Photothermal Microscopy of Coupled Nanostructures and the Impact of Nanoscale Heating in Surface Enhanced Raman Spectroscopy.
The optical properties of plasmonic nanoparticles are strongly dependent on interactions with other nanoparticles, which complicates analysis for systems larger than a few particles. In this work we examined heat dissipation in aggregated nanoparticles, and its influence on surface enhanced Raman scattering (SERS), through correlated photothermal heterodyne imaging, electron microscopy and SERS measurements. For dimers the per particle absorption cross-sections show evidence of interparticle coupling, however, the effects are much smaller than those for the field enhancements that are important for SERS. For larger aggregates the total absorption was observed to be simply proportional to aggregate volume. This observation allows us to model light absorption and heating in the aggregates by assuming that the particles act as independent heat sources. The heat dissipation calculations show that very high temperatures can be created at the nanoparticle surface, and that the temperature decreases with increasing thermal conductivity of the surroundings. This is in agreement with the SERS measurements that show faster signal degradation for air compared to water environments.


Content and Temporal Order Memory for Performed Activities in Parkinson's Disease.
This study examined content and temporal order memory for subject-performed activities in an incidental learning condition in cognitively healthy individuals with Parkinson's disease (PD) (N = 20) and controls (N = 20). Participant's free recall of activities provided a measure of content memory. Temporal order memory was assessed with a reconstruction task of activities. Self- and informant-reports of everyday memory were used to examine the relationship between everyday memory, and content and temporal order memory. Individuals with PD recalled fewer activities although recognition memory was intact. Temporal order memory was also impaired for individuals with PD. For the PD group, both self- and informant-reports of changes in current memory abilities were strongly associated with temporal order memory but not content memory for activities. These findings suggest that there is a strong link between everyday memory abilities and temporal order memory for activities, and support the need for additional study of temporal order memory abilities in PD.


Concentration dependent stereoselectivity of propafenone N-depropylation metabolism with human hepatic recombinant CYP1A2.
Concentration dependency of stereoselective N-depropylation metabolism of propafenone was studied by using transgenic cell line expressing human CYP1A2. Enantiomers of propafenone and N-depropylpropafenone were separated and assayed simultaneously by RP-HPLC with precolumn GITC chiral derivatization. The experimental results showed that CYP1A2 was involved in enantioselective N-depropylation of propafenone and that the metabolic stereoselectivity depends on substrate concentration. For racemic propafenone, stereoselectivity was observed at low substrate concentration and was not seen at high substrate concentration. For individual isomers, S-(+)-propafenone was metabolized faster than its antipode at higher enantiomer concentrations and R-(-)-propafenone was eliminated faster than its antipode at lower enantiomer concentrations. There is interaction between S- and R-propafenone. R-(-)-propafenone inhibited the metabolism of S-(+)-propafenone with IC50 0.225 mmol/L for human CYP1A2.


The suppression of MAPK/NOX/MMP signaling prompts renoprotection conferred by prenatal naproxen in weaning preeclamptic rats.
Although nonsteroidal antiinflammatory drugs (NSAIDs) are frequently used for fever and pain during pregnancy, their possible interaction with perinatal renal injury induced by preeclampsia (PE) has not been addressed. Here, studies were undertaken in the N(gamma)-nitro-L-arginine methyl ester (L-NAME) PE model to assess the influence of gestational NSAIDs on renal damage in weaning dams. PE-evoked increments and decrements in urine protein and creatinine clearance, respectively, were intensified by celecoxib and weakened by diclofenac or naproxen. Naproxen also improved renal cloudy swelling, necrosis, and reduced glomerular area evoked by PE. The concomitant rises in renal expression of markers of oxidative stress (NOX2/4), extracellular matrix metaloproteinase deposition (MMP9), and prostanoids (PGE2, PGF2α, TXA2) were all more effectively reduced by naproxen compared with celecoxib or diclofenac. Western blotting showed tripled expression of mitogen-activated protein kinases (MAPKs; p-p38, p-JNK1, p-ERK1, p-ERK2) in PE kidneys that was overturned by all NSAIDs, with naproxen producing the largest drop in p-ERK2 expression. The PE-provoked elevation in renal expression of autophagic marker LC3 was reduced by naproxen and diclofenac, but not celecoxib. The data suggests superior effect for naproxen over other NSAIDs in rectifying preeclamptic renal injury and predisposing inflammatory, oxidative, autophagic, and fibrotic signals.


Purification and functional characterization of integrin alpha v beta 5. An adhesion receptor for vitronectin.
We have purified a novel member of the integrin gene family from placenta that serves as a vitronectin receptor. This integrin is composed of the alpha v subunit and a beta subunit that we designate beta 5. Purification was accomplished by immunodepleting a placental extract of integrin alpha v beta 3, allowing us to purify alpha v beta 5 from the remaining extract by monoclonal antibody affinity chromatography on LM 142-Sepharose, which binds to the alpha v subunit. Purification to homogeneity was subsequently achieved by affinity chromatography on wheat germ lectin-Sepharose. Western blot analysis with antibodies raised against alpha v beta 5 and alpha v beta 3 demonstrated that beta 3 and beta 5 were distinct but confirmed that the alpha subunit of the two integrins were immunologically identical. Similarly, antibodies that bind beta 3 proximal to the ligand-binding site failed to react with beta 5, indicating an architectural difference at the ligand-binding site of these related integrins. This structural difference apparently results in a functional distinction, since purified alpha v beta 3 bound to vitronectin, fibrinogen, von Willebrand factor, and fibronectin, whereas integrin alpha v beta 5 bound preferentially to vitronectin. Finally, we demonstrate by three criteria that beta 5 and beta x, the latter of which was identified in lung carcinoma cells (Cheresh, D. A., Smith, J. W., Cooper, H. M., and Quaranta, V. (1989) Cell 57, 59-69), are identical. First, peptide maps of beta x and beta 5 are identical. Secondly, polyclonal antibodies raised against alpha v beta 5 immunoprecipitate both beta 5 and beta x, and finally, the amino-terminal amino acid sequences of beta x and beta 5 are identical.


Improved high sensitivity screen for Huntington disease using a one-step triplet-primed PCR and melting curve assay.
Molecular diagnosis of Huntington disease (HD) is currently performed by fluorescent repeat-flanking or triplet-primed PCR (TP-PCR) with capillary electrophoresis (CE). However, CE requires multiple post-PCR steps and may result in high cost in high-throughput settings. We previously described a cost-effective single-step molecular screening strategy employing the use of melting curve analysis (MCA). However, because it relies on repeat-flanking PCR, its efficiency in detecting expansion mutations decreases with increasing size of the repeat, which could lead to false-negative results. To address this pitfall, we have developed an improved screening assay coupling TP-PCR, which has been shown in CE-based assays to detect all expanded alleles regardless of size, with MCA in a rapid one-step assay. A companion protocol for rapid size confirmation of expansion-positive samples is also described. The assay was optimized on 30 genotype-known DNAs, and two plasmids pHTT(CAG)26 and pHTT(CAG)33 were used to establish the threshold temperatures (TTs) distinguishing normal from expansion-positive samples. In contrast to repeat-flanking PCR MCA, TP-PCR MCA displayed much higher sensitivity for detecting large expansions. All 30 DNAs generated distinct melt peak Tms which correlated well with each sample's larger allele. Normal samples were clearly distinguished from affected samples. The companion sizing protocol accurately sized even the largest expanded allele of ~180 CAGs. Blinded analysis of 69 clinical samples enriched for HD demonstrated 100% assay sensitivity and specificity in sample segregation. The assay targets the HTT CAG repeat specifically, tolerates a wide range of input DNA, and works well using DNA from saliva and buccal swab in addition to blood. Therefore, rapid, accurate, reliable, and high-throughput detection/exclusion of HD can be achieved using this one-step screening assay, at less than half the cost of fluorescent PCR with CE.


Primary arrest of circulating platelets on collagen involves phosphorylation of Syk, cortactin and focal adhesion kinase: studies under flow conditions.
After a vessel wall injury, platelets adhere to the subendothelium following a sequence of events: arrest of single platelets on the surface, progression to platelet spreading and final aggregation. Primary arrest of circulating platelets on subendothelial components occurs through platelet glycoprotein (GP) Ib and collagen receptors; then platelets spread and aggregate through a GPIIb-IIIa-dependent mechanism. A series of strategies were applied to analyse the tyrosine-phosphorylation mechanisms occurring at the different stages of platelet adhesion on subendothelial components under flow conditions, with special attention to primary arrest. To evaluate spread platelets, samples were exposed to acetylsalicylic acid, which blocks aggregate formation. To study single platelets in contact, a monoclonal antibody specific for GPIIb-IIIa was used to prevent platelet spreading and further aggregation. This experimental situation was also investigated using blood from two patients with Glanzmann's thrombasthenia (i.e. lacking GPIIb-IIIa). Results demonstrated that blockade of both spreading and aggregation results in significant changes in the tyrosine-phosphorylation patterns. Arrest of single platelets on collagen-rich surfaces resulted in phosphorylation of p125, identified as focal adhesion kinase (FAK), the 80/85 kDa doublet (cortactin), and p72, identified as Syk. Arrest of single platelets on von Willebrand factor as adhesive substrate showed that interaction through GPIb induces Syk phosphorylation, but not that of cortactin and FAK. Our data indicate that the initial arrest of platelets on subendothelial components involves Syk phosphorylation, which seems to be GPIb-dependent, and this is followed by activation and phosphorylation of cortactin and FAK. These processes seem to occur before GPIIb-IIIa becomes activated.


Insulin-like growth factor-binding protein (IGF-BP) inhibition of granulosa cell function: effect on cyclic adenosine 3',5'-monophosphate, deoxyribonucleic acid synthesis, and comparison with the effect of an IGF-I antibody.
The effects of insulin-like growth factor binding proteins (IGF-BPs) purified from porcine follicular fluid on granulosa cell function were examined using serum-free cultures of rat granulosa cells obtained from immature, diethylstilbestrol-treated rats. Both the so-called GH-dependent (IGF-BP3) and non-GH-dependent (IGF-BP2) proteins dose dependently inhibited granulosa cell estradiol and progesterone production with IC50s of 4.1-7.6 nM for IGF-BP3 and 12.6-12.9 nM for IGF-BP2, the actual value depending upon the steroid being measured. A specific antiserum directed against IGF-I also dose dependently suppressed both estradiol and progesterone production, although the effect on the latter was more marked. Experiments using cells that were primed with FSH to induce functional LH receptors showed that the inhibitory action of IGF-BP3 was specific to FSH. However, both IGF-BP3 and IGF-BP2 were capable of inhibiting both forskolin- and cholera toxin-stimulated steroidogenesis, confirming that neither compound was competing with FSH for binding to its receptor. Neither IGF-BP had any effect on either basal or FSH-stimulated cAMP production, while exogenously added IGF-I was stimulatory in this respect. However, both IGF-BPs inhibited FSH-stimulated [3H]thymidine uptake by the granulosa cells, while IGF-I had no effect on this parameter, suggestive of an IGF-independent effect on granulosa cell proliferation. Our data suggest that IGF-BPs have a multifaceted mode of action on granulosa cell function, and may therefore be an important regulator of follicular growth and differentiation.


Bone mineral density of the femoral neck in resurfacing hip arthroplasty.
Resurfacing total hip arthroplasty (RTHA) may preserve the femoral neck bone stock postoperatively. Bone mineral density (BMD) may be affected by the hip position, which might bias longitudinal studies. We investigated the dependency of BMD precision on type of ROI and hip position. We DXA-scanned the femoral neck of 15 resurfacing patients twice with the hip in 3 different rotations: 15 degrees internal, neutral, and 15 degrees external. For each position, BMD was analyzed with 3 surface area models. One model measured BMD in the total femoral neck, the second model divided the neck in two, and the third model had 6 divisions. When all hip positions were pooled, average coefficients of variation (CVs) of 3.1%, 3.6%, and 4.6% were found in the 1-, 2-, and 6-region models, respectively. The externally rotated hip position was less reproducible. When rotating in increments of 15 degrees or 30 degrees , the average CVs rose to 7.2%, 7.3%, and 12% in the 3 models. Rotation affected the precision most in the model that divided the neck in 6 subregions, predominantly in the lateral and distal regions. For larger-region models, some rotation could be allowed without compromising the precision. If hip rotation is strictly controlled, DXA can reliably provide detailed topographical information about the BMD changes around an RTHA. As rotation strongly affects the precision of the BMD measurements in small regions, we suggest that a less detailed model should be used for analysis in studies where the leg position has not been firmly controlled.


The Shank/ProSAP N-Terminal (SPN) Domain of Shank3 Regulates Targeting to Postsynaptic Sites and Postsynaptic Signaling.
Members of the Shank family of postsynaptic scaffold proteins (Shank1-3) link neurotransmitter receptors to the actin cytoskeleton in dendritic spines through establishing numerous interactions within the postsynaptic density (PSD) of excitatory synapses. Large Shank isoforms carry at their N-termini a highly conserved domain termed the Shank/ProSAP N-terminal (SPN) domain, followed by a set of Ankyrin repeats. Both domains are involved in an intramolecular interaction which is believed to regulate accessibility for additional interaction partners, such as Ras family G-proteins, αCaMKII, and cytoskeletal proteins. Here, we analyze the functional relevance of the SPN-Ank module; we show that binding of active Ras or Rap1a to the SPN domain can differentially regulate the localization of Shank3 in dendrites. In Shank1 and Shank3, the linker between the SPN and Ank domains binds to inactive αCaMKII. Due to this interaction, both Shank1 and Shank3 exert a negative effect on αCaMKII activity at postsynaptic sites in mice in vivo. The relevance of the SPN-Ank intramolecular interaction was further analyzed in primary cultured neurons; here, we observed that in the context of full-length Shank3, a closed conformation of the SPN-Ank tandem is necessary for proper clustering of Shank3 on the head of dendritic spines. Shank3 variants carrying Ank repeats which are not associated with the SPN domain lead to the atypical formation of postsynaptic clusters on dendritic shafts, at the expense of clusters in spine-like protrusions. Our data show that the SPN-Ank tandem motif contributes to the regulation of postsynaptic signaling and is also necessary for proper targeting of Shank3 to postsynaptic sites. Our data also suggest how missense variants found in autistic patients which alter SPN and Ank domains affect the synaptic function of Shank3.


A novel class of potent nonglycosidic and nonpeptidic pan-selectin inhibitors.
An early step of the inflammatory response, the rolling of leukocytes on activated endothelial cells, is mediated by selectin/carbohydrate interactions. The tetrasaccharide sialy Lewisx is a ligand for E-, P-, and L-selectin and therefore serves as a lead structure for the development of analogues. A combination of synthesis and structure-based design allowed rapid optimization. The current lead 2a was evaluated in our E-selectin cell flow chamber assay where it proved to inhibit rolling and adhesion with an IC50 of 28+/-7 microM. The assays used are predictive for the in vivo efficacy of test compounds as shown for 2a in a proteose peptone induced peritonitis model of acute inflammation in mice.


The novel high-affinity humanized antibody IMM40H targets CD70, eliminates tumors via Fc-mediated effector functions, and interrupts CD70/CD27 signaling.
A significant level of CD70 can be detected in various types of tumor tissues and CD27 is expressed on Treg cells, but CD70 expression is low in normal tissues. The interaction between CD70 and CD27 can stimulate the proliferation and survival of cancer cells and increase the level of soluble CD27, which is associated with poor prognosis in patients with lymphoma and certain solid tumors. Thus, it is a promising therapeutic target for the treatment of many major CD70+ cancer indications, including CD70+ lymphoma, RCC, NSCLC, HNSCC and OC. IMM40H was obtained through hybridoma screening and antibody humanization techniques. IMM40H was evaluated for its binding, blocking, Fc-dependent effector functions and antitumor activity characteristics in various in vitro and in vivo systems. The safety and tolerability profile of IMM40H were evaluated through single and repeated administration in cynomolgus monkeys. In vitro cell-based assays demonstrated that IMM40H had considerably stronger CD70-binding affinity than competitor anti-CD70 antibodies, including cusatuzumab, which enabled it to block the interaction of between CD70 and CD27 more effectively. IMM40H also exhibited potent Fc-dependent effector functions (ADCC/CDC/ADCP), and could make a strong immune attack on tumor cells and enhance therapeutic efficacy. Preclinical findings showed that IMM40H had potent antitumor activity in multiple myeloma U266B1 xenograft model, and could eradicate subcutaneously established tumors at a low dose of 0.3 mg/kg. IMM40H (0.3 mg/kg) showed therapeutic effects faster than cusatuzumab (1 mg/kg). A strong synergistic effect between IMM01 (SIRPα-Fc fusion protein) and IMM40H was recorded in Burkitt's lymphoma Raji and renal carcinoma cell A498 tumor models. In cynomolgus monkeys, the highest non-severely toxic dose (HNSTD) for repeat-dose toxicity was up to 30 mg/kg, while the maximum tolerated dose (MTD) for single-dose toxicity was up to 100 mg/kg, confirming that IMM40H had a good safety and tolerability profile. IMM40H is a high-affinity humanized IgG1 specifically targeting the CD70 monoclonal antibody with enhanced Fc-dependent activities. IMM40H has a dual mechanism of action: inducing cytotoxicity against CD70+ tumor cells via various effector functions (ADCC, ADCP and CDC) and obstructs the proliferation and activation of Tregs by inhibiting CD70/CD27 signaling.


Pulmonary sclerosing hemangioma with a rare symptom: A case report and review of the literature.
Pulmonary sclerosing hemangioma (PSH) is a relatively rare benign tumor. However, as it occurs only rarely, the natural course of the tumor is not well understood. In the present study, a case is presented of a 35-year-old woman who underwent intermittent fevers for more than one year. This case highlighted fever as a rare symptom of PSH. Fever is possibly one of the symptoms of PSH, although it is less likely to occur. Another symptom of the patient was that the tumor grew quickly in two months. The lesion was diagnosed as multiple sclerosing hemangioma of the lung (i.e., PSH), in which papillary, solid and sclerotic patterns appeared. Immunohistochemical evaluation of the lesion revealed positive staining for thyroid transcription factor 1 (TTF1), epithelial membrane antigen (EMA), pancytokeratin (PCK) and cytoskeleton 7 (CK7). In the present case study, the biological activity of PSH was identified to be aggressive. A review of the literature was performed in order to comment further on the clinical and pathological features of this rare disease.


Protein polymorphism in quail populations selected for large body size.
The polymorphism of five enzyme loci (amylase, alkaline phosphatase, albumin, for 4-week body weight was compared to that of the unselected control line (C). Three loci in the C line and two in the P line demonstrated polymorphism. Plasma amylase was separated into six bands and zymograms were classified on the basis of these bands into nine phenotypes. Three of the nine types were of relatively high activity and six were of relatively low activity. All nine types were found in the C line, whereas, all birds of the P line had only the most active type. Two alkaline phosphatase alleles (Akp-2B and Akp-2C) were segregating in the C line. Gene frequencies of alkaline phosphatase for the Akp-2B allele were 0.92 in the C line and 1.00 in the P line. Two albumin alleles (AlbQ1 and AlbQ2) were segregating in both populations. Gene frequencies for the AlbQ1 allele were 0.74 in the C line and 0.81 in the P line. Two red cell esterase-D alleles (Es-DF and Es-DS) were segregating in both populations. The gene frequency for the Es-DS allele (0.61) was higher than that of the Es-DF allele in the C line. In the P line the frequency of the Es-DF allele was higher than that of the Es-DS allele. Heterozygosities of the C and P lines were estimated as 0.2258 and 0.1560 respectively. The relative inbreeding coefficient of the P line, calculated from heterozygosities was 0.31.


Event distributions of polymer translocation.
We present event distributions for the polymer translocation obtained by extensive Langevin dynamics simulations. Such distributions have not been reported previously and they provide new understanding of the stochastic characteristics of the process. We extract at a high length scale resolution distributions of polymer segments that continuously traverse through a nanoscale pore. The obtained log-normal distributions together with the characteristics of polymer translocation suggest that it is describable as a multiplicative stochastic process. In spite of its clear out-of-equilibrium nature the forced translocation is surprisingly similar to the unforced case. We find forms for the distributions almost unaltered with a common cut-off length. We show that the individual short-segment and short-time movements inside the pore give the scaling relations τ∼Nα and τ∼f-β for the polymer translocation.


The Roles of Intuition and Informants' Expertise in Children's Epistemic Trust.
This study examined how children's intuitions and informants' expertise influence children's trust in informants' claims. Three- to 8-year-olds (N = 192) watched videos in which experts (animal/biology experts or artifact/physics experts) made either intuitively plausible or counterintuitive claims about obscure animals or artifacts. Claims fell either within or beyond experts' domains of expertise. Children of all ages were more trusting of claims made by informants with relevant, as opposed to irrelevant, expertise. Children also showed greater acceptance of intuitive rather than counterintuitive claims, a differentiation that increased with age as they developed firmer intuitions about what can ordinarily happen. In summary, children's trust in testimony depends on whether informants have the relevant expertise as well as on children's own developing intuitions.


Paclitaxel-loaded PLGA nanoparticles: potentiation of anticancer activity by surface conjugation with wheat germ agglutinin.
To potentiate the anticancer activity of paclitaxel-loaded PLGA nanoparticles through surface conjugation with wheat germ agglutinin (WGA). PLGA nanoparticles loaded with paclitaxel and isopropyl myristate (IPM) as release modifier were prepared by a solvent evaporation method. WGA was conjugated to the nanoparticle surface to give novel WIT-NP of 330+/-3 nm. In vitro cytotoxicity of WIT-NP against malignant (A549 and H1299) and normal (CCL-186) pulmonary cell lines was evaluated alongside control formulations. IC50 doses were determined by the MTT assay, while cellular apoptosis was detected by cell nuclei staining and DeadEndtrade mark Fluorometric TUNEL assay. Cell cycle arrest was confirmed by flow cytometry. Cellular uptake of 3[H]-paclitaxel from the test and control formulations was also quantified. In vivo anticancer efficacy was evaluated in the SCID mice model engrafted with the A549 tumor nodule. WIT-NP had superior anti-proliferation activity against the A549 and H1299 cell lines compared with conventional paclitaxel formulations as measured by IC50 doses. This was attributed to a more efficient intracellular accumulation of paclitaxel via WGA-receptor-mediated endocytosis and IPM-facilitated intracellular paclitaxel release. WIT-NP activity was associated with paclitaxel-induced apoptosis and cell arrest in the G2/M phase. A single intratumoral injection of WIT-NP at paclitaxel dose of 10 mg/kg inhibited the growth of A549 tumor nodules without inducing significant weight loss in the SCID mice over a period of 25 days. Tumor doubling time was greater than 25 days, compared with 11 days for nodules treated with conventional paclitaxel formulation. The formulation of WIT-NP, in which WGA is conjugated to the surface of paclitaxel and IPM-loaded PLGA nanoparticles, significantly potentiates the anticancer activity of paclitaxel.


Patient Experiences of Trauma Resuscitation.
Patient satisfaction is an increasingly common feature of quality measurement, and patient-centered care is a key aspect of high-quality clinical care. Incorporating patient preferences in an acute context, such as trauma resuscitation, presents distinct challenges; however, to our knowledge, patients' experiences of trauma resuscitation have not been explored. To describe patient experiences of trauma resuscitation and to identify opportunities to improve patient experience without compromising speed or thoroughness. This qualitative, descriptive study was conducted at an urban, academic, level I trauma center. Semistructured interviews and video observations were conducted from May to December 2015. Interview participants were adult English-speaking patients who had experienced trauma resuscitation and were clinically stable with no alteration in consciousness. We recruited interview participants and conducted video observations until thematic saturation was reached, resulting in 30 interviews and 20 observations. Video observation patients did not overlap with interview participants. The purposive sample included equal numbers of violently and nonviolently injured patients. Data were analyzed for thematic content from June 2015 to April 2016. The main outcomes reported are themes of patient experience. Of 30 interview participants, 25 were men (83.3%), and 21 were black (70.0%). Of 20 video observation patients, 16 were men (80.0%), and 17 were black (85.0%). Salient aspects of patient experience of trauma resuscitation included emotional responses, physical experience, nonclinical concerns, treatment and procedures, trauma team members' interactions, communication, and comfort. Participants drew satisfaction from trauma team members' demeanor, expertise, and efficiency and valued clear clinical communication, as well as words of reassurance. Dissatisfaction stemmed from the perceived absence of these attributes and from participants' emotional or physical discomfort. Observation data added insight into the components of care that may have contributed to participants' responses and those aspects of care that were not salient to participants. Although the urgency of trauma care limits explicit discussion and consideration of patient priorities, we found that patient concerns corresponded well with trauma team goals. Patients perceived trauma team members as competent, efficient, and caring. Focusing on patient communication could further improve patient-centeredness in this setting.


Acute rheumatic fever: a single center experience with 193 clinical cases.
Acute rheumatic fever is an inflammatory disease that develops via an auto-immune mechanism following group A beta hemolytic streptococcal tonsillopharyngitis. The aim of this study was to describe the clinical presentation of and cardiac involvement in acute rheumatic fever. The medical records of acute rheumatic fever patients admitted to the Pediatric Cardiology Unit between January 2001 and January 2013 were reviewed. The patients were divided into two groups: 53 patients admitted during January 2001-January 2007 were designated as group 1, and 140 patients admitted during January 2007-January 2013 were designated as group 2. A total of 193 patients were evaluated, including 53 in group 1 and 140 in group 2. There was no statistically significant difference in age, gender and latent period between the two groups. There was, however, a statistically significant difference between the annual number of cases (P=0.001). Moreover, 35 (66%) patients in group 1 and 89 (64%) patients in group 2 were admitted during the spring or winter. The most common finding, as the major criteria in the current study, was concurrent carditis and arthritis. The most common minor finding was the presence of increased acute-phase reactants. We noted a statistically significant difference between the two groups in terms of valvular involvement. Group 2 had significantly higher frequencies of isolated aortic and mitral regurgitation than group 1, but the composite frequency of these was lower. Acute rheumatic fever continues to be prevalent in Turkey despite the country's socioeconomic improvements. We conclude that echocardiography should be performed on all of the patients with suspected acute rheumatic fever because it markedly increases the detection of carditis.


Alterations in regional cerebral glucose metabolism across waking and non-rapid eye movement sleep in depression.
Depression is associated with sleep disturbances, including alterations in non-rapid eye movement (NREM) sleep. Non-rapid eye movement sleep is associated with decreases in frontal, parietal, and temporal cortex metabolic activity compared with wakefulness. To show that depressed patients would have less of a decrease than controls in frontal metabolism between waking and NREM sleep and to show that during NREM sleep, they would have increased activity in structures that promote arousal. Subjects completed electroencephalographic sleep and regional cerebral glucose metabolism assessments during both waking and NREM sleep using [(18)F]fluoro-2-deoxy-D-glucose positron emission tomography. General clinical research center. The study included 29 unmedicated patients who met the Structured Clinical Interview for DSM-IV criteria for current major depression and who had a score of 15 or greater on a 17-item Hamilton Rating Scale for Depression and 28 medically healthy subjects of comparable age and sex who were free of mental disorders. Electroencephalographic sleep and regional cerebral metabolism during waking and NREM sleep. Depressed patients showed smaller decreases than healthy subjects in relative metabolism in broad regions of the frontal, parietal, and temporal cortex from waking to NREM sleep. Depressed patients showed larger decreases than healthy subjects in relative metabolism in the left amygdala, anterior cingulate cortex, cerebellum, parahippocampal cortex, fusiform gyrus, and occipital cortex. However, in post hoc analyses, depressed patients showed hypermetabolism in these areas during both waking and NREM sleep. The smaller decrease in frontal metabolism from waking to NREM sleep in depressed patients is further evidence for a dynamic sleep-wake alteration in prefrontal cortex function in depression. Hypermetabolism in a ventral emotional neural system during waking in depressed patients persists into NREM sleep.


Medulloblastoma: molecular pathways and histopathological classification.
Malignant brain tumors are the leading cause of cancer death among pediatric patients, and medulloblastoma constitutes 20% of them. Currently, the treatment is risk-adapted. Maximum surgical resection is recommended, always followed by chemotherapy and neuroaxis radiotherapy. In spite of the improving survival rate, survivors succumb to treatment-induced side effects. To reduce toxic effects, molecular-targeted treatment is proposed. Medulloblastoma research is very robust, and new articles on the subject are published daily. In the current review we have tried to bring together molecular pathophysiology of the neoplasm and current pathological classification, thus making an effort to relate tumor biology and the histological picture.


HIV and the work intentions of public health nurses.
Studies have examined the association between attitudes about the human immunodeficiency virus (HIV) and nurses' willingness or intentions to work with infected persons. However, the relationship between these intentions and perceived concern from nurses' family and friends, or factors of professional nursing experience is relatively unexplored. An anonymous questionnaire was completed by 311 public health nurses from areas with high and low prevalence of acquired immunodeficiency syndrome (AIDS) in North Carolina. Multiple regression analysis showed that nurses had stronger intentions to work with HIV-infected clients if they had more favorable attitudes about the disease, perceived significant others [corrected] to be supportive of such work, had stronger professional ties to public health, and had worked fewer years in public health. In addition, nurses from low AIDS-prevalence areas had stronger intentions to work with these clients if they had professional nursing care experience with them. These findings are consistent with the Theory of Reasoned Action, but also identify professional nursing experience as independently associated with behavioral intentions. This suggests that attitudinal, normative, and professional experiences are all important in examining nurses' intentions to work with clients infected with HIV.


Genetic variation in regulatory DNA elements: the case of OCA2 transcriptional regulation.
Mutations within the OCA2 gene or the complete absence of the OCA2 protein leads to oculocutaneous albinism type 2. The OCA2 protein plays a central role in melanosome biogenesis, and it is a strong determinant of the eumelanin content in melanocytes. Transcript levels of the OCA2 gene are strongly correlated with pigmentation intensities. Recent studies demonstrated that the transcriptional level of OCA2 is to a large extent determined by the noncoding SNP rs12913832 located 21.5 kb upstream of the OCA2 gene promoter. In this review, we discuss current hypotheses and the available data on the mechanism of OCA2 transcriptional regulation and how this is influenced by genetic variation. Finally, we will explore how future epigenetic studies can be used to advance our insight into the functional biology that connects genetic variation to human pigmentation.


High-sensitivity cardiac troponin assays and acute coronary syndrome: a matter of sex?
: Advances in technology have led to an improvement in the ability to detect and quantify acute cardiomyocyte injury with the measurement of high-sensitivity cardiac troponin as compared with conventional assays. The upper reference limit for the high-sensitivity cardiac troponin assays is defined as the 99th percentile cutoff value in a healthy reference population. Since sex-related threshold levels of high-sensitivity cardiac troponin assays have been proposed, this review will focus on the diagnostic and prognostic implications of adopting sex-specific threshold troponin values in patients with a suspected acute coronary syndrome.


Ethylene-mediated improvement in sucrose accumulation in ripening sugarcane involves increased sink strength.
Sugarcane is a major crop producing about 80% of sugar globally. Increasing sugar content is a top priority for sugarcane breeding programs worldwide, however, the progress is extremely slow. Owing to its commercial significance, the physiology of sucrose accumulation has been studied extensively but it did not lead to any significant practical outcomes. Recent molecular studies are beginning to recognize genes and gene networks associated with this phenomenon. To further advance our molecular understanding of sucrose accumulation, we altered sucrose content of sugarcane genotypes with inherently large variation for sucrose accumulation using a sugarcane ripener, ethylene, and studied their transcriptomes to identify genes associated with the phenomenon. Sucrose content variation in the experimental genotypes was substantial, with the top-performing clone producing almost 60% more sucrose than the poorest performer. Ethylene treatment increased stem sucrose content but that occurred only in low-sugar genotype. Transcriptomic analyses have identified about 160,000 unigenes of which 86,000 annotated genes were classified into functional groups associated with carbohydrate metabolism, signaling, localization, transport, hydrolysis, growth, catalytic activity, membrane and storage, suggesting the structural and functional specification, including sucrose accumulation, occurring in maturing internodes. About 25,000 genes were differentially expressed between all genotypes and treatments combined. Genotype had a dominant effect on differential gene expression than ethylene treatment. Sucrose and starch metabolism genes were more responsive to ethylene treatment in low-sugar genotype. Ethylene caused differential gene expression of many stress-related transcription factors, carbohydrate metabolism, hormone metabolism and epigenetic modification. Ethylene-induced expression of ethylene-responsive transcription factors, cytosolic acid- and cell wall-bound invertases, and ATPase was more pronounced in low- than in high-sugar genotype, suggesting an ethylene-stimulated sink activity and consequent increased sucrose accumulation in low-sugar genotype. Ethylene-induced sucrose accumulation is more pronounced in low-sugar sugarcane genotype, and this is possibly achieved by the preferential activation of genes such as invertases that increase sink strength in the stem. The relatively high enrichment of differentially expressed genes associated with hormone metabolism and signaling and stress suggests a strong hormonal regulation of source-sink activity, growth and sucrose accumulation in sugarcane.


Room-temperature electrochemical reduction of epitaxial magnetite films to epitaxial iron films.
The electrochemical reduction of oxides to metals has been studied for decades. Earlier work produced polycrystalline bulk metals. Here, we report that pre-electrodeposited epitaxial face-centered cubic magnetite thin films can be electrochemically reduced to epitaxial body-centered cubic iron thin films in aqueous solution on single-crystalline gold substrates at room temperature. This technique opens new possibilities to produce special epitaxial metal/metal oxide heterojunctions and a wide range of epitaxial metallic alloy films from the corresponding mixed metal oxides.


Detection of oncostatin M in human plasma and serum by a sensitive enzyme immunoassay.
A sensitive and specific enzyme immunoassay was developed for detecting oncostatin M (OM) in human plasma and serum. The assay utilizes three anti-OM monoclonal antibodies that recognize mutually exclusive epitopes, including a neutralizing epitope. A sensitivity of 24 pg/ml was routinely obtainable. The assay showed no cross-reactivity with leukemia inhibitory factor (LIF) or interleukin-6 (IL-6), other members of the cytokine family that includes OM. The utility of the enzyme immunoassay (EIA) was demonstrated by detecting the time-dependent accumulation of OM in plasma from lipopolysaccharide (LPS)-treated human whole blood. The concentration of OM in human sera from normal donors was generally below the detection limits of the assay. However, concentrations of OM greater than 25 pg/ml were found in 17 of 212 serum samples from apparently normal donors. The detection of OM in human plasma and serum demonstrates that the EIA could be a useful tool in examining the role of OM in physiologic and pathologic states.


Synthesis and pharmacological evaluation of some 3-phenacyl-5-benzylidene-thiazolidine-2,4-diones.
The synthesis of 54 3-phenacyl-5-benzylidene-thiazolidine-2,4-diones is reported. Eight of them were tested for anti-oedema, analgesic and anticonvulsant activity. Only one compound showed significant anti-oedematous and analgesic activity. Three compounds protected against tonic seizures and death.


Vocabulary to support socially-valued adult roles.
Individuals who use augmentative and alternative communication (AAC) have new expectations for life after high school. However, the vocabulary needed to support socially-valued adult roles may not be available in their communication devices. This study explored whether vocabulary needed to participate in six adult roles currently existed in three widely used symbol sets. Electronic mailing lists were used to generate words needed for each adult role. From these vocabulary sets, discrepancy analyses were conducted to determine whether symbols or symbol combinations in each of the symbol sets studied could represent those words. Results suggest that, overall, an average of 55% of the identified words was currently available in these symbol sets. The need for easily accessible vocabulary that reflects socially-valued adult roles is discussed.


Malignant fibrous histiocytoma of the spermatic cord: a case report.
Malignant fibrous histiocytoma (MFH) of the spermatic cord represents an uncommon location for the most common soft-tissue tumor in adults. MFH of the spermatic cord is such a rare entity that only 28 case reports have been described in the literature to date. The rarity of MFH of the spermatic cord has made diagnosis, staging, and treatment difficult. Solutions to such questions will only be answered as our database continues to expand. Therefore, this case report is presented in hopes of lending statistical power to future analysis of the correct treatment planning, mortality rates, and prognostic indications of a relatively unknown subset of a common disease.


Application of Monte Carlo simulation in addressing key issues of complex coacervation formed by polyelectrolytes and oppositely charged colloids.
This paper reviews the recent advance of Monte Carlo (MC) simulation in addressing key issues of complex coacervation between polyelectrolytes and oppositely charged colloids. Readers were first supplied with a brief overview of current knowledge and experimental strategies in the study of complex coacervation. In the next section, the general MC simulation procedures as well as representative strategies applied in complex coacervation were summarized. The unique contributions of MC simulation in either capturing delicate features, easing the experimental trials or proving the concept were then elucidated through the following aspects: i) identify phase boundary and decouple interaction contributions; ii) clarify composition distribution and internal structure; iii) predict the influences of physicochemical conditions on complex coacervation; iv) delineate the mechanisms for "binding on the wrong side of the isoelectric point". Finally, current challenges as well as prospects of MC simulation in complex coacervation are also discussed. The ultimate goal of this review is to provide readers with basic guideline for synergistic design of experiments in combination with MC simulation, and deliver convincing interpretation and reliable prediction for the structure and behavior in polyelectrolyte-macroion complex coacervation.


Synthesis of Benzofuran-2-One Derivatives and Evaluation of Their Antioxidant Capacity by Comparing DPPH Assay and Cyclic Voltammetry.
The present work aimed to synthesise promising antioxidant compounds as a valuable alternative to the currently expensive and easily degradable molecules that are employed as stabilizers in industrial preparation. Taking into account our experience concerning domino Friedel-Crafts/lactonization reactions, we successfully improved and extended the previously reported methodology toward the synthesis of 3,3-disubstituted-3H-benzofuran-2-one derivatives 9-20 starting from polyphenols 1-6 as substrates and either diethylketomalonate (7) or 3,3,3-trifluoromethyl pyruvate (8) as electrophilic counterpart. The antioxidant capacity of the most stable compounds (9-11 and 15-20) was evaluated by both DPPH assay and Cyclic Voltammetry analyses performed in alcoholic media (methanol) as well as in aprotic solvent (acetonitrile). By comparing the recorded experimental data, a remarkable activity can be attributed to few of the tested lactones.


Interaction of clavulanic acid, sulbactam and cephamycin antibiotics with beta-lactamases.
The inhibitory effects of clavulanic acid, sulbactam and cephamycin antibiotics on chromosomally-mediated or plasmid-mediated beta-lactamases were investigated. The inhibition constants were determined by a non-linear regression analysis. Clavulanic acid and sulbactam had high affinities for the purified plasmid-mediated beta-lactamases such as SHV-1, TEM-1 and PSE-4, and were potent inhibitors as shown by their low Ki values. Except for Bacteroides beta-lactamase, which is sensitive to inhibition by cephamycin antibiotics, clavulanic acid and sulbactam were found not to be as effective against chromosomally-mediated beta-lactamases. The cephamycin antibiotics were better inhibitors of chromosomally-mediated beta-lactamases than those that are plasmid mediated. Except for P99 beta-lactamase, against which sulbactam and clavulanic acid were inactive, the cephamycin antibiotics were less effective inhibitors than sulbactam and clavulanic acid.


Causal association between inflammatory bowel disease and herpes virus infections: a two-sample bidirectional Mendelian randomization study.
Previous observational or retrospective studies have suggested an association between inflammatory bowel disease (IBD) and herpes virus infections. Using Mendelian randomization (MR) approach, our objective was to determine whether there was a causal association between IBD and herpes virus infections. In genome-wide association study (GWAS) datasets of the International Inflammatory Bowel Disease Genetics Consortium, we obtained genetic instrumental variables for three phenotypes from 34,652 participants (12,882 IBD cases and 21,770 controls), 27,432 participants [6,968 ulcerative colitis (UC) cases and 20,464 controls], and 20,883 participants [5,956 Crohn's disease (CD) cases and 14,927 controls], respectively. Summary statistics for herpes virus infections (chickenpox, herpes zoster, and mononucleosis) were obtained from the FinnGen database. MR results were expressed as odds ratio (OR) with 95% confidence interval (CI). Our study found no evidence of a causal effect of genetically predicted IBD on herpes virus infections [P value for inverse variance weighting (IVW): 0.063 to 0.652]. For the subtypes of IBD, UC had a suggestive association with mononucleosis (P value for IVW: 0.023). It appeared that CD was also weakly associated with mononucleosis (P value for IVW: 0.058; P value for Weighted median: 0.036). In addition, we found a suggestive causality for CD on chickenpox (P value for IVW: 0.038). Neither UC (P value for IVW: 0.574) nor CD (P value for IVW: 0.168) has a causal effect on herpes zoster. The results of the bidirectional MR analysis did not indicate that herpes virus infections were associated with IBD, UC or CD (P value for IVW: 0.239 to 0.888). This study showed a suggestive causality for both CD-chickenpox and UC-mononucleosis, despite no associations reaching a statistical significance value after corrections for multiple testing. There was no evidence of a causal association between IBD and its two subtypes on herpes zoster.


Susceptibility Risk Alleles of -238G/A, -308G/A and -1031T/C Promoter Polymorphisms of TNF-α Gene to Uterine Leiomyomas.
Uterine Leiomyomas (UL) are non-cancerous single celled mass of uterine smooth muscles distinguished by presence of large amounts of collagen, fibronectin and proteoglycans. Tumor necrosis factor-α (TNF-α), an inflammation inducing cytokine, plays a major role in various disorders of the immune system; is involved in tumor development and progression. It is proposed to study the influence of three functional promoter polymorphisms of TNF-α viz -238G/A, -308G/A and -1031T/C in the development and progression of UL. Study included 146 individuals positive for uterine fibroids and 150 healthy individuals. Genomic DNA was isolated from white blood corpuscles and subjected to PCR-RFLP analysis and Allele Specific PCR (ARMS). The significance of the obtained data in controls and patients was estimated and computed by adopting appropriate statistical tools. In this study an association between TNF-α -1031T/C polymorphism and UL was reported. A significant association of the TC genotype (χ(2) - 14.34; p=0.0008) and the C allele (χ(2) - 5.898 p=0.015) with uterine leiomyomas was observed. Likewise odds risk estimates of 2.56 (95% CI 1.56-4.20, p=0.0007) revealed a significant association of TC genotype and C allele with uterine leiomyomas. "TC" genotype and "C" allele of rs1799964 (-1031T/C) is associated with higher risks to leiomyomas. The "C" allele of -1031T/C results in an increased expression TNF-α leading to smooth cell proliferation and tumor progression, hence, may be a relevant molecular marker in the identification and establishment of UL.


How Much Do Common Imaging Studies Cost? A Nationwide Survey of Radiology Trainees.
The objective of this study was to gauge the knowledge of radiology trainees regarding the costs of common imaging services and to assess their perceptions of current relevant education. During mid-2014, an online survey of 5325 U.S. residents and fellows who were members of the American College of Radiology was conducted. Respondents were asked to provide information about year of training, relevant advanced degrees (e.g., Master of Business Administration or Master of Public Health), number of hours of formal education in health care economics provided annually by their training program, self-perception of knowledge of health care economics, and desire to learn more about the costs of imaging. Respondents were asked to estimate Medicare-allowable fees for five commonly performed imaging examinations: two-view chest radiography, contrast-enhanced CT of the abdomen and pelvis, unenhanced MRI of the lumbar spine, complete abdominal ultrasound, and unenhanced CT of the brain. Responses within ± 25% of published allowable amounts in the Medicare fee schedule were deemed correct. A total of 1066 of 5325 trainees (20.0%) returned surveys that were sufficiently complete for analysis. Only 17.1% of all responses were correct; 65.3% of responses were overestimations of actual costs, and 17.6% were underestimations. Almost half of the trainees (45.1%) incorrectly estimated the cost of every examination. Overall, knowledge of costs of examinations did not improve with advancing years of training, hours of education in health care economics, or attainment of a relevant advanced degree. Only 9.3% of trainees considered their knowledge of imaging costs to be adequate. An overwhelming 89.7% of trainees desired more focused education. Radiology trainees have limited knowledge of the costs of commonly performed imaging studies. Effective training program curricula currently appear to be lacking. Targeted education and integration of cost information into clinical decision support tools are probably warranted.


Moving toward reconciliation in indigenous child welfare.
The Touchstones of Hope reconciliation movement consists of principles (culture and language, self-determination, structural interventions, non discrimination, and holistic approach) that guide a reconciliation process of truth-telling, acknowledging, restoring and relating to reshape indigenous child welfare led by indigenous peoples and supported by their non-indigenous counterparts. This article describes a reconciliation movement in Canada grounded in Touchstones of Hope principles, involving a reconciliation process between indigenous and non-indigenous individuals, which has enabled culturally relevant concepts of child welfare and plans for child safety to emerge.


Student satisfaction and self report of CPR competency: HeartCode BLS courses, instructor-led CPR courses, and monthly voice advisory manikin practice for CPR skill maintenance.
This study evaluated the effects of brief monthly refresher training on CPR skill retention, confidence, and satisfaction with CPR skill level of 606 nursing students from ten different US schools. Students were randomized to course type, HeartCode™ Basic Life Support (BLS) or an instructor-led (IL) course, and then randomized to a practice group, six minutes of monthly practice or no further practice. End-of-study survey results were compiled and reported as percentages. Short answer data were grouped by category for reporting. Fewer HeartCode™ BLS students were satisfied with their CPR training compared to the IL students. Students who practiced CPR monthly were more confident than students who did not practice. Monthly practice improved CPR confidence, but initial course type did not. Students were most satisfied when they participated in the IL courses and frequent practice of CPR skills.


Identification and assessment of classification criteria attributes for systemic lupus erythematosus in a regional medical record data network.
To assess the application and utility of algorithms designed to detect features of SLE in electronic health record (EHR) data in a multisite, urban data network. Using the Chicago Area Patient-Centered Outcomes Research Network (CAPriCORN), a Clinical Data Research Network (CDRN) containing data from multiple healthcare sites, we identified patients with at least one positively identified criterion from three SLE classification criteria sets developed by the American College of Rheumatology (ACR) in 1997, the Systemic Lupus International Collaborating Clinics (SLICC) in 2012, and the European Alliance of Associations for Rheumatology and the ACR in 2019 using EHR-based algorithms. To measure the algorithms' performance in this data setting, we first evaluated whether the number of clinical encounters for SLE was associated with a greater quantity of positively identified criteria domains using Poisson regression. We next quantified the amount of SLE criteria identified at a single healthcare institution versus all sites to assess the amount of SLE-related information gained from implementing the algorithms in a CDRN. Patients with three or more SLE encounters were estimated to have documented 2.77 (2.73 to 2.80) times the number of positive SLE attributes from the 2012 SLICC criteria set than patients without an SLE encounter via Poisson regression. Patients with three or more SLE-related encounters and with documented care from multiple institutions were identified with more SLICC criteria domains when data were included from all CAPriCORN sites compared with a single site (p<0.05). The positive association observed between amount of SLE-related clinical encounters and the number of criteria domains detected suggests that the algorithms used in this study can be used to help describe SLE features in this data environment. This work also demonstrates the benefit of aggregating data across healthcare institutions for patients with fragmented care.


[In situ expression of IL-1 beta and IL-2 mRNA in thymuses from patients with myasthenia gravis].
The expression of IL-1 beta mRNA and IL-2 mRNA was analyzed in seven thymuses from patients with myasthenia gravis (MG) and in three normal thymuses using in situ hybridization techniques. Cells containing IL-beta mRNA were detected in all seven cases. These IL-1 beta producing cells were mainly located and clustered in the connective structures of thymic septae and peri-lobuler area like anti-keratin AE3 positive cells. The distribution of anti-CD68 positive cells was different from that of IL-1 beta producing cells in thymus of myasthenia gravis patients. IL-2 producing cells were also found in all seven cases, and their frequency (number of cells/mm2) had a tendency to correlate with the severity of the disease. On the other hand, we could not find both IL-1 beta mRNA and IL-2 mRNA in three normal thymuses. These results suggested a possible role of high IL-1 beta and IL-2 production to activate T cells in myasthenia gravis thymus. Furthermore, in situ production of IL-2 might be reflected in the severity of the disease.


Changes in lipid metabolism and β-adrenergic response of adipose tissues of periparturient dairy cows affected by an energy-dense diet and nicotinic acid supplementation.
Dairy cattle will mobilize large amounts of body fat during early lactation as an effect of decreased lipogenesis and increased lipolysis. Regulation of lipid metabolism involves fatty acid synthesis from acetate and β-adrenergic-stimulated phosphorylation of hormone-sensitive lipase (HSL) and perilipin in adipocytes. Although basic mechanisms of mobilizing fat storage in transition cows are understood, we lack a sufficiently detailed understanding to declare the exact regulatory network of these in a broad range of dairy cattle. The objective of the present study was to quantify 1) protein abundance of fatty acid synthase (FAS), 2) extent of phosphorylation of HSL and perilipin in vivo, and 3) β-adrenergic stimulated lipolytic response of adipose tissues in vitro at different stages of the periparturient period. We fed 20 German Holstein cows an energy-dense or an energetically adequate diet prepartum and 0 or 24 g/d nicotinic acid (NA) supplementation. Biopsy samples of subcutaneous and retroperitoneal adipose tissue were obtained at d 42 prepartum (d -42) and at d 1, 21, and 100 postpartum (d +1, d +21, d +100, respectively). To assess β-adrenergic response, tissue samples were incubated with 1 μ isoproterenol for 90 min at 37°C. The NEFA and glycerol release, as well as HSL and perilipin phosphorylation, was measured as indicators of in vitro stimulated lipolysis. In addition, protein expression of FAS and extent of HSL and perilipin phosphorylation were measured in fresh, nonincubated samples. There was no effect of dietary energy density or NA on the observed variables. The extent of HSL and perilipin phosphorylation under isoproterenol stimulation was strongly correlated with the release of NEFA and glycerol, consistent with the functional link between β-adrenergic-stimulated protein phosphorylation and lipolysis. In the nonincubated samples, FAS protein expression was decreased at d +1 and d +21, whereas HSL and perilipin phosphorylation increased from d -42 to d +1 and remained at an increased level throughout the first 100 d of lactation. In vitro lipolytic response was significant in prepartum samples at times when in vivo lipolysis was only minimally activated by phosphorylation. These data extend our understanding of the complex nature of control of lipolysis and lipogenesis in dairy cows and could be useful to the ongoing development of systems biology models of metabolism to help improve our quantitative knowledge of the cow.


Tumor-infiltrating B cells come into vogue.
Lymphocyte infiltration into solid tumors has been recognized as a main determinator of positive prognosis. For the most part this is attributed to cytotoxic T cells capable of directly destroying malignant cells. However, when considering the complex composition of the human immune system, recent findings of Nielsen et al on a potentially central role of tumor-infiltrating B cells is not really surprising. In this commentary article, I want to highlight the enormous potential impact of this observation for basic and translational research, prognostic procedures and ultimately for the development of future therapeutic concepts.


[Analysis of structure and function of meibomian glands in healthy population at different ages].
Objective: To observe the structure and function of meibomian glands in normal population at different ages. Methods: From October 2011 to August 2012, meibomian gland information was collected in healthy volunteers without any symptoms of ocular discomfort, aged more than 5 years. The people were grouped by every 10 years of age. The meibomian gland opening, secretion state and characteristics and Max's line were observed by slit lamp microscopic examination, and the meibomian gland dropouts were examined by noncontact infrared meibomian gland microscopy. The changes of meibomian glands were scored from 0 to 3, 0 for a normal state, 1 for mild abnormality, 2 for moderate abnormality and 3 for severe abnormality. The Mann-Whitney U test was used to compare the meibomian scores between male and female, and between left and right eyes. The correlation of these scores and the age of volunteers was analyzed by the Spearman test. Results: Among all the 100 volunteers, there were 47 males and 53 females, aged from 5 to 83 years (mean, 40.9±22.9). The meibomian gland dropouts were gradually increasing with age, significantly faster after 40 years old (scores for each age group were 2(1), 2(1), 2(1), 2(1), 3(2), 3.5(1.75), 4(3), 6(2). Meibomian gland opening, secretion traits and secretor status gradually became poorer with age, and changes were dramatically fast in the group of 40-49 years of age [scores of this group were 3(1.5), 3(3) and 2(2)], but slowed down after age of 50 years. Moreover, the Max's line position moved to the front gradually with age, with a marked change in the group of 40-49 years of age [scores for each age group were 0(1), 1(1), 2(2), 2(2), 3(2), 2(2), 3(2)], 4 gland changes showed a significantly positive relation to age(r=0.729, 0.635, 0.669, 0.639, 0.470. P<0.01), but not to gender and eye dominance (P>0.05). Conclusions: Meibomian gland opening and meibomian gland secretion become worse with age. The age of 50 years old is the key period for the meibomian gland changes. (Chin J Ophthalmol, 2017, 53: 528-533).


The emotion recognition system based on autoregressive model and sequential forward feature selection of electroencephalogram signals.
Electroencephalogram (EEG) is one of the useful biological signals to distinguish different brain diseases and mental states. In recent years, detecting different emotional states from biological signals has been merged more attention by researchers and several feature extraction methods and classifiers are suggested to recognize emotions from EEG signals. In this research, we introduce an emotion recognition system using autoregressive (AR) model, sequential forward feature selection (SFS) and K-nearest neighbor (KNN) classifier using EEG signals during emotional audio-visual inductions. The main purpose of this paper is to investigate the performance of AR features in the classification of emotional states. To achieve this goal, a distinguished AR method (Burg's method) based on Levinson-Durbin's recursive algorithm is used and AR coefficients are extracted as feature vectors. In the next step, two different feature selection methods based on SFS algorithm and Davies-Bouldin index are used in order to decrease the complexity of computing and redundancy of features; then, three different classifiers include KNN, quadratic discriminant analysis and linear discriminant analysis are used to discriminate two and three different classes of valence and arousal levels. The proposed method is evaluated with EEG signals of available database for emotion analysis using physiological signals, which are recorded from 32 participants during 40 1 min audio visual inductions. According to the results, AR features are efficient to recognize emotional states from EEG signals, and KNN performs better than two other classifiers in discriminating of both two and three valence/arousal classes. The results also show that SFS method improves accuracies by almost 10-15% as compared to Davies-Bouldin based feature selection. The best accuracies are %72.33 and %74.20 for two classes of valence and arousal and %61.10 and %65.16 for three classes, respectively.


[Morphologic characteristics of the urothelial bladder tumors].
Cancer of the urinary bladder is the fourth most common cancer in men and the ninth in women. Approximately 67,000 people (50,000 males and 17,000 females) develop bladder cancer each year in the United States, and 13,750 individuals (9,630 males and 4,120 females) are expected to die from it. In the showing of the morphologic characteristics of the tumors, authors underlining the increasing of the incidence, pathogenesis, premalignant lesions and the risk factors of disease.


Delay discounting as emotional processing: an electrophysiological study.
Both theoretical models and functional imaging studies implicate the involvement of emotions within the delay discounting process. However, defining this role has been difficult to establish with neuroimaging techniques given the automaticity of emotional responses. To address this, the current study examined electrophysiological correlates involved in the detection and evaluation of immediate and delayed monetary outcomes. Our results showed that modulation of both early and later ERP components previously associated with affective stimuli processing are sensitive to the signalling of delayed rewards. Together with behavioural reaction times that favoured immediacy, we demonstrated, for the first time, that time delays modify the incentive value of monetary rewards via mechanisms of emotional bias and selective visual attention. Furthermore, our data are consistent with the hypothesis that delayed and thus intangible rewards are perceived less saliently, and rely on emotion as a common currency within decision making. This study provides a new approach to delay discounting and highlights a potential novel route through which delay discounting may be investigated.


Drug approval prediction based on the discrepancy in gene perturbation effects between cells and humans.
Poor translation between in vitro and clinical studies due to the cells/humans discrepancy in drug target perturbation effects leads to safety failures in clinical trials, thus increasing drug development costs and reducing patients' life quality. Therefore, developing a predictive model for drug approval considering the cells/humans discrepancy is needed to reduce drug attrition rates in clinical trials. Our machine learning framework predicts drug approval in clinical trials based on the cells/humans discrepancy in drug target perturbation effects. To evaluate the discrepancy to predict drug approval (1404 approved and 1070 unapproved drugs), we analysed CRISPR-Cas9 knockout and loss-of-function mutation rate-based gene perturbation effects on cells and humans, respectively. To validate the risk of drug targets with the cells/humans discrepancy, we examined the targets of failed and withdrawn drugs due to safety problems. Drug approvals in clinical trials were correlated with the cells/humans discrepancy in gene perturbation effects. Genes tolerant to perturbation effects on cells but intolerant to those on humans were associated with failed drug targets. Furthermore, genes with the cells/humans discrepancy were related to drugs withdrawn due to severe side effects. Motivated by previous studies assessing drug safety through chemical properties, we improved drug approval prediction by integrating chemical information with the cells/humans discrepancy. The cells/humans discrepancy in gene perturbation effects facilitates drug approval prediction and explains drug safety failures in clinical trials. S.K. received grants from the Korean National Research Foundation (2021R1A2B5B01001903 and 2020R1A6A1A03047902) and IITP (2019-0-01906, Artificial Intelligence Graduate School Program, POSTECH).


Yin and yang of interleukin-17 in host immunity to infection.
The interleukin-17 (IL-17) family cytokines, such as IL-17A and IL-17F, play important protective roles in host immune response to a variety of infections such as bacterial, fungal, parasitic, and viral. The IL-17R signaling and downstream pathways mediate induction of proinflammatory molecules which participate in control of these pathogens. However, the production of IL-17 can also mediate pathology and inflammation associated with infections. In this review, we will discuss the yin-and-yang roles of IL-17 in host immunity to pathogens.


Intragastric Balloon Treatment for Obesity: Review of Recent Studies.
The FDA recently approved three intragastric balloon (IGB) devices, ReShape, ORBERA™, and Obalon for treatment of obesity. Given the high cost, complication risk, and invasiveness of bariatric surgery, IGB treatment may present a safer and lower cost option for weight reduction. IGBs are generally placed in the stomach endoscopically for up to 6 months to reduce gastric capacity, enhance feelings of fullness, and induce weight loss. The mechanism of action likely involves stimulation of gastric mechanoreceptors triggering short-acting vagal signals to brain regions implicated in satiety. Balloon efficacy may be influenced by balloon volume, patient gastric capacity, and treatment duration. This review focused on eight recent (2006-present) randomized controlled trials (RCTs) comparing percentage total body weight loss (%TBWL) between IGB and control groups including three reviewed by the FDA. %TBWL based on the reviewed studies was also compared with bariatric surgery and pharmacotherapy. Of the eight IGB studies, five had balloon treatment duration of 6 months. Efficacy at 6 months, based on a pooled weighted-mean %TBWL, was 9.7%, and the control-subtracted %TBWL was 5.6%. When one study without SDs was removed, the weighted mean %TBWL was 9.3 ± 5.7% SD, and control-subtracted %TBWL was 5.5 ± 7.8%, which was statistically greater than controls. IGB showed lower efficacy than bariatric surgery (median weight loss of 27% for Rouen-Y gastric bypass (RYGB). The control-subtracted %TBWL over 6 months of 5.5-5.6% is less than the most efficacious FDA-approved weight loss drug, Qsymia. At the recommended dose, Qsymia has a placebo-subtracted %TBWL at 6 months of approximately 6.6%. The weighted mean reported incidence of serious adverse events (SAEs) in the IGB group across all eight studies was 10.5%. Only six of the eight reviewed studies reported adverse events (AEs) in the IGB group, with a pooled reported incidence of 28.2%. Recently, the FDA reported new AEs including acute pancreatitis with ReShape and ORBERA™. Based on the available evidence, it is unlikely that IGB use will supplant other forms of obesity treatment. The estimated cost of endoscopic balloon implantation and retrieval is US $8,150. Collectively, a relatively small control-subtracted %TBWL and the potential for serious complications makes IGB unlikely to become widely adopted. Given the recent FDA warning, IGB longevity on the market is questionable.


A simple and effective protein folding activity suitable for large lectures.
This article describes a simple and inexpensive hands-on simulation of protein folding suitable for use in large lecture classes. This activity uses a minimum of parts, tools, and skill to simulate some of the fundamental principles of protein folding. The major concepts targeted are that proteins begin as linear polypeptides and fold to three-dimensional structures, noncovalent interactions drive this folding process, and the final folded shape of a protein depends on its amino acid sequence. At the start of the activity, students are given pieces of insulated wire from which they each construct and fold their own polypeptide. This activity was evaluated in three ways. A random sample of student-generated polypeptides collected after the activity shows that most students were able to create an appropriate structure. After this activity, students (n = 154) completed an open-ended survey. Their responses showed that more than three-quarters of the students learned one or more of the core concepts being demonstrated. Finally, a follow-up survey was conducted seven weeks after the activity; responses to this survey (n = 63) showed that a similar fraction of students still retained these key concepts. This activity should be useful in large introductory-level college biology or biochemistry lectures.


A response-time approach to comparing generalized rational and take-the-best models of decision making.
The authors develop and test generalized versions of take-the-best (TTB) and rational (RAT) models of multiattribute paired-comparison inference. The generalized models make allowances for subjective attribute weighting, probabilistic orders of attribute inspection, and noisy decision making. A key new test involves a response-time (RT) approach. TTB predicts that RT is determined solely by the expected time required to locate the 1st discriminating attribute, whereas RAT predicts that RT is determined by the difference in summed evidence between the 2 alternatives. Critical test pairs are used that partially decouple these 2 factors. Under conditions in which ideal observer TTB and RAT strategies yield equivalent decisions, both the RT results and the estimated attribute weights suggest that the vast majority of subjects adopted the generalized TTB strategy. The RT approach is also validated in an experimental condition in which use of a RAT strategy is essentially forced upon subjects.


Long-term outcome in patients registered with tuberculosis in Zomba, Malawi: mortality at 7 years according to initial HIV status and type of TB.
Zomba Central Hospital, Malawi. To determine the outcome of all adult patients who were registered for tuberculosis (TB) treatment 7 years previously according to initial human immunodeficiency virus (HIV) status and type of TB. A retrospective cohort study of adult patients registered for TB treatment between July and December 1995. Follow-up at patients' homes was performed at the end of treatment, at 32 months and at 84 months (7 years) from the time of TB registration. Eight hundred and twenty-seven TB patients were registered: 793 had concordant HIV test results, of whom 612 (77%) were HIV-positive. At 7 years, 136 (17%) patients were alive, 539 (65%) had died and 152 (18%) were lost to follow-up. The death rate for all TB patients was 23.7 per 100 person-years of observation. HIV-positive patients had higher death rates than HIV-negative patients (hazard ratio [HR] 2.2, 95% confidence interval [95%CI] 1.7-2.8). Death rates in smear-negative pulmonary TB patients (HR 2.1, 95%CI 1.7-2.6) and in patients with extra-pulmonary TB (HR 1.7, 95% CI 1.3-2.0) were higher than in patients with smear-positive PTB. There was a high mortality rate in TB patients during and after anti-tuberculosis treatment. Adjunctive treatments to reduce death rates are urgently needed.


Organism Detection in Permeable Pavement Parking Lot Infiltrates at the Edison Environmental Center, New Jersey.
Three types of permeable pavements were monitored at the Edison Environmental Center in Edison, New Jersey, for indicator organisms such as fecal coliform, enterococci, and Escherichia coli. Results showed that porous asphalt had a much lower concentration in monitored infiltrate compared to pervious concrete and permeable interlocking concrete pavers; concentrations of monitored organisms in infiltrate from porous asphalt were consistently below the bathing water quality standard and actually had limited detection. Fecal coliform and enterococci exceeded bathing water quality standards more than 72 and 34% of the time for permeable interlocking concrete pavers and pervious concrete, respectively. Concentration reductions greater than 90% were observed for all three indicator organisms for porous asphalt and fecal coliform and E. coli for pervious concrete when compared to runoff values, while permeable interlocking concrete pavers only had a modest (39%) observable reduction for E. coli only. The near absence of indicator organisms observed in the porous asphalt infiltrate may be due to the high pH potentially due to asphalt processing. Neither rain intensity nor temperature was demonstrated to have an observable effect in both concentrations of organisms and performance of permeable pavement; but this may due to the limitations of the dataset consisting of 16 events over an 8-month period.


Decreased lung function is associated with risk of developing non-alcoholic fatty liver disease: A longitudinal cohort study.
Decreased lung function is associated with non-alcoholic fatty liver disease (NAFLD), based on linking mechanisms such as insulin resistance and systemic inflammation However, its association with the risk of developing NAFLD is unclear. Our aim was to investigate whether baseline lung function is associated with incident NAFLD in middle-aged healthy Koreans. A cohort study of 96,104 subjects (mean age: 35.7 years) without NAFLD were followed up from 2002 to 2015. NAFLD was diagnosed by ultrasound after the exclusion of other possible causes of liver diseases. Baseline percent predicted forced expiratory volume in one second (FEV1%) and forced vital capacity (FVC%) were categorized in quartiles. Adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) (using the highest quartile as reference) were calculated for incident NAFLD at follow-up, controlling for covariates and potential confounders. During 579,714.5 person-years of follow-up, 24,450 participants developed NAFLD (incidence rate, 42.2 per 1,000 person-years). The mean follow-up period was 5.9±3.4 years. Regardless of smoking history, the risk for incident NAFLD increased with decreasing quartiles of FEV1 (%) and FVC (%) in a dose-response manner (p for trend<0.001). In never smokers, the aHRs (95% CIs) for incident NAFLD were 1.15 (1.08-1.21), 1.11 (1.05-1.18), and 1.08 (1.02-1.14) in quartiles 1-3 for FEV1 (%) and 1.12 (1.06-1.18), 1.11 (1.05-1.18), and 1.09 (1.03-1.15) in quartiles 1-3 for FVC (%), compared with the highest quartile reference. Similar inverse association was present in smoke-exposed subjects (aHR for incident NAFLD were 1.14, 1.21, 1.13 and 1.17, 1.11, 1.09 across FEV1(%) and FVC(%) quartile in increasing order, respectively). Reduced lung function was a risk factor for incident NAFLD in a large middle-aged Korean cohort with over half a million person-years of follow-up.


[Toxic effects of fluoride on rat cerebral cortex astrocytes in vitro].
To study astrocytes cellular cycle and the activities of SDH, 5'-NT and ACP in rat cerebral cortex astrocytes by NaF in vitro. Astrocytes of rat cerebral cortex were purified and cultured in vitro to obtain the highly purified cells (identified by immunochemistry of anti-GFAP). The constituent ratio of cell cycle was analyzed by FCM after the cells were cultured with different levels of NaF for different time span. Activities of SDH, 5'-NT and ACP were tested by UV colorimetry. Cell cycle arrest transited from S phase to G2/M phase and subG1 cells increased in 1-5 mmol/L in the astrocyte cycle treated with different levels of NaF for different time span by using FCM. There was inverse correlation between the relative amount of the subG1 DNA and activities of SDH and ACP respectively (SDH: r = -0.84148, P < 0.05; ACP: r = -0.90416, P < 0.01) that were inhibited by NaF and 5 mmol/L NaF can inactivate 5'-NT in astrocytes. NaF can induce cell cycle arrest from S to G2/M and inhibit activities of 5'-NT,SDH and ACP in astrocytes.


MICROSPORUM NANUM: FIRST RECORDED ISOLATION FROM ANIMALS IN THE UNITED STATES.
The first cases in the United States of swine infections caused by the fungus Microsporum nanum are reported. The infections occurred in a herd of Yorkshire swine in Pennsylvania. The dermatophyte, which readily produced experimental infections, was identified by isolation and studies in pure cultures.


Bedside selection of positive end-expiratory pressure by electrical impedance tomography in hypoxemic patients: a feasibility study.
Positive end-expiratory pressure (PEEP) is a key element of mechanical ventilation. It should optimize recruitment, without causing excessive overdistension, but controversy exists on the best method to set it. The purpose of the study was to test the feasibility of setting PEEP with electrical impedance tomography in order to prevent lung de-recruitment following a recruitment maneuver. We enrolled 16 patients undergoing mechanical ventilation with PaO2/FiO2 <300 mmHg. In all patients, under constant tidal volume (6-8 ml/kg) PEEP was set based on the PEEP/FiO2 table proposed by the ARDS network (PEEPARDSnet). We performed a recruitment maneuver and monitored the end-expiratory lung impedance (EELI) over 10 min. If the EELI signal decreased during this period, the recruitment maneuver was repeated and PEEP increased by 2 cmH2O. This procedure was repeated until the EELI maintained a stability over time (PEEPEIT). The procedure was feasible in 87% patients. PEEPEIT was higher than PEEPARDSnet (13 ± 3 vs. 9 ± 2 cmH2O, p < 0.001). PaO2/FiO2 improved during PEEPEIT and driving pressure decreased. Recruited volume correlated with the decrease in driving pressure but not with oxygenation improvement. Finally, regional alveolar hyperdistention and collapse was reduced in dependent lung layers and increased in non-dependent lung layers. In hypoxemic patients, a PEEP selection strategy aimed at stabilizing alveolar recruitment guided by EIT at the bedside was feasible and safe. This strategy led, in comparison with the ARDSnet table, to higher PEEP, improved oxygenation and reduced driving pressure, allowing to estimate the relative weight of overdistension and recruitment.


Renal vein thrombosis and nephrotic syndrome. A prospective study of 36 adult patients.
During 2 years we studied 36 of 41 consecutive patients with nephrotic syndrome. Twelve (Group 1) had renal vein thrombosis; the renal pathology was membranous glomerulonephritis in 10 and membranoproliferative glomerulonephritis in 2. Eighteen without renal vein thrombosis (Group 2) had either membranous (10 patients) or membranoproliferative (8 patients) glomerulonephritis. Clinical presentation, laboratory data, renal function, renal histology, and immunopathology were similar in both groups; thromboembolic phenomena were frequent. Ten of 12 patients with renal vein thrombosis were given oral anticoagulants and followed for 4 to 24 months. None died or had thromboembolic episodes. The results show that one third of the patients with nephrotic syndrome associated with either membranous or membranoproliferative glomerulonephritis had renal vein thrombosis, and there were no clinical, laboratory, histological, or immunopathological finding(s) diagnostic of renal vein thrombosis. Our data indicate that renal vein thrombosis is a frequent complication in nephrotic syndrome and membranous or membranoproliferative glomerulonephritis.


Degree of supersaturation-regulated chiral symmetry breaking in one crystal.
This paper aimed at studying chiral symmetry-breaking phenomena in one crystal. Preferential crystallization of racemic asparagines was carried out in nonseeded stagnant solutions through slow cooling. By varying the supersaturation, only one transparent crystal could be obtained at enough low supersaturation of dl-asparagine, and the crystal was not pure enantiomer with crystal enantiomeric excess increasing inversely with the degree of supersaturation. Crystal enantiomeric excess can amount up to 85% in one transparent crystal. Because no secondary nucleation occurred except for stochastic primary nucleation, we suggest that primary nucleation and competition between l- and d-nuclei were considered to be a mechanism for asymmetry amplification. High-performance capillary electrophoresis coupled with laser-induced fluorescence was used to separate and quantify l- and d-asparagine and the enantiomeric excess value can be calculated according to their concentration.


Monte Carlo Simulation of TRIM Algorithm in Ceramic Biomaterial in Proton Therapy.
Biomaterials play a crucial role in enhancing human health and quality of life. They are employed in applications such as tissue substitution, diagnostic tools, medical supplies, therapeutic treatments, regenerative medicine, and radiation dosimetric studies. However, their predisposition to proton therapy, which is a trending treatment in the world, has not been adequately studied. Ceramic biomaterials, known for their hardness and durability, offer versatile uses, especially in bone tissue replacements. The wide range of physical, mechanical, and chemical properties exhibited by ceramics has spurred extensive research, development, and application in this field. This study focuses on investigating and analyzing the ionization, recoils, phonon release, collision events, and lateral scattering properties of ceramic biomaterials that closely resemble bone tissue in proton therapy applications. Monte Carlo (MC) Transport of Ions in Matter (TRIM) simulation tools were utilized for this analysis. The results showed that Silicon dioxide exhibited the Bragg peak position closest to bone tissue, with a deviation of 10.6%. The average recoils differed by 1.7%, and the lateral scattering differed by 3.6%. The main innovation of this study lies in considering interactions such as recoil, collision events, phonon production, and lateral scattering when selecting biomaterials, despite their limited digitization and understanding. By evaluating all these interactions, the study aimed to identify the most suitable ceramic biomaterial to replace bone tissue in proton therapy.


A new preferentially outcrossing monoicous species of Volvox sect. Volvox (Chlorophyta) from Thailand.
Volvox sect. Volvox is an interesting group of green algae; it comprises mostly monoicous species, but evidence suggests an evolution towards dioicy. Based on cultured strains originating from Thailand, we describe Volvox longispiniferus, a novel species in Volvox sect. Volvox. This species is distinguished from others in the section by the large number of sperm packets in its monoicous sexual spheroids and by the long spines on its zygote wall. Phylogenetic analyses indicate that V. longispiniferus is distinct from the other species of two monophyletic groups within Volvox sect. Volvox. In addition, the novel species produces more zygotes when different cultures are combined compared with a single culture, suggesting a preference for outcrossing.


Temperature variability is integrated by a spatially embedded decision-making center to break dormancy in Arabidopsis seeds.
Plants perceive and integrate information from the environment to time critical transitions in their life cycle. Some mechanisms underlying this quantitative signal processing have been described, whereas others await discovery. Seeds have evolved a mechanism to integrate environmental information by regulating the abundance of the antagonistically acting hormones abscisic acid (ABA) and gibberellin (GA). Here, we show that hormone metabolic interactions and their feedbacks are sufficient to create a bistable developmental fate switch in Arabidopsis seeds. A digital single-cell atlas mapping the distribution of hormone metabolic and response components revealed their enrichment within the embryonic radicle, identifying the presence of a decision-making center within dormant seeds. The responses to both GA and ABA were found to occur within distinct cell types, suggesting cross-talk occurs at the level of hormone transport between these signaling centers. We describe theoretically, and demonstrate experimentally, that this spatial separation within the decision-making center is required to process variable temperature inputs from the environment to promote the breaking of dormancy. In contrast to other noise-filtering systems, including human neurons, the functional role of this spatial embedding is to leverage variability in temperature to transduce a fate-switching signal within this biological system. Fluctuating inputs therefore act as an instructive signal for seeds, enhancing the accuracy with which plants are established in ecosystems, and distributed computation within the radicle underlies this signal integration mechanism.


Burnout and self-efficacy: a study on teachers' beliefs when implementing an innovative educational system in the Netherlands.
In the Netherlands, secondary education has seen radical changes that originated with the national authorities, including the Study-home system, a pupil-centred approach in which teachers help develop pupils' independent working and creative thinking in order to get them to take responsibility for their own academic achievements. As educational innovations are more often than not accompanied by stress, the present study focuses on the onset of burnout among teachers who recently implemented this innovative system in the Netherlands. To test hypotheses that the extent to which teachers have a negative attitude towards the new instructional practices relates positively to their level of burnout, and that their self-efficacy beliefs regarding implementation of the practices and coping with stress involved in this relate negatively to their burnout levels. A random sample of 490 teachers employed in the Study-home system participated in this study. Three questionnaires were used. The Dutch version of the Maslach Burnout Inventory for teachers (Schaufeli & Van Horn, 1995) was used to assess the teachers' burnout level. Second, a specially developed self-efficacy questionnaire relating to the domains of: (1) guiding groups of students using the principle of differentiation, (2) involving pupils with tasks and (3) use of innovative educational practices. Last, a questionnaire on the teachers' attitudes concerning the usefulness and effectiveness of the Study-home as an educational innovation. Regression analyses showed that the self-efficacy beliefs for each of the three domains were significantly and negatively related to the depersonalisation and emotional exhaustion dimensions of burnout, and significantly positively related to the personal accomplishment dimension. Furthermore, the more negative the teachers' attitudes towards the Study-home appeared to be, the more they appeared to suffer from depersonalisation and emotional exhaustion, and the lower they scored on the personal accomplishment dimension of burnout. The study's results indicate that teachers' self-efficacy beliefs are related to their burnout level. Teachers with strong self-efficacy beliefs seem to be more prepared to experiment with, and later also to implement new educational practices.


MicroRNA-92a is a circadian modulator of neuronal excitability in Drosophila.
Many biological and behavioural processes of animals are governed by an endogenous circadian clock, which is dependent on transcriptional regulation. Here we address post-transcriptional regulation and the role of miRNAs in Drosophila circadian rhythms. At least six miRNAs show cycling expression levels within the pigment dispersing factor (PDF) cell-pacemaker neurons; only mir-92a peaks during the night. In vivo calcium monitoring, dynamics of PDF projections, ArcLight, GCaMP6 imaging and sleep assays indicate that mir-92a suppresses neuronal excitability. In addition, mir-92a levels within PDF cells respond to light pulses and also affect the phase shift response. Translating ribosome affinity purification (TRAP) and in vitro luciferase reporter assay indicate that mir-92a suppresses expression of sirt2, which is homologous to human sir2 and sirt3. sirt2 RNAi also phenocopies mir-92a overexpression. These experiments indicate that sirt2 is a functional mir-92a target and that mir-92a modulates PDF neuronal excitability via suppressing SIRT2 levels in a rhythmic manner.


Work-related interventions during office visits to occupational health physicians.
Systematically applied work-related interventions during visits to occupational health (OH) physicians support the preventive and health promotive goals of OH. The proportion of the visits including a work-related intervention was analyzed according to patient, health problem, and physician determinants in a sample of visits to OH physicians in Finland. A cross-sectional study was carried out among 55 Occupational Health Services (OHS) units. Office encounters with 4,404 male and 5,373 female employed patients ages 18-64 years, recorded by 114 OHS physicians, were analyzed. Altogether 856 (8.8%) encounters included a work-related intervention. The work-related interventions were distributed across all the main disease categories, the majority of which were musculoskeletal diseases. Of the patient determinants, occupational group (the residual group of non-white-collar or non-blue-collar workers) associated positively with a work-related intervention, while age or gender did not. The physician's female gender and experience associated positively with work-related interventions. Work-related interventions took place more often in integrated and joint model OHS than in municipal health care centers and private medical centers. Work-related interventions are used by OH physicians for diverse health problems. More research is needed to better understand the reasons for the observed differences in work-related interventions. Also, research is needed to evaluate the efficiency of such interventions.


Patient self-management of oral anticoagulation.
Patient self-management of oral anticoagulation is now widely practised in Germany and the USA. There are three different home-testing monitors available in the UK which are all reliable in terms of accuracy and reproducibility of results. Selected patients can be trained to perform their own International Normalized Ratio (INR) testing and dosing, with outcomes as good if not better than those from specialized anticoagulant clinics. Consensus on the frequency of testing and what quality control should be deployed is lacking. The cost-effectiveness in the UK is unproven.


Discovery of Pyrrolo[2,3-c]pyridines as Potent and Reversible LSD1 Inhibitors.
Lysine specific demethylase 1 (LSD1) acts as an epigenetic eraser by specifically demethylating mono- and histone 3 lysine 4 (H3K4) and H3 lysine 9 (H3K9) residues. LSD1 has been pursued as a promising therapeutic target for the treatment of human cancer, and a number of LSD1 inhibitors have been advanced into clinical development. In the present study, we describe our discovery of pyrrolo[2,3-c]pyridines as a new class of highly potent and reversible LSD1 inhibitors, designed on the basis of a previously reported LSD1 inhibitor GSK-354. Among them, 46 shows an IC50 value of 3.1 nM in inhibition of LSD1 enzymatic activity and inhibits cell growth with IC50 values of 0.6 nM in the MV4;11 acute leukemia cell line and 1.1 nM in the H1417 small-cell lung cancer cell line. Compound 46 (LSD1-UM-109) is a novel, highly potent, and reversible LSD1 inhibitor and serves as a promising lead compound for further optimization.


Phosphorus-rich structures and capsular architecture in Cryptococcus neoformans.
In this study, we aimed to analyze the relationship of phosphorus-rich structures with surface architecture in Cryptococcus neoformans. Phosphorus-rich structures in C. neoformans were analyzed by combining fluorescence microscopy, biochemical extraction, scanning electron microscopy, electron probe x-ray microanalysis and 3D reconstruction of high pressure frozen and freeze substituted cells by focused ion beam-scanning electron microscopy (FIB-SEM). Intracellular and surface phosphorus-enriched structures were identified. These molecules were required for capsule assembly, as demonstrated in experiments using polysaccharide incorporation by capsule-deficient cells and mutants with defects in polyphosphate synthesis. The demonstration of intracellular and cell wall-associated polyphosphates in C. neoformans may lead to future studies involving their participation in both physiologic and pathogenic events.


[Estimation of personal dose based on the dependent calibration of personal dosimeters in interventional radiology].
The purpose of present study is, in interventional radiology (IVR), to elucidate the differences between each personal dosimeter, and the dependences and calibrations of area or personal dose by measurement with electronic dosimeters in particular. We compare space dose rate distributions measured by an ionization survey meter with the value measured by personal dosimeter: an optically stimulated luminescence, two fluoroglass, and two electronic dosimeters. Furthermore, with electronic dosimeters, we first measured dose rate, energy, and directional dependences. Secondly, we calibrated the dose rate measured by electronic dosimeters with the results, and estimated these methods with coefficient of determination and Akaike's Information Criterion (AIC). The results, especially in electronic dosimeters, revealed that the dose rate measured fell by energy and directional dependences. In terms of methods of calibration, the method is sufficient for energy dependence, but not for directional dependence, because of the lack of stable calibration. This improvement poses a question for the future. The study suggested that these dependences of the personal dosimeter must be considered when area or personal dose is estimated in IVR.