A reflective approach to career trajectory in advanced practice nursing

In response to a university mandate and general faculty dissatisfaction with work assignments, faculty developed a faculty work load formula. The authors discuss the development of the teaching portion of the formula. Implementation of the formula and publication of teaching work loads has resulted in greater awareness of other's responsibilities, improved faculty morale, increased accountability, and a greater sense of control. Some problem areas are also discussed.     

Determination of cisapride and norcisapride in human plasma using high-performance liquid chromatography with ultraviolet detection

A simple, rapid and reproducible high-performance liquid chromatographic assay for cisapride and norcisapride in human plasma is described. Samples of plasma (150 microl) were extracted using a C18 solid-phase cartridge. Regenerated tubes were eluted with 1.0 ml of methanol, dried, redissolved in 150 microl of methanol and injected. Chromatography was performed at room temperature by pumping acetonitrile-methanol-0.015 M phosphate buffer pH 2.2-2.3 (680:194:126, v/v/v) at 0.8 ml/min through a C18 reversed-phase column. Cisapride, norcisapride and internal standard were detected by absorbance at 276 nm and were eluted at 4.3, 5.3 and 8.1 min, respectively. Calibration plots in plasma were linear (r>0.998) from 10 to 150 ng/ml. Intraday precisions for cisapride and norcisapride were 3.3% and 5.4%, respectively. Interday precisions for cisapride and norcisapride were 9.6% and 9.0%, respectively. Drugs used which might be coadministered were tested for interference.     

Biosynthesis of progesterone derived neurosteroids by developing avian CNS: in vitro effects on the GABAA receptor complex

Although enthusiasm for measuring health-related quality of life (HRQL) in clinical trials exists, information is limited on the meaning of scores. We examined the relation between scores from the 34-item Medical Outcomes Study HIV Health Survey (MOS-HIV) and the more detailed HIV Overview of Problems-Evaluation System (HOPES) using the responses of 318 HIV-infected outpatients being treated in Los Angeles and Baltimore. With the HOPES problem statements as independent variables, statistically significant predictors of the variation in MOS-HIV scores for the Physical Function, Mental Health, and Energy/Fatigue scales were identified using stepwise regression. Approximately 60% to 70% of the variation in each of the scores was explained by five to seven different HOPES problem statements, with a single item explaining 47% to 59% of the variation. We created illustrative profiles for each of the three MOS-HIV scales using the HOPES items identified in the regressions. Independent of the scale, persons scoring in the top MOS-HIV quartile tended to report few if any problems, whereas a decline in score to the next quartile was characterized by functional difficulties (e.g., "HIV interferes with work"). The onset of specific problems might trigger further evaluation and potential intervention from health care providers to help maintain patient functioning.     

Unwrapping of Digital Speckle-Pattern Interferometry Phase Maps by use of a Minimum L(0)-Norm Algorithm

The performance of a minimum L(0)-norm unwrapping algorithm is investigated by use of synthetic digital speckle-pattern interferometry (DSPI) wrapped phase maps that simulate experimentally obtained data. This algorithm estimates its own weights to mask inconsistent pixels. Particular features usually included in DSPI wrapped phase distributions, such as shears, speckle noise, fringe cuts, object physical limits, and superimposed phase maps, are analyzed. Some adequate approaches to solving these features are discussed. Finally, it is shown that a complex case in which shears and fringe cuts coexist in the wrapped phase cannot be solved satisfactorily with the minimum L(0)-norm algorithm by itself. To cope with this problem, we propose a new scheme.     

Combined hyperlipidemia in transgenic mice overexpressing human apolipoprotein Cl

We have generated transgenic mice over-expressing human apolipoprotein CI (apo CI) using the native gene joined to the downstream 154-bp liver-specific enhancer that we defined for apo E. Human apo CI (HuCI)-transgenic mice showed elevation of plasma triglycerides (mg/dl) compared to controls in both the fasted (211 +/- 81 vs 123 +/- 52, P = 0.0001) and fed (265 +/- 105 vs 146 +/- 68, P < 0.0001) states. Unlike the human apo CII (HuCII)- and apo CIII (HuCIII)-transgenic mouse models of hypertriglyceridemia, plasma cholesterol was disproportionately elevated (95 +/- 23 vs 73 +/- 23, P = 0.002, fasted and 90 +/- 24 vs 61 +/- 14, P < 0.0001, fed). Lipoprotein fractionation showed increased VLDL and IDL + LDL with an increased cholesterol/triglyceride ratio (0.114 vs 0.065, P = 0.02, in VLDL). The VLDL apo E/apo B ratio was decreased 3.4-fold (P = 0.05) and apo CII and apo CIII decreased in proportion to apo E. Triglyceride and apo B production rates were normal, but clearance rates of VLDL triglycerides and postlipolysis lipoprotein "remnants" were significantly slowed. Plasma apo B was significantly elevated. Unlike HuCII- and HuCIII-transgenic mice, VLDL from HuCI transgenic mice bound heparin-Sepharose, a model for cell-surface glycosaminoglycans, normally. In summary, apo CI overexpression is associated with decreased particulate uptake of apo B-containing lipoproteins, leading to increased levels of several potentially atherogenic species, including cholesterol-enriched VLDL, IDL, and LDL.     

Fatigue damage accumulation of cold expanded hole in aluminum alloys subjected to block loading

Fatigue damage accumulation of cold expanded hole in aluminum alloys used in land transportation components was investigated. Tests were carried out using pre-cracked SENT specimens and inserting an expanded hole at the crack tip. The degree of the cold expansion was chosen equal to 4.3%. Tests were performed in two and four block loading under constant amplitude. Two sequences were compared.The increasing and the decreasing magnitude were compared. The experimental results were compared to the damage calculated by the Miner's rule and a new simple fatigue damage indicator. This comparison shows that the ‘model of the damage stress’, which take into account of the loading history, yields a good estimation of the experimental results. Moreover, the error is minimized in comparison to the Miner's model.     

Increased socioeconomic differences in mortality in eight Spanish provinces

In Spain, the study of socioeconomic differences in mortality has been limited by the fact that death certificates often do not include complete information on occupation. In this study, we chose those geographic areas with the highest quality information on occupation of the deceased in order to study socioeconomic differences in mortality from various causes of death. We used information from the death certificates of males who died between 30 and 64 years of age in eight Spanish provinces to compare mortality from the leading causes of death in professionals and managers (group I) and in manual laborers (group II) in 1980-82 and 1988-90. In each period the standardized mortality ratios (SMRs) were higher in group II, except for ischaemic heart disease during the first period, and cancer of the colon and rectum in both, although in the latter case the differences were not statistically significant. The ratio between the SMR from all causes in group II and group I was 1.27 in 1980-82, and 1.72 in 1988-90; for cancer of the colon and rectum the ratio went from 0.98 to 0.84, and for ischaemic heart disease, from 0.80 to 1.31. Except for cancer of the colon and rectum, which resulted in higher mortality in occupational group I, the excess mortality in occupational group II increased between the first and second period. The relation between socioeconomic level and mortality for ischaemic heart disease was reversed, a phenomenon similar to that which took place in the 1960s and 1970s in the developed countries.(ABSTRACT TRUNCATED AT 250 WORDS)     

Establishing In-House Cutoffs of CSF Alzheimer’s Disease Biomarkers for the AT(N) Stratification of the Alzheimer Center Barcelona Cohort

Background: Clinical diagnosis of Alzheimer’s disease (AD) increasingly incorporates CSF biomarkers. However, due to the intrinsic variability of the immunodetection techniques used to measure these biomarkers, establishing in-house cutoffs defining the positivity/negativity of CSF biomarkers is recommended. However, the cutoffs currently published are usually reported by using cross-sectional datasets, not providing evidence about its intrinsic prognostic value when applied to real-world memory clinic cases. Methods: We quantified CSF Aβ1-42, Aβ1-40, t-Tau, and p181Tau with standard INNOTEST^® ELISA and Lumipulse G^® chemiluminescence enzyme immunoassay (CLEIA) performed on the automated Lumipulse G600II. Determination of cutoffs included patients clinically diagnosed with probable Alzheimer’s disease (AD, n = 37) and subjective cognitive decline subjects (SCD, n = 45), cognitively stable for 3 years and with no evidence of brain amyloidosis in 18F-Florbetaben-labeled positron emission tomography (FBB-PET). To compare both methods, a subset of samples for Aβ1-42 (n = 519), t-Tau (n = 399), p181Tau (n = 77), and Aβ1-40 (n = 44) was analyzed. Kappa agreement of single biomarkers and Aβ1-42/Aβ1-40 was evaluated in an independent group of mild cognitive impairment (MCI) and dementia patients (n = 68). Next, established cutoffs were applied to a large real-world cohort of MCI subjects with follow-up data available (n = 647). Results: Cutoff values of Aβ1-42 and t-Tau were higher for CLEIA than for ELISA and similar for p181Tau. Spearman coefficients ranged between 0.81 for Aβ1-40 and 0.96 for p181TAU. Passing–Bablok analysis showed a systematic and proportional difference for all biomarkers but only systematic for Aβ1-40. Bland–Altman analysis showed an average difference between methods in favor of CLEIA. Kappa agreement for single biomarkers was good but lower for the Aβ1-42/Aβ1-40 ratio. Using the calculated cutoffs, we were able to stratify MCI subjects into four AT(N) categories. Kaplan–Meier analyses of AT(N) categories demonstrated gradual and differential dementia conversion rates (p = 9.815⁻²⁷). Multivariate Cox proportional hazard models corroborated these findings, demonstrating that the proposed AT(N) classifier has prognostic value. AT(N) categories are only modestly influenced by other known factors associated with disease progression. Conclusions: We established CLEIA and ELISA internal cutoffs to discriminate AD patients from amyloid-negative SCD individuals. The results obtained by both methods are not interchangeable but show good agreement. CLEIA is a good and faster alternative to manual ELISA for providing AT(N) classification of our patients. AT(N) categories have an impact on disease progression. AT(N) classifiers increase the certainty of the MCI prognosis, which can be instrumental in managing real-world MCI subjects.     

Arabinoxylan and Pectin Metabolism in Crohn’s Disease Microbiota: An In Silico Study

Inflammatory bowel disease is a chronic disorder including ulcerative colitis and Crohn’s disease (CD). Gut dysbiosis is often associated with CD, and metagenomics allows a better understanding of the microbial communities involved. The objective of this study was to reconstruct in silico carbohydrate metabolic capabilities from metagenome-assembled genomes (MAGs) obtained from healthy and CD individuals. This computational method was developed as a mean to aid rationally designed prebiotic interventions to rebalance CD dysbiosis, with a focus on metabolism of emergent prebiotics derived from arabinoxylan and pectin. Up to 1196 and 1577 MAGs were recovered from CD and healthy people, respectively. MAGs of Akkermansia muciniphila, Barnesiella viscericola DSM 18177 and Paraprevotella xylaniphila YIT 11841 showed a wide range of unique and specific enzymes acting on arabinoxylan and pectin. These glycosidases were also found in MAGs recovered from CD patients. Interestingly, these arabinoxylan and pectin degraders are predicted to exhibit metabolic interactions with other gut microbes reduced in CD. Thus, administration of arabinoxylan and pectin may ameliorate dysbiosis in CD by promoting species with key metabolic functions, capable of cross-feeding other beneficial species. These computational methods may be of special interest for the rational design of prebiotic ingredients targeting at CD.