Miracle-dz/UniFAR-FTUs huggingface dataset:
Determination of Endogenous Cytokines in Chronic Wounds

ObjectiveThis study objectively characterized the microenvironment of indolent, chronic wounds by developing a method by which minute quantities of cytokines could be extracted from chronic wounds and separately identified. Summary Background DataRecombinant DNA technology and the ability to clone compounds such as cytokines allow new management schemes for the treatment of acute and chronic wounds. Before treatment with an exogenous cytokine is started, it would be helpful to know the endogenous level of that cytokine in the wound. Although various methods of extracting cytokines from acute wounds have been reported, no techniques have existed to reliably measure endogenous levels of cytokines in chronic wounds. MethodsPorous, inert hydrophilic dextranomer beads were tested for their ability to absorb or adsorb protein and cytokines in vitro with either albumin or albumin laced with various known amounts of cytokines, and then from chronic human pressure ulcers. The Bradford protein assay was used to determine protein levels. Enzyme-linked immunosorbent assay (ELISA) techniques were used to determine levels of platelet-derived growth factor (PDGF)-AB, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and transforming growth factor-Beta (TGF-β) extracted by the beads. ResultsBetween 88% and 98% of known amounts of albumin could be recovered. Similarly, more than 90% of the laced cytokines could be recovered. In 20 grade III/IV pressure ulcers, although protein concentrations were remarkably similar, endogenous levels of cytokine growth factors varied tremendously. Platelet-derived growth factor-AB ranged from 49 to 867 pg/mL; bFGF from 47 to 697 pg/mL; and EGF from nondetectable to 247.5 pg/mL. TGF-B was not detected in 17 of the 20 pressure ulcers. ConclusionsThis new technique appears useful for measuring endogenous levels of cytokines. Levels of cytokines found in these chronic wounds are much lower than those reported from acute wounds. The marked variation found among the 20 wounds may help to explain the differences reported in recent wound healing trials with exogenous cytokines.
Policy Changes in Major League Baseball: Improved Agent Behavior and Ancillary Productivity Outcomes

Offense in Major League Baseball (MLB) has decreased substantially since 2006, often attributed to increased testing and punitive action for use of performance enhancing drugs. However, there has been concurrent policy change affecting behavior of other league agents that may have also affected game play. I therefore examine the effect of these agents, MLB umpires, on offensive production in baseball. Estimates reveal that a substantial portion of the offensive reduction from 2008 through 2014 can be attributed to changes in the size of the strike zone. Implications are further discussed in the context of firm production relevant outcomes as they relate to the labor force and supervisor performance expectations. (JEL J44, Z22, Z28, L25)
Exploiting 3D structural templates for detection of metal‐binding sites in protein structures

High throughput structural genomics efforts have been making the structures of proteins available even before their function has been fully characterized. Therefore, methods that exploit the structural knowledge to provide evidence about the functions of proteins would be useful. Such methods would beneeded to complement the sequence‐based function annotation approaches. The current study describes generation of 3D‐structural motifs for metal‐binding sites from the known metalloproteins. It then scans all the available protein structures in the PDB database for putative metal‐binding sites. Our analysis predicted more than 1000 novel metal‐binding sites in proteins using three‐residue templates, and more than 150 novel metal‐binding sites using four‐residue templates. Prediction of metal‐binding site in a yeast protein YDR533c led to the hypothesis that it might function as metal‐dependent amidopeptidase. The structural motifs identified by our method present novel metal‐binding sites that reveal newer mechanisms for a few well‐known proteins. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Minimizing Deviant Behavior in Healthcare Organizations: The Effects of Supportive Leadership and Job Design

EXECUTIVE SUMMARY In an era when healthcare organizations are beset by intense competition, lawsuits, and increased administrative costs, it is essential that employees perform their jobs efficiently and without distraction. Deviant workplace behavior among healthcare employees is especially threatening to organizational effectiveness, and healthcare managers must understand the antecedents of such behavior to minimize its prevalence. Deviant employee behavior has been categorized into two major types, individual and organizational, according to the intended target of the behavior. Behavior directed at the individual includes such acts as harassment and aggression, whereas behavior directed at the organization includes such acts as theft, sabotage, and voluntary absenteeism, to name a few (Robinson and Bennett 1995). Drawing on theory from organizational behavior, we examined two important features of supportive leadership, leader‐member exchange (LMX) and perceived organizational support (POS), and two important features of job design, intrinsic motivation and depersonalization, as predictors of subsequent deviant behavior in a sample of over 1,900 employees within a large US healthcare organization. Employees who reported weaker perceptions of LMX and greater perceptions of depersonalization were more likely to engage in deviant behavior directed at the individual, whereas employees who reported weaker perceptions of POS and intrinsic motivation were more likely to engage in deviant behavior directed at the organization. These findings give rise to specific prescriptions for healthcare managers to prevent or minimize the frequency of deviant behavior in the workplace.
Accuracy of Breast Cancer Diagnosis by Physical, Radiologic and Cytologic Combined Examinations

Physical examination, mammography and fine-needle aspiration cytology were performed in 1498 consecutive cases with a solitary solid lump of the female breast. The intent was to verify the validity of this diagnostic triplet in the accuracy of the preoperative diagnosis of breast cancer. Clinically sure cancers were excluded from the study. The collected data were evaluated in terms of sensitivity, specificity and predictivity of any procedure alone or in combination. In 1138 cases confirmed by histology (514 carcinomas and 669 benign or non-neoplastic lesions), the physical examination and mammography were very sensitive (respectively 96% and 84%) but with a high rate of false-positive reports (respectively 20% and 18%). The cytologic diagnosis was less sensitive (65%), mostly due to many inadequate smears, but highly specific (93%) and predictive for malignancy (99%) when the cytologic report was frankly positive. Any single procedure improved the overall sensitivity, and taken together this triplet appears to be the most effective noninvasive diagnostic combination that provides in a short time with minimal cost and discomfort, a diagnosis of certain malignancy in about 50% of carcinomas with a predictivity close to 100%, when cytology detected malignancy.
Strategic and non-strategic problem gamblers differ on decision-making under risk and ambiguity.

AIMS To analyse problem gamblers' decision-making under conditions of risk and ambiguity, investigate underlying psychological factors associated with their choice behaviour and examine whether decision-making differed in strategic (e.g., sports betting) and non-strategic (e.g., electronic gaming machine) problem gamblers. DESIGN Cross-sectional study. SETTING Out-patient treatment centres and university testing facilities in Victoria, Australia. PARTICIPANTS Thirty-nine problem gamblers and 41 age, gender and estimated IQ-matched controls. MEASUREMENTS Decision-making tasks included the Iowa Gambling Task (IGT) and a loss aversion task. The Prospect Valence Learning (PVL) model was used to provide an explanation of cognitive, motivational and response style factors involved in IGT performance. FINDINGS Overall, problem gamblers performed more poorly than controls on both the IGT (P = 0.04) and the loss aversion task (P = 0.01), and their IGT decisions were associated with heightened attention to gains (P = 0.003) and less consistency (P = 0.002). Strategic problem gamblers did not differ from matched controls on either decision-making task, but non-strategic problem gamblers performed worse on both the IGT (P = 0.006) and the loss aversion task (P = 0.02). Furthermore, we found differences in the PVL model parameters underlying strategic and non-strategic problem gamblers' choices on the IGT. CONCLUSIONS Problem gamblers demonstrated poor decision-making under conditions of risk and ambiguity. Strategic (e.g. sports betting, poker) and non-strategic (e.g. electronic gaming machines) problem gamblers differed in decision-making and the underlying psychological processes associated with their decisions.
Line Bisection and Neglect Severity

The relationship between (horizontal) line length and bisection accuracy continues to be of theoretical interest in the study of visuospatial neglect. In a recent paper, Koyama, Ishiai, Seki and Nakayama (1997) claim that line bisection performance by patients with severe neglect is "not only quantitatively but also qualitatively different" from that of patients with moderate or mild neglect. In particular, they argue that line length does not control bisection displacements in severe neglect. Contrary to that position, I first demonstrate that the conclusion of Koyama et al. (1997) does not follow from their own data; second, I describe empirical results showing that bisection displacement in severe neglect is exquisitely sensitive to line length. The standard psychophysical models of line bisection in visuospatial neglect are not falsified by the results of Koyama et al.
IL-17A Induces Pro-Inflammatory Cytokines Production in Macrophages via MAPKinases, NF-κB and AP-1

Background: Interleukin (IL)-17A, a newly identified cytokine, may participate in the transition of a stable plaque into an unstable plaque. Macrophages play a critical role in the destabilization of atherosclerotic plaque. Methods: RAW 264.7 cells were stimulated with IL-17A. The mRNA expression of inflammatory cytokines was determined by RT-PCR. The cytokines production in the supernatants was measured by ELISA. Small interfering RNA (siRNA) was used to confirm that IL-17A-induced pro-inflammatory cytokines production via IL-17RA signaling. The western blot assay was used to detect the phosphorylation of MAPKinases including p38 and ERK1/2. The DNA binding activity of nuclear factor NF-κB and AP-1 were detected by EMSA. Results: IL-17A induced the production of pro-inflammatory cytokines in macrophages in a time- and dose-dependent manner, such as tumor necrosis factor (TNF)-a, IL-1ß, and IL-6. Meanwhile, IL-17A resulted in the phosphorylation of p38 and ERK1/2 and increased DNA-binding activity of NF-κB and AP-1. Pharmacological inhibitors of p38 and ERK1/2 partly attenuated IL-17A-induced TNF-a, IL-1ß, and IL-6 production. Either NF-κB inhibitor or AP-1 inhibitor also partly decreased the IL-17A-induced cytokine production. Conclusions: IL-17A induces pro-inflammatory cytokines production in macrophages via MAPKinases, NF-κB and AP-1 pathway.
Outbreak of hepatitis C virus infection in patients with hematologic disorders treated with intravenous immunoglobulins: different prognosis according to the immune status.

The influence of immunodeficiency on the course of hepatitis C virus (HCV) infection is still debated, although a worsening effect has been suggested. We compared the characteristics of hepatitis C in two groups of hematologic patients with different levels of immunocompetence who acquired the same virus strain after treatment with contaminated intravenous immunoglobulins (IVIG). Indications for IVIG therapy were idiopathic thrombocytopenic purpura (ITP) in six patients and hypogammaglobulinemia in 7 patients with various hematologic disorders, who were defined immunodeficient (ID). Infection rate was 100%. Five ID patients never developed HCV antibodies despite serum HCV-RNA positivity. The same HCV genotype was shown in 10 patients tested. Moreover, E1-E2 gene partial nucleotide sequencing, performed in four patients, showed identical or closely related amino acid sequences, thus strongly supporting the hypothesis of a common source of infection. Clinical acute infection did not differ significantly between the two groups, but subsequent liver failure developed in five of the seven ID patients and in none of the ITP patients (P = .04). Liver biopsy, performed in three cases, documented HCV as the only cause of liver damage. Six ID patients died, with liver disease being the primary cause of death in four cases and a contributory cause in two cases. Their median survival after IVIG was 12 months, significantly worse than that of ITP patients (P = .0028). We conclude that immunodeficiency markedly worsens the course of IVIG-acquired HCV infection in hematologic patients.
Harnessing dendritic cells for the induction of transplantation tolerance

Purpose of reviewThe unique properties of dendritic cells (DC) lend themselves to the modulation of antigen-specific immune responses, including allograft rejection. Central to their modulatory function is the capacity of DC to polarize naïve T cells towards a regulatory phenotype and to expand existing regulatory T cells (Treg). This review draws on current understanding of the interaction between these critical cell types to evaluate prospects for the use of DC as a therapeutic regimen. Recent findingsOver the past year, there have been significant developments in dissecting the molecular basis of DC-Treg interactions. Furthermore, it has proven possible to capitalize on this understanding to reinforce tolerance by conditioning DC through exposure to defined pharmacological agents. The use of these modulated DC in animal models of allograft rejection has highlighted the therapeutic potential of this approach but also the full extent of the challenges that remain to be addressed. SummaryThe use of DC to induce antigen-specific tolerance by tapping into the Treg network remains a viable prospect for future strategies for immune intervention in allograft rejection. Furthermore, principles learned from the study of whole organ transplantation may find application in the emerging field of regenerative medicine, in which the use of immune suppression is likely to be contraindicated.
Detection with synthetic oligonucleotide probes of nucleotide sequence variations in the genes encoding enterotoxins of Escherichia coli

We examined variations in the genes encoding heat-stable enterotoxin (ST) and heat-labile enterotoxin (LT) in 88 strains of Escherichia coli isolated from individuals with traveler's diarrhea to find suitable sequences for use as oligonucleotide probes. Four oligonucleotide probes of the gene encoding ST of human origin (STIb or STh), one oligonucleotide probe of the gene encoding ST of porcine origin (STIa or STp), and three oligonucleotide probes of the gene encoding LT of human origin (LTIh) were used in DNA colony hybridization tests. In 15 of 22 strains possessing the STh gene and 28 of 42 strains producing LT, the sequences of all regions tested were identical to the published sequences. One region in the STh gene examined with a 18-mer probe was relatively well conserved and was shown to be closely associated with the enterotoxicity of the E. coli strains in suckling mice. This oligonucleotide, however, hybridized with strains of Vibrio cholerae O1, V. parahaemolyticus, and Yersinia enterocolitica that gave negative results in the suckling mouse assay.
Effect of Vinorelbine, Ifosfamide, and Cisplatin Combination Chemotherapy in Advanced Non–Small-Cell Lung Cancer

Cisplatin-based chemotherapy is being tried in the treatment of nonoperable cases of non–small-cell lung cancer (NSCLC). However, the prognosis is unfavorable and to improve survival, clinical studies using various combinations of a variety of drugs as well as experimental material are in progress. We compared the efficacy and toxicities of combination chemotherapy using different doses of vinorelbine and ifosfamide with a constant dose of cisplatin in this study. Patients diagnosed with inoperable stage III or IV NSCLC between June 1997 and December 1998 were included. Cisplatin was administered at a constant dose of 80 mg/m2 on day 5, whereas vinorelbine on days 1 and 5 and ifosfamide on day 5 were administered in one of two different doses. In arm A, vinorelbine 25 mg/m2 and ifosfamide 3.0 g/m2 were administered. In arm B, vinorelbine 20 mg/m2 and ifosfamide 2.5 g/m2 were administered. Also, we reviewed for phase II and III studies that test 1) cisplatin, 2) vinorelbine monotherapy, and 3) vinorelbine/cisplatin/ifosfamide combination chemotherapy for stage IIIb-IV non-SCLC. Summation dose intensity (SDI) was calculated in each published and current study. Twenty patients in arm A and 35 patients in arm B were available for evaluation. There was no difference in patient activity, pathologic diagnosis, and differentiation or stage between the two arms. The median number of cycles was four in both arms. The response rate was 50% in arm A and 30% in arm B. The median survival times for arm A and B were 40 and 42 weeks, respectively, whereas the SDI was 1.94 and 1.7, respectively. More than grade III leukopenia was observed in 28.9% in arm A, which is more frequent than the 17.2% in arm B. There was a significant correlation between the SDIs and response rates and median survival (r2 = 0.629, p = 0.001;r2 = 0.453, p = 0.001, respectively). Although the follow-up period is relatively short, the survival time was similar in both arms. Because a high response rate may not be followed by a high survival time in combination chemotherapy of NSCLC, further studies on the appropriate dose of individual agents with regard to the relationship between response rate, severity, and incidence of toxicities and survival rate should be carried out.
Pharmacotherapy in restorative neurology

Purpose of reviewTo evaluate current evidence that recovery after stroke or traumatic brain injury (TBI) can be enhanced by drugs that modulate neurotransmission in the brain. Recent findingsSmall studies performed in chronic stroke patients have indicated that single doses of reboxetine or citalopram improved different aspects of motor functions and that long-lasting application of donepezil reduced aphasic symptoms. Methylphenidate shortened intensive care treatment periods in TBI patients and amantadine improved arousal and cognition. Recent studies in stroke patients did not find beneficial effects of levodopa or dextroamphetamine. SummaryEvidence of drug-related improvement of functions after stroke or TBI is still limited, either because of small and highly selected patient groups or due to conflicting results. Currently, most convincing evidence exists for piracetam for improvement of poststroke aphasia and amantadine for enhancing arousal and cognition after TBI. Some evidence can be found for improvement of stroke-related motor deficits by levodopa, enhanced speed of mental processing in TBI by methylphenidate and improvement of poststroke aphasia by dextroamphetamine. Large randomized controlled trials are needed to evaluate the effectiveness of serotonin reuptake inhibitors or noradrenaline reuptake inhibitors on motor functions.
Clinicians' perspective on quality of life assessment in paediatric clinical practice

Aim: This study was undertaken to investigate paediatric clinicians' views on and use of quality of life (QoL) assessment in clinical practice. Methods: A survey was conducted among members of the Dutch Paediatric Association via e‐mail. Results: Over half of the 303 respondents (57%) believed that it was possible to use QoL questionnaires in clinical practice. The majority indicated that assessing QoL was beneficial and that it was especially necessary to assess QoL in children with a chronic disease (82%). Although only a minority (17%) currently used QoL questionnaires, most respondents would want to use QoL questionnaires in the future (76%). Obstacles that prevent the use of QoL questionnaires are the extra time needed for assessment, the unavailability of standardized questionnaires and insufficient knowledge about QoL.
Plakin proteins are coordinately cleaved during apoptosis but preferentially through the action of different caspases

Abstract: In epithelial cells, cell–cell and cell–matrix junctions, desmosomes and hemidesmosomes, provide anchorage sites for the keratin‐intermediate filaments. The plakin proteins desmoplakin (DP), plectin, and periplakin represent intracellular constituents of these adhesion junctions. In staurosporine‐treated apoptotic HaCaT cells, DP, plectin, and periplakin became cleaved coordinately with the elimination of keratins 10 and 14, while involucrin, actin, and keratin 18 displayed considerable stability. The caspase inhibitor zVAD‐fmk prevented both the cell detachment and protein cleavage, indicating the function of caspases in these events. Closer examination in vitro revealed that while caspases 2 and 4 most efficiently cleaved DP, and plectin served as a target for caspases 3 and 7, periplakin as well as keratins were cleaved by caspase 6. The involvement of multiple caspases in the destruction of epithelial cell integrity ensures the efficient elimination of cytoskeleton, but also provides specificity for selectively targeting individual adhesion molecules.