Reversible B/Z-DNA transition under the low salt condition and non-B-form polydApolydT selectivity by a cubane-like europium-L-aspartic acid complex

We report here that a cubane-like europium-L-aspartic acid complex at physiological pH can discriminate between DNA structures as judged by the comparison of thermal denaturation, binding stoichiometry, temperature-dependent fluorescence enhancement, and circular dichroism and gel electrophoresis studies. This complex can selectively stabilize non-B-form DNA polydApolydT but destabilize polydGdCpolydGdC and polydAdTpolydAdT. Further studies show that this complex can convert B-form polydGdCpolydGdC to Z-form under the low salt condition at physiological temperature 37 degrees C, and the transition is reversible, similar to RNA polymerase, which turns unwound DNA into Z-DNA and converts it back to B-DNA after transcription. The potential uses of a left-handed helix-selective probe in biology are obvious. Z-DNA is a transient structure and does not exist as a stable feature of the double helix. Therefore, probing this transient structure with a metal-amino acid complex under the low salt condition at physiological temperature would provide insights into their transitions in vivo and are of great interest.

Bottom simulating reflector and gas seepage in Okinawa Trough: Evidence of gas hydrate in an active back-arc basin

To look for gas hydrate, 22 multi-channel and 3 single-channel seismic lines on the East China Sea (ECS) shelf slope and at the bottom of the Okinawa Trough were examined. It was found that there was indeed bottom simulating reflector (BSR) occurrence, but it is very rare. Besides several BSRs, a gas seepage was also found. As shown by the data, both the BSR and gas seepage are all related with local geological structures, such as mud diapir, anticline, and fault-controlled graben-like structure. However, similar structural "anomalies" are quite common in the tectonically very active Okinawa Trough region, but very few of them have developed BSR or gas seepage. The article points out that the main reason is probably the low concentration of organic carbon of the sediment in this area. It was speculated that the rare occurrence of gas hydrates in this region is governed by structure-controlled fluid flow. Numerous faults and fractures form a network of high-permeability channels in the sediment and highly fractured igneous basement to allow fluid circulation and ventilation. Fluid flow in this tectonic environment is driven primarily by thermal buoyancy and takes place on a wide range of spatial scales. The fluid flow may play two roles to facilitate hydrate formation: to help gather enough methane into a small area and to modulate the thermal regime.

Musculoskeletal symptoms among female garment factory workers in Sri Lanka.

OBJECTIVES: To assess the prevalence of musculoskeletal symptoms and their association with sociodemographic risk factors among female garment factory workers in Sri Lanka. METHODS: 1058 randomly selected female garment factory workers employed in the free trade zone of Kogalla, Sri Lanka were recruited to complete two interviewer-administered questionnaires assessing musculoskeletal symptoms and health behaviors. DISCUSSION: Musculoskeletal complaints among female garment workers in the FTZ of Kogalla are less common than expected. Sociocultural factors may have resulted in underreporting and similarly contribute to the low rates of healthcare utilization by these women. RESULTS: 164 (15.5%) of workers reported musculoskeletal symptoms occurring more than 3 times or lasting a week or more during the previous 12-month period. Back (57.3%) and knee (31.7%) were the most common sites of pain. Although most symptomatic women reported that their problems interfered with work and leisure activities, very few missed work as a result of their pain. Prevalence correlated positively with increased age and industry tenure of less than 12 months. Job type, body mass index, and education were not significant predictors of musculoskeletal symptoms.

Doubt, for narrator and orchestra

Doubt is a single-movement composition of roughly twelve minutes for narrator and orchestra (woodwinds, horns, and trumpets in pairs, timpani, percussion, strings). The piece explores the controversial issue of capital punishment. The text was compiled from resources found on the websites of Death Penalty Information Center (http://www.deathpenaltyinfo.org) and Anti-Death Penalty Information (http://www.antideathpenalty.org), as well as excerpts from the Bible. Doubt was conceived of as a dramatic work in which a narrator recites factual information in a direct and unemotional manner and the orchestra provides a response to the mixed emotions elicited by the text. The list of dates and case summaries presented in the middle section of the piece seemed most powerful and effective when recited in a natural speaking voice, which is why I chose not to set the text as song. Also, I chose the orchestral medium rather than a chamber setting because the nature of the topic demanded a larger range of colors and combinations, as well as a louder, fuller sound. Much of the music was composed while deciding which texts to include. Thus the music influenced the choice of text as much as the text suggested the musical setting. The four formal divisions of the piece are delineated primarily by the text. The first section is an orchestral introduction representing various emotional perspectives suggested by the texts. The narrator begins the second section with a Biblical verse over sparse orchestration. The third and main section of the piece begins with a new melody in the low strings that is closely related to the harmonic organization of the piece. The narrator lists dates of convictions, executions, exonerations and facts related to doubtful cases. The third section and the narration conclude with another brief passage from the Bible. The fourth section is a dramatic orchestral coda, bringing back the opening harmonies of juxtaposed perfect fifths. The final chord is full of tension and discord, reflecting the oppositions inherent in the topic of capital punishment: life vs. death, sympathy vs. reproach, pain vs. hope, but above all, doubt about guilt vs. innocence.

Low Molecular Weight Opioid Peptide Esters Could be Developed as a New Class of Analgesics.

Low molecular weight opioid peptide esters (OPE) could become a class of analgesics with different side effect profiles than current opiates. OPE may have sufficient plasma stability to cross the blood brain barrier (BBB), undergo ester hydrolysis and produce analgesia. OPE of dipeptides, tyr-pro and tyr-gly conjugated to ethanol have a structure similar to the anesthestic agent, etomidate. Based upon the analgesic activity of dipeptide opioids, Lipinski's criteria, and permeability of select GABA esters to cross the BBB, opioid peptides (OP) conjugated to ethanol, cholesterol or 3-glucose are lead recommendations. Preliminary animal data suggests that tyr-pro-ethyl ester crosses the BBB and unexpectedly produces hyperalgesia. Currently, there are no approved OP analgesics available for clinical use. Clinical trials of good manufacturing practice OP administered to patients suffering from chronic pain with indwelling intrathecal pumps could resolve the issue that OP may be superior to opiates and may redirect research.

Conservative Interventions for mobile Pes Planus in Adults: a systematic review

Antecedentes. Pes Adulto planus (pie plano) es un problema común encontrado por muchos profesionales de la salud. A pesar de la percepción de que el pie plano puede causar dolor y deteriorar su función, la disponibilidad y el uso generalizado de diversos tratamientos, no hay consenso sobre la estrategia óptima de tratamiento. Objetivo. Evaluar la efectividad de las intervenciones conservadoras (no quirúrgicos) para pie plano en los adultos. Método. Se realizó una búsqueda sistemática de la literatura. Esto incluye: el Registro Cochrane Central de Ensayos Controlados; los Juicios CMSG Especializados Registro; una búsqueda electrónica se realizó utilizando MEDLINE (1960 a junio de 2012), EMBASE (1980 a junio de 2012), y CINAHL (1982 - junio de 2012). Revistas especializadas, listas de referencias de ensayos y artículos de revisión se realizaron búsquedas manuales. Criterios de selección: Ensayos aleatorios o cuasialeatorios de intervenciones de tratamiento para el pie plano en los adultos. Se excluyeron los ensayos que incluyeron patologías específicas como el dolor plantar del talón, las fracturas por sobrecarga de los metatarsianos, disfunción del tendón tibial posterior-, fracturas de tobillo, patologías del pie reumatoide, enfermedades neuromusculares y las complicaciones del pie diabético. Recopilación y análisis de datos: Dos autores seleccionaron de forma independiente los resultados de la búsqueda para identificar a aquellos que satisfacen los criterios de inclusión y evaluaron la calidad de los incluidos mediante una lista de control basado en la Evaluación de la Colaboración Cochrane de Riesgo. Esta herramienta se centró en el riesgo de la selección, el rendimiento, la detección, la heterogeneidad y el sesgo de notificación. Resultados. Cuatro ensayos, con 140 sujetos, cumplieron los criterios de inclusión para la revisión. Los cuatro fueron juzgados como de alto riesgo de sesgo en al menos un área, y también estaban en riesgo de sesgo incierto en al menos otra zona. Todos anotaron altamente en relación al sesgo de deserción, debido al corto seguimiento tiempos y diseños experimentales utilizados. Los datos no se agruparon debido al alto nivel de heterogeneidad identificada en las intervenciones evaluadas, los participantes seleccionados y medir los resultados. Los resultados de un estudio sugieren que después de cuatro semanas de uso ortesis puede resultar en una mejora significativa en vaivén lateral medio, y pueden resultar en una mejor, aunque no significativa, en general relacionados con la calidad de vida de los pies (Roma 2004). Un estudio (Redmond 2009) sugiere que su efecto sobre la distribución de la presión plantar en el pie puede no depender de si son personalizados o dispositivos prefabricados. Aunque este estudio se identificaron cambios significativos en algunas variables de presión plantar tanto con la costumbre y dispositivos prefabricados, otro (Esterman 2005) no encontró ningún efecto significativo de longitud ¾ ortesis prefabricadas sobre el dolor, la incidencia de lesiones, salud pie o de calidad de vida en un grupo de reclutas de la fuerza aérea. El cuarto estudio (Jung 2009) sugiere que el ejercicio de los músculos intrínsecos del pie puede mejorar el efecto de las ortesis. A pesar de estos resultados, ya que cada estudio incurrió riesgo de sesgo en al menos un área no se pueden sacar conclusiones

Self-Management of Chronic Pain: Interventions, Strategies, Barriers, and Facilitators

Background & Purpose: Chronic pain is a prevalent chronic condition for which the best management options rarely provide complete relief. Individuals with chronic pain with neuropathic characteristics (NC) report more severe pain and experience less relief from interventions. Little is known about current self-management practices. The purpose of this dissertation was to inform self-management of chronic pain with and without NC at the individual, health system, and policy levels using the Innovative Care for Chronic Conditions Framework. Methods: The study included a systematic search and review and cross-sectional survey. The review evaluated the evidence for chronic pain self-management interventions and explored the role of health care providers in supporting self-management. The survey was mailed to 8,000 randomly selected Canadians in November 2011, and non-respondents were followed-up in May 2012. Screening questions were included for both chronic pain and NC. The questionnaire captured pain descriptions, self-management strategies, and self-management barriers, and facilitators. Results: Findings of the review suggested that self-management interventions are effective in improving pain and health outcomes. Health care professionals provided self-management advice and referred individuals to self-management interventions. The questionnaire was completed by 1,520 Canadians. Those with chronic pain (n=710) identified primary care physicians as the most helpful pain management professional. Overall, use of non-pharmaceutical medical self-management strategies was low. While use positive emotional self-management strategies was high, individuals with NC were more likely to use negative emotional self-management strategies compared to those without NC. Multiple self-management barriers and facilitators were identified, however those with NC were more likely than those without NC to experience low self-efficacy, depression and severe pain which may impair the ability to self-management. Conclusions: Health care professionals have the opportunity to improve chronic pain outcomes by providing self-management advice, referring to self-management interventions, and addressing self-management barriers and facilitators. Individuals with NC may require additional health services to address their greater self-management challenges, and further research is needed to identify non-pharmaceutical interventions effective in relieving chronic pain with NC. Public policy is needed to facilitate health systems in providing long-term self-management support for individuals with chronic pain.

High tolerance to gate misalignment in low voltage gate-underlap double gate MOSFETs

.In this letter, we demonstrate for the first time that gate misalignment is not a critical limiting factor for low voltage operation in gate-underlap double gate (DG) devices. Our results show that underlap architecture significantly extends the tolerable limit of gate misalignment in 25 nm devices. DG MOSFETs with high degree of gate misalignment and optimal gate-underlap design can perform comparably or even better than self-aligned nonunderlap devices. Results show that spacer-to-straggle (s/sigma) ratio, a key design parameter for underlap devices, should be within the range of 2.3-3.0 to accommodate back gate misalignment. These results are very significant as the stringent process control requirements for achieving self-alignment in nanoscale planar DG MOSFETs are considerably relaxed

Motivational trade-offs and potential pain experience in hermit crabs

One criterion of pain experience is that the emotional response to pain may be traded-off against other motivational requirements. This was tested in hermit crabs, housed in either preferred or unpreferred species of shells, by subjecting their abdomens to electric shocks of gradually increasing intensity. The first observable response was not affected by shell species but those in preferred shells evacuated at a higher shock level than those in poor quality shells. Thus, they seem to trade-off the requirement to retain a high quality shell with that of avoidance of the noxious stimulus. Some crabs returned to their shells and those that got back into the preferred species did so with less probing of the aperture before getting in and subsequently thrust their abdomen in and out less often in further investigation, thus confirming their shell species preference. Not all crabs returned to the vicinity of the shell and some attempted to climb the wall of the experimental chamber. Others engaged in shell rapping as if in a fight and grooming of the abdomen was noted. These findings are consistent with the idea of a pain experience rather than a nociceptive reflex. (C) 2009 Elsevier B.V. All rights reserved.

Are there clinical features of a sensitized cough reflex?

Cough reflex hypersensitization is a key feature in patients with troublesome cough. The clinical consequence of this hypersensitive state is typified by bouts of coughing often triggered by low threshold stimuli encountered by the patient during normal daily activities including exposure to aerosols, scents and odours, a change in air temperature and when talking or laughing. These features are often perceived by cough patients to be the most disruptive aspect of their condition and undoubtedly contribute to impaired quality of life. Patients with troublesome cough may describe a range of additional symptoms and sensations including an 'urge to cough' or the feeling of an 'itch' at the back of the throat, or a choking sensation and occasionally chest pain or breathlessness. It is uncertain if these features arise due to the processes responsible for cough reflex sensitization or as a direct consequence of the underlying cough aetiology. In an attempt to understand the clinical features of a sensitized cough reflex, the spectrum of symptoms typically described by cough patients will be reviewed and possible underlying mechanisms considered. Since an intact cough reflex is crucial to airway protection, anti-tussive treatment that attenuates the hypersensitive cough state rather than abolishing the cough reflex completely would be preferable. Identifying such agents remains a clinical, scientific and pharmacological challenge. (c) 2008 Elsevier Ltd. All rights reserved.

Genome-wide profiling of methylation identifies novel targets with aberrant hyper-methylation and reduced expression in low-risk myelodysplastic syndromes

Gene expression profiling signatures may be used to classify the subtypes of Myelodysplastic syndrome (MDS) patients. However, there are few reports on the global methylation status in MDS. The integration of genome-wide epigenetic regulatory marks with gene expression levels would provide additional information regarding the biological differences between MDS and healthy controls. Gene expression and methylation status were measured using high-density microarrays. A total of 552 differentially methylated CpG loci were identified as being present in low-risk MDS; hypermethylated genes were more frequent than hypomethylated genes. In addition, mRNA expression profiling identified 1005 genes that significantly differed between low-risk MDS and the control group. Integrative analysis of the epigenetic and expression profiles revealed that 66.7% of the hypermethylated genes were underexpressed in low-risk MDS cases. Gene network analysis revealed molecular mechanisms associated with the low-risk MDS group, including altered apoptosis pathways. The two key apoptotic genes BCL2 and ETS1 were identified as silenced genes. In addition, the immune response and micro RNA biogenesis were affected by the hypermethylation and underexpression of IL27RA and DICER1. Our integrative analysis revealed that aberrant epigenetic regulation is a hallmark of low-risk MDS patients and could have a central role in these diseases.

An Experimental Assessment of the Effects of Stator Vane Tip Clearance and Back Swept Blading on an Automotive Variable Geometry Turbocharger

Off-design performance is of key importance now in the design of automotive turbocharger turbines. Due to automotive drive cycles, a turbine that can extract more energy at high pressure ratios and lower rotational speeds is desirable. Typically a radial turbine provides peak efficiency at U/C values of 0.7, but at high pressure ratios and low rotational speeds, the U/C value will be low and the rotor will experience high values of positive incidence at the inlet. The positive incidence causes high blade loading resulting in additional tip leakage flow in the rotor as well as flow separation on the suction surface of the blade. An experimental assessment has been performed on a scaled automotive VGS (variable geometry system). Three different stator vane positions have been analyzed: minimum, 25%, and maximum flow position. The first tests were to establish whether positioning the endwall clearance on the hub or shroud side of the stator vanes produced a different impact on turbine efficiency. Following this, a back swept rotor was tested to establish the potential gains to be achieved during off-design operation. A single passage CFD model of the test rig was developed and used to provide information on the flow features affecting performance in both the stator vanes and turbine. It was seen that off-design performance was improved by implementing clearance on the hub side of the stator vanes rather than on the shroud side. Through CFD analysis and tests, it was seen that two leakage vortices form, one at the leading edge and one after the spindle of the stator vane. The vortices affect the flow angle at the inlet to the rotor, in the hub region. The flow angle is shifted to more negative values of incidence, which is beneficial at the off-design conditions but detrimental at the design point. The back swept rotor was tested with the hub side stator vane clearance configuration. The efficiency and MFR were increased at the minimum and 25% stator vane position. At the design point, the efficiency and MFR were decreased. The CFD investigation showed that the incidence angle was improved at the off-design conditions for the back swept rotor. This reduction in the positive incidence angle, along with the improvement caused by the stator vane tip leakage flow, reduced flow separation on the suction surface of the rotor. At the design point, both the tip leakage flow of the stator vanes and the back swept blade angle caused flow separation on the pressure surface of the rotor. This resulted in additional blockage at the throat of the rotor reducing MFR and efficiency.

Long-term consequences of pain in human neonates

The low tactile threshold in preterm infants when they are in the neonatal intensive care unit (NICU), while their physiological systems are unstable and immature, potentially renders them more vulnerable to the effects of repeated invasive procedures. There is a small but growing literature on pain and tactile responsivity following procedural pain in the NICU, or early surgery. Long-term effects of repeated pain in the neonatal period on neurodevelopment await further research. However, there are multiple sources of stress in the NICU, which contribute to inducing high overall 'allostatic load', therefore determining specific effects of neonatal pain in human infants is challenging.

Neonatal procedural pain and preterm infant cortisol response to novelty at 8 months

Stress systems may be altered in the long term in preterm infants for multiple reasons, including early exposure to procedural pain in neonatal intensive care. This question has received little attention beyond hospital discharge. Stress responses (cortisol) to visual novelty in preterm infants who were born at extremely low gestational age (ELGA; <or =28 weeks), very low gestational age (VLGA; 29-32 weeks), and term were compared at 8 months of age corrected for prematurity (corrected chronological age [CCA]). In addition, among the preterm infants, we evaluated whether cortisol levels at 8 months were related to neonatal exposure to procedural pain and morphine in the neonatal intensive care unit.

Are there developmentally distinct motor indicators of pain in preterm infants?

The aims of this study were to examine preterm infant reactions to pain in detail over prolonged time periods using multiple measures, and to assess the value of including specific body movements of the Neonatal Individualized Developmental Care and Assessment Program (NIDCAP) system to evaluate pain. Ten preterm infants born at 31 weeks mean gestational age (GA) and mean birth weight 1676 g were studied during a routine blood collection in a Level III neonatal intensive care unit (NICU). At 32-week post-conceptional age, computerized physiologic and video recordings were obtained continuously for 60 min (prior to, during and after lance). Motor and facial behaviors were coded independently, using the NIDCAP and the NFCS (Neonatal Facial Coding System), respectively, and compared with heart rate (HR) and oxygen saturation responses. Of the movements hypothesized to be stress cues in the NIDCAP model, extension of arms and legs (80%) and finger splay (70%) were the most common following lance. Contrary to the model, most infants (70%) had lower incidence of twitches and startles post-lance compared to baseline. Whereas all infants showed some NFCS response to lance, for three infants, the magnitude was low. HR increased and oxygen saturation decreased post-lance. Infants with more prior pain exposure, lower Apgar, and lower GA at birth, displayed more motor stress cues but less facial activity post-lance. Extension of extremities and finger splay, but not twitches and startles, from the NIDCAP, appear to be stress cues and show promise as clinical pain indicators to supplement facial and physiological pain measures in preterm infants.