Direct modeling of the electrochemistry in the three-phase boundary of solid oxide fuel cell anodes by density functional theory: a critical overview.

The first principles modeling of electrochemical reactions has proven useful for the development of efficient, durable and low cost solid oxide full cells (SOFCs). In this account we focus on recent advances in modeling of structural, electronic and catalytic properties of the SOFC anodes based on density functional theory (DFT) first principle calculations. As a starting point, we highlight that the adequate analysis of cell electrochemistry generally requires modeling of chemical reactions at the metal/oxide interface rather than on individual metal or oxide surfaces. The atomic models of Ni/YSZ and Ni/CeO2 interfaces, required for DFT simulations of reactions on SOFC anodes are discussed next, together with the analysis of the electronic structure of these interfaces. Then we proceed to DFT-based findings on charge transfer mechanisms during redox reactions on these two anodes. We provide a comparison of the electronic properties of Ni/YSZ and Ni/CeO2 interfaces and present an interpretation of their different chemical performances. Subsequently we discuss the computed energy pathways of fuel oxidation mechanisms, obtained by various groups to date. We also discuss the results of DFT studies combined with microkinetic modeling as well as the results of kinetic Monte Carlo simulations. In conclusion we summarize the key findings of DFT modeling of metal/oxide interfaces to date and highlight possible directions in the future modeling of SOFC anodes.

Urinary oxytocin and social bonding in related and unrelated wild chimpanzees.

Animals that maintain cooperative relationships show gains in longevity and offspring survival. However, little is known about the cognitive or hormonal mechanisms involved in cooperation. Indeed, there is little support for a main hypothesis that non-human animals have the cognitive capacities required for bookkeeping of cooperative exchanges. We tested an alternative hypothesis that cooperative relationships are facilitated by an endocrinological mechanism involving oxytocin, a hormone required for bonding in parental and sexual relationships across mammals. We measured urinary oxytocin after single bouts of grooming in wild chimpanzees. Oxytocin levels were higher after grooming with bond partners compared with non-bond partners or after no grooming, regardless of genetic relatedness or sexual interest. We ruled out other possible confounds, such as grooming duration, grooming direction or sampling regime issues, indicating that changes in oxytocin levels were mediated by social bond strength. Oxytocin, which is thought to act directly on neural reward and social memory systems, is likely to play a key role in keeping track of social interactions with multiple individuals over time. The evolutionary linkage of an ancestral hormonal system with complex social cognition may be the primary mechanism through which long-term cooperative relationships develop between both kin and non-kin in mammals.

Incidence and prevalence of copper deficiency following roux-en-y gastric bypass surgery.

INTRODUCTION AND OBJECTIVES: The frequency of copper deficiency and clinical manifestations following roux-en-y gastric bypass (RYGB) surgery is not yet clear. Objectives were to determine the prevalence and incidence of copper deficiency in patients who have undergone RYGB. DESIGN AND METHODS: We sought to determine the number of RYGB patients undergoing medical and nutritional follow-up visits at the Emory Bariatric Center who experienced copper deficiency and associated hematological and neurological complaints (n=136). Separately, in patients followed longitudinally before and during 6 and 24 months following RYGB surgery, we obtained measures of copper status (n=16). Systemic blood cell counts and measures of copper, zinc and ceruloplasmin were determined using standardized assays in reference laboratories including atomic absorption spectrometry and immunoassays. RESULTS: Thirteen patients were identified to have copper deficiency suggesting a prevalence of copper deficiency of 9.6%, and the majority of these had concomitant complications including anemia, leukopenia and various neuro-muscular abnormalities. In the longitudinal study, plasma copper concentrations and ceruloplasmin activity decreased over 6 and 24 months following surgery, respectively (P<0.05), but plasma zinc concentrations did not change. A simultaneous decrease in white blood cells was observed (P<0.05). The incidence of copper deficiency in these subjects was determined to be 18.8%. CONCLUSIONS: The prevalence and incidence of copper deficiency following RYGB surgery was determined to be 9.6% and 18.8%, respectively, with many patients experiencing mild-to-moderate symptoms. Given that copper deficiency can lead to serious and irreversible complications if untreated, frequent monitoring of the copper status of RYGB patients is warranted.

Influenza-associated hospitalisations in Finland from 1996 to 2010: unexpected age-specific burden during the influenza A(H1N1)pdm09 pandemic from 2009 to 2010.

To assess the burden of influenza on the Finnish healthcare system, we analysed hospitalisations during 1996-2010 using the International Classification of Diseases codes potentially related to influenza and its complications from the national hospital discharge registry. To compare the influenza A(H1N1)pdm09 pandemic with previous influenza seasons in 1996-2009, we calculated hospitalisation rates by age- and diagnostic groups. We built a negative binomial regression model based on times series analysis to assess the impact of the pandemic. Influenza-associated hospitalisation rates were higher during the pandemic compared to pre-pandemic influenza seasons for 5-24 year-olds (incidence rate ratio (IRR): 1.52, 95% confidence interval (CI): 1.44-1.60) and 25-64 year-olds (IRR: 1.33, 95% CI: 1.29-1.36), but did not differ for persons aged ≥ 65 years (IRR: 0.98, 95% CI: 0.97-1.00). Hospitalisation rates exceeded the upper limit of the prediction line by 177% in 5-24 year-olds, 66% in 0-4 year-olds and 57% in 25-64 year-olds. During the influenza season of 2003/04, all age groups had higher-than-expected hospitalisation rates, whereas other seasonal peaks were only notable among persons aged ≥ 65 years. These age-specific differences in the hospital burden underscore the importance of the continuous surveillance of hospitalisations in order to evaluate immunisation priorities for seasonal influenza and pandemic preparedness including use of antiviral medication.

Calorimeter with Bayesian unfolding of spectra of high-flux broadband x rays.

We report the development of a multipurpose differential x-ray calorimeter with a broad energy bandwidth. The absorber architecture is combined with a Bayesian unfolding algorithm to unfold high energy x-ray spectra generated in high-intensity laser-matter interactions. Particularly, we show how to extract absolute energy spectra and how our unfolding algorithm can reconstruct features not included in the initial guess. The performance of the calorimeter is evaluated via Monte Carlo generated data. The method accuracy to reconstruct electron temperatures from bremsstrahlung is shown to be 5% for electron temperatures from 1 to 50 MeV. We study bremsstrahlung generated in solid target interaction showing an electron temperature of 0.56 ± 0.04 MeV for a 700 µm Ti titanium target and 0.53 ± 0.03 MeV for a 50 µm target. We investigate bremsstrahlung from a target irradiated by laser-wakefield accelerated electrons showing an endpoint energy of 551 ± 5 MeV, inverse Compton generated x rays with a peak energy of 1.1 MeV, and calibrated radioactive sources. The total energy range covered by all these sources ranges from 10 keV to 551 MeV.

Proton beam quality enhancement by spectral phase control of a PW-class laser system.

We report on experimental investigations of proton acceleration from solid foils irradiated with PW-class laser-pulses, where highest proton cut-off energies were achieved for temporal pulse parameters that varied significantly from those of an ideally Fourier transform limited (FTL) pulse. Controlled spectral phase modulation of the driver laser by means of an acousto-optic programmable dispersive filter enabled us to manipulate the temporal shape of the last picoseconds around the main pulse and to study the effect on proton acceleration from thin foil targets. The results show that applying positive third order dispersion values to short pulses is favourable for proton acceleration and can lead to maximum energies of 70 MeV in target normal direction at 18 J laser energy for thin plastic foils, significantly enhancing the maximum energy compared to ideally compressed FTL pulses. The paper further proves the robustness and applicability of this enhancement effect for the use of different target materials and thicknesses as well as laser energy and temporal intensity contrast settings. We demonstrate that application relevant proton beam quality was reliably achieved over many months of operation with appropriate control of spectral phase and temporal contrast conditions using a state-of-the-art high-repetition rate PW laser system.

Outbreak of 2009 pandemic influenza A(H1N1) in a Finnish garrison--a serological survey.

In September 2009, an outbreak of 2009 pandemic influenza A(H1N1) took place in a Finnish garrison. In November 2009, we performed a serological survey among 984 recruits undergoing their military service at the garrison and related the results to self-reported upper respiratory tract infection (URTI) with or without fever. Of 346 volunteers who donated a blood sample, 169 (49%) had pandemic influenza A(H1N1) virus-specific antibodies. Of those, 84 (50%) reported no recent history of URTI, suggesting that a major part of those infected with pandemic influenza A(H1N1) virus may be asymptomatic.

High frequency of cross-reacting antibodies against 2009 pandemic influenza A(H1N1) virus among the elderly in Finland.

Since May 2009, the pandemic influenza A(H1N1) virus has been spreading throughout the world. Epidemiological data indicate that the elderly are underrepresented among the ill individuals. Approximately 1,000 serum specimens collected in Finland in 2004 and 2005 from individuals born between 1909 and 2005, were analysed by haemagglutination-inhibition test for the presence of antibodies against the 2009 pandemic influenza A(H1N1) and recently circulating seasonal influenza A viruses. Ninety-six per cent of individuals born between 1909 and 1919 had antibodies against the 2009 pandemic influenza virus, while in age groups born between 1920 and 1944, the prevalence varied from 77% to 14%. Most individuals born after 1944 lacked antibodies to the pandemic virus. In sequence comparisons the haemagglutinin (HA) gene of the 2009 pandemic influenza A(H1N1) virus was closely related to that of the Spanish influenza and 1976 swine influenza viruses. Based on the three-dimensional structure of the HA molecule, the antigenic epitopes of the pandemic virus HA are more closely related to those of the Spanish influenza HA than to those of recent seasonal influenza A(H1N1) viruses. Among the elderly, cross-reactive antibodies against the 2009 pandemic influenza virus, which likely originate from infections caused by the Spanish influenza virus and its immediate descendants, may provide protective immunity against the present pandemic virus.

Somatic gene editing ameliorates skeletal and cardiac muscle failure in pig and human models of Duchenne muscular dystrophy.

Frameshift mutations in the DMD gene, encoding dystrophin, cause Duchenne muscular dystrophy (DMD), leading to terminal muscle and heart failure in patients. Somatic gene editing by sequence-specific nucleases offers new options for restoring the DMD reading frame, resulting in expression of a shortened but largely functional dystrophin protein. Here, we validated this approach in a pig model of DMD lacking exon 52 of DMD (DMDΔ52), as well as in a corresponding patient-derived induced pluripotent stem cell model. In DMDΔ52 pigs1, intramuscular injection of adeno-associated viral vectors of serotype 9 carrying an intein-split Cas9 (ref. 2) and a pair of guide RNAs targeting sequences flanking exon 51 (AAV9-Cas9-gE51) induced expression of a shortened dystrophin (DMDΔ51-52) and improved skeletal muscle function. Moreover, systemic application of AAV9-Cas9-gE51 led to widespread dystrophin expression in muscle, including diaphragm and heart, prolonging survival and reducing arrhythmogenic vulnerability. Similarly, in induced pluripotent stem cell-derived myoblasts and cardiomyocytes of a patient lacking DMDΔ52, AAV6-Cas9-g51-mediated excision of exon 51 restored dystrophin expression and amelioreate skeletal myotube formation as well as abnormal cardiomyocyte Ca2+ handling and arrhythmogenic susceptibility. The ability of Cas9-mediated exon excision to improve DMD pathology in these translational models paves the way for new treatment approaches in patients with this devastating disease.

Social and hormonal mechanisms underlying male reproductive strategies in black howler monkeys (Alouatta pigra).

We investigated the social and hormonal mechanisms underlying male reproductive strategies in two multimale-multifemale groups of black howler monkeys (Alouatta pigra) during a 14-month study in Palenque National Park, Mexico. Fecal glucocorticoid (fGC) and androgen (fA) levels were analyzed for 343 fecal samples collected from 14 males during their presence in the study groups. Neither immigrating males nor resident males that remained in the group had elevated fGC and fA levels during 11 observed male migration events, suggesting that competition over group membership was not associated with variation in the fecal hormonal levels of males. Instead, fGC and fA levels were significantly higher in males who maintained a central position in the group and had almost exclusive access to fertile females than in other resident males. These "central" males were responsible for maintaining close spatial associations and cultivating strong affiliative relationships with cycling, sexually active females but not with noncycling, sexually inactive females. "Noncentral" males did not form strong social relationships with either cycling or noncycling females and had no or very few mating opportunities. Our findings suggest that male black howler monkeys compete nonaggressively by fostering relationships with cycling females and that the elevated fGC levels of central males may be indicative of the social challenges involved in their indirect competition.

Conversion of a CHO cell culture process from perfusion to fed-batch technology without altering product quality.

During the development of a new drug product, it is a common strategy to develop a first-generation process with the aim to rapidly produce material for pre-clinical and early stage clinical trials. At a later stage of the development, a second-generation process is then introduced with the aim to supply late-stage clinical trials as well as market needs. This work was aimed at comparing the performance of two different CHO cell culture processes (perfusion and fed-batch) used for the production of a therapeutically active recombinant glycoprotein at industrial pilot-scale. The first-generation process was based on the Fibra-Cel packed-bed perfusion technology. It appeared during the development of the candidate drug that high therapeutic doses were required (>100mg per dose), and that future market demand would exceed 100 kg per year. This exceeded by far the production capacity of the first-generation process, and triggered a change of technology from a packed-bed perfusion process with limited scale-up capabilities to a fed-batch process with scale-up potential to typical bioreactor sizes of 15m(3) or more. The productivity per bioreactor unit volume (in product m(-3)year(-1)) of the fed-batch process was about 70% of the level reached with the first-generation perfusion process. However, since the packed-bed perfusion system was limited in scale (0.6m(3) maximum) compared to the volumes reached in suspension cultures (15m(3)), the fed-batch was selected as second-generation process. In fact, the overall process performance (in product year(-1)) was about 18-fold higher for the fed-batch compared to the perfusion mode. Data from perfusion and fed-batch harvests samples indicated that comparable product quality (relative abundance of monomers dimers and aggregates; N-glycan sialylation level; isoforms distribution) was obtained in both processes. To further confirm this observation, purification to homogeneity of the harvest material from both processes, followed by a complementary set of studies (e.g. full physico-chemical characterization, assessment of in vitro and in vivo bioactivity, comparative pharmacokinetics and pharmacodynamics studies in relevant species, etc.) would be required. Finally, this illustrates the need to fix the production process early during the development of a new drug product in order to minimize process conversion efforts and to shorten product development time lines.

Hormonal correlates of life history characteristics in wild female Colobus vellerosus.

Documenting primate life history characteristics is important because it provides information about traits that affect the timing and rate of reproduction in these long-lived species. This study describes the hormonal correlates of female reproductive events and quantifies for the first time key life history variables for Colobus vellerosus, using hormonal and observational data. This study also biologically validates that the reproductive events determined in the hormone profiles correspond to observed reproductive events for each female. We collected behavioural data on 18 females in our four study groups during 12 months (May 2012-2013) at the Boabeng-Fiema Monkey Sanctuary, using 10-min continuous focal and ad libitum sampling. We concurrently collected faecal samples (n = 1866) every 2-3 days from these 18 females (prepubescent n = 2, cycling n = 2, lactating n = 12, pregnant, n = 7, and post-reproductive n = 1) and extracted oestrogen (E2) and progesterone (P) metabolites in the field using solid-phase extraction cartridges. We created a hormone profile for each female by analyzing 1586 of our samples for E2 using radio-immuno assays, and P using enzyme-immunoassays at the Wisconsin National Primate Research Center. Mean ovarian cycle length was 24 days ± 1 (n = 2 cycles). Mean gestation length was 23 weeks (range = 21-25 weeks, n = 2 complete pregnancies). For females whose infants survived to nutritional independence, the mean inter-birth interval (IBI) was significantly longer than for females whose infants died prior to reaching nutritional independence (Mann-Whitney U Test; U = 14.5, p = 0.006; IBI surviving infants: 17.75 months, range = 8-20.75 months, n = 11 vs. IBI infant death: 11.89 months, range = 8-18.5 months, n = 9). The values for most life history traits reported in this study are similar to those documented in other similarly sized colobine species. Some values are on the lower end of the range for similarly sized colobines; C. vellerosus shows a cycle of 24 days and gestation length of 5.75 months vs. a range of 24-29 days for cycle length and 5.25-7.5 months for gestation length in other colobines. This may be due to C. vellerosus' smaller body size, or their limited access to higher quality food resources.

A comparison of troponin T and troponin I as predictors of cardiac events in patients undergoing chronic dialysis at a Veteran's Hospital: a pilot study.

OBJECTIVE: The purpose of this study was to prospectively evaluate the usefulness of the cardiac troponins as predictors of subsequent cardiac events in patients with chronic renal failure undergoing dialysis. BACKGROUND: Cardiac troponin T (cTnT) and I (cTnI) are cardiac markers that are specific for cardiac muscle. They are also excellent prognostic indicators for patients presenting with chest pain. Although cardiac disease is the leading cause of death in dialysis patients, standard methods to diagnose acute coronary syndromes in patients with renal failure are often misleading. METHODS: A six-month prospective study was done in a university-affiliated Veterans Hospital's dialysis clinic. Forty-nine patients undergoing chronic dialysis with no complaints of chest pain were followed for cardiac events occurring in the six months after cardiac troponin measurements. These included unstable angina, acute myocardial infarction and cardiac death. An additional 83 patients with renal failure but who were not undergoing dialysis were also examined. RESULTS: Within six months all three dialysis patients with elevated cTnI at entry into the study suffered an adverse complication (specificity and positive predictive value = 100%). Twenty-five patients had cTnT elevated at >0.10 ng/ml (53%). Patients with diabetes were more likely to have elevated troponin T levels (64% vs. 25%, p = 0.01). All six patients developing cardiac events within three months had elevations of cTnT >0.1 ng/ml (sensitivity = 100%). Whereas the specificity of cTnT was only 56% for a near-term cardiac event, the negative predictive value of cTnT using a cutoff of < or = 0.1 ng/ml was 100%. On restratifying patients using a cutoff value of cTnT of >0.2 ng/ml, only nine of 49 dialysis patients (18%) had elevated levels. In patients with renal failure not undergoing dialysis, only three of 83 (4%) had elevated troponin I or T. None of these patients suffered a cardiac event in the next six months. CONCLUSIONS: This prospective pilot study clearly delineates the troponins as important prognosticators in asymptomatic otherwise "stable" patients on chronic dialysis, especially those with concomitant diabetes mellitus. It also appears that troponins are more likely to be elevated in dialysis patients than other patients with renal failure not on dialysis. The above suggests that the combination of cTnI and cTnT might be very effective in elucidating cardiac risks of patients with renal failure undergoing chronic dialysis.

The effect of a single, large bolus of vitamin D in healthy adults over the winter and following year: a randomized, double-blind, placebo-controlled trial.

BACKGROUND/OBJECTIVES: Although single, high doses of vitamin D effectively maintain vitamin D sufficiency in several populations, no studies have evaluated healthy adults over winter, during which vitamin D status declines. This study investigated whether high-dose vitamin D3 given once to healthy adults before winter will (1) prevent the wintertime decline in vitamin D status, (2) promote vitamin D sufficiency 1 year following the dose and (3) prevent the rise of parathyroid hormone (PTH) concentrations. SUBJECTS/METHODS: In this double-blind, placebo-controlled trial, we assessed plasma 25(OH)D and PTH concentrations at baseline, 5, 90 and 365 days after drug administration in 28 healthy adults. In all, >80% of subjects returned at each time point. RESULTS: At baseline, the young, healthy participants had a mean plasma 25(OH)D concentration of 17.5±6.1 ng/ml. Only two subjects exhibited plasma 25(OH)D concentrations >30 ng/ml. At 5 days, subjects randomized to vitamin D3 had a higher mean plasma 25(OH)D concentration compared with the placebo group (39.1 vs 19.1 ng/ml, P<0.001). Plasma 25(OH)D concentrations returned to baseline at 90 and 365 days in the vitamin D3 group and remained unchanged in the placebo group. PTH and calcium concentrations were unrelated to changes in 25(OH)D levels and similar between groups over time. CONCLUSIONS: A dose of 250,000 IU of vitamin D3 given once in November resulted in a robust increase in plasma 25(OH)D after 5 days, but it was unable to sustain this increase after 90 days. A larger or more frequent dosing regimen may be needed for long-term vitamin D sufficiency.

A comparison of rat small intestinal insulin and insulin-like growth factor I receptors during fasting and refeeding.

Insulin-like growth factor I (IGF-I) and insulin may be important regulators of intestinal growth. To investigate small intestinal IGF-I receptors (IGF-IR) and insulin receptors (IR) during intestinal cell atrophy and regeneration, we compared indexes of IGF-IR and IR expression in rat jejunum after 72 h of fasting and 24-72 h of enteral refeeding. Fasting induced intestinal atrophy, reduced plasma insulin and IGF-I concentrations, and markedly decreased jejunal IGF-I messenger RNA (mRNA) levels; these changes were reversed by refeeding. Fasting significantly increased jejunal specific insulin binding, IR content (to 230% of the fed control value), and the 9.6- and 7.4-kilobase IR mRNA transcript levels (to 202% and 218% of control values, respectively). These IR indexes rapidly decreased to control levels with refeeding. Levels of IGF-IR (by Scatchard analysis) and IGF-I-R mRNA were not significantly altered with fasting. The 11-kilobase IGF-IR mRNA transcript increased significantly during the first 24 h of refeeding (to 166% of the control value), and IGF-IR number rose 3-fold. We conclude that rat jejunal IR and IGF-IR are differentially regulated by nutrient availability. Up-regulation of jejunal IGF-I and IGF-IR expression during refeeding suggests a role for the IGF action pathway in gut trophic responses to enteral nutrients.

Intestinal adaptation after extensive small bowel resection: differential changes in growth and insulin-like growth factor system messenger ribonucleic acids in jejunum and ileum.

The distal small bowel exhibits greater adaptive growth than proximal segments after partial small intestine resection. To explore this process, we evaluated adaptive cellularity, intestinal insulin-like growth factor (IGF) system messenger RNA (mRNA) transcripts, and effects of recombinant IGF-I treatment in jejunum and ileum of adult rats. Gastrostomy-fed animals underwent 80% jejuno-ileal resection or intestinal transection and reanastomosis without resection, followed by infusion of human recombinant IGF-I (2.4 mg/kgXday) or vehicle. After 7 days, resected rats demonstrated modest adaptive growth in jejunum and marked cell proliferation in ileum. Resection increased IGF-I mRNA in both jejunum (183%) and ileum (249%) and up-regulated IGFBP-4 mRNA levels in both tissues. IGFBP-3 mRNA fell significantly in ileum after resection. IGF-I infusion modestly increased ileal cellularity after resection, but had no effect in jejunum. IGF-I markedly increased IGFBP-3 mRNA levels in jejunum after both transection and resection. These data confirm that bowel resection induces greater adaptive growth in ileum than jejunum. IGF-I administration modestly increases ileal, but not jejunal, growth after resection. Increased levels of intestinal IGF-I and IGFBP-4 mRNA suggest roles for IGF-I and IGFBP-4 in mediating small bowel adaptation. Higher levels of jejunal IGFBP-3 mRNA may be related to limited jejunal vs. ileal growth after extensive jejuno-ileal resection.

Nitric oxide synthase expression in endothelial cells exposed to mechanical forces.

Nitric oxide (NO) has been demonstrated to play a central role in vascular biology and pathobiology. The expression of endothelial NO synthase (eNOS) is regulated in part by blood flow-induced mechanical factors. The purpose of this study was to evaluate how the expression of eNOS mRNA correlates with the activation of its promoter in both arterial and venous endothelial cells (ECs) exposed to mechanical forces, ie, shear stress and cyclic circumferential stretch. Bovine aortic ECs (BAECs) and EA hy.926, a cell line derived from human umbilical vein ECs, were grown on the inside of elastic tubes and subjected to combinations of pressure, pulsatile shear stress, and cyclic circumferential stretch for 24 hours. Two patterns of shear stress were used: unidirectional (mean of 6, ranging from 3 to 9 dyne/cm2) and oscillatory (mean of 0.3, ranging from -3 to +3 dyne/cm2). The expression of eNOS mRNA was quantified by Northern blot analysis. Activation of the promoter was assessed by luciferase activity after the cells were transiently transfected before the flow experiments with a plasmid construct containing the fully functional eNOS promoter coupled to a luciferase reporter gene. Expression of eNOS mRNA was increased and promoter activity was enhanced by unidirectional shear stress compared with static control. Oscillatory shear slightly upregulated eNOS mRNA in BAECs, whereas it downregulated eNOS mRNA in EA hy.926. In both BAECs and EA hy.926, there was a good correlation between the increase in eNOS mRNA expression and promoter activation by unidirectional shear stress. In contrast, in both BAECs and EA hy.926 cells exposed to shear stress, cyclic stretch did not change eNOS mRNA expression, but the activation of eNOS promoter was significantly lower. Moreover, when ECs were exposed to oscillatory shear stress, there was a dramatic activation of the eNOS promoter. These results demonstrate that unidirectional shear stress increases eNOS mRNA expression via a transcriptional mechanism. However, oscillatory shear stress and cyclic stretch appear to control eNOS expression through posttranscriptional regulatory events.

Recombinant human growth hormone enhances the metabolic efficacy of parenteral nutrition: a double-blind, randomized controlled study.

This multicenter, randomized, double-blind study was performed to investigate whether recombinant GH improves the efficacy of total parenteral nutrition (TPN). Fifteen stable patients requiring parenteral feeding due to gastrointestinal/pancreatic disease were studied. Constant maintenance TPN providing approximately 30 kcal/kg day and approximately 1.6 g protein/kg.day was administered during an initial 7-day baseline period. After randomization, daily sc injections of saline (control, n = 9) or GH (10 mg/day, n = 6) were administered a 14-day treatment period as nutrient intake remained constant. Elemental balances for nitrogen (N), potassium (K), phosphorus (P), and sodium (Na) were determined daily and serial blood indices, vital signs, and other clinical parameters were monitored. Nutrient balances approached equilibrium during the baseline week in both groups. With GH administration, a significant increase in N, K, and P balance occurred; in contrast, nutrient balances did not change significantly from baseline values in control patients. The cumulative change (delta) in nutrient balances from the baseline week was also significantly greater in the GH-treated patients (delta N: control+2 +/- 7 g vs. GH+36 +/- 6. g, P less than 0.005; delta K:+57 +/- 45 mmol vs.+199 +/- 19 mmol, P less than 0.03; delta P: -27 +/- 30 mmol vs. +91 +/- 69 mmol, P less than 0.02). Plasma insulin-like growth factor-I concentrations rose 5-fold and serum cholesterol rose slightly with GH; no other significant change in group mean blood values occurred. One patient receiving GH and chronic prednisone therapy developed moderate hyperglycemia and mild peripheral edema; no other deleterious effects attributable to GH were observed. GH was well tolerated and significantly enhanced nutrient retention compared to standard parenteral feeding alone. GH improves the efficacy of parenteral nutrient utilization in patients requiring TPN.