bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Ammonia Inhalants in Humans: A Review of the Current Literature Regarding the Benefits, Risks, and Efficacy
Authors: Malecek Jan , Tufano James J. 
Published: April 2021

ABSTRACT
Ammonium inhalants (AIs) are used to improve athletic performance, but their use has preceded the research process. Oftentimes, strength-based athletes use AIs to postpone acute fatigue or increase arousal. Despite the widespread use of AIs, the amount of research examining its physiological effects, efficacy, and safety is low compared with other ergogenic aids that have been extensively researched. Therefore, the purpose of this review is to provide sports science researchers, strength and conditioning professionals, medical professionals, and other practitioners with the most up to date information about the benefits, risks, and physiological effects of AIs. To date, there is a lack of evidence to support anecdotal claims of increased cognitive arousal and greater strength performance. However, there may be a short-term effect of AIs on the cardiorespiratory system (possibly increasing breathing rate and heart rate approximately 15–30 seconds), but further research is needed to support these findings and to determine how the short-term cardiorespiratory effects may affect other physiological and performance measures. Finally, although evidence does not indicate that AIs are dangerous in healthy populations, sport and health professionals should be aware of the potential risks of AIs to prevent any unlikely, but possible, difficulties.
Predictive Value of Clinician “Gestalt” in Pediatric Community-Acquired Pneumonia
Authors: Gao Hans M. , Ambroggio Lilliam , Shah Samir S. , Ruddy Richard M. , Florin Todd A. 
Published: April 2021

OBJECTIVES:
Validated prognostic tools for pediatric community-acquired pneumonia (CAP) do not exist. Thus, clinicians rely on “gestalt” in management decisions for children with CAP. We sought to determine the ability of clinician gestalt to predict severe outcomes.

METHODS:
We performed a prospective cohort study of children 3 months to 18 years old presenting to a pediatric emergency department (ED) with lower respiratory infection and receiving a chest radiograph for suspected CAP from 2013 to 2017. Clinicians reported the probability that the patient would develop severe complications of CAP (defined as respiratory failure, empyema or effusion, lung abscess or necrosis, metastatic infection, sepsis or septic shock, or death). The primary outcome was development of severe complications.

RESULTS:
Of 634 children, 37 (5.8%) developed severe complications. Of children developing severe complications after the ED visit, 62.1% were predicted as having &lt;10% risk by the ED clinician. Sensitivity was &gt;90% at the &lt;1% predicted risk threshold, whereas specificity was &gt;90% at the 10% risk threshold. Gestalt performance was poor in the low-intermediate predicted risk category (1%–10%). Clinicians had only fair ability to discriminate children developing complications from those who did not (area under the receiver operator characteristic curve 0.747), with worse performance from less experienced clinicians (area under the receiver operator characteristic curve 0.693).

CONCLUSIONS:
Clinicians have only fair ability to discriminate children with CAP who develop severe complications from those who do not. Clinician gestalt performs best at very low or higher predicted risk thresholds, yet many children fall in the low-moderate predicted risk range in which clinician gestalt is limited. Evidence-based prognostic tools likely can improve on clinician gestalt, particularly when risk is low-moderate.
Influence of indentation size and spacing on statistical phase analysis via high-speed nanoindentation mapping of metal alloys
Authors: Besharatloo Hossein , Wheeler Jeffrey M. 
Published: April 2021

Abstract
The development of high-speed nanoindentation has enabled the acquisition of mechanical property maps over square millimeters of area with micron-scale resolution in reasonable amounts of time. This provides rich datasets which contain morphological and statistical data on the variation of mechanical properties in a microstructure. However, the influences of the indentation size and the deconvolution method employed on the extracted phase properties remain unclear. In this work, a range of depth/spacing increments was explored on two different materials systems, an Al-Cu eutectic alloy and a duplex stainless steel, representing an ‘easy’ and a ‘hard’ case for statistical deconvolution, respectively. A total of ~ 500,000 indentations were performed. A variety of statistical analyses were then employed and compared: the 1D analysis of Ulm et al. using 2 and 3 phases, a 2D rotated Gaussian fit, K-means clustering, and a visual comparison to 2D histograms. This revealed several different sensitivities of the deconvolution methods to various types of error in phase identification.

Graphic abstract
Modification of the Epidermal Growth Factor Response by Ammonia in Renal Cell Hypertrophy
Authors: FRANCH HAROLD A. 
Published: April 2021

Abstract.
Epidermal growth factor (EGF) causes proliferation in renal tubular cells but, when it is combined with transforming growth factor-β1, it causes hypertrophy by a mechanism that requires the activity of the retinoblastoma family of proteins. In contrast, ammonia causes hypertrophy by decreasing lysosomal proteolysis; in some cell types, it also decreases cellular proliferation. These studies were designed to determine whether ammonia, like transforming growth factor-β1, could convert EGF-induced hyperplasia to hypertrophy. Cultured NRK-52E cells were incubated with EGF and/or ammonia and the protein/DNA ratio was measured, as a marker of hypertrophy. Addition of ammonia to EGF-treated NRK-52E cells converted EGF-induced hyperplasia to hypertrophy, because of a decrease in DNA synthesis. The mechanism involved no change in EGF-induced protein synthesis. Inhibition of lysosomal function with a proton pump inhibitor or lysosomal protease inhibitors also converted the response of EGF-treated cells to hypertrophy. Expression of the human papilloma virus 16 E7 protein (which inactivates all members of the retinoblastoma family) prevented ammonia from converting EGF-induced hyperplasia to hypertrophy. It is concluded that ammonia converts EGF-induced hyperplasia to hypertrophy by a mechanism that involves suppression of lysosomal function and this response can be blocked by inhibiting the activity of the retinoblastoma family of proteins.
Upregulation of CD14 and CD18 on Monocytes In Vitro by Antineutrophil Cytoplasmic Autoantibodies
Authors: NOWACK RAINER , SCHWALBE KATHARINA , FLORES-SUÁREZ LUIS-FELIPE , YARD BENITO , VAN DER WOUDE FOKKO J. 
Published: April 2021

Abstract.
The expression of CD14, CD18, and major histocompatibility complex II on unprimed monocytes from healthy donors after incubation with IgG from patients with antineutrophil cytoplasmic autoantibody (ANCA)-positive active Wegener's granulomatosis (n = 6) and microscopic polyangiitis (n = 6) in comparison with IgG from healthy controls (n = 6) was studied. Monocytes were incubated with IgG (100 μg/ml) at 37°C, and expression of antigens was measured by fluorescence-activated cell sorter after 18 h. Cytoplasmic ANCA (C-ANCA) IgG and perinuclear ANCA (P-ANCA) IgG in comparison with control IgG increased the expression of CD14 (49.2% [SD: 37, P < 0.001], and 55.8% [SD: 41, P < 0.05]) and CD18 (11.4% [SD: 18, P < 0.01] and 8% [SD: 26, P < 0.05]) but did not change the major histocompatibility complex II expression. Upregulation of CD14 started after 6 h and reached a peak after 10 to 14 h of incubation and was not inhibited by polymyxin B. F(ab)2 fragments of C- and P-ANCA IgG also increased expression of CD14 and CD18 as compared with control IgG F(ab)2, but for CD14 less than with complete IgG. ANCA IgG depleted of antiproteinase 3 and antimyeloperoxidase antibodies by immunoadsorption failed to upregulate CD14. Monoclonal murine antibodies against proteinase 3 and myeloperoxidase yielded a strong upregulation of CD14 when compared with an isotype control or human control IgG. The data show that CD14 and CD18 are upregulated on monocytes by C- and P-ANCA IgG in vitro, as well as by monoclonal antibodies against proteinase 3 and myeloperoxidase and that this effect is not dependent on Fcγ receptor crosslinking. Upregulation of CD14 and CD18 on monocytes by ANCA suggests a pathogenetic role of ANCA monocyte interactions in systemic vasculitis.
Expression of Advanced Glycation End Products and Their Cellular Receptor RAGE in Diabetic Nephropathy and Nondiabetic Renal Disease
Authors: TANJI NOZOMU , MARKOWITZ GLEN S. , FU CAIFENG , KISLINGER THOMAS , TAGUCHI AKIHIKO , PISCHETSRIEDER MONIKA , STERN DAVID , SCHMIDT ANN MARIE , D'AGATI VIVETTE D. 
Published: April 2021

Abstract.
Advanced glycation end products (AGE) contribute to diabetic tissue injury by two major mechanisms, i.e., the alteration of extracellular matrix architecture through nonenzymatic glycation, with formation of protein crosslinks, and the modulation of cellular functions through interactions with specific cell surface receptors, the best characterized of which is the receptor for AGE (RAGE). Recent evidence suggests that the AGE-RAGE interaction may also be promoted by inflammatory processes and oxidative cellular injury. To characterize the distributions of AGE and RAGE in diabetic kidneys and to determine their specificity for diabetic nephropathy, an immunohistochemical analysis of renal biopsies from patients with diabetic nephropathy (n = 26), hypertensive nephrosclerosis (n = 7), idiopathic focal segmental glomerulosclerosis (n = 11), focal sclerosis secondary to obesity (n = 7), and lupus nephritis (n = 11) and from normal control subjects (n = 2) was performed, using affinity-purified antibodies raised to RAGE and two subclasses of AGE, i.e., Nε
-(carboxymethyl)-lysine (CML) and pentosidine (PENT). AGE were detected equally in diffuse and nodular diabetic nephropathy. CML was the major AGE detected in diabetic mesangium (96%), glomerular basement membranes (GBM) (42%), tubular basement membranes (85%), and vessel walls (96%). In diabetic nephropathy, PENT was preferentially located in interstitial collagen (90%) and was less consistently observed in vessel walls (54%), mesangium (77%), GBM (4%), and tubular basement membranes (31%). RAGE was expressed on normal podocytes and was upregulated in diabetic nephropathy. The restriction of RAGE mRNA expression to glomeruli was confirmed by reverse transcription-PCR analysis of microdissected renal tissue compartments. The extent of mesangial and GBM immunoreactivity for CML, but not PENT, was correlated with the severity of diabetic glomerulosclerosis, as assessed pathologically. CML and PENT were also identified in areas of glomerulosclerosis and arteriosclerosis in idiopathic and secondary focal segmental glomerulosclerosis, hypertensive nephrosclerosis, and lupus nephritis. In active lupus nephritis, CML and PENT were detected in the proliferative glomerular tufts and crescents. In conclusion, CML is a major AGE in renal basement membranes in diabetic nephropathy, and its accumulation involves upregulation of RAGE on podocytes. AGE are also accumulated in acute inflammatory glomerulonephritis secondary to systemic lupus erythematosus, possibly via enzymatic oxidation of glomerular matrix proteins.
Evidence In Vivo Showing Increase of Baseline Nitric Oxide Generation and Impairment of Endothelium-Dependent Vasodilation in Normotensive Patients on Chronic Hemodialysis
Authors: PASSAUER JENS , BÜSSEMAKER ECKHART , RANGE URSULA , PLUG MARIA , GROSS PETER 
Published: April 2021

Abstract.
Cardiovascular mortality is excessive in hemodialyzed patients. Observations in atherosclerosis suggest that endothelial dysfunction and impaired nitric oxide (NO) may be involved. However, the relation of endothelial NO to its vascular effects has not been studied conclusively in uremia. Therefore, to study these questions an invasive technique was used in normotensive patients who were on hemodialysis (HD; n = 11) and in matched control subjects (n = 11). Pharmacologic agents were infused into the brachial artery to test the chain of events from NO generation to smooth muscle cell relaxation, measuring forearm blood flow by venous occlusion plethysmography. Glyceroltrinitrate (GTN 1:2.2 nmol/min; GTN 2:4.4; GTN 3:8.8), infused to establish the reaction of the vessel wall to defined doses of NO, caused a reduced response in HD patients (control subjects: 183 ± 20 [SEM], 246 ± 26, and 338 ± 29%; HD patients: 161 ± 7, 206 ± 12, and 262 ± 24%; baseline = 100% for each group, P = 0.032 by ANOVA). All subsequent data were corrected for this decreased response to defined doses of NO in HD patients. L-arginine (10 mg/min), given to exclude substrate deficiency of NO synthase (NOS), caused no significant changes (control subjects: 108 ± 4%; HD patients: 103 ± 4%; P = NS). Acetylcholine (ACH 1:55 nmol/min; ACH 2:110; ACH 3:220), infused to stimulate endothelial NOS, had a significantly reduced effect in HD patients (control subjects: 246 ± 32, 340 ± 40, and 465 ± 52%; HD patients: 251 ± 55, 244 ± 36, and 318 ± 50%; P = 0.002). N-monomethyl-L-arginine (LMA 1:1 μmol/min; LMA 2:2; LMA 3:4), given to block baseline NO generation, showed an enhanced response in HD patients (control subjects: 90 ± 2, 83 ± 2, and 74 ± 4%; HD patients: 84 ± 3, 73 ± 3, and 64 ± 4%; P = 0.037). Vascular response to three doses of norepinephrine (60, 120, and 240 pmol/min) was comparable in both groups, which indicated similar endothelium-independent vasoconstriction. In summary, in normotensive HD patients, (1) vasodilation to defined doses of exogenous NO was reduced, (2) there was no evidence of substrate deficiency of NOS, and (3) stimulation of NOS was impaired; however, (4) baseline NO generation was increased. It is concluded that in HD patients, the NO system has a reduced capacity to regulate vascular tone and this impairment is most significant under conditions of NOS stimulation.
Influence of Tacrolimus on Glucose Metabolism before and after Renal Transplantation
Authors: DUIJNHOVEN ELLY M. VAN , BOOTS JOHANNES M. M. , CHRISTIAANS MAARTEN H. L. , WOLFFENBUTTEL BRUCE H. R. , HOOFF JOHANNES P. VAN 
Published: April 2021

Abstract.
Most studies concerning the influence of tacrolimus on glucose metabolism have been performed either in animals or after organ transplantation. These clinical studies have largely been transversal with patients who were using steroids. Therefore, this prospective, longitudinal study investigated the influence of tacrolimus on glucose metabolism before and after transplantation. Eighteen Caucasian dialysis patients underwent an intravenous glucose tolerance test before and 5 d after the start of tacrolimus. Insulin sensitivity index (kG), insulin resistance (insulin/glucose ratio and homeostasis model assessment), and C-peptide and insulin secretion were calculated. Trough levels of tacrolimus were measured. After transplantation, the occurrence of posttransplantation diabetes mellitus (PTDM) was prospectively monitored. Statistical analysis was performed using the Wilcoxon signed ranks test and Spearman's rho for correlation. Before tacrolimus, kG was indeterminate in three patients. During tacrolimus, kG decreased in 16 of 18 patients, from a median of 1.74 mmol/L per min to 1.08 mmol/L per min (P < 0.0001). The correlation between C-peptide and insulin data was excellent. Insulin secretion decreased from 851.0 mU × min/L to 558.0 mU × min/L (P = 0.014), whereas insulin resistance did not change. Insulin sensitivity correlated negatively with tacrolimus trough level. After transplantation, three patients developed PTDM; before tacrolimus, two had an indeterminate and one a low normal kG. During tacrolimus administration, kG decreased in almost all patients as a result of a diminished insulin secretion response to a glucose load, whereas insulin resistance did not change. Patients with an abnormal or indeterminate kG seem to be at risk of developing PTDM while on tacrolimus.
Survival in Recipients of Marginal Cadaveric Donor Kidneys Compared with Other Recipients and Wait-Listed Transplant Candidates
Authors: OJO AKINLOLU O. , HANSON JULIE A. , MEIER-KRIESCHE HERWIG-ULF , OKECHUKWU CHIKE N. , WOLFE ROBERT A. , LEICHTMAN ALAN B. , AGODOA LAWRENCE Y. , KAPLAN BRUCE , PORT FRIEDRICH K. 
Published: April 2021

Abstract.
An increasing number of cadaveric kidney transplants are now performed with organs from donors who would have been deemed unsuitable in earlier times. Although good allograft outcomes have been obtained with these marginal donor transplants, it is unclear whether recipients of marginal kidney transplants achieve a reduction in long-term mortality as do recipients of “ideal” kidneys. Patients with end-stage renal disease registered on the cadaveric renal transplant waiting list between January 1, 1992, and June 30, 1997, were studied for mortality risks according to three outcomes: wait-listed on dialysis treatment with no transplant (WLD); transplantation with marginal donor kidney (MDK); and “ideal” or optimal donor kidney transplantation (IDK). Thirty-four percent of wait-list registrants had received a cadaveric kidney transplant by June 30, 1998. Of these, 18% received a marginal kidney that had one or more of the following pretransplant factors: donor age >55 yr, non-heartbeating donor, cold ischemia time >36 h, and donor hypertension or diabetes mellitus of > 10 yr duration. Five-year graft and patient survival was 53% and 74% for MDK recipients compared with 67% (P < 0.001) and 80% (P < 0.001) for IDK recipients. Adjusted annual death rate and estimated remaining life time was 6.3%, 4.7%, and 3.3% and 15.3 yr, 20.4 yr, and 28.7 yr for WLD, MDK, and IDK groups, respectively. The average increase in life expectancy for MDK recipients compared with the WLD cohort was 5 yr, although this benefit varied from 3 to 10 yr depending on the recipient's characteristics. It is concluded that transplantation of a marginal kidney is associated with a significant survival benefit when compared with maintenance dialysis.
Functional, Molecular, and Biochemical Characterization of Streptozotocin-Induced Diabetes
Authors: WARD DONALD T. , YAU S. KAM , MEE ANDREW P. , MAWER E. BARBARA , MILLER CHRISTOPHER A. , GARLAND HUGH O. , RICCARDI DANIELA 
Published: April 2021

Abstract.
Altered divalent cation homeostasis with bone mineral loss, hypercalciuria, and hypomagnesemia have been associated consistently with human diabetes mellitus. This study investigated functional, molecular, and biochemical determinants that accompany this condition in chronically (2 wk) streptozotocin (STZ)-diabetic rats. Catheterized, conscious, diabetic rats on servo-controlled fluid replacement exhibited an increased GFR (+70%) and a substantially raised urinary calcium output (+568%) when compared with control rats. In addition, fractional calcium reabsorption was reduced, indicating that the hypercalciuria was not due solely to an osmotic effect but may involve an actual tubular defect. The expression of proteins involved in renal distal Ca2+ and water transport in STZ-diabetic rats were then studied by Western analysis and immunofluorescence microscopy to investigate the molecular basis of the hypercalciuria. Extracellular Ca2+-sensing receptor abundance was reduced to 52% of control in STZ-diabetes, whereas thiazide-sensitive NaCl cotransporter expression was increased by 192%. Subcutaneous insulin implant rectified both functional and molecular parameters. The levels of calbindin D28k, plasma membrane Ca2+ ATPase, and aquaporin 1 in whole kidney and of aquaporin 2 in inner medulla were unchanged in diabetic and/or insulin replacement. Blood levels of 1,25(OH)2D3 were reduced in diabetes as were levels of osteocalcin, a marker of bone formation. It is concluded that diabetic hypercalciuria in rats involves elevated GFR with raised urinary output, reduced Ca2+ reabsorption, and impaired bone deposition. Changes in Ca2+-sensing receptor and NaCl cotransporter protein expression could account for the altered divalent cation homeostasis seen during diabetes mellitus.
Detection of Verocytotoxin Bound to Circulating Polymorphonuclear Leukocytes of Patients with Hemolytic Uremic Syndrome
Authors: TE LOO D. MAROESKA W. M. , HINSBERGH VICTOR W. M. VAN , HEUVEL LAMBERTUS P. W. J. VAN DEN , MONNENS LEO A. H. 
Published: April 2021

Abstract.
The epidemic form of hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in children and is characterized by a prodromal phase of sometimes bloody diarrhea. The role of verocytotoxin (VT)-producing Escherichia coli has been strongly implicated. Although antibodies against VT have been detected in the serum of patients with HUS, VT itself has never been detected in circulating blood. In this study, VT-2 was detected in the systemic circulation in 9 of 10 patients with the epidemic form of HUS. In those cases, VT-2 was bound exclusively to polymorphonuclear leukocytes (PMN). The detection of VT-2 bound to PMN was associated with the presence of diarrhea at the time the blood samples were obtained. The one patient for whom VT was not detected presented with atypical HUS. For 5 of the 10 patients with HUS who were studied, the time course of VT binding was analyzed; binding decreased in four patients. The finding of VT bound to PMN in the systemic circulation of patients with HUS is important for a clearer understanding of the pathogenesis of HUS and suggests new approaches for treatment in the future.
Is C-Reactive Protein a Useful Predictor of Outcome in Peritoneal Dialysis Patients?
Authors: HERZIG KAREN ANN , PURDIE DAVID MICHAEL , CHANG WENDY , BROWN ALLISON MARGARET , HAWLEY CARMEL MARY , CAMPBELL SCOTT BRYAN , STURTEVANT JOANNA MARY , ISBEL NICOLE MAREE , NICOL DAVID LAWRENCE , JOHNSON DAVID WAYNE 
Published: April 2021

Abstract.
An elevated C-reactive protein (CRP) has recently been shown to be strongly predictive of mortality in hemodialysis patients. However, its predictive value in peritoneal dialysis (PD) patients has not been assessed. A cohort of 50 PD patients was followed prospectively for a 3-yr period, after initial determination of CRP. Patients with an elevated CRP (>6 mg/L; n = 29) had significantly reduced plasma prealbumin (0.36 ± 0.02 versus 0.44 ± 0.03 g/L; P < 0.05), decreased total weekly creatinine clearance (CCr; 52.5 ± 2.3 versus 63.1 ± 3.2 L/1.73 m2; P < 0.01), and increased left ventricular thickness (1.24 ± 0.05 versus 1.08 ± 0.06 cm; P < 0.05) at baseline compared with those who had a normal CRP (≤6 mg/L; n = 21). Baseline CRP (log-transformed) correlated weakly with baseline Kt/V, CCr, and pre-albumin. With the use of a multivariate Cox's proportional hazards model to adjust for potential confounding factors, an elevated CRP was predictive of myocardial infarction (adjusted hazard ratio, 4.8; 95% confidence interval [CI], 1.0 to 23; P = 0.048) and tended to be predictive of fatal myocardial infarction (adjusted hazard ratio, 6.0; 95% CI, 0.8 to 43; P = 0.07). However, CRP was not significantly associated with all-cause mortality (adjusted hazard ratio, 2.1; 95% CI,0.8 to 5.4; P = 0.15). In conclusion, CRP elevation occurs in a substantial proportion of PD patients and is independently predictive of future myocardial infarction. Such patients may warrant closer monitoring and attention to modifiable cardiovascular risk factors.