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.

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.

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.

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.

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.

Wrinkle reduction in post-menopausal women consuming a novel oral supplement: a double-blind placebo-controlled randomized study.

OBJECTIVE: The maintenance of youthful skin appearance is strongly desired by a large proportion of the world's population. The aim of the present study was therefore to evaluate the effect on skin wrinkling, of a combination of ingredients reported to influence key factors involved in skin ageing, namely inflammation, collagen synthesis and oxidative/UV stress. A supplemented drink was developed containing soy isoflavones, lycopene, vitamin C and vitamin E and given to post-menopausal women with a capsule containing fish oil. METHOD: We have performed a double-blind randomized controlled human clinical study to assess whether this cocktail of dietary ingredients can significantly improve the appearance of facial wrinkles. RESULTS: We have shown that this unique combination of micronutrients can significantly reduce the depth of facial wrinkles and that this improvement is associated with increased deposition of new collagen fibres in the dermis. CONCLUSION: This study demonstrates that consumption of a mixture of soy isoflavones, lycopene, vitamin C, vitamin E and fish oil is able to induce a clinically measureable improvement in the depth of facial wrinkles following long-term use. We have also shown, for the first time with an oral product, that the improvement is associated with increased deposition of new collagen fibres in the dermis.

Climbazole increases expression of cornified envelope proteins in primary keratinocytes.

OBJECTIVE: Dandruff is a troubling consumer problem characterized by flaking and pruritus of the scalp and is considered a multifactorial condition with sebum, individual susceptibility and the fungus Malassezia all thought to play a part. The condition is commonly treated with shampoo products containing antifungal ingredients such as zinc pyrithione and climbazole. It is hypothesized that these ingredients may be delivering additional scalp skin benefits besides their antifungal activity helping to relieve dandruff effectively. The objective of this study was to evaluate the anti-dandruff ingredient climbazole for potential skin benefits using genomics and in vitro assays. METHODS: Microarray analysis was performed to profile gene expression changes in climbazole-treated primary human keratinocyte cells. Results were independently validated using qPCR and analysis of protein expression using ELISA and immunocytochemistry. RESULTS: Microarray analysis of climbazole-treated keratinocytes showed statistically significant expression changes in genes associated with the gene ontology groups encompassing epidermal differentiation, keratinization, cholesterol biosynthesis and immune response. Upregulated genes included a number encoding cornified envelope proteins such as group 3 late-cornified envelope proteins, LCE3 and group 2 small-proline-rich proteins, SPRR2. Protein analysis studies of climbazole-treated primary keratinocytes using ELISA and immunocytochemistry were able to demonstrate that the increase in gene transcripts translated into increased protein expression of these cornified envelope markers. CONCLUSION: Climbazole treatment of primary keratinocytes results in an upregulation in expression of a number of genes including those encoding proteins involved in cornified envelope formation with further studies demonstrating this did translate into increased protein expression. A climbazole-driven increase in cornified envelope proteins may improve the scalp skin barrier, which is known to be weaker in dandruff. These studies suggest climbazole, besides its antifungal activity, is delivering positive skin benefits helping to relive dandruff symptoms effectively.

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.

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.

Conductance-based chemical sensing in metallic nanowires and metal-semiconductor nanostructures.

Conductance-based chemical sensing in metal-semiconductor nanostructures and all-metal nanowires of atomic dimensions is garnering increased interest. Adsorbed gas molecules can migrate to a metal-semiconductor junction, thereby shifting the magnitude of the Schottky barrier and altering electrical impedance, whereas atomic scale metal junctions can sensitively report the presence of adsorbates through their impact on ballistic electron transport.

Effectiveness of timing strategies for delivery of monochorionic diamniotic twins.

OBJECTIVE: The purpose of this study was to compare strategies for delivery timing of uncomplicated monochorionic diamniotic twin pregnancies. STUDY DESIGN: A decision tree compared 9 strategies that included scheduled delivery between 32 and 38 weeks' gestation, with or without confirmation of fetal lung maturity. Outcomes in the model included fetal death, infant death, respiratory distress syndrome, mental retardation, and cerebral palsy. RESULTS: A scheduled delivery at 38 weeks' gestation was the preferred strategy, which resulted in the highest quality adjusted life years under base-case assumptions. Decreased, but comparable, quality adjusted life years estimates resulted from scheduled deliveries at 36 and 37 weeks' gestation, with or without amniocentesis. Sensitivity analyses demonstrated that the optimal gestational age for delivery was always ≥36 weeks' gestation. CONCLUSION: This decision analysis suggests that, for women with uncomplicated monochorionic twins, delivery between 36 and 38 weeks' gestation is the preferred strategy for timing of delivery.

Potential shifts in dominant forest cover in interior Alaska driven by variations in fire severity.

Large fire years in which >1% of the landscape burns are becoming more frequent in the Alaskan (USA) interior, with four large fire years in the past 10 years, and 79 000 km2 (17% of the region) burned since 2000. We modeled fire severity conditions for the entire area burned in large fires during a large fire year (2004) to determine the factors that are most important in estimating severity and to identify areas affected by deep-burning fires. In addition to standard methods of assessing severity using spectral information, we incorporated information regarding topography, spatial pattern of burning, and instantaneous characteristics such as fire weather and fire radiative power. Ensemble techniques using regression trees as a base learner were able to determine fire severity successfully using spectral data in concert with other relevant geospatial data. This method was successful in estimating average conditions, but it underestimated the range of severity. This new approach was used to identify black spruce stands that experienced intermediate- to high-severity fires in 2004 and are therefore susceptible to a shift in regrowth toward deciduous dominance or mixed dominance. Based on the output of the severity model, we estimate that 39% (approximately 4000 km2) of all burned black spruce stands in 2004 had <10 cm of residual organic layer and may be susceptible a postfire shift in plant functional type dominance, as well as permafrost loss. If the fraction of area susceptible to deciduous regeneration is constant for large fire years, the effect of such years in the most recent decade has been to reduce black spruce stands by 4.2% and to increase areas dominated or co-dominated by deciduous forest stands by 20%. Such disturbance-driven modifications have the potential to affect the carbon cycle and climate system at regional to global scales.

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.

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.

An immunoglobulin light chain from a lupus-prone mouse induces autoantibodies in normal mice.

Autoantibodies against the 70-kD U1 RNP nucleoprotein autoantigen and DNA were elicited in normal BALB/c mice with a purified Ig light chain. This light chain, derived from a lupus-prone MRL-lpr/lpr mouse, has two distinctive properties: it contains an idiotypic marker recognized by a monoclonal MRL-lpr/lpr anti-snRNP autoantibody, and the amino acid sequence of its third hypervariable region (CDR3) is homologous to a sequence in an antigenic region of the 70-kD U1 RNP polypeptide. The results demonstrate that an Ig idiotype that mimics an autoantigen can induce autoimmunization.

High sensitivity hydrogen sensing with Pt-decorated porous gallium nitride prepared by metal-assisted electroless etching.

A unique hydrogen sensor structure based on Pt-decorated porous gallium nitride (PGaN) was fabricated by a two-step process consisting of metal-assisted electroless etching to produce PGaN with highly anisotropic pores followed by electroless deposition of Pt in the pores from an ammoniacal PtCl(6)(2-) solution. The Pt-decorated PGaN structure contains 50-100 nm diameter nanopores which are 400 nm to 1 microm deep and filled with Pt islands. Both electroless etching and deposition steps are done in solution and allow for large-scale production. An AC four-point probe conductivity measurement was implemented at f = 1 kHz, a frequency where the impedance of Pt-PGaN is nearly entirely resistive, and the change in conductance upon H(2) exposure was measured for three sample types: PGaN with a surface sputtered layer of Pt only; unetched GaN (CGaN) with both sputtered and electrolessly deposited Pt; and PGaN with both sputtered and electrolessly deposited Pt. The hydrogen sensing performance of the Pt-filled PGaN sensor was more than an order of magnitude better than either of the other two sample types under all experimental conditions, an observation attributed to the significant increase in Pt-GaN interfacial area in the electrolessly decorated PGaN samples, exhibiting a response to H2 concentrations as low as 1 ppm. The conductance changes are ascribed to adsorption-induced changes in interfacial polarization that produce changes in band bending and thus to the width of the space charge region near the Pt-GaN interface.

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.

Effects of captan on Apis mellifera brood development under field conditions in California almond orchards.

Three almond field trials were conducted during 2003 and 2004 at two locations in central (Fresno County) and northern (Yolo County) California to evaluate the potential effects of commercial applications of Captan on honey bees, Apis mellifera L. Captan was applied at 5.0 kg (AI)/ha during bloom. Hives were evaluated for hive health and brood development parameters for approximately 2 mo after application. This study showed that the application of Captan was not harmful to foraging honey bees or their brood. No treatment-related effects were noted on hive weights, dead bee deformity, number of dead bees, survival of individual larvae, weight of individual emerging adults, and other hive health parameters.