An analysis of the shortage of registered nurses (RNs) in acute care hospitals in El Paso, Texas

The purpose of this analysis of the shortage of Registered Nurses (RNs) in acute care hospitals in El Paso, Texas, was to evaluate twenty-two specific organizational and/or patient care unit (nursing unit) characteristics that effect the retention and turnover of professional nurses. Vacancy Rates were used to measure the level of the shortage in each hospital and nursing unit in the study. Vacancy Rates are a function of both RN retention and RN turnover. Seventy-three patient care units in five acute care hospitals were included in the study population.^ Fredrick Herzberg's motivational - hygiene theory was used to explain the types of characteristics or factors that can effect worker dissatisfaction. Dissatisfiers (hygiene factors) are those work place characteristics that influence workers to leave the job. The twenty-two potentially dissatisfying work place characteristics were either organizational or patient care unit specific in nature. The focus of the study was to evaluate high vacancy rates caused by both low retention of RNs and high turnover rates. Retention and turnover are a function of workers (RNs) not staying in their jobs, therefore hygiene factors were appropriate characteristics to study.^ Various multivariate analysis techniques were used to assess both the individual and combined effects of the hygiene factors on Vacancy Rates, Retention and Turnover. Results suggest that certain organizational and patient care unit characteristics are associated with and have a statistically significant effect on vacancy rates, and the retention and turnover of RNs. The type of Hospital was of particular interest in this regards. For-Profit facilities were less effected by most of the study variables than the Not-for-Profits. ^

Modular organization of the cortical connections linking visual areas V1, V2 and V4 in Macaque monkeys

The macaque cortical visual system is hierarchically organized into two streams, the ventral stream for recognizing objects and the dorsal stream for analyzing spatial relationships. The ventral stream extends from striate cortex or area V1 to inferior temporal cortex (IT) through extra-striate areas V2 and V4. Between V1 and V2, the ventral stream consists of two roughly parallel sub-streams, one extending from the cytochrome oxidase (CO) rich blobs in V1 to the CO rich thin stripes in V2, the other extending from the interblobs in V1 to interstripes, in V2. The blob-dominated sub-stream is thought to analyze the surface features such as color, whereas the interblob-dominated one is thought to analyze the contour features such as shape. ^ In the current study, the organization of cortical pathways linking V2 thin stripe and interstripe compartments with area V4 was investigated using a combination of physiological and anatomical techniques. Different compartments of V2 were first characterized, in vivo, using optical recording of intrinsic cortical signals. These functionally derived maps of V2 stripe compartments were then used to guide iontophoretic injections of multiple, distinguishable, anterograde tracers into specific V2 compartments. The distribution of labeled axons was analyzed either in horizontal sections through the prelunate gyrus, or in tangentially sectioned portions of physically unfolded cortex containing the lunate sulcus, prelunate gyrus and superior temporal sulcus. When a V2 thin stripe and adjacent interstripe were injected with distinguishable tracers, a large primary and several secondary foci were observed in V4. The primary focus from the thin stripe injection was spatially segregated from the primary focus from the V2 interstripe injection, suggesting a retention of the pattern of compartmentation. ^ We examined the distribution of retrogradely labeled cells in V1 following the injections of tracers into V2 different compartments, in order to quantitate just how parallel the two sub-streams are from V1 to V2. Our results suggest that both blobs and interblobs project to thin stripes in V2, whereas only interblobs project to interstripes. This asymmetrical segregation argues against the original proposal of strict parallelism. (Abstract shortened by UMI.) ^

Effects of butyrate on the colon cancer cell phenotype-chemosensitization and upregulation of proteins implicated in cancer progression

Colon cancer is the second leading cause of cancer mortality in the U.S. Surgery is the only truly effective human colon cancer (HCC) therapy due to marked intrinsic drug resistance. The inefficacy of therapies developed for metastatic HCC suggests that advances in colon cancer chemoprevention and chemotherapy will be needed to reduce HCC mortality. The dietary fiber metabolite butyrate (NaB) is a candidate cancer chemopreventive agent that inhibits growth, promotes differentiation and stimulates apoptosis of HCC cells. Epidemiological and experimental studies suggest that dietary fiber protects against the development of HCC, however, recent large prospective trials have not found significant protection. ^ The first central hypothesis of this dissertation project is that the diversity of phenotypic changes induced by NaB in HCC cells includes molecular alterations that oppose its chemopreventive action and thereby limit its efficacy. We investigated the effect of NaB on the expression/activity of epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in HCC HT29 cells. NaB treatment induced a 13-fold increase in EGFR expression in concert with its chemopreventive action in vitro, i.e., induction of growth suppression and G1 arrest, apoptosis and a differentiated phenotype. NaB-induced EGFR was active based on multiple lines of evidence. The EGFR was: (1) heavily phosphorylated at Tyrosine (P-Tyr); (2) associated with the cytoskeleton; (3) localized at the cell surface, and activated in response to EGF; and (4) NaB treatment of the cells induced activation of the EGFR effector Erk1/2. NaB treatment also induced a 7-fold increase in COX-2 expression. The NaB-induced COX-2 was active based on significantly increased PGE2 production. ^ The second central hypothesis is that NaB treatment would render HCC cells more chemosensitive to chemotherapy agents based on the increased apoptotic index induced by NaB. NaB treatment chemosensitized HT29 cells to 5-FU and doxorubicin, despite increases in the expression of P-glycoprotein and a related drug resistance protein (MRP). ^ These results raise the intriguing possibility that the chemopreventive effects of fiber may require concomitant treatment with EGFR and/or COX-2 inhibitors. Similarly, NaB may be a rational drug to combine with existing chemotherapeutic agents for the management of advanced HCC patients. ^

The long non-coding RNA NEAT1 is increased in IUGR placentas, leading to potential new hypotheses of IUGR origin/development.

INTRODUCTION Intrauterine Growth Restriction (IUGR) is a multifactorial disease defined by an inability of the fetus to reach its growth potential. IUGR not only increases the risk of neonatal mortality/morbidity, but also the risk of metabolic syndrome during adulthood. Certain placental proteins have been shown to be implicated in IUGR development, such as proteins from the GH/IGF axis and angiogenesis/apoptosis processes. METHODS Twelve patients with term IUGR pregnancy (birth weight < 10th percentile) and 12 CTRLs were included. mRNA was extracted from the fetal part of the placenta and submitted to a subtraction method (Clontech PCR-Select cDNA Subtraction). RESULTS One candidate gene identified was the long non-coding RNA NEAT1 (nuclear paraspeckle assembly transcript 1). NEAT1 is the core component of a subnuclear structure called paraspeckle. This structure is responsible for the retention of hyperedited mRNAs in the nucleus. Overall, NEAT1 mRNA expression was 4.14 (±1.16)-fold increased in IUGR vs. CTRL placentas (P = 0.009). NEAT1 was exclusively localized in the nuclei of the villous trophoblasts and was expressed in more nuclei and with greater intensity in IUGR placentas than in CTRLs. PSPC1, one of the three main proteins of the paraspeckle, co-localized with NEAT1 in the villous trophoblasts. The expression of NEAT1_2 mRNA, the long isoform of NEAT1, was only modestly increased in IUGR vs. CTRL placentas. DISCUSSION/CONCLUSION The increase in NEAT1 and its co-localization with PSPC1 suggests an increase in paraspeckles in IUGR villous trophoblasts. This could lead to an increased retention of important mRNAs in villous trophoblasts nuclei. Given that the villous trophoblasts are crucial for the barrier function of the placenta, this could in part explain placental dysfunction in idiopathic IUGR fetuses.

Dispersal Modeling of Fish Early Life Stages: Sensitivity with Application to Atlantic Cod in the Western Gulf of Maine

As an initial step in establishing mechanistic relationships between environmental variability and recruitment in Atlantic cod Gadhus morhua along the coast of the western Gulf of Maine, we assessed transport success of larvae from major spawning grounds to nursery areas with particle tracking using the unstructured grid model FVCOM (finite volume coastal ocean model). In coastal areas, dispersal of early planktonic life stages of fish and invertebrate species is highly dependent on the regional dynamics and its variability, which has to be captured by our models. With state-of-the-art forcing for the year 1995, we evaluate the sensitivity of particle dispersal to the timing and location of spawning, the spatial and temporal resolution of the model, and the vertical mixing scheme. A 3 d frequency for the release of particles is necessary to capture the effect of the circulation variability into an averaged dispersal pattern of the spawning season. The analysis of sensitivity to model setup showed that a higher resolution mesh, tidal forcing, and current variability do not change the general pattern of connectivity, but do tend to increase within-site retention. Our results indicate strong downstream connectivity among spawning grounds and higher chances for successful transport from spawning areas closer to the coast. The model run for January egg release indicates 1 to 19 % within-spawning ground retention of initial particles, which may be sufficient to sustain local populations. A systematic sensitivity analysis still needs to be conducted to determine the minimum mesh and forcing resolution that adequately resolves the complex dynamics of the western Gulf of Maine. Other sources of variability, i.e. large-scale upstream forcing and the biological environment, also need to be considered in future studies of the interannual variability in transport and survival of the early life stages of cod.

The treatment and outcome of peri-prosthetic infection of the ankle: a single cohort-centre experience of 34 cases

The treatment of peri-prosthetic joint infection (PJI) of the ankle is not standardised. It is not clear whether an algorithm developed for hip and knee PJI can be used in the management of PJI of the ankle. We evaluated the outcome, at two or more years post-operatively, in 34 patients with PJI of the ankle, identified from a cohort of 511 patients who had undergone total ankle replacement. Their median age was 62.1 years (53.3 to 68.2), and 20 patients were women. Infection was exogenous in 28 (82.4%) and haematogenous in six (17.6%); 19 (55.9%) were acute infections and 15 (44.1%) chronic. Staphylococci were the cause of 24 infections (70.6%). Surgery with retention of one or both components was undertaken in 21 patients (61.8%), both components were replaced in ten (29.4%), and arthrodesis was undertaken in three (8.8%). An infection-free outcome with satisfactory function of the ankle was obtained in 23 patients (67.6%). The best rate of cure followed the exchange of both components (9/10, 90%). In the 21 patients in whom one or both components were retained, four had a relapse of the same infecting organism and three had an infection with another organism. Hence the rate of cure was 66.7% (14 of 21). In these 21 patients, we compared the treatment given to an algorithm developed for the treatment of PJI of the knee and hip. In 17 (80.9%) patients, treatment was not according to the algorithm. Most (11 of 17) had only one criterion against retention of one or both components. In all, ten of 11 patients with severe soft-tissue compromise as a single criterion had a relapse-free survival. We propose that the treatment concept for PJI of the ankle requires adaptation of the grading of quality of the soft tissues. Cite this article: Bone Joint J 2014;96-B:772-7.

Rat lungs show a biphasic formation of new alveoli during postnatal development

Roughly 90% of the gas-exchange surface is formed by alveolarization of the lungs. To the best of our knowledge, the formation of new alveoli has been followed in rats only by means of morphological description or interpretation of semiquantitative data until now. Therefore, we estimated the number of alveoli in rat lungs between postnatal days 4 and 60 by unambiguously counting the alveolar openings. We observed a bulk formation of new alveoli between days 4 and 21 (17.4 times increase from 0.8 to 14.3 millions) and a second phase of continued alveolarization between days 21 and 60 (1.3 times increase to 19.3 million). The (number weighted) mean volume of the alveoli decreases during the phase of bulk alveolarization from ∼593,000 μm(3) at day 4 to ∼141,000 μm(3) at day 21, but increases again to ∼298,000 μm(3) at day 60. We conclude that the "bulk alveolarization" correlates with the mechanism of classical alveolarization (alveolarization before the microvascular maturation is completed) and that the "continued alveolarization" follows three proposed mechanisms of late alveolarization (alveolarization after microvascular maturation). The biphasic pattern is more evident for the increase in alveolar number than for the formation of new alveolar septa (estimated as the length of the free septal edge). Furthermore, a striking negative correlation between the estimated alveolar size and published data on retention of nanoparticles was detected.

Mechanisms of Ligand–Protein Interaction in Sec-14-like Transporters Investigated by Computer Simulations

We review our recent work on protein-ligand interactions in vitamin transporters of the Sec-14-like protein. Our studies focused on the cellular-retinaldehyde binding protein (CRALBP) and the alpha-tocopherol transfer protein (alpha-TTP). CRALBP is responsible for mobilisation and photo-protection of short-chain cis-retinoids in the dim-light visual cycle or rod photoreceptors. alpha-TTP is a key protein responsible for selection and retention of RRR-alpha-tocopherol, the most active isoform of vitamin E in superior animals. Our simulation studies evidence how subtle chemical variations in the substrate can lead to significant distortion in the structure of the complex, and how these changes can either lead to new protein function, or be used to model engineered protein variants with tailored properties. Finally, we show how integration of computational and experimental results can contribute in synergy to the understanding of fundamental processes at the biomolecular scale.

Stereochemistry of Amino Acid Spacers Determines the Pharmacokinetics of (111)In-DOTA-Minigastrin Analogues for Targeting the CCK2/Gastrin Receptor.

The metabolic instability and high kidney retention of minigastrin (MG) analogues hamper their suitability for use in peptide-receptor radionuclide therapy of CCK2/gastrin receptor-expressing tumors. High kidney retention has been related to N-terminal glutamic acids and can be substantially reduced by coinjection of polyglutamic acids or gelofusine. The aim of the present study was to investigate the influence of the stereochemistry of the N-terminal amino acid spacer on the enzymatic stability and pharmacokinetics of (111)In-DOTA-(d-Glu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 ((111)In-PP11-D) and (111)In-DOTA-(l-Glu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 ((111)In-PP11-L). Using circular dichroism measurements, we demonstrate the important role of secondary structure on the pharmacokinetics of the two MG analogues. The higher in vitro serum stability together with the improved tumor-to-kidney ratio of the (d-Glu)6 congener indicates that this MG analogue might be a good candidate for further clinical study.

Analysis of the chlorophyll catabolism pathway in leaves of an introgression senescence mutant of Lolium temulentum

igments, proteins and enzyme activity related to chlorophyll catabolism were analysed in senescing leaves of wild-type (WT) Lolium temulentum and compared with those of an introgression line carrying a mutant gene from stay-green (SG) Festuca pratensis. During senescence of WT leaves chlorophylls a and b were continuously catabolised to colourless products and no other derivatives were observed, whereas in SG leaves there was an accumulation of dephytylated and oxidised catabolites including chlorophyllide a, phaeophorbide a and 132 OH-chlorophyllide a. Dephytylated products were absent from SG leaf tissue senescing under a light-dark cycle. Retention of pigments in SG was accompanied by significant stabilisation of light harvesting chlorophyll-proteins compared with WT, but soluble proteins such as Rubisco were degraded during senescence at a similar rate in the two genotypes. The activity of phaeophorbide a oxygenase measured in SG tissue at 3d was less than 12% of that in WT tissue at the same time-point during senescence and of the same order as that in young pre-senescent WT leaves, indicating that the metabolic lesion in SG concerns a deficiency at the ring-opening step of the catabolic pathway. In senescent L. temulentum tissue two terminal chlorophyll catabolites were identified with chromatographic characteristics that suggest they may represent hitherto undescribed catabolite structures. These data are discussed in relation to current understanding of the genetic and metabolic control of chlorophyll catabolism in leaf senescence.

The cystatin C/creatinine ratio, a marker of glomerular filtration quality: associated factors, reference intervals, and prediction of morbidity and mortality in healthy seniors.

The ratio of cystatin C (cysC) to creatinine (crea) is regarded as a marker of glomerular filtration quality associated with cardiovascular morbidities. We sought to determine reference intervals for serum cysC-crea ratio in seniors. Furthermore, we sought to determine whether other low-molecular weight molecules exhibit a similar behavior in individuals with altered glomerular filtration quality. Finally, we investigated associations with adverse outcomes. A total of 1382 subjectively healthy Swiss volunteers aged 60 years or older were enrolled in the study. Reference intervals were calculated according to Clinical & Laboratory Standards Institute (CLSI) guideline EP28-A3c. After a baseline exam, a 4-year follow-up survey recorded information about overall morbidity and mortality. The cysC-crea ratio (mean 0.0124 ± 0.0026 mg/μmol) was significantly higher in women and increased progressively with age. Other associated factors were hemoglobin A1c, mean arterial pressure, and C-reactive protein (P < 0.05 for all). Participants exhibiting shrunken pore syndrome had significantly higher ratios of 3.5-66.5 kDa molecules (brain natriuretic peptide, parathyroid hormone, β2-microglobulin, cystatin C, retinol-binding protein, thyroid-stimulating hormone, α1-acid glycoprotein, lipase, amylase, prealbumin, and albumin) and creatinine. There was no such difference in the ratios of very low-molecular weight molecules (urea, uric acid) to creatinine or in the ratios of molecules larger than 66.5 kDa (transferrin, haptoglobin) to creatinine. The cysC-crea ratio was significantly predictive of mortality and subjective overall morbidity at follow-up in logistic regression models adjusting for several factors. The cysC-crea ratio exhibits age- and sex-specific reference intervals in seniors. In conclusion, the cysC-crea ratio may indicate the relative retention of biologically active low-molecular weight compounds and can independently predict the risk for overall mortality and morbidity in the elderly.

The Chemical Mechanism of a Brown-Rot Decay Mimtic System and its Application in Paper Recycling Processes

This work is aimed at improving our current knowledge of the non-enzymatic inecl~anisins involved in brown-rot decay, as well as the exploration of potential applications of a brown-rot mimetic model system in paper recycling processes. The study was divided into two parts. The first part focussed on the chemical mechanisms involved in chelation and reduction of iron by a low molecular weight chelator (isolated from the brown-rot fungus Gloeophyllz~m tmbeum) and its model compound 2,3- dihydroxybenzoic acid (2,3-DHBA). Chelation as well as free radical generation mediated by this system were studied by ESR measurement. The results indicate that the effects of the chelator/iron ratio, the pH, and other reaction parameters on hydroxyl radical generation by a Fenton type system could be determined using ESR spin-trapping techniques. The results also support the hypothesis that superoxide radicals are involved in the chelator-mediated Fenton process. In the second part of the study, the effect of a chelator-mediated Fenton system for the improvement of deinking efficiency and the n~odification of fiber and paper properties was studied. For the deinking study, copy paper was laser printed with an identical standard pattern. Then repulping and flotation operations were performed to remove ink particles. Under properly controlled deinking conditions, the chelator mediated treatment (CMT) resulted in a reduction in dirt count over that of conventional deinking procedures with no significant loss of pulp strength. To study the effect of the chelator system treatment on the quality of pulp with different fines content, a fully bleached hardwood kraft pulp was beaten to different freeness levels and treated with the chelator-mediated free radical system. The result shows that virgin fiber and heavily beaten fiber respond differently to the free radical treatment. Unbeaten fibers become more flexible and easier to collapse after free radical treatment, while beaten fibers show a reduction in fines and small materials after mild free radical treatment.

In vivo definition of genetic and cellular aspects of mammalian sexual differentiation

The differentiation of the reproductive organs is an essential developmental process required for the proper transmission of the genetic material. Müllerian inhibiting substance (MIS) is produced by testes and is necessary for the regression of the Müllerian ducts: the anlagen of the uterus, fallopian tubes and cervix. In vitro and standard transgenic mouse studies indicate that the nuclear hormone receptor Steroidogenic factor 1 (SF-1) and the transcription factor SOX9 play an essential role in the regulation of Mis. To test this hypothesis, mutations in the endogenous SF-1 and SOX9 binding sites in the mouse Mis promoter were introduced by gene targeting in embryonic stem (ES) cells. In disagreement with cell culture and transgenic mouse studies, male mice homozygous for the mutant SF-1 binding site correctly initiated Mis transcription in the fetal testes, although at significantly reduced levels. Surprisingly, sufficient Mis was produced for complete elimination of the Müllerian duct system. However, when the SF-1 binding site mutation was combined with an Mis -null allele, the further decrease in Mis levels led to a partial retention of uterine tissue, but only at a distance from the testes. In contrast, males homozygous for the mutant SOX9 binding site did not initiate Mis transcription, resulting in pseudohermaphrodites with a uterus and oviducts. These studies suggest an essential role for SOX9 in the initiation of Mis transcription, whereas SF-1 appears to act as a quantitative regulator of Mis transcript levels perhaps for influencing non-Müllerian duct tissues. ^ The Mis type II receptor, a member of the TGF- b superfamily, is also required for the proper regression of the Müllerian ducts. Mis type II receptor-deficient human males and their murine counterparts develop as pseudohermaphrodites. A lacZ reporter cassette was introduced into the mouse Mis type II receptor gene, by homologous recombination in ES cells. Expression studies, based on b -galactosidase activity, show marked expression of the MIS type II receptor in the postnatal Sertoli cells of the testis as well as in the prenatal and postnatal granulosa cells of the ovary. Expression is also seen in the mesenchymal cells surrounding the Müllerian duct and in the longitudinal muscle layer of the uterus. ^

Assessment of English Language Learners Seeking a Graduate Degree in Speech Language Pathology

A shortage of bilingual/bicultural speech language pathologists may reflect a problem with recruitment and retention of bilingual/bicultural students. The purpose of the present study was to survey graduate training programs in speech language pathology to determine typical policies and practices concerning students who apply and are admitted as ELLs. With a growing number of ELL children needing services from a bilingual SLP, it seems that little is being done to address the issue. The problem may be with the reluctance of programs to not only accept ELL students, but there also seems to be a disinclination for any sort of training program to be established for these ELL students. Clinic directors were asked to complete a survey about ELLs seeking clinical training in speech language pathology. In particular, we were interested in obtaining information about whether clinical training programs a) provided opportunities for ELL to participate in clinic, b) assessed the English skills of these students, and c) provided remediation if these students English skills were judged to be less than proficient.

Role of entorhinal cortical plasticity in spatial and contextual memory

It is well accepted that the hippocampus (HIP) is important for spatial and contextual memories, however, it is not clear if the entorhinal cortex (EC), the main input/output structure for the hippocampus, is also necessary for memory storage. Damage to the EC in humans results in memory deficits. However, animal studies report conflicting results on whether the EC is necessary for spatial and contextual memory. Memory consolidation requires gene expression and protein synthesis, mediated by signaling cascades and transcription factors. Extracellular-signal regulated kinase (ERK) cascade activity is necessary for long-term memory in several tasks, including those that test spatial and contextual memory. In this work, we explore the role of ERK-mediated plasticity in the EC on spatial and contextual memory. ^ To evaluate this role, post-training infusions of reversible pharmacological inhibitors specific for the ERK cascade that do not affect normal neuronal activity were targeted directly to the EC of awake, behaving animals. This technique provides spatial and temporal control over the inhibition of the ERK cascade without affecting performance during training or testing. Using the Morris water maze to study spatial memory, we found that ERK inhibition in the EC resulted in long-term memory deficits consistent with a loss of spatial strategy information. When animals were allowed to learn and consolidate a spatial strategy for solving the task prior to training and ERK inhibition, the deficit was alleviated. To study contextual memory, we trained animals in a cued fear-conditioning task and saw an increase in the activation of ERK in the EC 90 minutes following training. ERK inhibition in the EC over this time point, but not at an earlier time point, resulted in increased freezing to the context, but not to the tone, during a 48-hour retention test. In addition, animals froze maximally at the time the shock was given during training; similar to naïve animals receiving additional training, suggesting that ERK-mediated plasticity in the EC normally suppresses the temporal nature of the freezing response. These findings demonstrate that plasticity in the EC is necessary for both spatial and contextual memory, specifically in the retention of behavioral strategies. ^