Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical outcomes during the first three months posttransplant in renal allograft recipients managed by C2 monitoring of cyclosporine microemulsion

Background. MO2ART (monitoring of 2-hr absorption in renal transplantation) is the first prospective, multicenter trial of cyclosporine (CsA) blood level 2 hr postdose (C2) monitoring in de novo kidney recipients receiving CsA microemulsion (ME) (Neoral; Novartis, Basel, Switzerland). Efficacy and safety results from the first 3 months are presented here. Methods. MO2ART is a 12-month, open-label, randomized study involving 296 patients. In all patients, the dose of CsA-ME was adjusted to achieve protocol-defined C2 targets of 1.6 to 2.0 &mgr;g/mL for the first month, with subsequent tapering. Randomization into two target groups occurred at 3 months. All patients received steroids and mycophenolate mofetil (89%) or azathioprine. For patients with delayed graft function, the protocol permitted reduced C2 targets and prophylactic administration of antibodies. Results. At 3 months, overall incidence of biopsy-proven acute rejection was 11.5%. Median serum creatinine was 132 &mgr;mol/L. Patient and graft survival were 96.6% and 91.2%, respectively. C2 levels greater than 1.6 &mgr;g/mL were achieved within 5 days by 60.6% of patients with immediate graft function and 19.5% of patients with delayed graft function. Prophylactic antibodies were used in 15% of the total population. Twenty-four patients (8.1%) experienced serious adverse events with a suspected relation to CsA, and 26 patients (8.8%) discontinued the study because of adverse events (n=15) or after a switch in immunosuppression after rejection episodes (n=11). Conclusions. Patient management by C2 monitoring resulted in a low incidence of biopsy-proven acute rejection in standard risk de novo kidney recipients, 85% of whom did not receive prophylactic antibodies. CsA-ME with C2 monitoring provides excellent short-term efficacy and safety among de novo renal transplant patients.
The dynamics of international strategic alliances : A study of freight transport companies

Strategic alliances have historically been an important way of internationalizing for transport companies, in part because of the rules and regulations governing transportation and transport companies in different countries. Another important reason is the necessity to access domestic networks for transport in foreign countries. Transport companies, therefore, have a history of forming, developing, and even breaking strategic alliances, usually with other transport companies. As many countries have deregulated or harmonized their rules and regulations concerning transport, conditions have changed. Furthermore, the manufacturing industry has developed its own international networks of distributors, sales, and production subsidiaries. Today, many industrial production subsidiaries are large autonomous units that are going through their own process of internationalization.
Induction of P-Glycoprotein by Antiretroviral Drugs in Human Brain Microvessel Endothelial Cells

ABSTRACT The membrane-associated drug transporter P-glycoprotein (P-gp) plays an essential role in drug efflux from the brain. Induction of this protein at the blood-brain barrier (BBB) could further affect the ability of a drug to enter the brain. At present, P-gp induction mediated by antiretroviral drugs at the BBB has not been fully investigated. Since P-gp expression is regulated by ligand-activated nuclear receptors, i.e., human pregnane X receptor (hPXR) and human constitutive androstane receptor (hCAR), these receptors could represent potential pathways involved in P-gp induction by antiretroviral drugs. The aims of this study were (i) to determine whether antiretroviral drugs currently used in HIV pharmacotherapy are ligands for hPXR or hCAR and (ii) to examine P-gp function and expression in human brain microvessel endothelial cells treated with antiretroviral drugs identified as ligands of hPXR and/or hCAR. Luciferase reporter gene assays were performed to examine the activation of hPXR and hCAR by antiretroviral drugs. The hCMEC/D3 cell line, which is known to display several morphological and biochemical properties of the BBB in humans, was used to examine P-gp induction following 72 h of exposure to these agents. Amprenavir, atazanavir, darunavir, efavirenz, ritonavir, and lopinavir were found to activate hPXR, whereas abacavir, efavirenz, and nevirapine were found to activate hCAR. P-gp expression and function were significantly induced in hCMEC/D3 cells treated with these drugs at clinical concentrations in plasma. Together, our data suggest that P-gp induction could occur at the BBB during chronic treatment with antiretroviral drugs identified as ligands of hPXR and/or hCAR.
Metabolism of Compound A by Renal Cysteine-S-Conjugate beta-Lyase Is Not the Mechanism of Compound A-Induced Renal Injury in the Rat

Compound A [CF2 double bond C(CF3)OCH2 F], a vinyl ether produced by CO2 absorbents acting on sevoflurane, can produce corticomedullary junction necrosis (injury to the outer stripe of the outer medullary layer, i.e., corticomedullary junction) in rats. Several halogenated alkenes produce a histologically similar corticomedullary necrosis by converting glutathione conjugates of these alkenes to halothionoacetyl halides. To test whether this mechanism explained the nephrotoxicity of Compound A, we blocked three metabolic steps which would lead to formation of a halothionoacetyl halide: 1) we depleted glutathione by administering dl-buthionine-S,R-sulfoximine (BSO); 2) we blocked cysteine S-conjugate formation by administering acivicin (AT-125); and 3) we inhibited subsequent metabolism by renal cysteine conjugate beta-lyase to the nephrotoxic halothionoacetyl halides by administering aminooxyacetic acid (AOAA). These treatments were given alone or in combination to separate groups of 10 or 20 Wistar rats before their exposure to Compound A. We hypothesized that blocking these metabolic steps should decrease the injury produced by breathing 150 ppm of Compound A for 3 h. However, we found either no change or an increase in renal injury, suggesting that this pathway mediates detoxification rather than toxicity. Our findings suggest that the cysteine-S-conjugate-mediated pathway is not the mechanism of Compound A nephrotoxicity and, therefore, observed interspecies differences in the activity of this activating pathway may not be relevant in the prediction of the nephrotoxic potential of Compound A in clinical practice. (Anesth Analg 1996;82:770-4)
Long-term results of the first 500 cases of acoustic neuroma surgery.

OBJECTIVE This retrospective study focuses on 2 outcome results after surgical intervention for acoustic neuroma: (1) facial nerve status, and (2) hearing preservation. STUDY DESIGN A total of 484 patients with an acoustic neuroma. RESULTS Postoperative facial nerve outcomes were significantly different (P < 0.001) according to the size of the tumors. Tumor size had even more influence on the immediate postoperative results. In addition, statistical significance (P < 0.05) was demonstrated in comparing facial nerve outcomes with the surgeon's surgical experience. We also noted that as the patient's age increases, the likelihood for facial dysfunction may increase for all postoperative intervals. The overall success rate of retaining useful hearing was 27% (26 of 95). Class A hearing was retained in 66% (10 of 15) of cases operated on through middle fossa approach in the last 5 years. CONCLUSION This study demonstrates that tumor size and surgeon's experience are the most significant factors influencing the facial nerve status and hearing outcome after removal of acoustic neuroma.
A comparative study of spray keratinocytes and autologous meshed split-thickness skin graft in the treatment of acute burn injuries.

BACKGROUND ReCell (Avita Medical, Northridge, CA) is an autologous cell harvesting (ACH) device that enables a thin split-thickness skin biopsy to be processed to produce a cell population that includes a mixed population of keratinocytes, melanocytes, Langerhans cells, and papillary dermal fibroblasts for immediate delivery via a spray applicator onto a prepared skin surface. MATERIALS AND METHODS In this Institutional Review Board-approved US Food and Drug Administration phase 2 study, the authors prospectively evaluated the treatment of partial-thickness burns in patients with two 320 cm2 areas, 1 area treated with the ACH device and the other with a meshed split-thickness skin graft (MSTSG) as a control. The authors compared the treatment areas for graft take, pigmentation, and color match to surrounding healthy tissue, scarring, and pain. RESULTS In this preliminary study, 10 patients were treated with this protocol. Eight patients had 100% take to both treatment areas and 2 patients had significant non-take and graft loss attributable to underexcised wound beds and difficulty with the spray applicator. Pigmentation and color match ratings were identical at week 52 and the Modified Vancouver Scar Scale scores were comparable. One subject rated the autologous cell harvesting site as having a better appearance, while the remaining subjects rated their ACH and MSTSG sites' appearances as being comparable. In early follow-up visits, pain ratings were slightly elevated in the ACH group due to graft healing; however, in visits following week 2, pain ratings at the ACH and MSTSG sites were rated similarly by all patients. CONCLUSION This preliminary report describes an early experience with the ACH device and the treatment of partial-thickness burn injuries. In this 10-patient series, patients benefitted from having a decreased donor site size and comparable outcomes with MSTSG treatment. While this preliminary underpowered study has provided positive results, there is a learning curve with choosing the proper wound for treatment with the ACH device, as well as with using the device.
Forecasting Effectiveness of Foreign Currency Futures

While numerous articles [2,3,4] report empirical evidence on the relationships be tween forward and spot foreign currency exchange markets, little work [5] exists on the value of the future currency exchange market as a source of information on future spot rates. Both forward and futures mar kets are used to reduce risk in foreign cur rency holdings; however, structural differ ences between the future and forward currency markets may result in their differ ing in forecasting performance. In addition within the existing futures market, different currencies may vary in their forecasting ef ficiency. In this paper the effectiveness of the futures currency market in forecasting fu ture spot rates is analyzed for five curren cies. Results indicate that with some minor exceptions rates in the foreign currency fu tures market are on average unbiased fore casts of the future spot rates and exhibit lower degrees of forecast efficiency the longer the forecast horizon.
Programmed death‐1 receptor and interleukin‐10 in liver transplant recipients at high risk for late cytomegalovirus disease

A. Krishnan, W. Zhou, S.F. Lacey, A.P. Limaye, D.J. Diamond, C. La Rosa. Programmed death‐1 receptor and interleukin‐10 in liver transplant recipients at high risk for late cytomegalovirus disease. Transpl Infect Dis 2010: 12: 363–370. All rights reserved
Replication Stress-Induced Chromosome Breakage Is Correlated with Replication Fork Progression and Is Preceded by Single-Stranded DNA Formation

Chromosome breakage as a result of replication stress has been hypothesized to be the direct consequence of defective replication fork progression, or “collapsed” replication forks. However, direct and genome-wide evidence that collapsed replication forks give rise to chromosome breakage is still lacking. Previously we showed that a yeast replication checkpoint mutant mec1-1, after transient exposure to replication impediment imposed by hydroxyurea (HU), failed to complete DNA replication, accumulated single-stranded DNA (ssDNA) at the replication forks, and fragmented its chromosomes. In this study, by following replication fork progression genome-wide via ssDNA detection and by direct mapping of chromosome breakage after HU exposure, we have tested the hypothesis that the chromosome breakage in mec1 cells occurs at collapsed replication forks. We demonstrate that sites of chromosome breakage indeed correlate with replication fork locations. Moreover, ssDNA can be detected prior to chromosome breakage, suggesting that ssDNA accumulation is the common precursor to double strand breaks at collapsed replication forks.
MULTIPLE DONOR ALLOTRANSPLANTATION: A NEW APPROACH TO PANCREATIC ISLET TRANSPLANTATION

Currently it is not feasible to isolate sufficient numbers of islets from a single pancreas for clinical transplantation. We examined whether small numbers of islets obtained from multiple donors could be used for transplantation. Islets were isolated from four inbred strains of mice (DBA/2, DBA/1, C3H, and A.SW) by a stationary collagenase digestion and Ficoll separation and transplanted into the renal subcapsular space of spreptozotocin-induced diabetic B6AF1 mice. At least 200 handpicked islets were required to produce nor-moglycemia in syngeneic and allogeneic diabetic recipient mice. None of the mice given 50 islets became normoglycemic within 2 weeks postgrafting. When various numbers of purified islets from a single donor were transplanted, the survival was significantly better for 200-islet allografts than for 800-islet and 400-islet allografts. When a 200-islet composite graft was prepared from four donors (50 fresh handpicked islets from each donor), the survival of the composite graft as measured by sustained normoglycemia in nonimmunosuppressed recipients was dramatic, with 17 of 18 recipients maintaining normoglycemia indefinitely (>200 days). Similarly, when islets isolated from four donors and cultured for various periods were mixed and transplanted (200 islets/recipient) all recipient mice (n=8) enjoyed indefinite graft survival. Use of higher numbers of purified islets or crude islets in a composite multiple-donor islet allograft was less effective in achieving indefinite graft survival. Thus, transplantation of a composite graft made up with subtherapeutic numbers of islets from multiple histoincompatible donors to provide adequate therapeutic numbers is a practical solution to the lack of islet availability. In addition, composite islet grafts appear to possess immunological advantages, with significantly prolonged survival over that produced by single-donor islet grafts.
5-Aza-2'-Deoxycytidine and CDDP Synergistically Induce Apoptosis in Renal Carcinoma Cells via Enhancing the APAF-1 Activity.

BACKGROUND It has been reported that the hypermethylation of APAF-1, DAPK-1 and other tumor suppressive genes (TSGs) correlates with progression of renal cell carcinoma and exerts prognostic and diagnostic relevance in renal cell carcinoma. A recent study has confirmed that demethylation regulates the TSGs expression and proliferation of various types of cancer cells. The present study was to recognize a potential anti-tumor effect of 5-aza-2'-deoxycytidine (DAC), a demethylation agent. METHODS We evaluated the DNA demethylation by DAC in human renal carcinoma cells and determined the synergism of the demethylation with the toxicity of Cisplatin (CDDP), which is a commonly utilized anti-tumor agent for renal carcinoma. RESULTS It was demonstrated that DAC promoted a significant global genomic demethylation and improved APAF-1 expression at both mRNA and protein levels. The DAC treatment deteriorated the CDDP-induced viability decreasing Caki or ACHN cells and synergized the apoptosis induction of CDDP in ACHN cells. The treatment with both DAC and CDDP promoted a significantly higher level of renal carcinoma cell apoptosis than singular DAC or CDDP treatment. The APAF-1 knockdown significantly inhibited the synergism of DAC with the CDDP-induced apoptosis in ACHN cells. CONCLUSIONS The present study confirmed that DAC demethylated the CpGs, particularly APAF-1 in renal carcinoma cells, and that the demethylation synergized the cytotoxity of CDDP in renal carcinoma cells via enhancing the CDDP-induced apoptosis.
Pre-exercise carbohydrate and fluid ingestion: influence of glycemic response on 10-km treadmill running performance in the heat.

BACKGROUND The purpose of this study was to determine the influence of ingesting solutions containing mixtures of carbohydrate (CHO) types on pre-exercise glycemic response, exercise-induced hypoglycemia, metabolic responses, and 10-km treadmill running performance in a warm environment. METHODS Ten trained runners completed 6, self-paced 10-km treadmill runs one hour after ingesting 900 ml of one of the following test solutions: a water placebo (WP), an 8 g 100 ml-1 high fructose corn syrup solution (HFG; 72 g CHO), a 6 g 100 ml-1 glucose solution (GLU; 54 g CHO), a 6 g.100 ml-1 sucrose/glucose mixture (SUG; 54 g CHO), or banana with water to equal 900 ml (BAN; approx. 54 g CHO). The sixth condition was 675 ml of an 8 g.100 ml-1 HFCS solution (LFG; 54 g CHO). Blood samples were taken prior to ingestion and every 15 min during rest and at 15 and 30 min, and at the end of the 10-km run. Blood was analyzed for glucose (BG) insulin (IN), glycerol, lactate, and percent change in plasma volume. Urine volume during the 1 hour of rest and change in body mass during exercise were also determined. RESULTS A significant (p < 0.05) correlation (r = -0.684) was seen between the pre-exercise glycemic response (PEGR = area under the resting BG curve) and the change in BG from pre-EX to 15 min of exercise. BG at 15 min of exercise was significantly higher in the WP (5.22 mM) versus the other conditions (HFG = 3.32, LFG = 3.91, GLU = 3.38, BAN = 3.74 & SUG = 3.63 mM). Pre-exercise IN was lower in the WP (6.54 U ml-1) condition versus the other conditions (HFG = 22.1, LFG = 16.2, GLU = 23.3, BAN = 18.8 & SUG = 12.8 U.ml-1). Ten km performance times were not different (WP = 41.87, HFG = 41.66, LFG = 41.79, GLU = 41.65, BAN = 41.53, and SUG = 41.75 min). A significantly greater body mass loss occurred due to urine production during the 60 min of rest in the WP compared to the other conditions. The degree of exercise-induced decline in blood glucose was related to the PEGR; however, the decline in BG did not affect 10-km running performance. In addition, there were no differences in the metabolic responses during exercise between the different CHO types, nor did the type of CHO influence running performance. Finally, the presence of CHO and/or electrolytes in the hydration solutions produced a better fluid retention during the 60-min pre-exercise rest period compared to water. CONCLUSIONS The results confirmed that if a competitive athlete consumed a breakfast prior to ingesting a CHO-electrolyte beverage, a practice that is common, the glycemic responses may be different.
Colon injury after blunt abdominal trauma: results of the EAST Multi-Institutional Hollow Viscus Injury Study.

BACKGROUND Blunt injury to the colon is rare. Few studies of adequate size and design exist to allow clinically useful conclusions. The Eastern Association for the Surgery of Trauma Multi-institutional Hollow Viscus Injury (HVI) Study presents a unique opportunity to definitively study these injuries. METHODS Patients with blunt HVI were identified from the registries of 95 trauma centers over 2 years (1998-1999). Patients with colon injuries (cases) were compared with blunt trauma patient undergoing a negative laparotomy (controls). Data were abstracted by chart review. RESULTS Of the 227,972 patients represented, 2,632 (1.0%) had an HVI and 798 had a colonic/rectal injury (0.3%). Of patients diagnosed with HVI, 30.2% had a colon injury. No physical findings or imaging modalities were able to discriminate colonic injury. Logistic regression modeling yielded no clinically useful combination of findings that would reliably predict colonic injury. In patients undergoing laparotomy, presence of colon injury was associated with a higher risk of some complications but not mortality. Colon injury was associated with increased hospital (17.4 vs. 13.1, p < 0.001) and intensive care unit (9.7 vs. 6.9, p = 0.003) length of stay. Almost all colon patients (92.0%) underwent laparotomy within 24 hours of injury. CONCLUSION Colonic injury after blunt trauma is rare and difficult to diagnose. No diagnostic test or combination of findings reliably excluded blunt colonic injury. Despite the inadequacy of current diagnostic tests, almost all patients with colonic injury were taken to the operating room within 24 hours. Even with relatively prompt surgery, patients with colon injury were at significantly higher risk for serious complications and increased length of stay. In contrast to small bowel perforation, delay in operative intervention appears to be less common but is still associated with serious morbidity.
Secondary electron yield measurements from materials with application to collectors of high-power microwave devices

An experimental test facility has been established for measuring the secondary electron yield (SEY) of materials thought to be suitable for low yield vacuum electronic applications such as collectors in high-power microwave (HPM) tubes. Experiments can be broadly divided into two energy-regimes: a high-energy (1-50 keV) and a low-energy (10 eV-1 keV) regime. Measurements of SEY at high energies are presented for the following materials: copper, titanium, and Poco graphite. Observation of time-dependent SEY behavior in these samples suggests that surface processes play an important role during measurements. In addition, SEY at low energies and as a function of the angle of incidence of primary electrons has been measured for plasma sprayed boron carbide (PSBC). The experimental results presented here are benchmarked with existing SEY data in the literature, empirically and to first principle formulae
Prevalence of refractive errors in schoolchildren ranging from 6 to 18 years of age.

PURPOSE The aim of the paper was to study the prevalence of myopia, hyperopia and astigmatism in schoolchildren ranging from 6-18 years of age. MATERIAL AND METHODS 5724 children from elementary schools, junior high schools and high schools were examined (2765 boys and 2959 girls, aged 6-18 years, mean age 11.7, SD = 3.2). The examined students were Caucasian and resided in and around Szczecin, Poland. The examination included retinoscopy under cycloplegia. The refractive error readings were expressed as the spherical equivalent (SE). Myopia was defined as SE of at least -0.5 D, hyperopia as SE of at least +1.0 D. Astigmatism was diagnosed when the difference in the refraction of axes in one eye was greater than 0.5 DC. The statistical analysis of data was performed by calculating the linear correlation coefficients and the coefficients for the regression equation. Additionally, Spearman's rank correlation coefficient was calculated. P values of less than 0.05 were considered statistically significant. RESULTS It was observed that 13% of Polish students in the age group from 6 to 18 were myopic, 38% of students were hyperopic and 4% were astigmatic. Besides, a positive correlation was found between the prevalence of myopia and age (p <0.001) as well as a negative correlation between prevalence of hyperopia and age (p < 0.001). An association between the prevalence of astigmatism and age was not observed.