Miracle-dz/UniFAR-FTUs huggingface dataset:
Arterial lactate concentration, hospital survival, sepsis and SIRS in critically ill neonatal foals.

REASONS FOR PERFORMING STUDY Blood lactate concentration has been shown to be a useful clinical indicator in human patients, but has not been formally investigated in critically ill foals. OBJECTIVE To investigate the association of blood lactate with hospital survival, markers of cardiovascular status, metabolic acid base status, sepsis and systemic inflammatory response syndrome (SIRS). METHODS A database containing clinical, haematological, plasma biochemical and hospital outcome data on neonatal foals referred to an intensive care unit in 2000-2001 was analysed. Seventy-two foals for which arterial lactate was measured at admission were included in the study. RESULTS Sixty-one foals had an admission lactate concentration > 2.5 mmol/l. Admission lactate was statistically associated with hospital survival, mean arterial pressure, blood creatinine concentration, bacteraemia, anion gap, lactate concentration at 18-36 h after admission and evidence of SIRS, but not with packed cell volume or heart rate. Lactate at 18-36 h was also associated with survival and evidence of SIRS. Anion gap, base excess, base excess due to unidentified anions (BEua), simplified strong ion gap or bicarbonate correctly classified foals for presence of hyperlactaemia (> 5 mmol/l) in < or = 80% of animals. CONCLUSIONS Admission blood lactate gives important prognostic information. Lactate should be measured rather than assumed from the anion gap, base excess, BEua, simplified strong ion gap or bicarbonate. POTENTIAL RELEVANCE Blood lactate concentrations at admission are clinically relevant in neonatal foals and warrant further investigation. This should include the clinical value of measuring changes in lactate in response to treatment.
UvA-DARE ( Digital Academic Repository ) Inhibitors of XIAP sensitize CD 40-activated chronic lymphocytic leukemia cells to CD 95-mediated apoptosis

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A retrospective study of paediatric oral lesions from Thailand.

AIM To survey the paediatric oral lesions in Thailand. DESIGN Biopsy records over a 15-year period (1990-2004) were retrieved from the files of the Department of Oral Pathology, Faculty of Dentistry, Chulalongkorn University. Paediatric cases with an age of 16 years or younger were selected. The age of the patients was divided into three groups according to the dentition period. The lesions were classified into three categories: inflammatory/reactive lesions, cystic lesions, and tumour/tumour-like lesions. RESULTS From a total of 8314 oral biopsies, 1251 cases (15.05%) were in the paediatric population. The greatest number of lesions fell into the cystic category, followed closely by the inflammatory/reactive category and tumour/tumour-like category, respectively. The top ten most frequently encountered lesions in the present study were dentigerous cyst, mucocele, pyogenic granuloma, ameloblastoma, radicular cyst, odontoma, odontogenic keratocyst, irritation fibroma (focal fibrous hyperplasia), fibrous dysplasia, and osteomyelitis. The majority of lesions were found in the mixed dentition period (49.24%). There was no statistical difference in the occurrence between genders in this study. CONCLUSIONS The present study shows an almost similar trend to previous studies except in the ranking among and within categories. These differences may be attributable to the nature of the population studied and because Chulalongkorn University is a major referral centre.
gbx2 Homeobox gene is required for the maintenance of the isthmic region in the zebrafish embryonic brain

We isolated cDNA clones for the zebrafish gbx2 gene, which is implicated in the establishment of the midbrain–hindbrain boundary (MHB) in other vertebrates. Spatially localized expression of gbx2 was observed at the MHB from 90% epiboly through to the hatching stage. Comparisons with the expression of otx2, wnt1, and krox20 showed that gbx2 is expressed in the anterior hindbrain. Ectopic expression of gbx2 by mRNA injection caused cyclopia or truncation of the fore‐ and midbrain and severely affected isthmic and cerebellar structures, while hindbrain formation was not significantly affected. At the molecular level, gbx2 suppressed the expression of otx2 in the fore/midbrain, six3 in the anterior forebrain, and MHB‐specific genes such as eng2 and wnt1. In contrast, gbx2 did not down‐regulate the expression of the hindbrain marker genes. Therefore, gbx2 specifically suppressed the formation of the entire fore/midbrain. Meanwhile, misexpression of otx2 suppressed the expression of gbx2 in the embryonic brain. Abrogation of gbx2 expression with an antisense morpholino oligonucleotide disrupted the midbrain/anterior hindbrain region, and these loss‐of‐function effects were rescued by activating the Gbx2 protein immediately after the end of gastrulation. Taken together, these results suggest that the zebrafish gbx2 gene is essential for the maintenance of MHB and/or the formation of the isthmic structure during somitogenesis, rather than for the MHB establishment during gastrulation. We also suggest that other factors, including gbx1, is required for the establishment of the MHB during gastrulation. Developmental Dynamics, 2003. © 2003 Wiley‐Liss, Inc.
Antibiotic timing and errors in diagnosing pneumonia.

BACKGROUND The percentage of patients with community-acquired pneumonia (CAP) whose time to first antibiotic dose (TFAD) is less than 4 hours of presentation to the emergency department (ED) has been made a core quality measure, and public reporting has been instituted. We asked whether these time pressures might also have negative effects on the accuracy of diagnosis of pneumonia. METHODS We performed a retrospective review of adult admissions for CAP for 2 periods: group 1, when the core quality measure was a TFAD of less than 8 hours; and group 2, when the TFAD was lowered to less than 4 hours. We examined the accuracy of diagnosis of CAP by ED physicians. RESULTS A total of 548 patients diagnosed as having CAP were studied (255 in group 1 and 293 in group 2). At admission, group 2 patients were 39.0% less likely to meet predefined diagnostic criteria for CAP than were group 1 patients (odds ratio, 0.61; 95% confidence interval, 0.42-0.86) (P = .004). At discharge, there was agreement between the ED physician's diagnosis and the predefined criteria for CAP in 62.0% of group 1 and 53.9% of group 2 patients (P = .06) and between the ED physician's admitting diagnosis and that of the discharging physician in 74.5% of group 1 and 66.9% of group 2 patients (P = .05). The mean (SD) TFAD was similar in group 1 (167.0 [118.6] minutes) and group 2 (157.8 [96.3] minutes). CONCLUSION Reduction in the required TFAD from 8 to 4 hours seems to reduce the accuracy by which ED physicians diagnose pneumonia, while failing to reduce the actual TFAD achieved for patients.
Self‐Assembled Poly(butadiene)‐b‐poly(ethylene oxide) Polymersomes as Paclitaxel Carriers

In this work, self‐assembled poly(butadiene)‐ b‐poly(ethylene oxide) (PB‐PEO) polymersomes (polymer vesicles) and worm micelles were evaluated as paclitaxel carriers. Paclitaxel was successfully incorporated into PB‐PEO polymersomes and worm micelles. The loading capacity of paclitaxel inside PB‐PEO colloids ranged from 6.7% to 13.7% w/w, depending on the morphology of copolymer colloids and the molecular weight of diblock copolymer. Paclitaxel loaded OB4 (PB219‐PEO121) polymersome formulations were colloidally stable for 4 months at 4 °C and exhibited slow steady release of paclitaxel over a 5 week period at 37 °C. Evaluation of the in vitro cytotoxicity of paclitaxel‐polymersome formulations showed that the ability of paclitaxel‐loaded polymersomes to inhibit proliferation of MCF‐7 human breast cancer cells was less compared to paclitaxel alone. By increasing the concentration of paclitaxel in polymersomes from 0.02 to 0.2 μg/mL, paclitaxel‐polymersome formulations showed comparable activity in inhibiting the growth of MCF‐7 cells. Taken together, these results demonstrate that paclitaxel‐polymersomes have desirable restrained release profile and exhibit long‐term stability.
Thyroid Nodules: Nondiagnostic Cytologic Results according to Thyroid Imaging Reporting and Data System before and after Application of the Bethesda System.

PURPOSE To compare the malignancy rates and the effectiveness of the Thyroid Imaging Reporting and Data System (TIRADS) for risk stratification of nodules with nondiagnostic results classified before and after application of the Bethesda System for Reporting Thyroid Cytopathology. MATERIALS AND METHODS This retrospective study was approved by an institutional review board, with waiver of informed consent. A total of 763 patients with 790 thyroid nodules and nondiagnostic cytologic results were included (mean age ± standard deviation, 52.3 years ± 11.5), 485 nodules from the pre-Bethesda period (from March 2007 to December 2008) and 305 nodules from the post-Bethesda period (from May 2011 to May 2012). A TIRADS category was assigned to each thyroid nodule on the basis of the number of features that appeared suspicious for cancer at ultrasonography (US). Malignancy rates and TIRADS categories during the two periods were compared. Correlation between TIRADS category and malignancy risk between the two periods was evaluated and compared. RESULTS The malignancy rates of nodules with nondiagnostic cytologic results were not significantly different between the two periods (P = .148). Malignancy risk of TIRADS category 3, 4a, 4b, 4c, and 5 was 1.8%, 5.7%, 4.1%, 29.8%, and 16.7%, for the pre-Bethesda period, and 1.6%, 3.0%, 7.1%, 16.3%, and 25.0% for the post-Bethesda period, respectively. Near-perfect correlation was seen between the TIRADS category and malignancy risk in the post-Bethesda period (r = 0.961, P = .009), while no significant correlation was found in the pre-Bethesda period (r = 0.731, P = .161). CONCLUSION Malignancy risk stratification with TIRADS was more effective for nodules with nondiagnostic cytologic results classified according to the Bethesda System. When these Bethesda-classified nodules with nondiagnostic results are evaluated as TIRADS category 3 or 4a, they may be treated conservatively with follow-up US, but when other cytologic classifications are applied, follow-up US and fine- needle aspiration must be considered for nodules showing one or more features suspicious for cancer at US.
Virus‐cell and cell‐cell fusion mediated by the HIV‐1 envelope glycoprotein is inhibited by short gp41 N‐terminal membrane‐anchored peptides lacking the critical pocket domain

The interactions between the N‐ and C‐terminal heptad repeat (NHR and CHR) regions of the human immunodeficiency virus (HIV‐1) glycoprotein gp41 create a structure comprising a 6‐helix bundle (SHB). A sequence in the SHB named the “pocket” is crucial for the SHB's stability and for the fusion inhibitory activity of 36‐residue NHR peptide N36. We report that a short 27‐residue peptide, N27, which lacks the pocket sequence, exhibits potent inhibitory activity in both cell‐cell and virus‐cell fusion assays when fatty acids were conjugated to its N but not C terminus. Furthermore, mutations in the positions that prevent interaction with the CHR but not with the NHR resulted in a dramatic reduction in N27 activity. These data support a mechanism in which N27 mainly targets the CHR rather than the internal NHR coiled‐coil, reveal the N‐terminal edge of the endogenous core structure in situ and hence complement our recent findings of the C‐terminal edge of the core, and provide a new approach for designing short inhibitors from the NHR region of other lentiviruses due to similarities in their envelope proteins. —Wexler‐Cohen, Y. , Ashkenazi, A. , Viard, M. , Blumenthal, R. , Shai, Y. Virus‐cell and cell‐cell fusion mediated by the HIV‐1 envelope glycoprotein is inhibited by short gp41 N‐terminal membrane‐anchored peptides lacking the critical pocket domain. FASEB J. 24, 4196–4202 (2010). www.fasebj. org
Effect of cytolethal distending toxin on F-actin assembly and cell division in Chinese hamster ovary cells

Cytolethal distending toxin (CDT) is a newly described toxin produced by a number of enteropathogens, including Campylobacter jejuni, various Escherichia coli strains, and a few Shigella species. CDT induces distension and eventual death of a number of transformed cell lines. Here, we extend previous studies by demonstrating that morphological changes in CDT-treated Chinese hamster ovary cells are coincident with changes in cytoskeletal structure and an inhibition of cell proliferation. CDT-treated cells underwent a progressive accumulation of F-actin assemblies which microscopically resembled actin stress fibers. Accumulation of the stress fiber-like structures in CDT-treated cells was accompanied by an apparent blockage of cell division. Multinucleation was detected in some cells but did not constitute a significant feature of CDT action. Although toxin-treated cells failed to divide, cell viability remained high for the first 4 days following toxin treatment, as evidenced by trypan blue exclusion and neutral red uptake. [3H]thymidine incorporation studies on CDT-treated cells were consistent with a blockage of cell proliferation without a direct inhibition of DNA synthesis. Although the progression of toxin action developed slowly, a 2-min exposure to CDT resulted in an irreversible development of toxicity. Together, our data indicate that CDT affects F-actin assembly within target cells and may interrupt the regulation or function of cell cycle-dependent events leading to cytokinesis.
The effects of eating marine- or vegetable-fed farmed trout on the human plasma proteome profiles of healthy men

Most human intervention studies have examined the effects on a subset of risk factors, some of which may require long-term exposure. The plasma proteome may reflect the underlying changes in protein expression and activation, and this could be used to identify early risk markers. The aim of the present study was to evaluate the impact of regular fish intake on the plasma proteome. We recruited thirty healthy men aged 40 to 70 years, who were randomly allocated to a daily meal of chicken or trout raised on vegetable or marine feeds. Blood samples were collected before and after 8 weeks of intervention, and after the removal of the twelve most abundant proteins, plasma proteins were separated by two-dimensional gel electrophoresis. Protein spots < 66 kDa with a pI >4·3 visualised by silver staining were matched by two-dimensional imaging software. Within-subject changes in spots were compared between the treatment groups. Differentially affected spots were identified by matrix-assisted laser desorption ionisation-time of flight/time of flight MS and the human Swiss-Prot database. We found 23/681 abundant plasma protein spots, which were up- or down-regulated by the dietary treatment (P< 0·05, q< 0·30), and eighteen of these were identified. In each trout group, ten spots differed from those in subjects given the chicken meal, but only three of these were common, and only one spot differed between the two trout groups. In both groups, the affected plasma proteins were involved in biological processes such as regulation of vitamin A and haem transport, blood fibrinolysis and oxidative defence. Thus, regular fish intake affects the plasma proteome, and the changes may indicate novel mechanisms of effect.
The YouTube Generation: Implications for Medical Professionalism

While medical education has remained relatively constant over the past century, the rising popularity of internet-based technologies, such as applications for social networking, media sharing, or blogging, has drastically changed the way in which physicians-in-training interact with educators, peers, and the outside world. The implementation of these new technologies creates new challenges and opportunities for medical educators. Representation, the absence of established policies and legal precedents, and the perception of the lay public exemplify some of the issues that arise when considering the digital images used by trainees. While some of these issues affect higher education generally, medical schools are faced with additional challenges to ensure that graduates exemplify the ideals of medical professionalism. We present a case vignette with subsequent discussion to highlight the complexities of ensuring medical professionalism in the digital age.
Assembly of urokinase receptor-mediated plasminogen activation complexes involves direct, non-active-site interactions between urokinase and plasminogen.

The binding of the zymogenic form of urokinase-type plasminogen activator (pro-uPA) to its specific cellular receptor, uPAR, leads to a large potentiation of plasmin generation. This is dependent on the concurrent cellular binding of plasminogen, and is completely abrogated by the plasminogen lysine-binding site ligand, 6-aminohexanoic acid. Previous data have provided circumstantial evidence for the formation of specific complexes to mediate the kinetically favorable reciprocal interactions between the protease and zymogen components [Ellis, V. , and Dano, K. (1993) J. Biol. Chem. 268, 4806-4813]. To further investigate the formation of these putative complexes, we have studied the effect of various lysine-binding site ligands on the binding and activation of plasminogen on U937 cells. Lysine-binding site ligands resembling internal lysine residues, such as Nalpha-acetyl-L-lysine methyl ester, were found to specifically inhibit uPAR-mediated cell-surface plasminogen activation at concentrations up to 40-fold lower than those inhibiting the cellular binding of 125I-labeled plasminogen (IC50s 300 microM vs 8.5 mM). By contrast, 6-aminohexanoic acid, resembling a C-terminal lysine residue, did not display this disparity (IC50s 25 vs 30 microM). These lysine analogues were also found to compete a non-active-site interaction between uPA and plasminogen, detected by surface plasmon resonance (Kd 50 nM), at concentrations correlating with their effect on cell-surface plasminogen activation, suggesting that this interaction is part of the kinetic mechanism. Consistent with this, synthetic peptides corresponding to the sequence uPA149-158 (GQKTLRPRFK) and uPA149-157 (GQKTLRPRF) specifically abolished the amplification of cell-surface plasminogen activation. These data demonstrate that a novel non-active-site interaction between uPA and plasminogen is necessary for the assembly and efficiency of cell-surface plasminogen activation complexes.
HIV-1 mutants escaping neutralization by the human antibodies 2F5, 2G12, and 4E10: in vitro experiments versus clinical studies

Objective:The human monoclonal antibodies (mAb) 2F5, 2G12, and 4E10 are three of the most broadly neutralizing antibodies against HIV-1. Although they have been shown to prevent de novo infection in vivo, their potential for treatment of chronic infection is less clear. One major obstacle may be the emergence of resistant viruses during mAb treatment. Design:To assess whether escape mutants can be generated in vitro which are resistant to all three mAbs, two neutralization-sensitive T-cell line-adapted viruses and two primary isolates were passaged in the presence of increasing concentrations of 2F5, 2G12, 4E10, and a 1: 1: 1 mixture. To get insight into viral escape in vivo, viruses were isolated from eight patients treated with repeated infusions of 2F5/2G12/4E10. Results:In vitro, viruses resistant to a single mAb emerged after 3–22 weeks. Generation of viruses resistant to the triple-combination was a slower process characterized by recurrent loss of virus replication. Some generated triple-resistant viruses seemed to be impaired in their replicative fitness. Neutralization resistance to 2F5 and partly 4E10 could be attributed to amino acid mutations in the mAb epitopes, but not for 2G12. In vivo, none of the patients developed detectable viruses that escaped neutralization by all three mAbs within the 77-day observation period. Virus escape occurred only to 2G12 in three patients. Conclusions:In summary, the findings of the in vivo study and the difficulty in generating multi-resistance in vitro together with the fact that some generated viruses seemed to have impaired replication fitness indicate that 2F5, 2G12, and 4E10 may be useful for therapy in HIV-1 infection.
Quality of life of patients on haemodialysis for end-stage renal disease.

AIM The aims of the study were (a) to measure the overall quality of life of people receiving haemodialysis, (b) to compare the quality of life of the sample with that of the general population and (c) to identify any differences between the quality of life of people who are adequately dialysed and those inadequately dialysed, as determined by Kt/V(urea) (dialysis adequacy) measurements. BACKGROUND End stage renal disease is a progressive, debilitating, chronic illness requiring nursing and medical interventions. The development of the disease affects quality of life, potentially influencing physical and mental health, functional status, independence, general well-being, personal relationships and social functioning. METHOD A descriptive, cross-sectional, survey was carried out of the quality of life of patients undergoing haemodialysis treatment at a hospital in the Republic of Ireland. A non-probability sample of 97 patients was chosen. Health-related quality of life was assessed using the 36-item Short Form Health Survey questionnaire. FINDINGS Patients receiving haemodialysis identified limitations in a number of areas including vitality, physical functioning and physical role limitations. They also reported significantly lower physical functioning when compared with general population norm-based scores. Differences were also found in mental health scores between patients who were well-dialysed and those less well-dialysed. CONCLUSION End-stage renal disease and its ensuing treatments negatively affect quality of life. Nurses aware of this evidence can explore new ways to assess more accurately and identify specific problem areas for individual patients and take action to ameliorate these.