745.

Prevalence of Previously Undiagnosed Abdominal Aortic Aneurysms in Patients with Intracranial Aneurysms: From the Brain and Aortic Aneurysms Study (BAAS).

BACKGROUND: A relationship between intracranial and abdominal aortic aneurysms (AAA) has been appreciated through genome-wide association studies suggesting a shared pathophysiology. However, the actual prevalence of AAA in patients presenting with ruptured intracranial aneurysms is not known. Our aim was to estimate the prevalence of previously undiagnosed AAA in patients presenting with aneurysmal subarachnoid hemorrhage (aSAH) to see if it may be high enough to justify formally testing the utility of screening. METHODS: A prospective, observational inception cohort study of 81 consecutive patients presenting to Mayo Clinic Florida with aSAH was performed from August 14, 2011 to February 10, 2014. These individuals were then screened using an abdominal ultrasound technique for an AAA. Our primary end point was detection of AAA. Our secondary end points were 30-day good-to-fair functional status (modified Rankin scale < 4) and all-cause mortality. RESULTS: We detected an AAA in 10 patients (rate: 12%; 95% CI 6-22%) with aSAH. The mean diameter of these AAA was 3.4 ± 1.0 cm. Among these 10 patients, there was one death within the first month of aSAH hospitalization. There were no significant differences in demographic or clinical characteristics based on AAA detection status. Mean follow-up time was 4.7 years. The rate of good-to-fair functional status at 30-days was 79%. All-cause mortality during follow-up at 1-year was higher for patients with AAA (36%; 95% CI 0-61%) compared to patients without AAA (7%; 95% CI 1-14%) (log-rank p = 0.045). CONCLUSIONS: The co-prevalence of AAA in patients presenting with ruptured brain aneurysms may be sufficiently high such that screening for AAA among likely survivors of aSAH might be appropriate. Larger studies would be needed to establish a net clinical benefit from screening AAA and then treating newly identified large AAAs in this morbid population.

TGFß1 single-nucleotide polymorphism C-509T alters mucosal cell function in pediatric eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic Th2 antigen-driven disorder associated with tissue remodeling. Inflammation and remodeling lead to esophageal rigidity, strictures, and dysphagia. TGFß1 drives esophageal remodeling including epithelial barrier dysfunction and subepithelial fibrosis. A functional SNP in the TGFß1 gene that increases its transcription (C-509T) is associated with elevated numbers of esophageal TGFß1-expressing cells. We utilized esophageal biopsies and fibroblasts from TT-genotype EoE children to understand if TGFß1 influenced fibroblast and epithelial cell function in vivo. Genotype TT EoE esophageal fibroblasts had higher baseline TGFß1, collagen1α1, periostin, and MMP2 (p < 0.05) gene expression and distinct contractile properties compared with CC genotype (n = 6 subjects per genotype). In vitro TGFß1 exposure caused greater induction of target gene expression in genotype CC fibroblasts (p < 0.05). Esophageal biopsies from TT-genotype subjects had significantly less epithelial membrane-bound E-cadherin (p < 0.01) and wider cluster distribution at nanometer resolution. TGFß1 treatment of stratified primary human esophageal epithelial cells and spheroids disrupted transepithelial resistance (p < 0.001) and E-cadherin localization (p < 0.0001). A TGFß1-receptor-I inhibitor improved TGFß1-mediated E-cadherin mislocalization. These data suggest that EoE severity can depend on genotypic differences that increase in vivo exposure to TGFß1. TGFß1 inhibition may be a useful therapy in subsets of EoE patients.

Nodular melanoma presenting as an exophytic subungual mass.

Despite being recognised and reported in the literature for decades, subungual melanoma of the foot remains a diagnostic pitfall, with it commonly being mistaken for benign conditions. We present an interesting case of delayed diagnosis of subungual melanoma of the hallux that was misdiagnosed in the community for over one year. With melanoma being the fourth most commonly diagnosed cancer in Australia in 2013, this case serves as a reminder to all clinicians about the importance of maintaining a high index of suspicion for melanoma of the foot.

Ultrasensitive Single-Molecule Enzyme Detection and Analysis Using a Polymer Microarray.

This report describes a novel method for isolating and detecting individual enzyme molecules using polymer arrays of picoliter microwells. A fluidic flow-cell device containing an array of microwells is fabricated in cyclic olefin polymer (COP). The use of COP microwell arrays simplifies experiments by eliminating extensive device preparation and surface functionalization that are common in other microwell array formats. Using a simple and robust loading method to introduce the reaction solution, individual enzyme molecules are trapped in picoliter microwells and subsequently isolated and sealed by fluorinated oil. The sealing is stable for hours in the COP device. The picoliter microwell device can measure enzyme concentrations in the low-femtomolar range by counting the number of active wells using a digital read-out. These picoliter microwell arrays can also easily be regenerated and reused.

Longitudinal Analysis of Quality of Life, Clinical, Radiographic, Echocardiographic, and Laboratory Variables in Dogs with Preclinical Myxomatous Mitral Valve Disease Receiving Pimobendan or Placebo: The EPIC Study.

BACKGROUND: Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and cardiomegaly have not been described. OBJECTIVES: To investigate the effect of pimobendan on clinical variables and the relationship between a change in heart size and the time to congestive heart failure (CHF) or cardiac-related death (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan-treated dogs differ from dogs receiving placebo at onset of CHF. ANIMALS: Three hundred and fifty-four dogs with MMVD and cardiomegaly. MATERIALS AND METHODS: Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4-0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart-size variables in both groups were measured and compared at different time points (day 35 and onset of CHF) and over the study duration. Relationships between short-term changes in echocardiographic variables and time to CHF or CRD were explored. RESULTS: At day 35, heart size had reduced in the pimobendan group: median change in (Δ) LVIDDN -0.06 (IQR: -0.15 to +0.02), P < 0.0001, and LA:Ao -0.08 (IQR: -0.23 to +0.03), P < 0.0001. Reduction in heart size was associated with increased time to CHF or CRD. Hazard ratio for a 0.1 increase in ΔLVIDDN was 1.26, P = 0.0003. Hazard ratio for a 0.1 increase in ΔLA:Ao was 1.14, P = 0.0002. At onset of CHF, groups were similar. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan treatment reduces heart size. Reduced heart size is associated with improved outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable from those receiving placebo.

Reliability of patellar height indices in children with cerebral palsy and spina bifida.

BACKGROUND: The Koshino (KI) and Caton-Deschamps (CDI) indices are used to measure patellar height in children, with the CDI showing excellent reliability in typically developing (TD) children. Reliability of such measures in children with cerebral palsy (CP) and spina bifida (SB) is unknown. METHODS: Lateral knee radiographs were reviewed retrospectively for children with TD (n = 49), CP (n = 48) and SB (n = 42). Five raters took measurements from radiographs twice, at least two weeks apart. Measurements included the CDI, Insall-Salvati Index (ISI) and KI. Systematic variability (bias) and random variability were examined using repeated measures ANOVA, 95% limits of agreement (LOA) and coefficients of variation (CV). RESULTS: Mean values of all three indices differed among raters (p < 0.0001). A significant difference was seen between the first and second measurements for CDI and KI indicating a learning effect. LOA ranges were large for the CDI (intra-rater: 0.37-0.95, inter-rater: 0.60-1.04) and ISI (intra-rater: 0.25-0.49, inter-rater: 0.51-0.57) for all patient groups. The KI showed a clinically acceptable range for TD participants (intra-rater: 0.14-0.16, inter-rater: 0.11-0.14) with larger ranges for CP (intra-rater: 0.26-0.33, inter-rater 0.0.2-0.35) and SB patients (intra-rater: 0.23-0.27, inter-rater: 0.19-0.25). CVs were lowest (best) for KI (3.8% to 7.4%) and highest (worst) for CDI (14.7% to 23.1%) for all three groups. Results were similar for patients with both open and closed physes. CONCLUSIONS: The KI is the most reliable patellar height measure for paediatric patients with TD, CP and SB, with either open or closed physes. The KI is more complex and experience may be important for valid, reliable measurement.

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study-A Randomized Clinical Trial.

BACKGROUND: Pimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown. HYPOTHESIS/OBJECTIVES: Administration of pimobendan (0.4-0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac-related death, or euthanasia. ANIMALS: 360 client-owned dogs with MMVD with left atrial-to-aortic ratio ≥1.6, normalized left ventricular internal diameter in diastole ≥1.7, and vertebral heart sum >10.5. METHODS: Prospective, randomized, placebo-controlled, blinded, multicenter clinical trial. Primary outcome variable was time to a composite of the onset of CHF, cardiac-related death, or euthanasia. RESULTS: Median time to primary endpoint was 1228 days (95% CI: 856-NA) in the pimobendan group and 766 days (95% CI: 667-875) in the placebo group (P = .0038). Hazard ratio for the pimobendan group was 0.64 (95% CI: 0.47-0.87) compared with the placebo group. The benefit persisted after adjustment for other variables. Adverse events were not different between treatment groups. Dogs in the pimobendan group lived longer (median survival time was 1059 days (95% CI: 952-NA) in the pimobendan group and 902 days (95% CI: 747-1061) in the placebo group) (P = .012). CONCLUSIONS AND CLINICAL IMPORTANCE: Administration of pimobendan to dogs with MMVD and echocardiographic and radiographic evidence of cardiomegaly results in prolongation of preclinical period and is safe and well tolerated. Prolongation of preclinical period by approximately 15 months represents substantial clinical benefit.

The Impact of Gestational Age at Delivery on Urologic Outcomes for the Fetus with Hydronephrosis.

OBJECTIVE: Compare short-term urologic outcomes with delivery timing in fetuses with severe hydronephrosis. METHODS: An ultrasound database was queried for severe hydronephrosis. Cases were categorized into late preterm/early term (36 0/7 - 38 6/7 weeks) and full term (39 0/7 weeks or greater) groups. Baseline characteristics were compared using standard statistical methods. Spearman's correlation analysis was performed for grade and severity of hydronephrosis on first postnatal ultrasound with gestational age at delivery. RESULTS: Of 589 cases, 79 (33 late preterm/early term, 46 full term) met criteria. Baseline characteristics were similar between groups. Spearman's correlation coefficients (rs) indicated that increased postnatal Society for Fetal Urology grade, rs= -0.26 (95% CI [-.48, -.002]), and severity of hydronephrosis, rs= -0.39 (95% CI [-.59, -.14]), both correlated with earlier delivery. CONCLUSION: Late preterm/early term delivery resulted in worse short-term postnatal renal outcomes. Unless otherwise indicated, delivery for fetal hydronephrosis should be deferred until 39 weeks.

MEK and PI3K-AKT inhibitors synergistically block activated IL7 receptor signaling in T-cell acute lymphoblastic leukemia.

We identified mutations in the IL7Ra gene or in genes encoding the downstream signaling molecules JAK1, JAK3, STAT5B, N-RAS, K-RAS, NF1, AKT and PTEN in 49% of patients with pediatric T-cell acute lymphoblastic leukemia (T-ALL). Strikingly, these mutations (except RAS/NF1) were mutually exclusive, suggesting that they each cause the aberrant activation of a common downstream target. Expressing these mutant signaling molecules-but not their wild-type counterparts-rendered Ba/F3 cells independent of IL3 by activating the RAS-MEK-ERK and PI3K-AKT pathways. Interestingly, cells expressing either IL7Ra or JAK mutants are sensitive to JAK inhibitors, but respond less robustly to inhibitors of the downstream RAS-MEK-ERK and PI3K-AKT-mTOR pathways, indicating that inhibiting only one downstream pathway is not sufficient. Here, we show that inhibiting both the MEK and PI3K-AKT pathways synergistically prevents the proliferation of BaF3 cells expressing mutant IL7Ra, JAK and RAS. Furthermore, combined inhibition of MEK and PI3K/AKT was cytotoxic to samples obtained from 6 out of 11 primary T-ALL patients, including 1 patient who had no mutations in the IL7R signaling pathway. Taken together, these results suggest that the potent cytotoxic effects of inhibiting both MEK and PI3K/AKT should be investigated further as a therapeutic option using leukemia xenograft models.

Maternal-Fetal Medicine physicians' practice patterns for 22-week delivery management.

OBJECTIVE: To describe Maternal-Fetal Medicine (MFM) physicians' practice patterns for 22-week delivery management. MEHODS: Surveyed 750 randomly-sampled members of the Society of Maternal-Fetal Medicine, querying MFMs' practices and policies guiding 22-week delivery management. RESULTS: Three hundred and twenty-five (43%) MFMs responded. Nearly all (87%) would offer induction. Twenty-eight percent would order steroids, and 12% would perform cesarean for a patient desiring resuscitation. Offering induction differed significantly based on the provider's practice setting, region, religious service attendance and political affiliation. In multivariable analyses, political affiliation remained a significant predictor of offering induction (p = 0.03). CONCLUSIONS: Most MFMs offer induction for PPROM at 22 weeks. A noteworthy proportion is willing to order steroids and perform cesarean. Personal beliefs and practice characteristics may contribute to these decisions. While little is known about the efficacy of these interventions at 22 weeks, some MFMs will offer obstetrical intervention if resuscitation is intended.