Miracle-dz/UniFAR-FTUs huggingface dataset:
Histone deacetylase 1 (HDAC1), but not HDAC2, controls embryonic stem cell differentiation

Histone deacetylases (HDAC) 1 and 2 are highly similar enzymes that help regulate chromatin structure as the core catalytic components of corepressor complexes. Although tissue-specific deletion of HDAC1 and HDAC2 has demonstrated functional redundancy, germ-line deletion of HDAC1 in the mouse causes early embryonic lethality, whereas HDAC2 does not. To address the unique requirement for HDAC1 in early embryogenesis we have generated conditional knockout embryonic stem (ES) cells in which HDAC1 or HDAC2 genes can be inactivated. Deletion of HDAC1, but not HDAC2, causes a significant reduction in the HDAC activity of Sin3A, NuRD, and CoREST corepressor complexes. This reduced corepressor activity results in a specific 1.6-fold increase in histone H3 K56 acetylation (H3K56Ac), thus providing genetic evidence that H3K56Ac is a substrate of HDAC1. In culture, ES cell proliferation was unaffected by loss of either HDAC1 or HDAC2. Rather, we find that loss of HDAC1 affects ES cell differentiation. ES cells lacking either HDAC1 or HDAC2 were capable of forming embryoid bodies (EBs), which stimulates differentiation into the three primary germ layers. However, HDAC1-deficient EBs were significantly smaller, showed spontaneous rhythmic contraction, and increased expression of both cardiomyocyte and neuronal markers. In summary, our genetic study of HDAC1 and HDAC2 in ES cells, which mimic the embryonic epiblast, has identified a unique requirement for HDAC1 in the optimal activity of HDAC1/2 corepressor complexes and cell fate determination during differentiation.
[Production of soluble intracellular adhesion molecule-1 (sICAM-1) in human endometrial cell culture].

UNLABELLED Soluble ICAM-1 could play different roles in pathological mechanisms of human endometrium found in such diseases as endometriosis, spontaneous abortion and infertility. The aim of our study was to evaluate in vitro sICAM-1 secretion to medium dependent on menstrual cycle and estradiol (E2) stimulation. MATERIAL AND METHOD Hysteroscopic biopsies in 19 infertile women. We established 16 cell cultures. Tissue was collected on DMEM, 5% FCS, 5% BSA with Penicillin, Streoptomycin, Gentamycin (2.5 mg/ml). Isolation was performed during 4 hours. Tissue was washed twice, treated with collagenase 1A (1 mg/ml, 37 degrees C 2 hours), centrifuged 10 min by 1200 rpm. Cells were cultured in DMEM/5% FCS/5% BSA with Penicillin/Streptomycin. After 2 days of endometrial and stromal cells coculture D-Valine was used to stop fibroblasts' growth. Number of cells was calculated according to Buerker method. After 2 days estradiol in concentration of 10(-10 M) was added to some cultures. Soluble ICAM-1 concentrations in supernatants were evaluated using standard ELISA kit. T-Student test was used for statistical analysis, p value < 0.05 was considered significant. RESULTS Median culture time was 14.9 (+/- 3.3) days. Longer cultures were obtained from women in follicular phase. The addition of estradiol prolonged culture by 3.8 days. The level of soluble ICAM-1 in supernatants in follicular phase was 17.6 ng/ml, in luteal 8.8 ng/ml. E2 influenced sICAM-1 production in culture (15.8 vs. 10.6 ng/ml). CONCLUSIONS Endometrial cells produce sICAM-1 constitutively. Soluble ICAM-1 concentrations are higher in follicular phase. Estradiol increases the excretion of sICAM-1.
Influence of Multidrug Resistance and Appropriate Empirical Therapy on the 30-Day Mortality Rate of Pseudomonas aeruginosa Bacteremia

ABSTRACT Infections due to multidrug-resistant (MDR) Pseudomonas aeruginosa are increasing. The aim of our study was to evaluate the influences of appropriate empirical antibiotic therapy and multidrug resistance on mortality in patients with bacteremia due to P. aeruginosa (PAB). Episodes of PAB were prospectively registered from 2000 to 2008. MDR was considered when the strain was resistant to ≥3 antipseudomonal antibiotics. Univariate and multivariate analyses were performed. A total of 709 episodes of PAB were studied. MDR PAB (n = 127 [17.9%]) was more frequently nosocomial and associated with longer hospitalization, bladder catheter use, steroid and antibiotic therapy, receipt of inappropriate empirical antibiotic therapy, and a higher mortality. Factors independently associated with mortality were age (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.002 to 1.033), shock (OR, 6.6; 95% CI, 4 to 10.8), cirrhosis (OR, 3.3; 95% CI, 1.4 to 7.6), intermediate-risk sources (OR, 2.5; 95% CI, 1.4 to 4.3) or high-risk sources (OR, 7.3; 95% CI, 4.1 to 12.9), and inappropriate empirical therapy (OR, 2.1; 95% CI, 1.3 to 3.5). To analyze the interaction between empirical therapy and MDR, a variable combining both was introduced in the multivariate analysis. Inappropriate therapy was significantly associated with higher mortality regardless of the susceptibility pattern, and there was a trend toward higher mortality in patients receiving appropriate therapy for MDR than in those appropriately treated for non-MDR strains (OR, 2.2; 95% CI, 0.9 to 5.4). In 47.9% of MDR PAB episodes, appropriate therapy consisted of monotherapy with amikacin. In conclusion, MDR PAB is associated with a higher mortality than non-MDR PAB. This may be related to a higher rate of inappropriate empirical therapy and probably also to amikacin as frequently the only appropriate empirical therapy given to patients with MDR PAB.
Public policy on career education, information, advice and guidance: developments in the United Kingdom and Norway

This chapter considers the role of career education, information, advice and guidance (CEIAG) services. On the one hand, it looks at public policy in England, where such services have a 20-year record of instability; on the other, the chapter considers Norway, where CEIAG services are beginning a new era in supporting young people’s entry into employment. As well as examining how effectively CEIAG policy and practice are framed in the two countries, we identify barriers to delivery and explore whether Norway can learn lessons from England in a process of policy transfer. The chapter is informed by NEGOTIATE research findings1 and by the voices of informants who experienced unemployment in their youth.
The comparison of Proseal laryngeal mask airway and endotracheal tube in patients undergoing laparoscopic surgeries under general anaesthesia

Aims to compare the efficacy of Proseal laryngeal mask airway(PLMA) and endotracheal tube (ETT) in patients undergoing laparoscopic surgeries under general anaesthesia. This prospective randomised study was conducted on 60 adult patients, 30 each in two groups, of ASA I-II who were posted for laparoscopic procedures under general anaesthesia. After preoxygenation, anaesthesia was induced with propofol, fentanyl and vecuronium. PLMA or ETT was inserted and cuff inflated. Nasogastric tube (NGT) was passed in all patients. Anaesthesia was maintained with N2 O, O2, halothane and vecuronium. Ventilation was set at 8 ml/kg and respiratory rate of 12/min. The attempts and time taken for insertion of devices, haemodynamic changes, oxygenation, ventilation and intraoperative and postoperative laryngopharyngeal morbidity (LPM) were noted. There was no failed insertion of devices. Time taken for successful passage of NGT was 9.77 s (6-16 s) and 11.5 s (8-17 s) for groups P and E, respectively. There were no statistically significant differences in oxygen saturation (SpO2) or end-tidal carbon dioxide (EtCO2) between the two groups before or during peritoneal insufflation. Median (range) airway pressure at which oropharyngeal leak occurred during the leak test with PLMA was 35 (24-40) cm of H2O. There was no case of inadequate ventilation, regurgitation, or aspiration recorded. No significant difference in laryngopharyngeal morbidity was noted. A properly positionedPLMA proved to be a suitable and safe alternative to ETT for airway management in elective fasted, adult patients undergoing laparoscopic surgeries. It provided equally effective pulmonary ventilation despite high airway pressures without gastric distention, regurgitation, and aspiration.
Nitric oxide regulates monocyte chemotactic protein-1.

BACKGROUND Monocyte chemotactic protein-1 (MCP-1) is a 76-amino-acid chemokine thought to be the major chemotactic factor for monocytes. We and others have demonstrated that NO inhibits monocyte-endothelial cell interactions and atherogenesis. We hypothesize that the antiatherogenic effect of NO may be due in part to its inhibition of MCP-1 expression. METHODS AND RESULTS Smooth muscle cells (SMCs) were isolated from normal rabbit aortas by the explant method. Cells were then exposed to LPS (10 microg/mL), native LDL, or oxidized LDL (30 microg/mL) for 6 hours. The expression of MCP-1 in SMCs and chemotactic activity in the conditioned medium were induced by lipopolysaccharide (LPS) or by oxidized LDL but not native LDL. The induction of MCP-1 by cytokines or oxidized lipoproteins was associated with an increased generation of superoxide anion by the SMCs and increased activity of the transcriptional protein nuclear factor-kappaB (NFkappaB). The induced expression of MCP-1 and activation of NFkappaB were reduced by previous exposure of the SMCs to the NO donor DETA-NONOate (100 micromol/L) (P<.05). To determine whether NO exerted its effect at a transcriptional level, SMCs and COS cells were transfected with a 400-bp fragment of the MCP-1 promoter. Promoter activity was enhanced by oxidized LDL, and LPS was inhibited by DETA-NO. Nuclear run-on assays confirmed that the effect of NO occurred at a transcriptional level. To investigate the role of endogenous NO in the regulation of MCP-1 in vivo, New Zealand White rabbits were fed normal chow, normal chow plus nitro-L-arginine (LNA), high-cholesterol diet (Chol), or high-cholesterol diet supplemented with L-arginine (Arg). After 2 weeks, thoracic aortas were harvested and total RNA was isolated. Northern analysis using full-length MCP-1 cDNA demonstrated increased expression in Chol and LNA aortas; this expression was decreased in aortas from Arg animals. CONCLUSIONS These studies indicate that the antiatherogenic effect of NO may be mediated in part by its inhibition of MCP-1 expression.
Characterization of Sporohalobacter salinus sp. nov., an anaerobic, halophilic, fermentative bacterium isolated from a hypersaline lake.

Halophilic, obligately anaerobic, Gram-stain-negative bacterial strains were isolated from a sediment sample taken from under the salt crust of El-Jerid hypersaline lake in southern Tunisia by using tryptone or glucose as the substrate. One strain, CEJFT1B(T), was characterized phenotypically and phylogenetically. Cells were non-motile, non-spore-forming, short rods. Strain CEJFT1B(T) was able to grow in the presence of 5-30 % (w/v) NaCl (optimum 20 %) and at 30-60 °C (optimum 45 °C). It grew at pH 5.5-7.8 and the optimum pH for growth was 6.8. The isolate required yeast extract for growth. Substrates utilized by strain CEJFT1B(T) as the sole carbon source included glucose, fructose, sucrose, pyruvate, Casamino acids and starch. Individual amino acids such as glutamate, lysine, methionine, serine, tyrosine, and amino acid mixtures formed by the Stickland reaction such as alanine-glycine, valine-proline, leucine-proline, isoleucine-proline were also utilized. Products of glucose fermentation were acetate (major product), butyrate, H2 and CO2. The genomic DNA G+C content of strain CEJFT1B(T) was 32.3 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CEJFT1B(T) should be assigned to the genus Sporohalobacter. The sequence similarity between strain CEJFT1B(T) and Sporohalobacter lortetii was 98.5 %, but DNA-DNA hybridization between the two strains revealed a relatedness value of 56.4 %, indicating that they are not related at the species level. The combination of phylogenetic analysis, DNA-DNA hybridization data, and differences in substrate utilization support the view that strain CEJFT1B(T) represents a novel species of the genus Sporohalobacter, for which the name Sporohalobacter salinus sp. nov. is proposed. The type strain is CEJFT1B(T) ( = DSM 26781(T) = JCM 19279(T)).
Rising incidence of psychiatric disorders before diagnosis of immune-mediated inflammatory disease

Aims. After the diagnosis of immune-mediated inflammatory diseases (IMID) such as inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA), the incidence of psychiatric comorbidity is increased relative to the general population. We aimed to determine whether the incidence of psychiatric disorders is increased in the 5 years before the diagnosis of IMID as compared with the general population. Methods. Using population-based administrative health data from the Canadian province of Manitoba, we identified all persons with incident IBD, MS and RA between 1989 and 2012, and cohorts from the general population matched 5 : 1 on year of birth, sex and region to each disease cohort. We identified members of these groups with at least 5 years of residency before and after the IMID diagnosis date. We applied validated algorithms for depression, anxiety disorders, bipolar disorder, schizophrenia, and any psychiatric disorder to determine the annual incidence of these conditions in the 5-year periods before and after the diagnosis year. Results. We identified 12 141 incident cases of IMID (3766 IBD, 2190 MS, 6350 RA) and 65 424 matched individuals. As early as 5 years before diagnosis, the incidence of depression [incidence rate ratio (IRR) 1.54; 95% CI 1.30–1.84) and anxiety disorders (IRR 1.30; 95% CI 1.12–1.51) were elevated in the IMID cohort as compared with the matched cohort. Similar results were obtained for each of the IBD, MS and RA cohorts. The incidence of bipolar disorder was elevated beginning 3 years before IMID diagnosis (IRR 1.63; 95% CI 1.10–2.40). Conclusion. The incidence of psychiatric comorbidity is elevated in the IMID population as compared with a matched population as early as 5 years before diagnosis. Future studies should elucidate whether this reflects shared risk factors for psychiatric disorders and IMID, a shared final common inflammatory pathway or other aetiology.
Early loading of four or five Astra Tech fixtures with a fixed cross-arch restoration in the mandible.

BACKGROUND A change in implant placement has emerged recently from two-stage to one-stage surgery and to earlier and even immediate loading of the fixtures. PURPOSE The aim of this study was to verify whether four or five fixtures installed in the edentulous mandible were suitable for early loading with a cross-arch fixed restoration. MATERIALS AND METHODS In 25 consecutively treated patients (28-88 yr), four or five Astra Tech fixtures (Mölndal, Sweden) were installed in edentulous mandibles. During the same surgical procedure, the abutments were connected. An impression was taken immediately after surgery. All patients received a fixed prosthetic rehabilitation of 10 to 12 teeth made of a cast metal framework and acrylic teeth/gingiva within a month. The fixtures were followed up clinically and radiographically for 7 to 24 months. Bone level was measured from the most coronal point of the vertical part of the fixture to the most apical bone level mesially or distally. RESULTS No fixtures were lost during follow-up. No postoperative complications occurred. Radiographic analysis showed a mean bone level of 0.6 mm after 7 to 12 months. Fixtures followed up from 13 to 18 and 19 to 24 months showed a mean bone level of 0.7 mm. Around two fixtures, the bone level was found at the first implant thread. All other fixtures showed the bone level somewhere along the vertical unthreaded part of the fixture. CONCLUSIONS Early loading within 1 month of four or five Astra Tech fixtures in the edentulous mandible is a predictable procedure for a follow-up period of 6 to 24 months.
Theoretical probes of conformational fluctuations in S‐peptide and RNase A/3′–UMP enzyme product complex

The dynamic properties of the RNase A/3′–UMP enzyme/product complex and the S‐peptide of RNase A have been investigated by molecular dynamics simulations using suitable generalization of ideas introduced to probe the energy landscape in structural glasses. We introduce two measures, namely, the kinetic energy fluctuation metric and the force metric, both of which are used to calculate the time needed for sampling the conformation space of the molecules. The calculation of the fluctuation metric requires a single trajectory whereas the force metric is computed using two independent trajectories. The vacuum MD simulations show that for both systems the time required for kinetic energy equipartitioning is surprisingly long even at high temperatures. We show that the force metric is a powerful means of probing the nature and relative importance of conformational substates which determine the dynamics at low temperatures. In particular the time dependence of the non‐bonded force metric is used to demonstrate that at low temperatures the system is predominantly localized hi a single cluster of conformational substates. The force metric is used to show that relaxation of long range (in sequence space) interactions must be mediated by a sequence of local dihedral angle transitions. We also argue that the time needed for compact structure formation is intimately related to the time needed for the relaxation of the dihedral angle degrees of freedom. The tame for non‐bonded interactions, which drive protein molecules to fold under appropriate conditions, to relax becomes extremely long as the temperature is lowered suggesting that the formation of maximally compact structure hi proteins must be a very slow process. © 1993 Wiley‐Liss, Inc.
Stable Solution of Time-Domain Combined Field Integral Equations for Transient Electromagnetic Scattering by Composite Structures Based on Nyström Scheme and Laguerre Function

Transient electromagnetic scattering by composite structures is formulated by time-domain combined field integral equations (TDCFIEs). Traditionally, the TDCFIEs are solved by combining the method of moments (MoMs) in space domain and march-on-in-time (MoT) scheme in time domain. The space-domain MoM requires two basic functions to represent the electric and magnetic current densities on material interfaces, respectively, and the conventional choice of n̂ RWG basis function for representing the magnetic current density may not be good in the TDCFIEs. In addition, the MoT scheme has a well-known late-time instability problem, which will aggravate in the surface integral equations with penetrable media. In this communication, the TDCFIEs for composite structures are solved by a different approach in which the Nyström method is used to discretize the space domain, while the Galerkin method with Laguerre basis and testing functions is employed to discretize the time domain. The proposed approach can fully overcome the drawbacks of the traditional approach as demonstrated by numerical examples.
Arthroscopic reattachment of osteochondritis dissecans lesions using resorbable polydioxanone pins.

REASONS FOR PERFORMING STUDY Debridement of osteochondritis dissecans (OCD) cartilage lesions results in fibrocartilage and imperfect hyaline repair tissue, and forms a permanent irregularity to the subchondral bone plate. OBJECTIVE To evaluate the clinical, radiographic and outcome effects of OCD cartilage flap reattachment for select lesions as an alternative to OCD debridement. HYPOTHESIS Separated cartilage flaps resulting from OCD lesions may be re-incorporated into the hyaline cartilage surface by reattachment rather than debridement and removal. METHODS Resorbable polydioxanone pins were used to reattach OCD flap lesions in 16 joints of 12 horses. Criteria for attachment, rather than removal, included an unmineralised cartilage flap on preoperative radiographs and a relatively smooth surface with some residual perimeter attachment at surgery. RESULTS There were 12 subjects, 6 males and 6 females, 7 Thoroughbred or Standardbred weanlings, 3 Warmbloods, 1 Arabian and 1 Quarter Horse, mean age at surgery 6.8 months. All horses had effusion of the affected femoropatellar joint (n = 9), tarsocrural joint (n = 1) or fetlock (n = 2). Radiographic lesions varied in length between 1.8-6.3 cm; reattachment was used in 16 of 18 affected joints and the OCD cartilage was not satisfactory for salvage in 2 stifles. Number of pins required was 2-10. One horse was subjected to euthanasia due to a tendon laceration 8 weeks after surgery; of the remaining 11 horses, mean duration of follow-up was 3.9 years (range 4 months-8 years). Nine of these were sound and had entered work, while 2 were sound but remained unbroken 4 and 6 months post operatively, respectively. Radiographic resolution of the OCD lesion occurred in 14 of 16 pinned joints in the 9 horses with long-term follow-up. The 2 remaining joints had a 3 and a 5 mm mineralised flap in the original defect sites. CONCLUSIONS This study indicated cartilage flap reattachment was an alternative to removal in selected OCD lesions. POTENTIAL RELEVANCE Relatively smooth OCD cartilage flaps may be salvaged by reattachment and can result in normal radiographic subchondral contour and a high likelihood of athletic performance. Further case numbers are required to determine which lesions are too irregular or contain too much mineral for effective incorporation after reattachment.
Foot-and-mouth disease virus replicates independently of phosphatidylinositol 4-phosphate and type III phosphatidylinositol 4-kinases

Picornaviruses form replication complexes in association with membranes in structures called replication organelles. Common themes to emerge from studies of picornavirus replication are the need for cholesterol and phosphatidylinositol 4-phosphate (PI4P). In infected cells, type III phosphatidylinositol 4-kinases (PI4KIIIs) generate elevated levels of PI4P, which is then exchanged for cholesterol at replication organelles. For the enteroviruses, replication organelles form at Golgi membranes in a process that utilizes PI4KIIIβ. Other picornaviruses, for example the cardioviruses, are believed to initiate replication at the endoplasmic reticulum and subvert PI4KIIIα to generate PI4P. Here we investigated the role of PI4KIII in foot-and-mouth disease virus (FMDV) replication. Our results showed that, in contrast to the enteroviruses and the cardioviruses, FMDV replication does not require PI4KIII (PI4KIIIα and PI4KIIIβ), and PI4P levels do not increase in FMDV-infected cells and PI4P is not seen at replication organelles. These results point to a unique requirement towards lipids at the FMDV replication membranes.