Operando reaction cell for high energy surface sensitive x-ray diffraction and reflectometry.

A proof of concept is shown for the design of a high pressure heterogeneous catalysis reaction cell suitable for surface sensitive x-ray diffraction and x-ray reflectometry over planar samples using high energy synchrotron radiation in combination with mass spectrometry. This design enables measurements in a pressure range from several tens to hundreds of bars for surface investigations under realistic industrial conditions in heterogeneous catalysis or gaseous corrosion studies.

Intranasally-administered deferoxamine mitigates toxicity of 6-OHDA in a rat model of Parkinson׳s disease.

Deferoxamine (DFO) has shown therapeutic promise for the treatment of Parkinson׳s disease (PD) as it has reduced both behavioral and biochemical deficits when injected into the brain of rodent models of PD. Intranasally administered DFO targets the brain directly but non-invasively and has been effective in animal models of stroke and Alzheimer׳s disease. In this study we sought to determine whether intranasal (IN) DFO could be neuroprotective for PD in a rat model. PD was induced with a unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle, while sham surgery rats received saline injections. Rats were pre-treated three times with either IN DFO or saline (starting 4 days before 6-OHDA), and post-treated twice/wk for one month before behavioral tests. In the apomorphine-induced rotational test, IN DFO significantly decreased the number of contralateral turns after injection of apomorphine HCl (p<0.05). Also, IN DFO significantly decreased limb asymmetry in the rearing tube as measured with contralateral limb touches (p<0.05). The IN DFO treatment yielded a trend towards decreased contralateral foot-slips on the tapered balance beam, though the difference was not significant. Finally, IN DFO-treated rats had increased preservation of tyrosine hydroxylase immunoreactive neurons in the substantia nigra (p<0.05). These results confirm that DFO is beneficial in a 6-OHDA model and demonstrate improvement in motor deficits and dopaminergic neuronal survival with non-invasive intranasal delivery, making this an attractive potential treatment for PD.

Intranasal deferoxamine improves performance in radial arm water maze, stabilizes HIF-1α, and phosphorylates GSK3ß in P301L tau transgenic mice.

Deferoxamine (DFO), a metal chelator, has been previously reported to slow the loss of spatial memory in a mouse model of amyloid accumulation when delivered intranasally (IN). In this study, we determined whether IN DFO also has beneficial effects in the P301L mouse, which accumulates hyperphosphorylated tau. Mice were intranasally treated three times per week with either 10% DFO (2.4 mg) or saline for 5 months, and a battery of behavioral tests were conducted before tissue collection and biochemical analyses of brain tissue with Western blot and ELISA. Wild-type (WT) mice statistically outperformed transgenic (TG) saline mice in the radial arm water maze, while performance of TG-DFO mice was not different than WT mice, suggesting improved performance in the radial arm water maze. Other behavioral changes were not evident. Beneficial changes in brain biochemistry were evident in DFO-treated mice for several proteins. The TG mice had significantly less pGSK3ß and HIF-1α, with more interleukin-1ß and total protein oxidation than wild-type controls, and for each protein, DFO treatment significantly reduced these differences. There was not a significant decrease in phosphorylated tau in brain tissue of DFO-treated mice at the sites we measured. These data suggest that IN DFO is a potential treatment not only for Alzheimer's disease, but also for other neurodegenerative diseases and psychiatric disorders in which GSK3ß and HIF-1α play a prominent role.

Observaciones sobre la patogénesis de la anorexia asociada a cáncery su regulación por el sistema nervioso central / Neural pathophysiology of cancer anorexia

Introducción: Se estima que dos terceras partes de los pacientes con cáncer sufren de anorexia o pérdida significativa de apetito, lo que conduce a la disminución acentuada de peso y desnutrición, con repercusiones significativas en la calidad de vida y morbimortalidad de los afectados. Aún se desconocen los mecanismos precisos que originan la pérdida de apetito; diversas hipótesis proponen que la patogénesis es multifactorial, destacándose las características biológicas del tumor, del huésped y las relacionadas al tratamiento. Existen nuevas teorías que señalan diversas substancias con efectos antimetabólicos en el sistema nervioso central y que parecen asociarse con resistencia a señales periféricas que informan al hipotálamo sobre el estado de consumo y gasto energético corporal. El objetivo de la revisión es describir conceptos actuales sobre la patogénesis de la anorexia asociada al cáncer, con particular interés en alteraciones del sistema nervioso central. Conclusiones: Es necesario continuar investigando los mecanismos participantes a nivel neural involucrados en la regulación alimentaria, con la finalidad de implementar mejores medidas de alimentación y tratamiento de los pacientes oncológicos con pérdida de apetito, mejorar su estado nutricio, su calidad de vida y sobre todo, reducir la morbimortalidad asociada a desnutrición (AU)

Introduction: Approximately two thirds of cancer patients at advanced stages of the disease suffer from anorexia. Defined as the loss of the desire to eat, anorexia lower the energy intake which further exacerbates a progressive deterioration of the patient nutritional status. Malnutrition has a large impact on morbidity and mortality affecting the quality of life. Cancer anorexia etiologyis multifactorial including complex interactions among the tumor, host metabolism and antineoplastic treatment. New related theories include peripheral and brain mechanisms affecting hypothalamic pathways; inducing behavioral and metabolic failure of responses to energy balance. The aim of this review is to describe actual concepts involved in the pathogenesis of cancer anorexia with special interest in brain mechanisms. Conclusions: Anorexia and reduced food in take are important issues in the management of cancer patients, more knowledge about pathogenic mechanism is needed to improve therapeutic options, prognosis and quality of life in cancer patients (AU)

[Neural pathophysiology of cancer anorexia]. / Observaciones sobre la patogénesis de la anorexia asociada a cáncer y su regulación por el sistema nervioso central.

INTRODUCTION: Approximately two thirds of cancer patients at advanced stages of the disease suffer from anorexia. Defined as the loss of the desire to eat, anorexia lower the energy intake which further exacerbates a progressive deterioration of the patient nutritional status. Malnutrition has a large impact on morbidity and mortality affecting the quality of life. Cancer anorexia etiology is multifactorial including complex interactions among the tumor, host metabolism and antineoplastic treatment. New related theories include peripheral and brain mechanisms affecting hypothalamic pathways; inducing behavioral and metabolic failure of responses to energy balance. The aim of this review is to describe actual concepts involved in the pathogenesis of cancer anorexia with special interest in brain mechanisms. CONCLUSIONS: Anorexia and reduced food intake are important issues in the management of cancer patients, more knowledge about pathogenic mechanism is needed to improve therapeutic options, prognosis and quality of life in cancer patients.

Use of logistic regression for developing risk-adjusted quality indicators in nursing.

OBJECTIVES: A low rate of newly developed pressure ulcers is considered as an important quality indicator in nursing. However, the result of a hospital depends not only on the quality of care but on the risk profile of its patients as well. Therefore, based on multiple logistic regression models we describe a method for calculating risk-adjusted quality indicators in nursing. METHOD: Based on data of 1,009,989 patients from 1747 hospitals in 2009, we developed two multiple logistic regression models to identify and to weigh a possible joint influence of several risk factors on newly developed pressure ulcers. In a further step, we calculated risk-adjusted rates. RESULTS: Factors remaining in the regression models were "micro-movements on admission", "diabetes mellitus", "age" and "days on intensive care unit". Based on the corresponding regression coefficients and the logistic function, the expected rate of newly developed pressure ulcers was calculated for every hospital. Finally, expected rates and observed rates both were used to calculate risk-adjusted rates. CONCLUSION: The simultaneous consideration of relevant risk factors by means of risk-adjusted quality indicators ensures a fair comparison of hospitals.

[Primary documentation quality for paper-assisted digital mission data documentation. Initial results from the air rescue service]. / Primäre Dokumentationsqualität bei papiergestützter digitaler Einsatzdokumentation. Erste Ergebnisse aus dem Luftrettungsdienst.

BACKGROUND: With the assistance of digital pen and paper technology in the field of prehospital data reporting, it seems to be possible to fulfill the requirements of "documentation" as well as the requirements of "quality management". The aim of this study was to determine the "primary documentation quality" (PDQ) of a data reporting system based on digital pen and paper technology (so-called DINO) within a helicopter emergency medical service (HEMS) over a 6-month period. RESULTS: The PDQ is defined as the proportion of prehospital documented data, which is primarily recorded correctly by the data reporting system. For the national uniform core dataset (so-called MIND2) the PDQ was 96.7%, for "checkbox" and "numeric data fields" the PDQ was 99.8% and 93.6%, respectively and for "vital data" the PDQ was 96.7% [heart rate (HF), measurement of blood pressure] and 84.1% [peripheral oxygen saturation (S(p)O2), end tidal carbon dioxide concentration (etCO2), oxygen administration (O2)]. For "measurements" the PDQ was 96.9% (time stamps) and 86.9% (time frames), for "drugs" the PDQ was 43.6% (drug name) and 69.8% (drug dosage) and for"placement of infusion" 42% (infusion name) and 85.3% (infusion time), respectively. The average time for the "verification process" after mission completion was 1.5+/-0.4 min/mission. CONCLUSIONS: The "primary documentation quality" of prehospital mission data reporting with the assistance of a digital pen and paper based documentation system (DINO) has been shown to completely fulfill the requirements of rapid and safe data documentation in actual missions, even at this early stage of development.

[Paper-assisted digital Mission documentation in air rescue services. Quality management in preclinical emergency medicine]. / Papiergestützte digitale Einsatzdokumentation im Luftrettungsdienst. Qualitätsmanagement in der präklinischen Notfallmedizin.

BACKGROUND: Recording of adequate mission data is of utmost importance in prehospital emergency medicine. For this, a nationwide uniform core dataset for prehospital data reporting, the so-called MIND 2, was introduced. With this procedure adequate information about structure and outcome quality, but only little information about process quality, can be obtained. Regarding the quality of data recording, primarily computer-based techniques are superior to other techniques. Against this background, the aim of this study was to develop a documentation system, which sets new standards regarding documentation dataset and documentation quality. RESULTS: A primarily computer-based documentation system based on the "digital paper" technology was achieved. This technology allows conventional data entry via a (digital) pen and documentation on conventional paper. As the core-dataset MIND 2 was realized - furthermore, the measurements performed during prehospital management as well as data on vital signs (blood pressure, heart frequency, S(a)O(2), p(et)CO(2) etc.) were included into routine data recording. Integration of this documentation system into an already existing medical quality management system was achieved via a defined interface. Testing of this new system over a 3-month period at the helicopter emergency medical service (HEMS) "Christoph 22" showed a high degree of functionality and stability of the system. Serious problems, especially a total break-down of the whole system, were not observed during the study period. CONCLUSIONS: The new data recording concept, which is based on the "digital paper" technology, has proven to be completely satisfactory with respect to functionality and documentation quality during the test period.

Nucleon axial charge in full lattice QCD.

The nucleon axial charge is calculated as a function of the pion mass in full QCD. Using domain wall valence quarks and improved staggered sea quarks, we present the first calculation with pion masses as light as 354 MeV and volumes as large as (3.5 fm)3. We show that finite volume effects are small for our volumes and that a constrained fit based on finite volume chiral perturbation theory agrees with experiment within 7% statistical errors.

Charmed-meson decay constants in three-flavor lattice QCD.

We present the first lattice QCD calculation with realistic sea quark content of the D+-meson decay constant f(D+). We use the MILC Collaboration's publicly available ensembles of lattice gauge fields, which have a quark sea with two flavors (up and down) much lighter than a third (strange). We obtain f(D+)=201+/-3+/-17 MeV, where the errors are statistical and a combination of systematic errors. We also obtain f(Ds)=249+/-3+/-16 MeV for the Ds meson.

Clinical evaluation of idiopathic paroxysmal kinesigenic dyskinesia: new diagnostic criteria.

BACKGROUND: Paroxysmal kinesigenic dyskinesia (PKD) is a rare disorder characterized by short episodes of involuntary movement attacks triggered by sudden voluntary movements. Although a genetic basis is suspected in idiopathic cases, the gene has not been discovered. Establishing strict diagnostic criteria will help genetic studies. METHODS: The authors reviewed the clinical features of 121 affected individuals, who were referred for genetic study with a presumptive diagnosis of idiopathic PKD. RESULTS: The majority (79%) of affected subjects had a distinctive homogeneous phenotype. The authors propose the following diagnostic criteria for idiopathic PKD based on this phenotype: identified trigger for the attacks (sudden movements), short duration of attacks (<1 minute), lack of loss of consciousness or pain during attacks, antiepileptic drug responsiveness, exclusion of other organic diseases, and age at onset between 1 and 20 years if there is no family history (age at onset may be applied less stringently in those with family history). In comparing familial and sporadic cases, sporadic cases were more frequently male, and infantile convulsions were more common in the familial kindreds. Females had a higher remission rate than males. An infantile-onset group with a different set of characteristics was identified. A clear kinesigenic trigger was not elicited in all cases, antiepileptic response was not universal, and some infants had attacks while asleep. CONCLUSIONS: The diagnosis of idiopathic paroxysmal kinesigenic dyskinesia (PKD) can be made based on historical features. The correct diagnosis has implications for treatment and prognosis, and the diagnostic scheme may allow better focus in the search for the PKD gene(s).

Transverse structure of nucleon parton distributions from lattice QCD.

This work presents the first calculation in lattice QCD of three moments of spin-averaged and spin-polarized generalized parton distributions in the proton. It is shown that the slope of the associated generalized form factors decreases significantly as the moment increases, indicating that the transverse size of the light-cone quark distribution decreases as the momentum fraction of the struck parton increases.

Chiral extrapolation of lattice moments of proton quark distributions.

We present the resolution of a long-standing discrepancy between the moments of parton distributions calculated from lattice QCD and their experimental values. We propose a simple extrapolation formula for the moments of the nonsinglet quark distribution u-d, as a function of quark mass, which embodies the general constraints imposed by the chiral symmetry of QCD. The inclusion of the leading nonanalytic behavior leads to an excellent description of both the lattice data and the experimental values of the moments.

A highly purified RNA polymerase II elongation control system.

Studying the sensitivity of transcription to the nucleotide analog 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole has led to the discovery of a number of proteins involved in the regulation of transcription elongation by RNA polymerase II. We have developed a highly purified elongation control system composed of three purified proteins added back to isolated RNA polymerase II elongation complexes. Two of the proteins, 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole sensitivity-inducing factor (DSIF) and negative elongation factor (NELF), act as negative transcription elongation factors by increasing the time the polymerase spent at pause sites. P-TEFb reverses the negative effect of DSIF and NELF through a mechanism dependent on its kinase activity. TFIIF is a general initiation factor that positively affects elongation by decreasing pausing. We show that TFIIF functionally competes with DSIF and NELF, and this competition is dependent on the relative concentrations of TFIIF and NELF.

A case of primary amenorrhea, diabetes and anosmia.

This case details a patient with primary amenorrhea with an unusual cause. She presented at age 16 with short stature, minimal sexual development and no prior menses. Her history was significant for poorly controlled type 1 diabetes. She had been evaluated previously for growth hormone deficiency, and had received a short course of growth hormone therapy. Of greatest significance was the fact that she had also had a decreased sense of smell since her youth. Although a previous computerized tomography scan had been reported as normal, follow-up magnetic resonance imaging demonstrated the absence of olfactory bulbs. Smell testing confirmed the absence of smell and testing of gonadotropin releasing hormone demonstrated an inadequate response. All of these features suggested Kallmann syndrome. This syndrome commonly presents with delayed onset of puberty and decreased or absent sense of smell. There are also many associated features, and the disease is remarkable for its great genotypic and phenotypic variability. Current understanding of its pathogenesis, the commonly associated features of Kallmann syndrome and the impact of diabetes on growth and sexual development are reviewed.