Postsynaptic α1-Adrenergic vasoconstriction is impaired in young patients with vasovagal syncope and is corrected by nitric oxide synthase inhibition

BACKGROUND: Syncope is a sudden transient loss of consciousness and postural tone with spontaneous recovery; the most common form is vasovagal syncope (VVS). During VVS, gravitational pooling excessively reduces central blood volume and cardiac output. In VVS, as in hemorrhage, impaired adrenergic vasoconstriction and venoconstriction result in hypotension. We hypothesized that impaired adrenergic responsiveness because of excess nitric oxide can be reversed by reducing nitric oxide. METHODS AND RESULTS: We recorded cardiopulmonary dynamics in supine syncope patients and healthy volunteers (aged 15-27 years) challenged with a dose-response using the α1-agonist phenylephrine (PE), with and without the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine, monoacetate salt (L-NMMA). Systolic and diastolic pressures among control and VVS were the same, although they increased after L-NMMA and saline+PE (volume and pressor control for L-NMMA). Heart rate was significantly reduced by L-NMMA (P<0.05) for control and VVS compared with baseline, but there was no significant difference in heart rate between L-NMMA and saline+PE. Cardiac output and splanchnic blood flow were reduced by L-NMMA for control and VVS (P<0.05) compared with baseline, while total peripheral resistance increased (P<0.05). PE dose-response for splanchnic flow and resistance were blunted for VVS compared with control after saline+PE, but enhanced after L-NMMA (P<0.001). Postsynaptic α1-adrenergic vasoconstrictive impairment was greatest in the splanchnic vasculature, and splanchnic blood flow was unaffected by PE. Forearm and calf α1-adrenergic vasoconstriction were unimpaired in VVS and unaffected by L-NMMA. CONCLUSIONS: Impaired postsynaptic α1-adrenergic vasoconstriction in young adults with VVS can be corrected by nitric oxide synthase inhibition, demonstrated with our use of L-NMMA

Valgus and varus deformity after wide-local excision, brachytherapy and external beam irradiation in two children with lower extremity synovial cell sarcoma: case report

BACKGROUND: Limb-salvage is a primary objective in the management of extremity soft-tissue sarcoma in adults and children. Wide-local excision combined with radiation therapy is effective in achieving local tumor control with acceptable morbidity and good functional outcomes for most patients. CASE PRESENTATION: Two cases of deformity after wide-local excision, brachytherapy and external beam irradiation for lower-extremity synovial cell sarcoma are presented and discussed to highlight contributing factors, time course of radiation effects and orthopedic management. In an effort to spare normal tissues from the long-term effects of radiation therapy, more focal irradiation techniques have been applied to patients with musculoskeletal tumors including brachytherapy and conformal radiation therapy. As illustrated in this report, the use of these techniques results in the asymmetric irradiation of growth plates and contributes to the development of valgus or varus deformity and leg-length discrepancies. CONCLUSIONS: Despite good functional outcomes, progressive deformity in both patients required epiphysiodesis more than 3 years after initial management. There is a dearth of information related to the effects of radiation therapy on the musculoskeletal system in children. Because limb-sparing approaches are to be highlighted in the next generation of cooperative group protocols for children with musculoskeletal tumors, documentation of the effects of surgery and radiation therapy will lead to improved decision making in the selection of the best treatment approach and in the follow-up of these patients

An Optimized, Chemically Regulated Gene Expression System for Chlamydomonas

BACKGROUND: Chlamydomonas reinhardtii is a model system for algal and cell biology and is used for biotechnological applications, such as molecular farming or biological hydrogen production. The Chlamydomonas metal-responsive CYC6 promoter is repressed by copper and induced by nickel ions. However, induction by nickel is weak in some strains, poorly reversible by chelating agents like EDTA, and causes, at high concentrations, toxicity side effects on Chlamydomonas growth. Removal of these bottlenecks will encourage the wide use of this promoter as a chemically regulated gene expression system. METHODOLOGY: Using a codon-optimized Renilla luciferase as a reporter gene, we explored several strategies to improve the strength and reversibility of CYC6 promoter induction. Use of the first intron of the RBCS2 gene or of a modified TAP medium increases the strength of CYC6 induction up to 20-fold. In the modified medium, induction is also obtained after addition of specific copper chelators, like TETA. At low concentrations (up to 10 microM) TETA is a more efficient inducer than Ni, which becomes a very efficient inducer at higher concentrations (50 microM). Neither TETA nor Ni show toxicity effects at the concentrations used. Unlike induction by Ni, induction by TETA is completely reversible by micromolar copper concentrations, thus resulting in a transient "wave" in luciferase activity, which can be repeated in subsequent growth cycles. CONCLUSIONS: We have worked out a chemically regulated gene expression system that can be finely tuned to produce temporally controlled "waves" in gene expression. The use of cassettes containing the CYC6 promoter, and of modified growth media, is a reliable and economically sustainable system for the temporally controlled expression of foreign genes in Chlamydomonas

Metabolomics demonstrates divergent responses of two Eucalyptus species to water stress

Past studies of water stress in Eucalyptus spp. generally highlighted the role of fewer than five “important” metabolites, whereas recent metabolomic studies on other genera have shown tens of compounds are affected. There are currently no metabolite profiling data for responses of stress-tolerant species to water stress. We used GC–MS metabolite profiling to examine the response of leaf metabolites to a long (2 month) and severe (Ψpredawn < −2 MPa) water stress in two species of the perennial tree genus Eucalyptus (the mesic Eucalyptus pauciflora and the semi-arid Eucalyptus dumosa). Polar metabolites in leaves were analysed by GC–MS and inorganic ions by capillary electrophoresis. Pressure–volume curves and metabolite measurements showed that water stress led to more negative osmotic potential and increased total osmotically active solutes in leaves of both species. Water stress affected around 30–40% of measured metabolites in E. dumosa and 10–15% in E. pauciflora. There were many metabolites that were affected in E. dumosa but not E. pauciflora, and some that had opposite responses in the two species. For example, in E. dumosa there were increases in five acyclic sugar alcohols and four low-abundance carbohydrates that were unaffected by water stress in E. pauciflora. Re-watering increased osmotic potential and decreased total osmotically active solutes in E. pauciflora, whereas in E. dumosa re-watering led to further decreases in osmotic potential and increases in total osmotically active solutes. This experiment has added several extra dimensions to previous targeted analyses of water stress responses in Eucalyptus, and highlights that even species that are closely related (e.g. congeners) may respond differently to water stress and re-waterin

Telepresence and the Role of the Senses

The telepresence experience can be evoked in a number of ways. A well-known example is a player of videogames who reports about a telepresence experience, a subjective experience of being in one place or environment, even when physically situated in another place. In this paper we set the phenomenon of telepresence into a theoretical framework. As people react subjectively to stimuli from telepresence, empirical studies can give more evidence about the phenomenon. Thus, our contribution is to bridge the theoretical with the empirical. We discuss theories of perception with an emphasis on Heidegger, Merleau-Ponty and Gibson, the role of the senses and the Spinozian belief procedure. The aim is to contribute to our understanding of this phenomenon. A telepresence-study that included the affordance concept is used to empirically study how players report sense-reactions to virtual sightseeing in two cities. We investigate and explore the interplay of the philosophical and the empirical. The findings indicate that it is not only the visual sense that plays a role in this experience, but all senses

Percutaneous Exposure Incidents of the Health Care Personnel in a Newly Founded Tertiary Hospital: A Prospective Study

BACKGROUND: Percutaneous exposure incidents (PEIs) and blood splashes on the skin of health care workers are a major concern, since they expose susceptible employees to the risk of infectious diseases. We undertook this study in order to estimate the overall incidence of such injuries in a newly founded tertiary hospital, and to evaluate possible changes in their incidence over time. METHODOLOGY/PRINCIPAL FINDINGS: We prospectively studied the PEIs and blood splashes on the skin of employees in a newly founded (October 2000) tertiary hospital in Athens, Greece, while a vaccination program against hepatitis B virus, as well as educational activities for avoidance of injuries, were taking place. The study period ranged from October 1, 2002 to February 28, 2005. Serologic studies for hepatitis B (HBV) and C virus (HCV) as well as human immunodeficiency virus (HIV) were performed in all injured employees and the source patients, when known. High-titer immunoglobulin (250 IU anti-HBs intramuscularly) and HBV vaccination were given to non-vaccinated or previously vaccinated but serologically non-responders after exposure. Statistical analysis of the data was performed using Mc Nemar's and Fisher's tests. 60 needlestick, 11 sharp injuries, and two splashes leading to exposure of the skin or mucosa to blood were reported during the study period in 71 nurses and two members of the cleaning staff. The overall incidence (percutaneous injuries and splashes) per 100 full-time employment-years (100 FTEYs) for high-risk personnel (nursing, medical, and cleaning staff) was 3.48, whereas the incidence of percutaneous injuries (needlestick and sharp injuries) alone per 100 FTEYs was 3.38. A higher incidence of injuries was noted during the first than in the second half of the study period (4.67 versus 2.29 per 100 FTEYs, p = 0.005). No source patient was found positive for HCV or HIV. The use of high-titer immunoglobulin after adjustment for the incidence of injuries was higher in the first than in the second half of the study period, although the difference was not statistically significant [9/49 (18.37%) vs 1/24 (4.17%), p = 0.15]. CONCLUSIONS/SIGNIFICANCE: Our data show that nurses are the healthcare worker group that reports most of PEIs. Doctors did not report such injuries during the study period in our setting. However, the possibility of even relatively frequent PEIs in doctors cannot be excluded. This is due to underreporting of such events that has been previously described for physicians and surgeons. A decrease of the incidence of PEIs occurred during the operation of this newly founded hospital

Prognostic significance of circumferential resection margin involvement following oesophagectomy for cancer

The factors affecting long-term survival following oesophagectomy for oesophageal cancer are poorly understood. We examined the significance of microscopic tumour involvement at the circumferential resection margin (CRM) on postoperative survival following oesophagectomy. The case notes of 329 patients who underwent a potentially curative oesophagectomy for squamous or adenocarcinoma were reviewed retrospectively. As part of the procedure, all patients underwent an en-bloc resection of their periesophageal tissue. The presence of tumour either at, or within, 1 mm of the CRM was recorded and correlated with their TNM and survival data. A total of 67 patients (20%) were noted to have a positive CRM, of which 40 cases (12%) had tumour at the resection margin and the remainder had tumour within 1 mm of the margin. Univariate analysis showed no statistically significant association between survival and either category of CRM involvement. Multivariate analysis showed that only T-stage, nodal status and tumour grade were prognostic markers. In conclusion, the presence of microscopic tumour at the CRM following an en-bloc oesophagectomy is not a significant prognostic marker

Discovery of Porcine microRNAs and Profiling from Skeletal Muscle Tissues during Development

MiRNAs (microRNAs) play critical roles in many important biological processes such as growth and development in mammals. In this study, we identified hundreds of porcine miRNA candidates through in silico prediction and analyzed their expression in developing skeletal muscle using microarray. Microarray screening using RNA samples prepared from a 33-day whole embryo and an extra embryo membrane validated 296 of the predicted candidates. Comparative expression profiling across samples of longissimus muscle collected from 33-day and 65-day post-gestation fetuses, as well as adult pigs, identified 140 differentially expressed miRNAs amongst the age groups investigated. The differentially expressed miRNAs showed seven distinctive types of expression patterns, suggesting possible involvement in certain biological processes. Five of the differentially expressed miRNAs were validated using real-time PCR. In silico analysis of the miRNA-mRNA interaction sites suggested that the potential mRNA targets of the differentially expressed miRNAs may play important roles in muscle growth and development

Does dog-ownership influence seasonal patterns of neighbourhood-based walking among adults? A longitudinal study

<p>Abstract</p> <p>Background</p> <p>In general dog-owners are more physically active than non-owners, however; it is not known whether dog-ownership can influence seasonal fluctuations in physical activity. This study examines whether dog-ownership influences summer and winter patterns of neighbourhood-based walking among adults living in Calgary, Canada.</p> <p>Methods</p> <p>A cohort of adults, randomly sampled from the Calgary metropolitan area, completed postal surveys in winter and summer 2008. Both winter and summer versions of the survey included questions on dog-ownership, walking for recreation, and walking for transportation in residential neighbourhoods. <b>Participation </b>in neighbourhood-based walking was compared, among dog-owners and non-owners, and in summer and winter, using general linear modeling. <b>Stability </b>of participation in neighbourhood-based walking across summer and winter among dog-owners and non-owners was also assessed, using logistic regression.</p> <p>Results</p> <p>A total of 428 participants participated in the study, of whom 115 indicated owning dogs at the time of both surveys. Dog-owners reported more walking for recreation in their neighbourhoods than did non-owners, both in summer and in winter. Dog-owners were also more likely than non-owners to report participation in walking for recreation in their neighbourhoods, in summer as well as in winter. Dog-owners and non-owners did not differ in the amount of walking that they reported for transportation, either in summer or in winter.</p> <p>Conclusions</p> <p>By acting as cues for physical activity, dogs may help their owners remain active across seasons. Policies and programs related to dog-ownership and dog-walking, such as dog-supportive housing and dog-supportive parks, may assist in enhancing population health by promoting physical activity.</p