Background: High mobility group box 1 (HMGB1), soluble receptor of advanced glycation end products (sRAGE) and programmed cell death markers PD-1 and PD-L1 are immunogenic serum biomarkers that may ...serve as novel diagnostic tools for cancer diagnosis. Methods: We investigated the four markers in sera of 231 women, among them 76 with ovarian cancer, 87 with benign diseases and 68 healthy controls, using enzyme immunoassays. Discrimination between groups was calculated using receiver operating characteristic (ROC) curves and sensitivities at fixed 90% and 95% specificities. Results: HMGB1 levels were significantly elevated and sRAGE levels were decreased in cancer patients as compared to benign and healthy controls. In consequence, the ratio of HMGB1 and sRAGE discriminated best between diagnostic groups. The areas under the curve (AUCs) of the ROC curves for differentiation of cancer vs. healthy were 0.77 for HMGB1, 0.65 for sRAGE and 0.78 for the HMGB1/sRAGE ratio, and slightly lower for the differentiation of cancer vs. benigns with 0.72 for HMGB1, 0.61 for sRAGE and 0.74 for the ratio of both. The highest sensitivities for cancer detection at 90% specificity versus benign diseases were achieved using HMGB1 with 41.3% and the HMGB1/sRAGE ratio with 39.2%, followed by sRAGE with 18.9%. PD-1 showed only minor and PD-L1 no power for discrimination between ovarian cancer and benign diseases. Conclusion: HMGB1 and sRAGE have differential diagnostic potential for ovarian cancer detection and warrant inclusion in further validation studies.
Summary Despite the clinical significance of complications due to intravascular catheters, the inappropriate use of intravascular catheters in hospitalised patients has not been adequately ...characterised. The objective of this prospective observational study was to develop definitions for appropriate intravascular device use, to estimate the frequency of inappropriate use of intravascular devices, and to examine risk factors and outcomes associated with inappropriate use in hospitalised patients. Among 436 patients admitted between October and December 2007, a total of 2909 hospitalisation days and use of 876 intravascular devices was observed. Of the 3806 total catheter-days recorded, 1179 (31%) were found to be inappropriate based on the study criteria. Logistic regression analysis indicated that age, total number of catheters used and total duration of catheterisation were risk factors for inappropriate device use ( P < 0.05). Inappropriate usage was strongly associated with increased intensive care unit admission ( P < 0.05) and length of hospital stay (4.9 ± 4.3 days for appropriate vs 8.5 ± 12.6 days for inappropriate; P < 0.05). Use of central venous catheters was not a predictor for inappropriate device use. Inappropriate intravascular device use is a very common phenomenon in hospitalised patients and is strongly linked to adverse device-related outcomes. These results may be used to develop strategies to systematically reduce excessive intravascular device use which would be expected to reduce adverse events associated with morbidity, mortality, and excess healthcare costs.
Background. Liver biopsy remains critical for staging liver disease in hepatitis C virus (HSV)—infected persons, but is a bottleneck to evaluation, follow-up, and treatment of HCV. Our analysis ...sought to validate APRI (aspartate aminotransferase AST—to-platelet ratio index) and FIB-4, an index from serum fibrosis markers (alanine aminotransferase ALT, AST, and platelets plus patient age) to stage liver disease. Methods. Biopsy results from HCV patients in the Chronic Hepatitis Cohort Study were mapped to an F0–F4 equivalent scale; APRI and FIB-4 scores at the time of biopsy were then mapped to the same scale. Results. We identified 2372 liver biopsies from HCV-infected patients with contemporaneous laboratory values for imputing APRI and FIB-4. Fibrosis stage distributions by the equivalent biopsy scale were 267 (11%) F0; 555 (23%) F1; 648 (27%) F2; 394 (17%) F3; and 508 (21%) F4. Mean APRI and FIB-4 values significantly increased with successive fibrosis levels (P < .05). The areas under the receiver operating characteristic curve (AUROC) analysis distinguishing severe (F3–F4) from mild-to-moderate fibrosis (F0–F2) were 0.80 (95% confidence interval CI, .78–.82) for APRI and 0.83 (95% CI, .81–.85) for FIB-4. There was a significant difference between the AUROCs of FIB-4 and APRI (P < .001); 88% of persons who had a FIB-4 score ≥2.0 were at stage F2 or higher. Conclusions. In a large observational cohort, FIB-4 was good at differentiating 5 stages of chronic HCV infection. It can be useful in screening patients who need biopsy and therapy, for monitoring patients with less advanced disease, and for longitudinal studies.
Background: Nowadays there still is no sufficient screening tool for ovarian and uterine cancer. Objective: The current study aimed to investigate whether cancer antigen 125 (CA-125), tissue ...polypeptide antigen (TPA) or the combination of both markers are able to act as screening tools for ovarian or uterine cancer. Methods: A total of 275 blood samples from different cohorts (ovarian cancer, uterine cancer, benign control group) were prospectively drawn and analyzed. Results: Established biomarkers TPA and CA-125 showed elevated serum concentrations in patients with malignant tumors as compared to healthy women and women with benign diseases. In ROC curve analyses, both biomarkers were well able to discriminate between malignant and healthy, benign or overall non-malignant cases in the whole sample, with AUCs of 0.842 and above. While TPA was the best diagnostic marker in patients with uterine cancer, CA 125 was the best in patients with ovarian cancer. Conclusions: TPA and CA-125 both showed promising results for the detection of gynecologic malignancies. The combination of CA-125 and TPA did not improve sensitivity in comparison to single markers.
The saeRS two-component regulatory system regulates transcription of multiple virulence factors in Staphylococcus aureus. In the present study, we demonstrated that the saePQRS region in ...Staphylococcus epidermidis is transcriptionally regulated in a temporal manner and is arranged in a manner similar to that previously described for S. aureus. Studies using a mouse foreign body infection model demonstrated that the virulence of strain 1457 and the virulence of a mutant, strain 1457 saeR, were statistically equivalent. However, histological analyses suggested that the polymorphonuclear neutrophil response at 2 days postinfection was significantly greater in 1457-infected mice than in 1457 saeR-infected mice, demonstrating that SaeR influences the early, acute phases of infection. Microarray analysis demonstrated that a saeR mutation affected the transcription of 65 genes (37 genes were upregulated and 28 genes were downregulated); in particular, 8 genes that facilitate growth under anaerobic conditions were downregulated in 1457 saeR. Analysis of growth under anaerobic conditions demonstrated that 1457 saeR had a decreased growth rate compared to 1457. Further metabolic experiments demonstrated that 1457 saeR had a reduced capacity to utilize nitrate as a terminal electron acceptor and exhibited increased production of lactic acid in comparison to 1457. These data suggest that in S. epidermidis SaeR functions to regulate the transition between aerobic growth and anaerobic growth. In addition, when grown anaerobically, 1457 saeR appeared to compensate for the redox imbalance created by the lack of electron transport-mediated oxidation of NADH to NAD⁺ by increasing lactate dehydrogenase activity and the subsequent oxidation of NADH.
Background and purpose
It is unknown whether changes to the peripheral nervous system following spinal cord injury (SCI) are relevant for functional recovery or the development of neuropathic pain ...below the level of injury. Magnetic resonance neurography (MRN) at 3 T allows detection and localization of structural and functional nerve damage. This study aimed to combine MRN and clinical assessments in individuals with chronic SCI and nondisabled controls.
Methods
Twenty participants with chronic SCI and 20 controls matched for gender, age, and body mass index underwent MRN of the L5 dorsal root ganglia (DRG) and the sciatic nerve. DRG volume, sciatic nerve mean cross‐sectional area (CSA), fascicular lesion load, and fractional anisotropy (FA), a marker for functional nerve integrity, were calculated. Results were correlated with clinical assessments and nerve conduction studies.
Results
Sciatic nerve CSA and lesion load were higher (21.29 ± 5.82 mm2 vs. 14.08 ± 4.62 mm2, p < 0.001; and 8.70 ± 7.47% vs. 3.60 ± 2.45%, p < 0.001) in individuals with SCI compared to controls, whereas FA was lower (0.55 ± 0.11 vs. 0.63 ± 0.08, p = 0.022). DRG volumes were larger in individuals with SCI who suffered from neuropathic pain compared to those without neuropathic pain (223.7 ± 53.08 mm3 vs. 159.7 ± 55.66 mm3, p = 0.043). Sciatic MRN parameters correlated with electrophysiological results but did not correlate with the extent of myelopathy or clinical severity of SCI.
Conclusions
Individuals with chronic SCI are subject to a decline of structural peripheral nerve integrity that may occur independently from the clinical severity of SCI. Larger volumes of DRG in SCI with neuropathic pain support existing evidence from animal studies on SCI‐related neuropathic pain.
1 Department of Kinesiology and Health, Georgia State University, Atlanta, Georgia; and
2 School of Applied Physiology, Georgia Institute of Technology, Atlanta, Georgia
Submitted 14 August 2009
; ...accepted in final form 15 November 2009
Junctophilins (JP1 and JP2) are expressed in skeletal muscle and are the primary proteins involved in transverse (T)-tubule and sarcoplasmic reticulum (SR) membrane apposition. During the performance of eccentric contractions, the apposition of T-tubule and SR membranes may be disrupted, resulting in excitation-contraction (EC) coupling failure and thus reduced force-producing capacity. In this study, we made three primary observations: 1 ) through the first 3 days after the performance of 50 eccentric contractions in vivo by the left hindlimb anterior crural muscles of female mice, both JP1 and JP2 were significantly reduced by 50% and 35%, respectively, while no reductions were observed after the performance of nonfatiguing concentric contractions; 2 ) following the performance of a repeated bout of 50 eccentric contractions in vivo, only JP1 was immediately reduced ( 30%) but recovered by 3-day postinjury in tandem with the recovery of strength and EC coupling; and 3 ) following the performance of 10 eccentric contractions at either 15° or 35°C by isolated mouse extensor digitorum longus (EDL) muscle, isometric force, EC coupling, and JP1 and JP2 were only reduced after the eccentric contractions performed at 35°C. Regression analysis of JP1 and JP2 content in tibialis anterior and EDL muscles from each set of experiments indicated that JP damage is significantly associated with early (0–3 days) strength deficits after performance of eccentric contractions ( R = 0.49; P < 0.001). As a whole, the results of this study indicate that JP damage plays a role in early force deficits due to EC coupling failure following the performance of eccentric contractions.
mitsugumin; muscle injury or damage; mice; excitation-contraction
Address for reprint requests and other correspondence: B. T. Corona, Institute for Regenerative Medicine, Wake Forest Univ., 391 Technology Way, Winston-Salem, NC 27101 (e-mail: bcorona{at}wfubmc.edu ).
Of the estimated 1.4 million salmonella infections that occur each year in the United States, most are in children and the elderly and approximately 600 are fatal.
1
Septicemia complicates at least 7 ...percent of the 40,000 culture-confirmed infections that are reported each year.
1
,
2
Although antibiotics are not essential for the treatment of most cases of salmonellosis, they can be lifesaving in persons with invasive disease. Expanded-spectrum cephalosporins (e.g., ceftriaxone) are commonly used to treat salmonella infections in children because of their pharmacodynamic properties and the very low prevalence of resistance to these agents. Since 1991, salmonella species that are . . .
PDF
