Light therapies for acne: abridged Cochrane systematic review including GRADE assessments.

We undertook a Cochrane review of randomized controlled trials (RCTs) evaluating the effects of light-based interventions for acne vulgaris. We searched the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, ISI Web of Science and grey literature sources (September 2015). We used the Grading of Recommendations Assessment, Development and Evaluation Working Group approach to assess the quality of evidence (QoE). We included 71 RCTs (4211 participants, median sample size 31). Results from a single study (n = 266, low QoE) showed little or no difference in effectiveness on participants' assessment of improvement between 20% aminolaevulinic acid (ALA) photodynamic therapy (PDT), activated by blue light, vs. vehicle plus blue light, whereas another study (n = 180) comparing ALA-PDT (red light) concentrations showed that 20% ALA-PDT was no more effective than 15% ALA-PDT but better than 10% and 5% ALA-PDT. Pooled data from three studies (n = 360, moderate QoE) showed that methyl aminolaevulinate PDT, activated by red light, had a similar effect on changes in lesion counts vs. placebo cream with red light. Several studies compared yellow light with placebo or no treatment, infrared light with no treatment, gold microparticle suspension with vehicle and clindamycin/benzoyl peroxide (C/BPO) combined with pulsed dye laser with C/BPO alone. None of these showed any clinically significant effects. Most studies reported adverse effects, but inadequately, with scarring reported as absent, and blistering only in studies on intense pulsed light, infrared light and PDT (very low QoE). Carefully planned studies, using standardized outcome measures and common acne treatments as comparators, are needed.

Phylogenetic investigation of enteric bovine coronavirus in Ireland reveals partitioning between European and global strains.

BACKGROUND: Bovine coronavirus is a primary cause of neonatal calf diarrhea worldwide, and is also associated with acute diarrhea in adult cattle during the winter season. There are no reports on molecular characterization of bovine coronavirus in Ireland, and little data exists apart from serological studies. FINDINGS: In this study, 11 neonatal (mean age 9 days) calf BCoV strains from the south of Ireland were collected over a one year period and characterized using molecular methods. The spike gene which encodes a protein involved in viral entry, infectivity and immune response shows the most variability amongst the isolates and was subsequently selected for in depth analysis. Phylogenetic analysis of the spike gene revealed that the Irish strains clustered with novel BCoV strains from Europe in a unique clade, possibly indicating lineage partitioning. Direct analysis of alignments identified amino acid changes in the spike protein unique to the Irish clade. CONCLUSION: Thus, monitoring of bovine coronavirus in Ireland is important as the current isolates in circulation in the south of Ireland may be diverging from the available vaccine strain, which may have implications regarding future BCoV vaccine efficacy.

The cost-effectiveness of installing sidewalks to increase levels of transport-walking and health.

OBJECTIVE: This study investigated the cost-effectiveness of installing sidewalks to increase levels of transport-walking. METHODS: Secondary analysis using logistic regression established the association of sidewalks with transport-walking using two transport-walking thresholds of 150 and 60 min/week using Western Australian data (n=1394) from 1995 to 2000. Minimum, moderate and maximum interventions were defined, associated respectively with one sidewalk, at least one sidewalk and sidewalks on both sides of the street. Costs, average and incremental cost-effectiveness ratios were calculated for each intervention and expressed as 'the cost per person who walks for transport for more than 150 min/week (60 min/week) after the installation of new sidewalks'. A sensitivity analysis examined the robustness of the incremental cost-effectiveness ratios to varying model inputs. Costs are in 2012 Australian dollars. RESULTS: A positive relationship was found between the presence of sidewalks and transport-walking for both transport-walking thresholds of 150 and 60 min/week. The minimum intervention was found to be the most cost-effective at $2330/person and $674/person for the 150 and 60 min/week transport-walking thresholds respectively. Increasing the proportion of people transport-walking and increasing population density by 50% improved the cost-effectiveness of installing side-walks to $346/person. CONCLUSIONS: To increase levels of transport-walking, retrofitting streets with one sidewalk is most cost-effective.

A comparison of the efficiency of ELISA and selected primer sets to detect Norovirus isolates in southern Ireland over a four-year period (2002-2006): variation in detection rates and evidence for continuing predominance of NoV GII.4 genotype.

Norovirus (NoV) gastroenteritis occurs in all age groups and is the most common cause of gastroenteritis in the community. However, detection methods and rates vary widely, and few data are available to compare these, particularly in Ireland. Detection of noroviruses through antigen and molecular-based strategies was carried out on 135 suspected NoV-positive samples, collected over the course of three NoV outbreaks, from 2002 to 2006, in the southern region of Ireland. A commercially available ELISA and a panel of six primer sets were evaluated to determine their suitability for NoV detection in Irish clinical samples. The key findings of this study were the detection of both GGI and GGII noroviruses by ELISA, but the detection of only GGII noroviruses by RT-PCR. In addition to this, a variation in the levels of detection from 9.4 % to 17.3 % was observed for conventional PCR assays, while a detection rate of 46.3 % was observed for the real-time PCR assay. A proportion (17.8 %) of samples were found to be negative by all detection strategies, suggesting the possibility of reporting false positives for these samples or low-copy positives that do not often repeat. Sequencing information from selected samples also revealed nucleotide polymorphisms, compromising efficient primer binding in the case of one primer pairing. Phylogenetic analysis of the partial polymerase gene identified NoV GII.4 as the dominant genotype, in accordance with previous NoV studies in Ireland. Investigating the NoV diversity of the circulating strains and the dynamics of strain replacement is important to better assess the efficacy of future NoV vaccines and to facilitate the early detection of changes in circulating NoV strains.

Molecular characterization of group A rotavirus found in elderly patients in Ireland; predominance of G1P[8], continued presence of G9P[8], and emergence of G2P[4].

Rotavirus is a major cause of gastroenteritis in young children worldwide. There have been several recent reports concerning rotavirus isolation from adults, particularly in the elderly, presenting with gastroenteritis. In this study, the authors report on rotavirus outbreaks in five separate elderly care facilities between April, and June 2011 in Ireland. The following genotypes were detected; G1P[8] (n = 5/11), G2P[4] (n = 2/11), and G9P[8] (n = 2/11). Thus, similarities to previous reports were found in that G1P[8] predominated, G9P[8] was still detected but G2P[4] was detected for the first time in a geriatric population in Ireland. Here also described is the detection of Group 2 lineage IIC rotavirus in Ireland for the first time.

Label-free quantitation of a cancer biomarker in complex media using silicon photonic microring resonators.

Recent advances in label-free biosensing techniques have shown the potential to simplify clinical analyses. With this motivation in mind, this paper demonstrates for the first time the use of silicon-on-insulator microring optical resonator arrays for the robust and label-free detection of a clinically important protein biomarker in undiluted serum, using carcinoembryonic antigen (CEA) as the test case. We utilize an initial-slope-based quantitation method to sensitively detect CEA at clinically relevant levels and to determine the CEA concentrations of unknown samples in both buffer and undiluted fetal bovine serum. Comparison with a commercial enzyme-linked immunosorbent assay (ELISA) kit reveals that the label-free microring sensor platform has a comparable limit of detection (2 ng/mL) and superior accuracy in the measurement of CEA concentration across a 3 order of magnitude dynamic range. Notably, we report the lowest limit of detection to date for a microring resonator sensor applied to a clinically relevant cancer biomarker. Although this report describes the robust biosensing capabilities of silicon photonic microring resonator arrays for a single parameter assay, future work will focus on utilizing the platform for highly multiplexed, label-free bioanalysis.

Built environment and cardio-metabolic health: systematic review and meta-analysis of longitudinal studies.

Built environment attributes may be related to cardio-metabolic diseases (e.g. type 2 diabetes, heart disease and stroke) and their risk factors, potentially by influencing residents' physical activity. However, existing literature reviews on the built environment and health for the most part focus on obesity as the outcome and rely on cross-sectional studies. This systematic review synthesized current evidence on longitudinal relationships between built environment attributes and cardio-metabolic health outcomes among adults and on the potential mediating role of physical inactivity. By searching eight databases for peer-reviewed journal articles published in the English language between January 2000 and July 2016, the review identified 36 articles. A meta-analysis method, weighted Z-test, was used to quantify the strength of evidence by incorporating the methodological quality of the studies. We found strong evidence for longitudinal relationships of walkability with obesity, type 2 diabetes and hypertension outcomes in the expected direction. There was strong evidence for the impact of urban sprawl on obesity outcomes. The evidence on potential mediation by physical activity was inconclusive. Further longitudinal studies are warranted to examine which specific built environment attributes influence residents' cardio-metabolic health outcomes and how physical inactivity may be involved in these relationships.

Rapid advances in auto-segmentation of organs at risk and target volumes in head and neck cancer.

Advances in technical radiotherapy have resulted in significant sparing of organs at risk (OARs), reducing radiation-related toxicities for patients with cancer of the head and neck (HNC). Accurate delineation of target volumes (TVs) and OARs is critical for maximising tumour control and minimising radiation toxicities. When performed manually, variability in TV and OAR delineation has been shown to have significant dosimetric impacts for patients on treatment. Auto-segmentation (AS) techniques have shown promise in reducing both inter-practitioner variability and the time taken in TV and OAR delineation in HNC. Ultimately, this may reduce treatment planning and clinical waiting times for patients. Adaptation of radiation treatment for biological or anatomical changes during therapy will also require rapid re-planning; indeed, the time taken for manual delineation currently prevents adaptive radiotherapy from being implemented optimally. We are therefore standing on the threshold of a transformation of routine radiotherapy planning via the use of artificial intelligence. In this article, we outline the current state-of-the-art for AS for HNC radiotherapy in order to predict how this will rapidly change with the introduction of artificial intelligence. We specifically focus on delineation accuracy and time saving. We argue that, if such technologies are implemented correctly, AS should result in better standardisation of treatment for patients and significantly reduce the time taken to plan radiotherapy.

Proteomic analysis of childhood leukemia.

Childhood acute lymphoblastic and myeloid leukemias are stratified into molecular and cytogenetic subgroups important for prognosis and therapy. Studies have shown that gene expression profiles can discriminate between leukemia subtypes. Thus, proteome analysis similarly holds the potential for characterizing different subtypes of childhood leukemia. We used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to analyze cell lysates from childhood leukemia cell lines as well as pretreatment leukemic bone marrow derived from childhood leukemia cases. Comparison of the acute myeloid leukemia (AML) cell line, Kasumi, and the biphenotypic myelomonocytic cell line, MV4;11, with the acute lymphoblastic leukemia (ALL) cell lines, 697 and REH, revealed many differentially expressed proteins. In particular, one 8.3 kDa protein has been identified as a C-terminal truncated ubiquitin. Analysis of childhood leukemia bone marrow showed differentially expressed proteins between AML and ALL, including a similar peak at 8.3 kDa, as well as several proteins that differentiate between the ALL t(12;21) and hyperdiploid subtypes. These results demonstrate the potential for proteome analysis to distinguish between various forms of childhood leukemia. Future analyses are warranted to validate these findings and to investigate the role of the C-terminal truncated ubiquitin in the etiology of ALL.

Chromosome 3p14 alterations in lung cancer: evidence that FHIT exon deletion is a target of tobacco carcinogens and asbestos.

Alterations in the FHIT gene region have been previously associated with smoking status and the occurrence of lung tumors. In the current study, we examined the nature of the mutations that occur at FHIT and the types of carcinogen exposures that are associated with FHIT alterations. We screened 40 primary lung tumors for the presence of point mutations within the coding exons of FHIT using PCR-single-strand conformational polymorphism. Tumors were also analyzed for allelic loss using microsatellite markers located in or near FHIT. No tumors contained point mutations within the coding region of the FHIT gene. However, several samples failed to generate a PCR product, suggesting that regions of the gene are homozygously deleted. Samples were reanalyzed for exon loss using PCR; 13 of 30 tumors failed to generate a PCR product, and 20 of 30 tumors were missing at least one FHIT exon or had loss (loss of heterozygosity or deletion) of one microsatellite marker, suggesting that regions of the gene are homozygously deleted. These data indicate that the FHIT gene has a novel pattern of mutational inactivation not seen previously with other tumor suppressor genes, most likely influenced by the proximity of the FRA3B region. There were no associations of age, sex, p53, or k-ras mutation and FHIT exon deletion. However, there was an association of smoking duration and asbestos exposure with FHIT exon loss, indicating that carcinogenic exposures may be causal in the generation of alterations in the FHIT region.

Central inhibition by gamma-aminobutyric acid and muscimol of the release of vasopressin and oxytocin by an osmotic stimulus in the rat.

1. In water-loaded rats under ethanol anaesthesia, the injection of 2-4 microliters 1.54M NaCl solution (hypertonic saline:HS) into a lateral cerebral ventricle (i.c.v.) produced an antidiuretic and a pressor response, together with increased urinary excretion of vasopressin and 'oxytocin-like radioimmunoreactivity' (OLRI). In lactating rats HS also produced a milk-ejection response which was shown to be due to the release of oxytocin. 2. The injection of 20-40 micrograms gamma-aminobutyric acid (GABA) or 40-80 ng muscimol i.c.v. 2 min before HS inhibited the antidiuretic, pressor and milk-ejection responses and reduced the urinary excretion of vasopressin and OLRI. 3. The pressor response to HS was abolished by a ganglion blocking agent but it was not reduced by a vasopressin antagonist. After the antagonist, the antidiuretic response to HS was abolished and the pressor response was accompanied by a diuresis both of which were blocked by muscimol. 4. The threshold dose of HS for an antidiuretic response was 4-8 times higher on injection into the cisterna magna (i.cist.) than when injected i.c.v. GABA, i.v. or i.cist, did not inhibit the response to HS i.c.v. 5. The results confirm other evidence that, in the rat, in contrast some other species, an osmotic stimulus causes release of both vasopressin and oxytocin. This release is blocked by GABA and muscimol. These drugs and HS act at a site reached not from the subarachnoid space but from the cerebral ventricles, probably the hypothalamus. The pressor response to HS under the experimental conditions used is due entirely to central sympathetic stimulation and this effect, as well as the release of vasopressin and oxytocin, is blocked by muscimol.

Construction of pancreaticocystogastrostomy using an automatic stapling device.

The difficulties in employing standard techniques in the management of pancreatic pseudocysts led to the development and evaluation of a new approach. The advent of surgical stapling instruments has allowed the anastomotic procedures to be done in a more expeditious manner. For that reason, it was decided to treat pancreatic pseudocysts in two patients by constructing a pancreaticocystogastrostomy with the use of an automatic stapling instrument. The performance of the technique and the uneventful postoperative course encourages its continued use in cysts that are adjacent to the posterior gastric wall.

Rapid transfer of low copy-number episomal plasmids from Saccharomyces cerevisiae to Escherichia coli by electroporation.

A simple and reproducible method for transferring low copy-number episomal plasmids from yeast to Escherichia coli has been developed. Although slightly more time-consuming than direct transfer methods, which are effective with high copy number plasmids, the method is significantly faster than methods that require purification of yeast DNA. Plasmid DNA is released from yeast cells during brief treatments involving grinding with glass beads and heating. The treated yeast are cooled, electrocompetent E. coli is added, the mixture is electroporated, and transformants are selected using standard conditions for E. coli electrotransformation. The procedure typically yields sufficient transformants for most applications.

Potential sources of artefact in the co-axial bioassay.

The apparent release of relaxant activity from airway epithelium (epithelium-derived relaxing factor, EpDRF) has been examined in a co-axial bioassay system. The endothelium-denuded rat aorta, placed inside either the epithelium-intact guinea-pig trachea or rabbit bronchus relaxed in response to acetylcholine. In a modification of the standard preparation, the airway was slit longitudinally and immobilised inside a silicone rubber tube. Under these conditions, the acetylcholine-induced relaxation was abolished. Under the conditions of the co-axial bioassay, the oxygen tension in the lumen of either airway tube was lower than that of the bathing fluid. Upon addition of acetylcholine at concentrations which caused relaxation in the co-axial bioassay, the oxygen tension inside the epithelium-intact, but not the epithelium-denuded guinea-pig trachea was depressed to levels which would have affected the contractile response of a rat aorta. We suggest that the assay of relaxant activity from airways using co-axial preparations may be complicated by changes in volume and oxygen tension in the lumen of the donor airway and discuss how such problems might be avoided.

Measurement of interleukin-1 alpha and interleukin-6 in pregnancy-associated tissues.

The concentrations of interleukin-1 alpha (IL-1 alpha) and IL-6 in pregnancy-associated tissues were investigated in term labour and delivery in the absence of labour (elective Caesarean section). Samples of amniotic fluid, placenta, fetal membranes, umbilical venous and, where possible, umbilical arterial blood were collected at delivery (37-41 weeks of gestation). Maternal blood was sampled during labour. Fluid and tissue extracts were assayed for IL-1 alpha and IL-6 by radioimmunoassay. Placenta and membranes were examined histologically for evidence of infection. Concentrations of IL-1 alpha and IL-6 in amniotic fluid and membrane extract, and IL-1 alpha in maternal and fetal blood, were raised after the onset of labour. Concentrations of both cytokines in the placenta remained unchanged. There was a good correlation between concentrations of both cytokines in amniotic fluid and membranes. There was also a significant correlation between concentrations of IL-1 alpha and IL-6 in amniotic fluid, placenta and membranes. It is suggested that the fetal membranes or maternal decidua, but not the placenta, internal fetal or maternal tissues, are the main sources of IL-1 alpha and IL-6 during labour.

IGFBP-1 in the placenta, membranes and fetal circulation: levels at term and preterm delivery.

Samples of maternal blood, amniotic fluid, placenta, fetal membranes and umbilical venous blood were collected from 59 women at vaginal delivery (32-41 weeks gestation) and 15 women at delivery by Caesarean section (37-41 weeks gestation). Umbilical vein levels of IGFBP-1 were significantly lower in deliveries prior to the onset of labour (elective Caesarean section) than those during normal vaginal delivery. These levels were, in turn, significantly lower than those delivered by emergency Caesarean section. This difference was not seen in any of the other tissues examined. Concentrations of IGFBP-1 were lower in placenta and membrane extracts from preterm deliveries than in term deliveries. This difference was not observed in maternal or fetal serum or in amniotic fluid. This study confirms that the fetal membranes are a major source of IGFBP-1 and that fetal circulating levels are raised where there is evidence of fetal hypoxia. The absence of a comparable rise in levels in placenta, membranes or amniotic fluid suggests that the origin of this increase is from fetal tissue.

Relaxin levels in amniotic fluid, extraembryonic coelomic fluid and maternal serum in early human pregnancy.

Separately identified samples of amniotic fluid and extraembryonic coelomic fluid together with maternal serum were collected from 22 women between 8 and 11 weeks of pregnancy and analysed for relaxin by immunoassay. Relaxin levels in maternal serum (median 1085 pg/ml; range 390-1259 pg/ml) were substantially higher than those in extraembryonic coelomic fluid (median 57.5 pg/ml; range 17-145 pg/ml; P < 0.0001; Mann-Whitney U-test). In turn, the levels of relaxin in coelomic fluid were higher than those in amniotic fluid (median 10 pg/ml; range 10-37 pg/ml; P < 0.0001; Mann-Whitney U-test). A linear correlation was found between relaxin levels in maternal serum and coelomic fluid (r = 0.68; P = 0.001) but there was no relation between levels in the other fluid compartments.

Circulating levels of relaxin are normal in pregnant women with pelvic pain.

OBJECTIVE: The hormone relaxin induces loosening of the pelvic ligaments and joints in several species. Previous studies have suggested a similar role for relaxin during human pregnancy. Furthermore, a correlation has been noted between high circulating levels of this hormone and severe pelvic pain in pregnant women. The present study was designed to evaluate whether serum relaxin concentrations were elevated in pregnant women with clear subjective and objective evidence of pain attributable to relaxation of the pelvic ligaments. STUDY DESIGN: Serum relaxin was measured at week 33 of gestation in 455 pregnant women with clearly defined pain in their pelvic joints and 455 normal pregnant controls matched for age and parity. All participants underwent an examination consisting of a structured questionnaire and fifteen specific tests for pelvic joint pain. The group with pain was further subdivided into four subgroups with different levels of disability and prognosis. Relaxin concentrations were measured using enzyme-linked immunoassay. RESULTS: There was no difference in serum relaxin concentration between the control and study group, nor between the subgroups of women with pelvic pain. CONCLUSION: We failed to confirm an earlier claim that circulating relaxin levels are related to pelvic girdle pain in pregnant women.

Delayed luteo-placental shift of progesterone production in IVF pregnancy.

OBJECTIVE: To observe absolute and relative levels of progesterone, 17 alpha-hydroxyprogesterone (17-OHP) and human chorionic gonadotrophin (hCG) in in vitro fertilization (IVF) pregnancies after withdrawal of luteal support. METHOD: Single blood samples were obtained from 41 pregnant women following IVF treatment and 43 normal pregnant women at various weeks gestation within the first trimester. Progesterone, 17-OHP and hCG were measured by immunoassay. RESULTS: Serum levels of progesterone, but not of hCG, in IVF pregnancies were significantly greater than in normal pregnancies up to 8 weeks post-conception, despite discontinuing luteal support 2 weeks after conception. The ratio of progesterone to 17-OHP, a predominantly ovarian product, in normal pregnancies rose between 4 and 9 weeks but did not change over the same period in IVF pregnancies. CONCLUSION: The luteal contribution to maternal serum levels of progesterone is much higher in IVF pregnancies compared with normal pregnancies. This is sustained throughout the first trimester without the need for luteal support and obscures the placental contribution of progesterone for much longer than in normal pregnancies. Progesterone or hCG supplements may therefore be unnecessary in IVF pregnancy.