Assessment of the estrogenic activity of flue gases from burning processes by means of the yeast based human estrogen receptor (hER) bioassay.
Combustion processes are known to produce organic micro-pollutants in the flue gas at concentrations ranging over several orders of magnitude. Some organic micro-pollutants are suspected of being pseudo-estrogens and as such they can affect the public health. In this study, the possible application of the yeast based human estrogen receptor (hER) bioassay to screen flue gas streams for the presence of estrogenic active micro-pollutants was explored. Specifically, the protocol was modified to allow the detection and quantification of the potential estrogenic active non-polar organic micro-pollutants contained in the flue gas matrix. The modified assay was calibrated using a model estrogenic compound (17-alpha-ethinylestradiol (EE2)) dissolved in methylene chloride at concentrations ranging from 3 ng l(-1) to 3000 ng l(-1). The effective concentration to elucidate a 50% response (EC50) was 87 ng l(-1) of equivalent dissolved in methylene chloride. Samples of methylene chloride used to trap non-polar micro-pollutants in flue gas from combustion of pine wood were found to clearly register estrogenic activity by the bioassay under certain conditions. The combustion tests were performed with pinewood alone and with pine wood in the presence of both Copper-naphthenate and copper(II)chloride at 600 degrees C and 1000 degrees C. These conditions must be considered as experimental rather than practical. Overall, the results suggest that, by means of this modified assay, it is possible and warranted to screen systematically for estrogens in flue gas combustion processes.


Serotonin receptors in rat jugular vein: presence and involvement in the contraction.
Serotonin (5-hydroxytryptamine; 5-HT) is released during platelet aggregation, a phenomenon commonly observed in blood clot formation and venous diseases. Once released, 5-HT can interact with its receptors in the peripheral vasculature to modify vascular tone. The goal of this study was to perform a detailed pharmacological characterization of the 5-HT receptors involved in the contractile response of the rat jugular vein (RJV) using recently developed drugs with greater selectivity toward 5-HT receptor subtypes. We hypothesized that, as for other blood vessels, the 5-HT(1B/1D) and 5-HT(2B) receptor subtypes mediate contraction in RJV alongside the 5-HT(2A) receptor subtype. Endothelium-intact RJV rings were set up in an isolated organ bath for isometric tension recordings, and contractile concentration-effect curves were obtained for 13 distinct serotonergic receptor agonists. Surprisingly, the 5-HT(1A) and the mixed 5-HT(1A/1B) receptor agonists (+/-)-2-dipropyl-amino-8-hydroxyl-1,2,3,4-tetrahydronapthalene (8-OH-DPAT) and 5-methoxy-3 (1,2,3,6-tetrahydropyridin-4-yl) (1H indole) (RU24969) caused contractions that were antagonized by the 5-HT(1A) receptor antagonist [O-methyl-3H]-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide (WAY100135). The contractile curve to 5-HT was shifted to the right by WAY100135, 3-[2-[4-(4-fluoro benzoyl)-piperidin-1-yl]ethyl]-1H-quinazoline-2,4-dione (ketanserin; 5-HT(2A/C) receptor antagonist), and 1-(2-chloro-3,4-dimethoxybenzyl)-6-methyl-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole hydrochloride (LY266097; 5-HT(2B) receptor antagonist). Ketanserin also caused rightward shifts of the contractile curves to 8-OH-DPAT, RU24969, and the 5-HT(2B) receptor agonist (alpha-methyl-5-(2-thienylmethoxy)-1H-indole-3-ethanamine) (BW723C86). Agonists for 5-HT(1B/1D/1F), 5-HT(3), 5-HT(6), and 5-HT(7) receptors were inactive. In real-time polymerase chain reaction experiments that have never been performed in this tissue previously, we observed mRNA expression for the 5-HT(2A), 5-HT(2B), and 5-HT(7) receptors, whereas no significant mRNA expression was found for 5-HT(1A), 5-HT(1B), and 5-HT(1D) receptors. These results support the 5-HT(2A) receptor as the main subtype targeted by 5-HT to contract the RJV.


Nepalese patients' anti-diabetic medication taking behaviour: an exploratory study.
To explore anti-diabetic medication taking behaviour in Nepalese patients with type 2 diabetes and investigate the factors impacting medication taking in this population. Face-to-face interviews (n = 48) were conducted with Nepalese patients with type 2 diabetes in Sydney (Australia) and Kathmandu (Nepal). All interviews were audio-recorded, transcribed verbatim and thematically analysed. Participants' medication adherence was also assessed quantitatively using the summary of diabetes self-care activity (SDSCA) questionnaire. The medication taking behaviour of Nepalese participants aligned with the Stages of Change Model, with some notable patterns of behaviour. Most participants initiated and implemented anti-diabetic medications soon after obtaining their prescription. However, a few, delayed initiation and/or ceased medications after initiation to recommence later. Nonetheless, upon recommencement, participants persisted fairly well with their medications. The self-reported medication adherence was high (97.3%). Although some participants expressed adherence as a challenge at the start of therapy, medication taking on a day-to-day basis was not reported as difficult. Factors such as participants' reluctance towards using medications and preference for natural methods of treatment, together with inadequate understanding about diabetes and treatment resulted in the delay in initiating therapy, and contributed to cessation of therapy. On the other hand, ooccasional non-adherence in daily medication taking was mostly related to inconsistency in meal practices and forgetfulness. Encouragement from doctors and increased awareness about the disease and treatment facilitated medication adherence, including initiation of therapy. This study demonstrates that Nepalese patients are likely to delay or cease anti-diabetic medications until they fully accept and acknowledge the benefits and necessity of medications for effective diabetes management. Thus, educating patients about the need for medications, as well as implementing strategies to address patients' psychological resistance towards medications will be essential for effective medication management.


Second-Sphere Polyhedron-Distortion-Induced Broadened and Red-Shifted Emission in Lu3(MgxAl2-x)(Al3-xSix)O12:Ce3+ for Warm WLED.
Orange-yellow phosphors with extended broadband emission are highly desirable for warmer white-light-emitting diodes (WLED) with a higher color-rendering index. Targeted phosphors Ce3+-doped Lu3(MgxAl2-x)(Al3-xSix)O12 (x = 0, 0.25, 0.50, 0.75, and 1.00) were developed by chemical composition modification for luminescent tuning from green to orange-yellow with spectral broadening. The correlation between structure evolution and luminescent properties was elucidated by the local structure, fluorescence lifetime, and Eu3+ luminescence as a structural probe. The polyhedron distortion in the second-sphere coordination leads to the site differentiation and symmetry degradation of Ce3+ with the accommodation of (MgSi)6+ pairs, comprehensively resulting in the red shift (540 → 564 nm) and broadening in emission spectra. The WLED fabrication results demonstrate that the red shift and broadening in the emission of Lu3(MgxAl2-x)(Al3-xSix)O12:Ce3+ make it more suitable for the single-phosphor converted warm WLED.


An oral microjet vaccination system elicits antibody production in rabbits.
Noninvasive immunization technologies have the potential to revolutionize global health by providing easy-to-administer vaccines at low cost, enabling mass immunizations during pandemics. Existing technologies such as transdermal microneedles are costly, deliver drugs slowly, and cannot generate mucosal immunity, which is important for optimal immunity against pathogens. We present a needle-free microjet immunization device termed MucoJet, which is a three-dimensional microelectromechanical systems-based drug delivery technology. MucoJet is administered orally, placed adjacent to the buccal tissue within the oral cavity, and uses a self-contained gas-generating chemical reaction within its two-compartment plastic housing to produce a high-pressure liquid jet of vaccine. We show that the vaccine jet ejected from the MucoJet device is capable of penetrating the buccal mucosal layer in silico, in porcine buccal tissue ex vivo, and in rabbits in vivo. Rabbits treated with ovalbumin by MucoJet delivery have antibody titers of anti-ovalbumin immunoglobulins G and A in blood serum and buccal tissue, respectively, that are three orders of magnitude higher than rabbits receiving free ovalbumin delivered topically by a dropper in the buccal region. MucoJet has the potential to accelerate the development of noninvasive oral vaccines, given its ability to elicit antibody production that is detectable locally in the buccal tissue and systemically via the circulation.


Changes in the fatty acid composition of cerebrosides and sulfatides of human nervous tissue with age.
Sphingogalactolipids (galactocerebrosides and sulfatides) have been isolated in almost quantitative yields from normal human nervous tissue (mostly brain) at different ages and their fatty acid compositions have been determined by gas-liquid chromatography. The ratio of hydroxy acids to normal acids increased slightly during myelination and then remained rather constant; in adults the ratio for cerebrosides was about 2, and for sulfatides, 0.6-0.8. In adult nervous tissue the two predominant fatty acids of cerebrosides and sulfatides were the C(24) monounsaturated and 2-hydroxy saturated acids. The infant brain galactolipids had (compared with child and adult) a lower percentage of C(22)-C(26) fatty acids and a much lower percentage of monoenoic acids, both of normal and hydroxy acids. Low activities of fatty acid elongation and desaturation systems during myelination are inferred. Fatty acid changes with age were the same for cerebrosides and sulfatides but occurred later in the sulfatides, which supports the hypothesis that the cerebrosides are precursors of the sulfatides. The adult pattern of fatty acid composition with regard to degree of unsaturation and total percentage of C(22)-C(26) acids was reached as early as at 2 yr of age, but the percentage of odd-numbered (C(23) and C(25)) fatty acids continued to increase up to the age of 10-15 yr. The fatty acid composition of the galactolipids of peripheral nerves differed mainly in its lower percentages of C(25) and C(26) acids and higher percentages of C(22) and C(16) acids. This composition is thus intermediate between those of brain and of extraneural organs.


A Model for Determining the Effect of the Wind Velocity on 100 m Sprinting Performance.
This paper introduces an equation for determining instantaneous and final velocity of a sprinter in a 100 m run completed with a wind resistance ranging from 0.1 to 4.5 m/s. The validity of the equation was verified using the data of three world class sprinters: Carl Lewis, Maurice Green, and Usain Bolt. For the given constant wind velocity with the values + 0.9 and + 1.1 m/s, the wind contribution to the change of sprinter velocity was the same for the maximum as well as for the final velocity. This study assessed how the effect of the wind velocity influenced the change of sprinting velocity. The analysis led to the conclusion that the official limit of safely neglecting the wind influence could be chosen as 1 m/s instead of 2 m/s, if the velocity were presented using three, instead of two decimal digits. This implies that wind velocity should be rounded off to two decimal places instead of the present practice of one decimal place. In particular, the results indicated that the influence of wind on the change of sprinting velocity in the range of up to 2 m/s and was of order of magnitude of 10-3 m/s. This proves that the IAAF Competition Rules correctly neglect the influence of the wind with regard to such velocities. However, for the wind velocity over 2 m/s, the wind influence is of order 10-2 m/s and cannot be neglected.


[Expression of Erwinia chrysanthemi ENA49 uvr gene in Escherichia coli K12 cells].
The uvrA gene of Erwinia chrysanthemi ENA49 similar to uvrA gene of Escherichia coli K12 has been cloned in vivo in Escherichia coli AB1886 uvrA6 cells using the plasmid pULB113 (RP4mini Mu). The presence of pULB113 carrying uvrA gene of Erwinia in Escherichia coli K12 uvrA- cells resulted in suppression of this mutation while uvrB and uvrC are not suppressed by this locus. The genetic control of excision repair of UV-damage in Erwinia chrysanthemi ENA49 is concluded to be similar to the one in Escherichia coli K12.


[Hybrid cardiac SPECT-CT proves safe and effective: diagnosis of coronary heart disease completed in one day].
Hybrid cardiac SPECT-CT is a technique in which data from both nuclear single photon emission tomography (SPECT) and a CT scan are combined. These techniques are complementary to each other, as CT provides information about anatomy of coronary arteries (stenosis, calcification, aberrant vessels) while SPECT detects functional consequences such as myocardial ischemia. In 2009, the Isala Hospital in Zwolle (the Netherlands) was one of the first centres in Europe to introduce this technique. Hybrid cardiac SPECT-CT has proved to be effective and safe in reaching a comprehensive diagnosis and gives the physician the ability to reach a diagnosis in only one day. In addition, it has led to about 20% fewer invasive coronary angiograms. Utilising this technique requires close collaboration between cardiologists and nuclear medicine specialists.


Iloprost antagonizes endothelin-induced vasoconstriction in macro- and microcirculation.
In conscious Wistar rats, endothelin (ET-I) caused a dose-dependent long-lasting blood pressure increase, which was more pronounced after indomethacin pretreatment. The initial blood pressure drop was also enhanced after indomethacin. The stable prostacyclin analogue iloprost completely reversed the pressor effect of endothelin. In the hamster cheek pouch, ET-I caused a rapidly developing, long-lasting constriction of arterioles, which could be completely reversed by iloprost. The results demonstrate that prostacyclin can act as a potent functional antagonist of endothelin-induced systemic and local pressor responses.


Studies on kidney function in subjects exposed to organic solvents. I. Excretion of albumin and beta-2-microglobulin in the urine.
The urine of 134 subjects, exposed to different organic solvents, and 48 unexposed subjects has been analysed with reference to albumin and beta-2-microglobulin excretion. The exposed subjects excreted significantly larger quantities of albumin than the unexposed. Those exposed to styrene excreted the largest amounts. No significant difference in beta-microglobulin excretion could be demonstrated between the groups.


Assessing the Readability of Freely Available ICU Notes.
Unstructured data stored in an electronic health record (EHR) system can be very informative but require techniques such as natural language processing to extract the information. Developing such techniques requires shared data, but clinical data are often not easy to access. A freely available intensive care unit database, MIMIC-III, was released in 2016 to address this issue and benefit the informatics research community. While the database has been utilized by a few studies, the text characteristics of the notes have not been summarized. In this study, we present the summary of the basic text characteristics and the readability of the MIMIC-III ICU notes. We further compare the results with our previous study where proprietary EHR notes were used. The results show that the text characteristics of MIMIC-III notes were comparable with proprietary EHR notes, although the note readability index was slightly lower. The clinical notes in MIMIC-III can be a viable option for researchers who are interested in clinicians' language use but have no access to proprietary EHR systems.


Association of P2X7R gene polymorphisms with systemic lupus erythematosus in a Chinese population.
The P2X7 receptor is a ligand-gated cationic channel receptor that is actived by ATP and normally expressed by a variety of immune system cells, including macrophages and lymphocytes. Because it leads to release of IL-1β and cell death by apoptosis or necrosis, it is a potential therapeutic target for a variety of autoimmune inflammatory diseases, such as systemic lupus erythematosus (SLE). The P2X7R gene is highly polymorphic, and many single-nucleotide polymorphisms (SNPs) have been detected. A case-control study was performed to investigate the associations of SNPs in the P2X7R gene (rs1718119, rs2230911 and rs3751143) with susceptibility to SLE in 535 Chinese SLE patients and 532 controls. Results showed that rs1718119 was associated with SLE; in particular carriers of the A allele and AA/AG/(AG+AA) genotypes were at lower risk of the disease [A versus G, P < 0.001, odds ratio (OR) = 0.543, 95% CI: 0.424-0.697; AG versus GG, P = 0.018, OR = 0.659, 95% CI: 0.466-0.931; AA versus GG, P = 0.011, OR = 0.176, 95% CI: 0.046-0.668; AG+AA versus GG, P = 0.004, OR = 0.607, 95% CI: 0.433-0.850], but no significant differences in rs2230911 and rs3751143 were observed between SLE patients and controls. Stratification of cases for the presence of nephritis showed that rs2230911 G allele and CG/(CG+GG) genotypes were at a lower risk of SLE with nephritis (LN) (G versus C, P = 0.011, OR = 0.640, 95% CI: 0.454-0.903; CG versus CC, P = 0.035, OR = 0.645, 95% CI: 0.429-0.970; GG versus CC, P = 0.101, OR = 0.349, 95% CI: 0.099-1.228; CG+GG versus CC, P = 0.015 OR = 0.612, 95% CI: 0.411-0.910), but rs1718119 and rs3751143 were not associated with LN. Analysis of the haplotypes revealed one haplotype (ACA) that appeared to be a significantly 'protective' haplotype (P = 0.009, OR = 0.708, 95% CI: 0.546-0.918) with SLE. The findings suggest that the P2X7R gene might contribute to SLE susceptibility in the Chinese population.


Expression of a cholera toxin B subunit-neutralizing epitope of the porcine epidemic diarrhea virus fusion gene in transgenic lettuce (Lactuca sativa L.).
Transgenic plants have been used as a safe and economic expression system for the production of edible vaccines. A synthetic cholera toxin B subunit gene (CTB) was fused with a synthetic neutralizing epitope gene of the porcine epidemic diarrhea virus (sCTB-sCOE), and the sCTB-sCOE fusion gene was introduced into a plant expression vector under the control of the ubiquitin promoter. This plant expression vector was transformed into lettuce (Lactuca sativa L.) using the Agrobacterium-mediated transformation method. Stable integration and transcriptional expression of the sCTB-sCOE fusion gene was confirmed using genomic DNA PCR analysis and northern blot analysis, respectively. The results of western blot analysis with anti-cholera toxin and anti-COE antibody showed the synthesis and assembly of CTB-COE fusion protein into oligomeric structures with pentameric sizing. The biological activity of CTB-COE fusion protein to its receptor, G(M1)-ganglioside, in transgenic plants was confirmed via G(M1)-ELISA with anti-cholera toxin and anti-COE antibody. Based on G(M1)-ELISA, the expression level of CTB-COE fusion proteins reached 0.0065% of the total soluble protein in transgenic lettuce leaf tissues. Transgenic lettuce successfully expressing CTB-COE fusion protein will be tested to induce efficient immune responses against porcine epidemic diarrhea virus infection by administration with raw material.


Demonstration of a releasable pool of glutamate in cerebellar mossy and parallel fibre terminals by means of light and electron microscopic immunocytochemistry.
The chemical substance(s) responsible for the fast signalling in the mossy fibre to granule cell synapses in the cerebellum has not been identified, although recent studies suggest that glutamate is a strong candidate. In the present investigation, this issue was explored by means of a quantitative electron microscopic immunocytochemical procedure. Ultrathin sections of plastic-embedded rat cerebella were treated with an antiserum specific for glutaraldehyde-fixed glutamate, followed by a secondary antibody coupled to colloidal gold particles. The gold particle density over mossy fibre terminals was assessed in tissue that had been rapidly fixed by perfusion, as well as in tissue that had been incubated in artificial cerebrospinal fluid in vitro before immersion fixation. In both preparations the mossy fibres appeared as the most intensely glutamate-immunoreactive profile type in the cerebellar cortex, and the parallel fibre terminals were also strongly labelled. Corresponding results were obtained at the light microscopic level. Most of the immunoreactivity in the mossy and parallel fibre terminals could be depleted in a Ca(+)-dependent manner by depolarization with a high K+ concentration. These data suggest that the mossy and parallel fibre terminals contain a glutamate pool that behaves as a transmitter pool.


Tissue-specific deletion of the retinoblastoma protein in the pancreatic beta-cell has limited effects on beta-cell replication, mass, and function.
Animal studies show that G(1/S) regulatory molecules (D-cyclins, cdk-4, p18, p21, p27) are critical for normal regulation of beta-cell proliferation, mass, and function. The retinoblastoma protein, pRb, is positioned at the very end of a cascade of these regulatory proteins and is considered the final checkpoint molecule that maintains beta-cell cycle arrest. Logically, removal of pRb from the beta-cell should result in unrestrained beta-cell replication, increased beta-cell mass, and insulin-mediated hypoglycemia. Because global loss of both pRb alleles is embryonic lethal, this hypothesis has not been tested in beta-cells. We developed two types of conditional knockout (CKO) mice in which both alleles of the pRb gene were inactivated specifically in beta-cells. Surprisingly, although the pRb gene was efficiently recombined in beta-cells of both CKO models, changes in beta-cell mass, beta-cell replication rates, insulin concentrations, and blood glucose levels were limited or absent. Other pRb family members, p107 and p130, were not substantially upregulated. In contrast to dogma, the pRb protein is not essential to maintain cell cycle arrest in the pancreatic beta-cell. This may reflect fundamental inaccuracies in models of beta-cell cycle control or complementation for pRb by undefined proteins.


Absent latissimus dorsi muscle and anhidrotic axilla in Poland's syndrome. Case report.
The case of an 18-year-old female with absence of the right breast, sternocostal part of the major pectoral muscle and total absence of the minor pectoral muscle and the latissimus dorsi muscle, is presented. She also had decreased sweating capacity and absence of terminal hairs in the central part of her right axilla. Histological examination of skin specimens from this area of the axilla demonstrated hypoplasia of the apocrine sweat glands, but normal eccrine sweat glands, indicating an apocrine dependent axillary sweating function. The breast was constructed using a direct subcutaneous prosthesis implant, giving a final result that was good in regard to shape and softness. This provides grounds for reconsidering the use of the latissimus dorsi muscle flap in breast constructions in Poland's syndrome.


Null mutation of the transcription factor inhibitor of DNA binding 3 (id3) affects spermatozoal motility parameters and epididymal gene expression in mice.
ID3 is a transcription factor that acts as a dominant-negative regulator of other transcription factors by sequestering them, thus rendering them unable to bind DNA. We have shown previously that ID3 is expressed in a unique, region-specific manner along the epididymis, a highly specialized tissue of the male reproductive tract that functions in the transport and maturation of spermatozoa. The goal of these studies was to test the hypothesis that ID3 plays a role in the epididymis in the region-specific regulation of gene expression that is responsible for establishing the microenvironment required to carry out sperm-related functions. The consequences of ID3 deficiency on epididymal histology and gene expression profiles, as well as spermatozoal motility parameters, were determined. Although ID3 deficiency (Id3(-/-) mice) had no noticeable impact on epididymal histology, the targeted mutation adversely affected sperm motility parameters. Moreover, principal component analysis of microarray data indicated that the gene expression signatures for tissues obtained from Id3(-/-) mice and their genotypic controls were distinct from each other in each epididymal region. The predominant effect of the Id3 null mutation was in the cauda region where the expression of many transcription factors, including Hoxb8 and Bclaf1, was markedly affected. ID3 may play an important role in the molecular circuitry involved in the establishment and maintenance of the region-specific differences in gene expression that are characteristic of the epididymis.


Lymphocyte Antigen 6 Complex, Locus C+ Monocytes and Kupffer Cells Orchestrate Liver Immune Responses Against Hepatitis B Virus in Mice.
To understand the mechanism(s) of age-dependent outcomes of hepatitis B virus (HBV) infection in humans, we previously established an age-related HBV mouse model in which 6-week-old (N6W) C3H/HeN mice exhibited virus tolerance whereas 12-week-old (N12W) counterparts presented virus clearance. By investigating the hepatic myeloid cell dynamics in mice of these two ages, we aim to identify factors associated with HBV clearance. C3H/HeN mice were transfected with an HBV plasmid by hydrodynamic injection. Serum HBV markers were monitored weekly. Hepatic leucocyte populations and their cytokine/chemokine productions were examined at baseline, day 3 (D3), day 7 (D7), and day 14 after injection. C-C chemokine receptor type 2 (CCR2) antagonist and clodronate (CLD) were respectively administered to N12W and N6W mice to study the roles of lymphocyte antigen 6 complex, locus C (Ly6C)+ monocytes and Kupffer cells (KCs) in viral clearance. N12W mice had a significantly higher number of TNF-α-secreting Ly6C+ monocytes and fewer IL-10-secreting KCs at D3 in the liver than their younger N6W counterparts after HBV transfection. In addition, the elevated number of interferon-γ+ TNF-α+ CD8+ T cells at D7 was only seen in the older cohort. The enhanced Ly6C+ monocyte induction in N12W mice resulted from elevated C-C motif chemokine ligand 2 (CCL2) secretion by hepatocytes. CCR2 antagonist administration hampered Ly6C+ monocyte recruitment and degree of KC reduction and delayed HBV clearance in N12W animals. Depletion of KCs by CLD liposomes enhanced Ly6C+ monocyte recruitment and accelerated HBV clearance in N6W mice. Conclusions: Ly6C+ monocytes and KCs may, respectively, represent the resistance and tolerance arms of host defenses. These two cell types play an essential role in determining HBV clearance/tolerance. Manipulation of these cells is a promising avenue for immunotherapy of HBV-related liver diseases.


Function of abnormal corpora lutea in vivo after GnRH-induced ovulation in the anoestrous ewe.
Anoestrous Romney Marsh ewes with and without progesterone treatment (+P, -P) were treated with small-dose (250 ng) multiple injections of GnRH at 2-h intervals for 48 h. Animals were slaughtered on Days 4, 5, 7 and 11 after the end of GnRH treatment and luteal function was assessed by the measurement of daily plasma progesterone concentrations. In all animals which ovulated (29/32, 91%) peripheral progesterone concentrations rose to 0.5-1.0 ng/ml within 3 days of the end of GnRH treatment. In 7/7 (100%) +P animals and 5/22 (23%) -P animals, progesterone concentrations continued to rise and were maintained at levels greater than 1.5 ng/ml until slaughter. In the remaining -P animals, plasma progesterone concentrations declined to reach basal levels by Day 5. Corpora lutea recovered from these animals showed signs of premature regression on Day 5 and were fully regressed by Day 7. Progesterone priming delayed the occurrence of the LH surge which occurred 39.1 +/- 3.6 h after the end of GnRH treatment in the +P animals compared to 20.2 +/- 1.74 h (P less than 0.001) in the -P animals in which luteal function was abnormal and 22.4 +/- 4.35 h in the -P animals in which luteal function was normal. These results show that abnormal luteal function occurs in the majority of GnRH-treated ewes in the absence of progesterone pretreatment.(ABSTRACT TRUNCATED AT 250 WORDS)


Load bearing capacity of fibre-reinforced and particulate filler composite resin combination.
Longevity of particulate filler resin (PFR) is controversial for large restorations with high occlusal-stresses. The aim of this study was to reinforce PFR with fiber reinforced composite (FRC) and to evaluate the effect of thickness of FRC substructure and thickness of overlaying PFR, on the static load-bearing capacity of the material combination. A total of 336 test specimens having a FRC substructure (short random or continuous bidirectional fibre orientation) and layer of restorative PFR were prepared for this study. In Group A, the specimens contained short random oriented fibres (length: 2-3mm) and in Group B, there were continuous bidirectionally oriented fibres. The specimens (n = 12/group) were polymerized with a hand light-curing unit and were either dry-stored or thermocycled before they were statically loaded with a steel ball until fracture, using a universal testing machine. Increase the volume fraction of the short random FRC versus the fraction of PFR, the load-bearing capacity of the specimen increased (p < 0.001). Short random FRC revealed significantly different behavior than the bidirectionally oriented FRC (p < 0.001). By combining the FRC layer of 0.5mm in thickness with a layer of 2.5mm of PFR gave load values of 1462N and 1196N, which were considerably higher than values for plain PFR of 3mm in thickness (782N and 729N). The results suggest that by adding a FRC substructure under the PFR, the load-bearing capacity of the material combination was increased.


Health education and teleinformatics.
In the course of the last years, the development of teleinformatics caused that the Internet services have become more and more popular. The Internet means reaching new possibilities, which are provided by fast, easy and two-direction access to the required information. These features make the Internet one of the most important tools applied in health education increasing the knowledge, skill and motivation of an individual for health self-care.


An Atypical Presentation of a Pyogenic Liver Abscess Caused by Fusobacterium nucleatum Post-ruptured Appendix.
A rare formation of a pyogenic liver abscess can be found in patients with a ruptured appendix. Here, we discuss a 49-year-old male with a past medical history significant for drug-induced pancreatitis from metformin, type II diabetes, obesity, and hypertension who presented with right upper quadrant pain. He was diagnosed with a 12.6 cm pyogenic liver abscess. Upon further chart review, the patient had a laparoscopic appendectomy done nine months ago, with the findings of a ruptured appendix. The liver abscess cultures grewFusobacterium nucleatum - a common culprit of acute appendicitis reported in several case studies and clinical trials. This case report highlights the importance of including appendectomy as an essential part of history-taking and diagnostic differential for pyogenic liver abscesses.


Strong electromechanical coupling of an atomic force microscope cantilever to a quantum dot.
We present theoretical and experimental results on the mechanical damping of an atomic force microscope cantilever strongly coupled to a self-assembled InAs quantum dot. When the cantilever oscillation amplitude is large, its motion dominates the charge dynamics of the dot which in turn leads to nonlinear, amplitude-dependent damping of the cantilever. We observe highly asymmetric line shapes of Coulomb blockade peaks in the damping that reflect the degeneracy of energy levels on the dot. Furthermore, we predict that excited state spectroscopy is possible by studying the damping versus oscillation amplitude, in analogy with varying the amplitude of an ac gate voltage.


Expression of PD-1 and Its Ligands, PD-L1 and PD-L2, in Smokers and Never Smokers with KRAS-Mutant Lung Cancer.
Clinical responses to immune checkpoint blockade by anti-programmed cell death protein-1 (PD-1)/PD-L1 monoclonal antibodies in non-small-cell lung cancer (NSCLC) are associated with PD-L1 expression and smoking status. We aimed to determine the expression profile of PD-1 and its ligands, PD-L1 and PD-L2, in both smokers and never smokers patients with KRAS-mutant NSCLC. We retrospectively analyzed the clinical and molecular characteristics of 114 KRAS-mutant NSCLC patients (84 smokers and 30 never smokers) and their clinical tumor samples for the expression of PD-1, PD-L1, and PD-L2 by immunohistochemistry (IHC). We used murine monoclonal antibodies anti-PD-L1 (clone 9A11) and anti-PD-L2 (clone 9E5) to examine for tumor cell expression (0, negative; 1, weak; 2, moderate; 3, intense) and anti-PD-1 (clone EH33) for tumor-infiltrating lymphocytes. PD-L1 expression was detected in 27 of 114 patients (24%; 95% confidence interval [CI], 16-33%) and associated with smoking status (current smokers, 44%; former smokers, 20%; never smokers, 13%; p = 0.03). Higher intensity of PD-L1 expression (IHC-2+/IHC-3+) was more frequently observed in smokers and associated with more pack-years. PD-L2 was positive in 54 of 114 patients (47%; 95% CI, 38-57%) and not related to smoking status. PD-1-positive tumor-infiltrating lymphocytes were present in 77 of 114 tumor specimens tested (68%; 95% CI, 59-77%) including 21 of 27 samples with PD-L1 expression and 39 of 54 samples with PD-L2-positive expression. We found that PD-L1 expression fades with the age of the specimens used for analyses decreasing beyond 3 years (p = 0.016). The expression of PD-1 and its ligands PD-L1 and PD-L2 is heterogeneous within KRAS-mutant NSCLC and suggests an inducible expression of PD-L1 by smoking.


[Avian mycobacteria].
The avian mycobacteria have been identified first in relation to their virulence for hens. But this property was not definitely to correlate with serovars. Furthermore, this heterogenicity was to confirm on molecular level. Therefore it was necessary to introduce a M.avium complex beside true M.avium. M.avium has special relevance to AIDS patients. This fact shows that the reasons for infections by these facultatively pathogenic mycobacteria are more complicated as accepted.


Evidence for a decrease in transmission of Ebola virus--Lofa County, Liberia, June 8-November 1, 2014.
Lofa County has one of the highest cumulative incidences of Ebola virus disease (Ebola) in Liberia. Recent situation reports from the Liberian Ministry of Health and Social Welfare (MoHSW) have indicated a decrease in new cases of Ebola in Lofa County. In October 2014, the Liberian MoHSW requested the assistance of CDC to further characterize recent trends in Ebola in Lofa County. Data collected during June 8-November 1, 2014 from three sources were analyzed: 1) aggregate data for newly reported cases, 2) case-based data for persons admitted to the dedicated Ebola treatment unit (ETU) for the county, and 3) test results for community decedents evaluated for Ebola. Trends from all three sources suggest that transmission of Ebola virus decreased as early as August 17, 2014, following rapid scale-up of response activities in Lofa County after a resurgence of Ebola in early June 2014. The comprehensive response strategy developed with participation from the local population in Lofa County might serve as a model to implement in other affected areas to accelerate control of Ebola.


Effect of pinacidil on ion permeability in resting and contracted resistance vessels.
Pinacidil is thought to cause vasodilatation by opening K+ channels and consequent hyperpolarization. This proposed mechanism of action is based mainly on membrane potential measurements and 42K or 86Rb efflux experiments under resting conditions. We have measured the simultaneous effect of pinacidil on force and membrane potential in resting and norepinephrine-contracted rat mesenteric resistance vessels. Also the effect of pinacidil on 42K and 36Cl efflux and 22Na uptake in the absence and presence of norepinephrine was examined. From the membrane potential and ion flux measurements the ion permeabilities were calculated. In both resting and norepinephrine-contracted vessels, pinacidil caused a large hyperpolarization, the latter situation being associated with an almost complete relaxation. In both resting and norepinephrine-stimulated vessels, pinacidil caused a large increase in K+ permeability and a decrease in Cl-permeability, whereas no significant change of Na+ permeability was found. Our results suggest that pinacidil causes vasodilation due to hyperpolarization. The major cause for the hyperpolarization is an increase in K+ permeability.


[Cœliac disease: a rare cause of recurrent miscarriages].
Cœliac disease is an autoimmune disorder associated with Gluten intolerance resulting in progressive destruction of the villi of the small intestine. Symptoms are very diverse and can occur at any age. Abortive illness is a rare symptom leading to the detection of cœliac disease. We report the case of a patient with a history of 12 consecutive miscarriages whose etiology was finally related to cœliac disease.


Helping to distinguish primary from secondary transfer events for trace DNA.
DNA is routinely recovered in criminal investigations. The sensitivity of laboratory equipment and DNA profiling kits means that it is possible to generate DNA profiles from very small amounts of cellular material. As a consequence, it has been shown that DNA we detect may not have arisen from a direct contact with an item, but rather through one or more intermediaries. Naturally the questions arising in court, particularly when considering trace DNA, are of how DNA may have come to be on an item. While scientists cannot directly answer this question, forensic biological results can help in discriminating between alleged activities. Much experimental research has been published showing the transfer and persistence of DNA under varying conditions, but as of yet the results of these studies have not been combined to deal with broad questions about transfer mechanisms. In this work we use published data and Bayesian networks to develop a statistical logical framework by which questions of transfer mechanism can be approached probabilistically. We also identify a number of areas where further work could be carried out in order to improve our knowledge base when helping to address questions about transfer mechanisms. Finally, we apply the constructed Bayesian network to ground truth known data to determine if, with current knowledge, there is any power in DNA quantities to distinguish primary and secondary transfer events.


Multi-competencies: a challenge for the allied health professions.
The 21st century brings new challenges to academic medical centers and universities who are responsible to prepare health professionals. These academics medical centers and universities need to respond more effectively to the demands of the health market place. The Health Care reform has brought about many changes within the health care field. Perhaps none of these changes is more dramatic than the impact on the allied health professional. No longer can this professional rely on "skills of old" to compete in today's market place. One of the most important strategy will be the transformation of the specialized allied health professional to a multi-skilled, multi-layered generalized health care provider. Advance practice nurses and paramedics will take over some of physicians' duties such as diagnose and prescription of medications and treatment to the patients. For individuals to move vertically to positions and to be marketable in health care settings, they need to increased their personal and technical skills, and health care knowledge. In order to survive, the health care professional will need to gain increased competencies and skills in several areas rather than obtain proficiency in one specific area.


Comparison of 6-year Follow-up Result of Hybrid Surgery and Anterior Cervical Discectomy and Fusion for the Treatment of Contiguous Two-segment Cervical Degenerative Disc Diseases.
A retrospective study. To compare the mid-term outcomes of hybrid surgery (HS) and anterior cervical discectomy and fusion (ACDF) for the treatment of contiguous two-segment cervical degenerative disc diseases. HS has become one of the most controversial subjects in spine communities, and the comparative studies of HS and ACDF in the mid- and long-term follow-up are rarely reported. From 2009 to 2012, 42 patients who underwent HS (n = 20) or ACDF (n = 22) surgery for symptomatic contiguous two-level cervical degenerative disc diseases were included. Clinical and radiological records, including Japanese Orthopedic Association (JOA), Neck Disability Index (NDI), Visual Analogue Scale (VAS), local cervical lordosis, and range of motion (ROM), were reviewed retrospectively. Complications were recorded and evaluated. Mean follow-up was 77.25 and 79.68 months in HS group and ACDF group, respectively (P > 0.05). Both in HS group and ACDF group, significant improvement for the mean JOA, NDI, and VAS scores was found at 2-week postoperation and at the last follow-up (P < 0.05). However, there were no significant differences between the two groups (P > 0.05). At the last follow-up, the range of motion (ROM) of superior adjacent segments in ACDF group was significantly larger than HS group (P < 0.05), while the ROM of C2-C7 was significantly smaller (P < 0.05). In the HS group, two (10%) sagittal wedge deformities, one (5%) heterotopic ossification, and one (5%) anterior migration of the Byran disc prosthesis were found. No symptomatic adjacent segment degeneration occurred in two groups. HS appears to be an acceptable option in the management of contiguous two-segment cervical degenerative disc diseases. It yielded similar mid-term clinical improvement to ACDF, and demonstrated better preservation of cervical ROM. The incidence of postoperative sagittal wedge deformity was low; however, it can significantly reduce the cervical lordosis. 4.


Homograft reconstruction of the right ventricular outflow tract in adults with congenital heart disease: a systematic review.
Reconstruction of the right ventricular outflow tract with a homograft is an established surgical method in congenital heart disease. Studies from children and adolescents suggest that homograft durability is shorter than the life expectancy of the patient; therefore, durability in adults is addressed in this systematic review. The PubMed database was searched in May 2012 and repeated in May 2015 with the terms 'homograft AND pulmonary valve', generating 665 hits. We included only studies involving more than 50 patients with a mean or median age >18 years. Six studies with a cumulative total of 560 patients were included. The long-term mortality rate was 2-8.8% at 8.1-10 years. Reintervention was common during patients' life spans, with a 10-year event-free survival rate of 78-80%. Early postoperative echocardiographic or magnetic resonance imaging defects appear to predict rapid homograft degeneration. Further studies on various malformations and risk markers for degeneration are needed to make qualified and accurate decisions regarding lifetime management.


Dapagliflozin attenuates high glucose-and hypoxia/reoxygenation-induced injury via activating AMPK/mTOR-OPA1-mediated mitochondrial autophagy in H9c2 cardiomyocytes.
This study investigated the protective effect of dapagliflozin on H9c2 cardiomyocyte function under high glucose and hypoxia/reoxygenation (HG-H/R) conditions and identified the underlying molecular mechanisms. Dapagliflozin reduced the level of lactate dehydrogenase and reactive oxygen species in cardiomyocytes under HG-H/R conditions and was accompanied by a decrease in caspase-3/9 activity. In addition, Dapagliflozin significantly reduced mitochondrial permeability transition pore opening and increased ATP content, accompanied by upregulation of OPA1 with autophagy-related protein molecules and activation of the AMPK/mTOR signalling pathway in HG-H/R treated cardiomyocytes. OPA1 knockdown or compound C treatment attenuated the protective effects of dapagliflozin on the cardiomyocytes under HG-H/R conditions. Downregulation of OPA1 expression increased mitochondrial intolerance in cardiomyocytes during HG-H/R injury and the AMPK-mTOR-autophagy signalling is a key mechanism for protecting mitochondrial function and reducing cardiomyocyte apoptosis. Collectively, dapagliflozin exerted protective effects on the cardiomyocytes under HG-H/R conditions. Dapagliflozin attenuated myocardial HG-H/R injury by activating AMPK/mTOR-OPA1-mediated mitochondrial autophagy.


"Coach Really Knew What I Needed and Understood Me Well as a Person": Effective Communication Acts in Coach-Athlete Interactions among Korean Olympic Archers.
The purpose of this study is to qualitatively explore situations in which athletes perceived communication with their coach to be important and determine the effect of this communication on the athletes. Literature on the communication process in sports emphasizes the distinct characteristics of each sports and its setting. However, previous research has not studied various settings in detail, and archery is yet to be explored. The qualitative process included an in-depth, semi-structured interview with eight Olympic archers. Thematic analysis was used to interpret the data. Athletes perceived communication with coaches to be important during their performance, while dealing with psychological crises, and during their training. Our analysis suggests that, depending on the communicative actions, a coach may positively or negatively impact an athlete's self-awareness, self-confidence, anxiety, autonomy, and motivation. A noteworthy finding of this study is that archers perceive communication with coaches about the selection and management of equipment as important. This study emphasizes the critical role of an athlete's communication with the coach in various situations and discusses the theoretical and practical implications in the context of sports performance.


The influence of methylphenidate on the sympathoadrenal reactivity in children diagnosed as hyperactive.
In order to investigate whether catecholamines play a role in the hyperkinetic child syndrome, we determined noradrenaline and adrenaline plasma levels before and after treatment with methylphenidate. The children were separated into drug responders and non-responders according to the efficacy of methylphenidate on behavioral symptoms. 21 children, 6-13 years of age, participated in this double-blind placebo controlled cross-over study. Conners' questionnaire was used to estimate the extent of the hyperactivity and to assess the drug response. Blood samples were drawn under resting and exercise conditions and plasma catecholamine concentrations determined as an indication of the amine release rate and the reactivity of the sympathoadrenal system. The results may be summarized: The postexercise noradrenaline levels of untreated hyperkinetic children were slightly, but not significantly higher than those of an age-matched control group. After 3-4 weeks of stimulant medication the noradrenaline release induced by physical exercise was significantly lower than after placebo. 12 out of 21 children showed an alleviation of their symptoms during methyl- phenidate therapy and thus could be assumed as drug-responders. When children were separated into drug-responders and non-responders according to the degree of the clinical improvement, both groups showed the same catecholamine release in response to exercise. Methylphenidate reduced the noradrenaline release in 9 out of 11 children in the responder group and in 7 out of 9 children in the non-responder group. In conclusion, catecholamines may be involved in the hyperkinetic child syndrome, but because of the heterogenity of this syndrome the depression of the plasma catecholamines as observed under methylphenidate could not differentiate between drug-responders and non-responders.


Clinical outcomes in patients who received lapatinib plus capecitabine combination therapy for HER2-positive breast cancer with brain metastasis and a comparison of survival with those who received trastuzumab-based therapy: a study by the Anatolian Society of Medical Oncology.
In this study, we investigated the effect of lapatinib plus capecitabine treatment in HER2-positive breast cancer patients with brain metastasis. Of 405 metastatic breast cancer patients with brain metastases at referral centers in Turkey, 46 were treated with lapatinib plus capecitabine only after the development of brain metastasis. Patients who only received trastuzumab-based therapy after the development of brain metastases were accepted as the historic control group for survival analyses (n = 65). Patients who received both drugs consecutively or sequentially were excluded from the analyses (n = 34). Median age among 46 patients who received lapatinib plus capecitabine therapy was 45 years (27-76), and median time for development of brain metastases was 11.9 months (0-69 months). Twenty-six out of 38 patients who received lapatinib plus capecitabine and had extracranial metastasis showed partial response or stable diseases (68.4 %). Grade 3-4 toxicity was observed in eight patients (17.3 %). Median overall survival (OS) in patients treated with lapatinib plus capecitabine was significantly increased compared to that in patients treated with trastuzumab-based therapy (19.1 vs. 12 months, respectively, p = 0.039). The incidence of cerebral death was slightly decreased in patients who received lapatinib plus capecitabine compared to those who received trastuzumab-based therapy (32 vs. 43.4 %, p = 0.332). In the multivariate analysis, lapatinib plus capecitabine therapy remained an independent positive predictor for survival [odds ratio (OR), 0.57; p = 0.02]. Although this retrospective multicenter study had several limitations, the results suggest that undergoing lapatinib plus capecitabine therapy after the diagnosis of brain metastasis may further improve survival compared to undergoing only trastuzumab-based therapy.


RNA diversification by a self-reproducing ribozyme revealed by deep sequencing and kinetic modelling.
We demonstrate that a recombinase ribozyme achieves multiple functions in the same reaction network: self-reproduction, iterative elongation and circularization of other RNAs, leading to synthesis of diverse products predicted by a kinetic model. This shows that key mechanisms can be integrated and controlled toward Darwinian evolution in RNA reaction networks.


Disparate letter and semantic category fluency deficits in autopsy-confirmed frontotemporal dementia and Alzheimer's disease.
Patients with autopsy-confirmed frontotemporal dementia (FTD; n = 16) and Alzheimer's disease (AD; n = 32) were compared on first-letter and semantic category fluency tasks. Despite being matched on age, education, and dementia severity, FTD patients performed worse overall and showed similar impairment in letter and semantic category fluency, whereas AD patients showed greater impairment in semantic category than letter fluency. A measure of the disparity between letter and semantic category fluency (the semantic index) was effective in differentiating FTD from AD patients, and this disparity increased with increasing severity of dementia. These unique patterns of letter and semantic category fluency deficits may be indicative of differences in the relative contribution of frontal-lobe-mediated retrieval deficits and temporal-lobe-mediated semantic deficits in FTD and AD.


Histamine release from human leukocytes: modulation by a cytochalasin B-sensitive barrier.
Cytochalasin B, a metabolic product of several fungi, enhances up to 10-fold the sensitivity and reactivity of human leukocytes to antigen E or anti-IgE-mediated histamine release. The effect of cytochalasin B is a result of its action on the second, antigen-independent, stage of histamine release. These data suggest that normally, antigen-triggered histamine release is modulated by a cytochalasin-sensitive barrier (CSB). This CSB modulation of histamine release can be separated from the modulating effect of cyclic adenosine monophosphate (AMP).


Experimental infection of cattle with highly pathogenic avian influenza virus (H5N1).
Four calves were experimentally inoculated with highly pathogenic avian influenza virus A/cat/Germany/R606/2006 (H5N1) isolated from a cat in 2006. All calves remained healthy, but several animals shed low amounts of virus, detected by inoculation of nasal swab fluid into embryonated chicken eggs and onto MDCK cells. All calves seroconverted.


Testican-1: a differentially expressed proteoglycan with protease inhibiting activities.
Testican-1 is a highly conserved, multidomain proteoglycan that is most prominently expressed in the thalamus of the brain, and is upregulated in activated astroglial cells of the cerebrum. Several functions of this gene product have now been demonstrated in vitro including membrane-type matrix metalloproteinase inhibition, cathepsin L inhibition, and low-affinity calcium binding. The purified gene product has been shown to inhibit cell attachment and neurite extensions in culture. Functions of testican in vivo have yet to be demonstrated in knockout mice or other models. Testican has been shown to carry substantial amounts of chondroitin sulfate as well as other oligosaccharides, but the biological significance of these embellishments is not yet known.


Renal nitric oxide production is decreased in diabetic rats and improved by AT1 receptor blockade.
Diabetes mellitus is associated with increased incidence of cardiovascular complications. Lack of nitric oxide production may exacerbate these complications. We hypothesized that diabetes decreases renal nitric oxide (NO) production, an effect that is reversed via inhibition of angiotensin subtype-1 receptor. We monitored changes in renal interstitial fluid nitric oxide by a microdialysis technique in the renal cortex of conscious Sprague-Dawley rats. Rats (n = 8 each group) were given streptozotocin 30 mg/kg intravenously to induce diabetes. Changes in renal interstitial fluid angiotensin II and NO were evaluated at baseline before and over 12 weeks during the development of diabetes and at 4 and 8 h after oral administration of the angiotensin subtype-1 (AT1) receptor blockers, losartan (30 mg/kg) or valsartan (10 mg/kg). Renal interstitial fluid angiotensin II significantly increased after development of diabetes. In contrast, basal renal interstitial fluid nitric oxide decreased significantly over 12 weeks after development of diabetes. Both losartan and valsartan caused a further increase in renal angiotensin II levels. Some 4 h after administration, there was significantly greater increase in renal nitric oxide after administration of valsartan than of losartan. At 8 h post- treatment, only valsartan caused a significant increase in renal nitric oxide levels. These results demonstrate that diabetes mellitus is associated with an increase in renal production of angiotensin II, while renal production of nitric oxide is reduced. The decrease in renal NO is reversed by AT1 receptor blockade.


[Effect of different amounts of carbamide on the state of health of broilers. I].
Three experiments were carried out with a total of 100 broilers each, divided into five groups of 20 birds. The effect was tested of urea on their health status, it being added to a ration that was balanced in terms of protein in progressively rising amounts of 0.3 to 6.0 per cent within the period of from the 20th to the 60th day. It was found that in amounts of 0.3 to 3.0 per cent urea does not lead to any clinical and morphological changes in the organism of the treated birds. At rates of 4.5 and 6.0 per cent, however, there appear disturbances in the alimentary tract, lack of appetite, thirst, diuresis, hyperemia and hypertrophy of the kidneys. The addition of urea in such amounts to the ration raises the content of urea in the organism from 2 to 5 times, and the amount of retained nitrogen (NPN)--as much as twice in the blood.


[Clinical Analysis of Surgical treatment of long bone metastases].
To evaluate the safety and efficacy of microwave ablation combined with curettage in the treatment of long bone metastases. From April 2010 to June 2015, 38 patients with long bone metastases were adopted, who all underwent microwave ablation combined with curettage with 40 lesions involved in Department of Orthopaedic Oncology, Beijing Jishuitan Hospital. There were 22 males and 16 females with an average age of 58.3 years (range from 32 to 83 years). Solitary metastases were found in 9 cases and multiple metastases in 29 patients. Primary malignancies included: 15 cases of lung cancer, 7 cases of renal carcinoma, 4 cases of breast cancer, 3 cases of liver cancer, 1 case of thyroid carcinoma, 1 case of endometrial carcinoma, 1 case of cervical carcinoma, 1 case of esophageal carcinoma and 6 cases of carcinoma of unknown primary. The operative sites included the femur (n=21), the humerus (n=12) and the tibia (n=7). There were 23 cases of pathologic fractures which included: 12 in femur, 10 in humerus and 1 in tibia. Curettage after in situ microwave ablation was performed in 40 lesions. Reconstructions were carried out in all lesions: bone cement filling alone in 1 lesion and bone cement filling with metal implants in the other 39 lesions. The mean follow-up was 6.9 months (range; 1-65 months). During the follow-up, 22 patients died and 16 patients were alive. The 6-month overall survival (OS) was 73.7%, and the 1-year and 2-year OS were 48.6% and 28.1% respectively. The postoperative survival time was 7.1 months on average (range 2-40 months) in the 22 patients who finally died. The occurrence of pathological fracture had a significant effect on the OS (χ(2)=5.606, P=0.018). The local recurrence rate was 10% (4/40), which occurred at 6.8 months after the operation on average (range 2-14 months). No complications occurred in the perioperative period, and there were no complications such as internal fixation failure or pathological fracture noticed during the follow-up period. The scores of VAS, KPS and ECOG were significantly improved after operation. The mean MSTS score was 22 points (range 17-28 points) in 33 evaluable locations and the rate of excellent and good was 72.7%. Microwave ablation combined with curettage appears to be a safe and effective approach in the surgical treatment of long bone metastases, which can relieve local pain and control the local development of bone metastases.


Insulin Resistance and Metabolic Syndrome as Risk Factors for Hospitalization in Patients with COVID-19: Pilot Study on the Use of Machine Learning.
Aim: Conditions linked to metabolic syndrome, such as obesity, hypertension, insulin resistance, and dyslipidemia, are common in patients with severe coronavirus disease 2019 (COVID-19). These conditions can act synergistically to contribute to negative outcomes. We describe and analyze the relationship between metabolic syndrome and COVID-19 severity in terms of risk of hospitalization. Methods: We designed a retrospective, cross-sectional study, including patients with confirmed COVID-19 diagnosis. Clinical and laboratory parameters regarding metabolic syndrome were collected. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was used to assess insulin resistance. The outcome was needed for hospitalization. Logistic regression was used to calculate odds ratios, and to determine the association between variables and risk of hospitalization. Advanced approaches using machine learning were also used to identify and interpret the effects of predictors on the proposed outcome. Results: We included 2716 COVID-19 patients with a mean age of 61.8 years. Of these, 48.9% were women, 28.9% had diabetes, and 50.6% were diagnosed with metabolic syndrome. Overall, 212 patients required hospitalization. Patients with metabolic syndrome had a 58% greater chance of hospitalization if they were men, 32% if they had metabolic syndrome, and 23% if they were obese. Machine learning methods identified body mass index, metabolic syndrome, systolic blood pressure, and HOMA-IR as the most relevant features for our predictive model. Conclusion: Metabolic syndrome and its related biomarkers increase the odds for a severe clinical course of COVID-19 and the need for hospitalization. Machine learning methods can aid understanding of the effects of single features when assessing risks for a given outcome.


Radiofrequency-induced hyperthermia in the prostate.
A high frequency radiator has been developed for the treatment of prostate cancer by hyperthermia. The applicator produces a deep seated hot spot. The radiator has an outer diameter of 20 mm and an insertable length of about 175 mm. A high frequency cylindrical slot antenna inside the applicator is cooled by water. The frequency used is 433.9 MHz, one of the frequencies allowed for medical therapy in the F.R.G. A control system regulating the power output of the radiator avoids damage to the tissue around the prostate, especially the rectum mucosa and the tissue between rectum and prostate. About 60 experiments with male dogs proved that local heating of the prostate is possible with the help of the developed applicator without any damage in the surrounding tissue.


A Rare, yet Classic Case of Colloid Cyst of Third Ventricle.
Colloid cyst of third ventricle is a rare, benign, congenital lesion that usually presents with headache, and associated with altered cognition, nausea, vomiting, gait ataxia, and blurred vision. A large cyst/growing cyst can cause obstructive hydrocephalus leading to acute rapid neurological deterioration and sudden death. Here we report a classic clinical presentation and histopathological features of colloid cyst of third ventricle with specific emphasis on the importance of rapid diagnosis and management to avoid potentially fatal complications of this otherwise benign lesion. Newer modalities like neuroendoscopy or stereotactic aspiration of cyst are now the preferred choices of management. Awareness of this entity for early diagnosis and management with minimally invasive procedures such as neuroendoscopy or stereotactic aspiration of cyst is crucial for better prognosis and patient care.


From neurogenic pulmonary edema to fat embolism syndrome: a brief review of experimental and clinical investigations of acute lung injury and acute respiratory distress syndrome.
Acute respiratory distress syndrome (ARDS) is the most devastating form of acute lung injury (ALI) or pulmonary edema (PE). We presented the experimental studies and clinical investigations of two serious forms of ALI. Drastic and severe PE could be induced by intracranial hypertension or cerebral compression (CC). The CC-induced PE was attributed to overactivation of the medullary sympathetic mechanism. Sympathetic vasoconstriction of the systemic and pulmonary resistance and capacitance vessels caused shift of blood volume from the splanchnic vascular beds to the lung. The hemodynamic changes led to systemic and pulmonary hypertension. Consequently, left ventricular failure as evidenced by dramatic decline in aortic flow with a slow decrease in pulmonary flow resulted in pressure and volume loading in the pulmonary circulation. These changes finally produced severe alveolar flooding and sudden death. Vasodilators such as sodium nitroprusside or nitroglycerin were capable of reducing the CC-induced pulmonary pathology and hemodynamic alterations. Fat embolism syndrome (FES) is a serious clinical problem in patients suffering from long bone fractures. ARDS may develop and cause mortality. Our laboratory reported a total of 14 subjects associated with FES and died of ARDS. We also developed a simple technique to produce FES. Corn oil was mixed with distilled water to form fatty micelles. Intravenous administration of or introduction of fatty micelles in anesthetized rats or isolated perfused lungs caused severe alveolar damage. Our clinical observation and animal experimentation revealed that infusion of fatty acids caused physical phase, resulting in microvascular obstruction accompanied by pulmonary hypertension and increased capillary permeability. Thereafter, the lipases in the lung hydrolyzed the neutral fat and released free fatty acids and biochemical mediators which were toxic to the lung. Our data have suggested that nitric oxide (NO), inducible NO synthase (iNOS), phospholipase A2, free radical and inflammatory cytokines (tumor necrosis factor alpha, interleukin-1beta and interleukin-6) are involved in the biochemical phase of FES with ARDS. The alveolar macrophages are the major source of iNOS. Later study also found that neutrophil elastase and myeloperoxidase were elevated following fat embolism. N-acetylcysteine (an antioxidant), and NOS inhibitors such as Nomega nitro-L-arginine methyl ester (L-NAME), S-methylisothiourea (SMT) or L-N6 (1-iminoethyl)-lysine (L-Nil) were able to abrogate the FES or the fat embolism-induced changes.


From maximum power to a trade-off optimization of low-dissipation heat engines: Influence of control parameters and the role of entropy generation.
For a low-dissipation heat engine model we present the role of the partial contact times and the total operational time as control parameters to switch from maximum power state to maximum Ω trade-off state. The symmetry of the dissipation coefficients may be used in the design of the heat engine to offer, in such switching, a suitable compromise between efficiency gain, power losses, and entropy change. Bounds for entropy production, efficiency, and power output are presented for transitions between both regimes. In the maximum power and maximum Ω trade-off cases the relevant space of parameters are analyzed together with the configuration of minimum entropy production. A detailed analysis of the parameter's space shows physically prohibited regions in which there is no longer a heat engine and another region that is physically well behaved but is not suitable for possible optimization criteria.


Contact lens hydrophobicity and roughness effects on bacterial adhesion.
This study was designed to assess whether hydrogel contact lens (CL) surface hydrophobicity and roughness affect Staphylococcus epidermidis adhesion. Bacterial adhesion experiments were performed on two unworn silicone hydrogel and three unworn conventional hydrogel CLs using the S.epidermidis strain CECT 4184. Microbial colonization was assessed by conducting counts expressed as colony-forming units. CL hydrophobicity was determined through water contact angle measurements and the roughness parameters such as mean surface roughness (Ra), kurtosis (Rku), and skewness (Rsk) were determined through atomic force microscopy in Tapping Mode. The conventional CLs showed similar water contact angles (p > 0.05) and were classified as hydrophilic. The silicone hydrogel CLs yielded hydrophobic contact angles with no significant differences between them (p > 0.05). The lenses with the highest (nelfilcon A and ocufilcon B) or lowest (comfilcon A and omafilcon A) Ra values displayed a lesser or greater extent of spikiness of their surfaces, respectively. All lenses showed a predominance of peaks (Rsk > 0) over troughs. S. epidermidis adhered more to the hydrophobic CLs (p < 0.05). Omafilcon A and comfilcon A, which showed the lowest Ra values among the hydrophilic and hydrophobic lenses, respectively, returned the lowest bacterial adhesion scores (p < 0.05). Our results suggest that more hydrophobic CLs are more prone to S. epidermidis adhesion. Although the Ra appears to be related to S. epidermidis adhesion, the influence of Rku and Rsk on this variable remains unclear.


Correcting density-driven errors in projection-based embedding.
Projection-based embedding provides a simple and numerically robust framework for multiscale wavefunction-in-density-functional-theory (WF-in-DFT) calculations. The approach works well when the approximate DFT is sufficiently accurate to describe the energetics of the low-level subsystem and the coupling between subsystems. It is also necessary that the low-level DFT produces a qualitatively reasonable description of the total density, and in this work, we study model systems where delocalization error prevents this from being the case. We find substantial errors in embedding calculations on open-shell doublet systems in which self-interaction errors cause spurious delocalization of the singly occupied orbital. We propose a solution to this error by evaluating the DFT energy using a more accurate self-consistent density, such as that of Hartree-Fock (HF) theory. These so-called WF-in-(HF-DFT) calculations show excellent convergence towards full-system wavefunction calculations.


Effects of maternal left lateral position and rest on amniotic fluid index: a prospective clinical study.
To compare the effect of both maternal rest and activity on the amniotic fluid index (AFI). Power analysis indicated that in order to achieve 20 mm of increase in AFI with 90% of power at one side alpha of 0.01, we needed at least 51 women in each group. The study group was comprised of pregnant women (n = 152) with a normal AFI and a singleton pregnancy at 26-40 weeks' gestation. Their AFI was determined by averaging the 2 repetitive measurements of the 4 amniotic fluid quadrants. The "rest" group (n = 77) was instructed to lie and rest in the left lateral position, and the "mild activity" group (n = 75) was instructed to sit and walk. AFI increased significantly, from 151.25 +/- 37.40 mm to 173.79 +/- 39.76 mm, in the "rest" group (p = 0.00). However, the change from 153.69 +/- 37.94 to 152.34 +/- 36.62 mm was not significant in the "mild activity" group (p = 0.167). Maternal rest in the left lateral position increases the AFI.


Ureteral J stents: followup is not optional.
Double J ureteral stents are an example of a commonly used implanted medical device. Three case studies illustrate the necessity of good followup care to prevent morbidity. This provides an opportunity to devise a proactive system to assist in ensuring the proper patient followup care by establishing an efficient tracking system.


Radioimmunoassay for benzo[a]pyrene.
A benzo[a]pyrene (BP)-bovine serum albumin conjugate was synthesized and used to immunize 2.5- to 3.0-kg New Zealand White rabbits. The resulting antisera to BP bound trace amounts of [3H] (55 pg; 6,000 counts/min). A radioimmunoassay (RIA) to BP was developed by the antiserum first being titered with the [3H]BP and then a standard curve being constructed from the addition of unlabeled BP (0.4-15.8 pmoles; 0.1-4.0 ng/assay tube). The RIA could reliably detect 0.4 pmoles (0.1 ng) BP. The specificity with respect to structurally related polycyclic aromatic hydrocarbons was examined by means of competitive binding. Here concentrations of 4.0-400 pmoles of the compound were used, and the resulting competitive curves were compared for relative cross-reactivity at 50% B/B0 (counts per minute labeled BP bound to antiserum in the presence of corresponding concentrations of unlabeled BP/counts per minute labeled BP bound to antiserum in the absence of unlabeled BP). The antiserum B4-3 was specific to BP with the closest cross-reacting substance being 3-hydroxybenzo[a]pyrene (20% relative cross-reactivity). BP added to pooled human serum was measurable by the RIA at 1 ng/ml. A BP RIA may have potential use for the quantification of the absorbed dose of this carcinogen in man.


Prevalence and Correlates of Observed Sun Protection Behaviors Across Different Public Outdoor Settings in Melbourne, Australia.
Skin cancer prevention efforts in Australia have increasingly incorporated a focus on protection during incidental sun exposure. This complements the long-present messages promoting protection in high-risk settings and avoidance of acute intense bouts of sun exposure. Data from two waves of a cross-sectional direct observational survey was used to assess the prevalence and correlates of N = 12,083 adolescents' and adults' sun protection behavior (arm and leg cover, hat, sunglasses, and shade cover). Individuals were observed in public outdoor settings in Melbourne, Australia during peak ultraviolet (UV) times (11 a.m.-3 p.m.) on summer weekends. Settings included pools and beaches, parks and gardens, and for the first time in 2018, outdoor streets and cafés which may capture more incidental forms of sun exposure and represent another public setting where Australians commonly spend time outdoors. Females and older adults were consistently better protected than males and adolescents. Physical activity was strongly associated with low shade cover across settings. Weather was more strongly associated with sun protection at outdoor streets/cafes and parks/gardens than at pools/beaches but use of observed sun protection (particularly arm cover and covering hat) was low across settings. Continued public education about UV risk and its relation to weather and the seasons is needed to promote the routine use of multiple forms of sun protection during outdoor activities in peak UV times, especially among males and adolescents. Findings also highlight the importance of considering activity demands of public spaces in shade planning to optimize sun protection during outdoor activities in public spaces.


Data mining results from an electronic clinical log for nurse practitioner students.
Traditional techniques for collecting data on clinical experiences have been greatly flawed. Data cannot be easily collected in real time to make programmatic or placement changes "on the fly". Furthermore, it is difficult to look at data across students, specialty areas, and years because the data is typically not in a digital format. In response to this problem, the Vanderbilt University School of Nursing has created a web/PDA based clinical log to document the kinds of clinical experiences the students are having. Since our initial report, three years ago, we have collected three years worth of data, over 220,000 different patient encounters. This past year the data has been very complete, giving a full picture of the types of experiences the students are having. Our faculty have begun to analyze the data in the clinical log to examine the kind of experiences the students are having and to make programmatic changes and placement adjustments in real time. In general, the results supported that students in the various specialties managed patients and performed services appropriate to their specialty. Patients varied in ages, ethnic groups, payment sources, and medical diagnoses. Students did progress from an observer role to a more independent role in either a linear fashion or in a more biphasic mode with an increase in the observer role at the start of a new semester.


Poly(ADP-ribose) polymerase activation and cell injury in the course of rat heart heterotopic transplantation.
Free radicals and other reactive species generated during reperfusion of ischemic tissues may cause DNA damage and, consequently, the activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP). An excessive PARP activation may result in a depletion of intracellular NAD+ and ATP, hence cell suffering and, ultimately, cell death. The present study is aimed at clarifying the role of PARP in a heart transplantation procedure and the contribution of myocyte necrosis and/or apoptosis to this process. In our experimental model, rat heart subjected to heterotopic transplantation, low temperature global ischemia (2 h) was followed by an in vivo reperfusion (30 or 60 min). Under these conditions clear signs of oxidative stress, such as lipoperoxidation and DNA strand breaks, were evident. In addition to a marked activation, accompanied by a significant NAD+ and ATP depletion, PARP protein levels significantly increased after 60 min of reperfusion. Ultrastructural analysis showed nuclear clearings, intracellular oedema and plasma membrane discontinuity. Other relevant observations were the absence of typical signs of apoptosis like caspase-3 activation and PARP cleavage, random DNA fragmentation, rise in serum levels of heart damage markers. Our results suggest that during heart transplantation, the activation of PARP, causing energy depletion, results in myocardial cell injury whose dominant feature, at least in our experimental model, is necrosis rather than apoptosis.


Effects of N-acetyl-L-cysteine and glutathione on antioxidant status of human serum and 3T3 fibroblasts.
The effectiveness of several sulfhydryl compounds in the treatment of paraquat intoxication has been previously tested based on their antioxidant ability. However, practical guidelines for their clinical use remain to be determined. As a preliminary pharmacokinetic study on sulfhydryl compounds, we attempted to establish the optimal concentration of N-acetyl-L-cysteine, glutathione, superoxide dismutase, and catalase. We measured the antioxidant effect of these antioxidants in normal pooled plasma and on intracellular reactive oxygen species (ROS) induced by paraquat. N-acetyl-L-cysteine begins to suppress the production of ROS in plasma at concentrations as low as 5 mM, with the suppression being maximal at 40 mM. In the same way, glutathione increased the total antioxidant status in plasma at concentrations of 5-40 mM in a dose-dependent manner. Complete suppression of ROS in plasma induced by exposure to 500 micro M paraquat for 40 min was observed when using 40 mM N-acetyl-L-cysteine and 5 mM glutathione. These concentrations are comparable with 50 units of catalase, which reduced ROS at concentrations of 5-100 units. Further pharmacokinetic study into the systemic administration of these antioxidants is necessary, using effective concentrations of 5-40 mM for both N-acetyl-L-cysteine and glutathione, and 1-50 units of catalase.


Transplantation and immunosuppression: a review of novel transplant-related immunosuppressant drugs.
Immunosuppressive drugs used in the transplantation period are generally defined as induction and maintenance therapy. The use of immunosuppressants, which are particularly useful and have fewer side effects, decreased both mortality and morbidity. Many drugs such as steroids, calcineurin inhibitors (cyclosporine-A, tacrolimus), antimetabolites (mycophenolate mofetil, azathioprine), and mTOR inhibitors (sirolimus, everolimus) are used as immunosuppressive agents. Although immunosuppressant drugs cause many side effects such as hypertension, infection, and hyperlipidemia, they are the agents that should be used to prevent organ rejection. This shows the importance of individualized drug use. The optimal immunosuppressive therapy post-transplant is not established. Therefore, discovering less toxic but more potent new agents is of great importance, and new experimental and clinical studies are needed in this regard.Our review discussed the mechanism of immunosuppressants, new agents' discovery, and current therapeutic protocols in the transplantation.


Pancreatic hormone expression in the murine thymus: localization in dendritic cells and macrophages.
The expression of preproinsulin (ppIns), proglucagon, prosomatostatin, and propancreatic polypeptide was investigated in thymic extracts, thymic cells, and thymic cell lines from C57BL/6 mice by RT-PCR. The expression of pancreatic hormones was similar in thymic extracts taken from neonatal and 2-, 4-, and 8-week-old animals, but was decreased in 20-week-old animals. Pancreatic hormone expression was not observed in mouse liver, salivary gland, or spleen. Analysis of thymic cell populations revealed a 10- to 20-fold enrichment in expression of all hormones in low buoyant density cells. No expression was detected in high buoyant density cells (predominantly thymocytes) or in thymic epithelial cell lines, primary cultures of epithelial cells, or peripheral macrophages. In addition, immunoreactive insulin, measured by specific RIA, was detectable in the low buoyant density population, but not in high buoyant density cells. The enriched cell population was depleted of contaminating lymphocytes and sorted based on reactivity to the cell surface markers F4/80 (macrophage) or N418 (dendritic cells). Cells gated for N418 demonstrated expression for ppIns, but not the other pancreatic hormones. Conversely, expression for proglucagon, prosomatostatin, and propancreatic polypeptide, but not ppIns, was detected in F4/80-gated cells. Our data indicate that pancreatic endocrine hormones are differentially expressed by dendritic cells and macrophages in a normal mice.


Gene expression to contaminated or not contaminated Triatoma dimidiata faeces with Trypanosoma cruzi in vivo and in vitro assay.
Triatoma dimidiata is considered one of the most important vectors in the spread of Chagas disease in Mesoamerica. Hematophagous insects may deposit faeces contaminated or not with Trypanosoma cruzi on the surface of the skin during the feeding process. In endemic areas humans can be in contact several times to this fluid before get infection. Due to limited work on the of immune response to insect's fluids in mammals. In this work, we explored the early response of chemokine and cytokines of skin tissue at the inoculation site against faeces from T. dimidiata contaminated or not with T. cruzi in murine model, also we explored the in vitro response of epitheloid cells line "HeLa cells" to this fluid. Mice were exposed intradermically to faeces free of metacyclic trypomastigotes, oneor multiple times along the experiment before challenged with faeces contaminated with metacyclic trypomastigotes, mimicking natural conditions. In in vitro assay with HeLa cells only one exposure was carried out. It was observed that mice multiexposed to faeces, induced the strong response of TNF-α and CXCL3 expression at the inoculation site; but faeces contaminated with metacyclic trypomastigotes lower the response of TNF-α, and CXCL3. In in vitro assay with HeLa cell line, the faeces induced a strong response of CXCL8 and IL-6, but the presence of faeces contaminated with metacyclic trypomastigotes lower the response of CXCL8. In contrast, to in vivo model null response of TNF α and IL-1-α was observed in HeLa cells. In conclusion, Triatoma dimidiata faeces induces at the inoculation site chemokines that mediate preferentially chemotaxis of neutrophils and macrophages but the presence of metacyclic trypomastigotes moderate their induction. Epithelial cells act as efficient sentinels producing chemokines that may recruit neutrophils and monocytes.


The role of diet and nutrition on mental health and wellbeing.
Mental, neurological and substance-use disorders presently represent the greatest global burden of disease. Likewise, depression and other psychopathologies are elevated risk comorbidities of other health hazards, such as obesity. Nutrition has been implicated in behaviour, mood and in the pathology and treatment of mental illness. In this brief editorial, we aim to set the scale of the problem in context and overview advances and recent evidence linking nutrition to psychological outcomes. The purpose of the 2016 Nutrition Society Winter Meeting, 'Diet, nutrition and mental health and wellbeing' was to review where the evidence is strong, where there are unmet needs for research and to draw together the communities working in this area to share their findings. The papers presented demonstrated clear advancements that are being made in this field. The meeting illustrated compelling support for nutrition as a modifiable risk factor. The present research in the field and evidence presented at the 2016 Nutrition Society Winter Meeting lead us to postulate that even interventions with relatively modest effect sizes may plausibly and significantly curtail the disease burden of mental and neurological disease by food- and nutrient-based approaches.


Lipid droplets fusion in adipocyte differentiated 3T3-L1 cells: a Monte Carlo simulation.
Several human worldwide diseases like obesity, type 2 diabetes, hepatic steatosis, atherosclerosis and other metabolic pathologies are related to the excessive accumulation of lipids in cells. Lipids accumulate in spherical cellular inclusions called lipid droplets (LDs) whose sizes range from fraction to one hundred of micrometers in adipocytes. It has been suggested that LDs can grow in size due to a fusion process by which a larger LD is obtained with spherical shape and volume equal to the sum of the progenitors' ones. In this study, the size distribution of two populations of LDs was analyzed in immature and mature (5-days differentiated) 3T3-L1 adipocytes (first and second populations, respectively) after Oil Red O staining. A Monte Carlo simulation of interaction between LDs has been developed in order to quantify the size distribution and the number of fusion events needed to obtain the distribution of the second population size starting from the first one. Four models are presented here based on different kinds of interaction: a surface weighted interaction (R2 Model), a volume weighted interaction (R3 Model), a random interaction (Random model) and an interaction related to the place where the LDs are born (Nearest Model). The last two models mimic quite well the behavior found in the experimental data. This work represents a first step in developing numerical simulations of the LDs growth process. Due to the complex phenomena involving LDs (absorption, growth through additional neutral lipid deposition in existing droplets, de novo formation and catabolism) the study focuses on the fusion process. The results suggest that, to obtain the observed size distribution, a number of fusion events comparable with the number of LDs themselves is needed. Moreover the MC approach results a powerful tool for investigating the LDs growth process.


The adjuvant use of stromal vascular fraction and platelet-rich fibrin for autologous adipose tissue transplantation.
Autologous adipose transplantation is rapidly gaining popularity for the restoration of soft tissue defects and lipoatrophy as well as for aesthetic improvements (e.g., facial reconstruction and rejuvenation). However, the current technique is crude that suffers from serious demerits, particularly the long-term unpredictability of volume maintenance due to resorption of the grafted adipose tissue and limited adipogenesis. We hypothesized that the adjuvant use of patient-derived adipose stromal vascular fraction (SVF) and platelet-rich fibrin (PRF) may enhance the overall outcome of autologous fat grafting in plastic and reconstructive surgery. Autologous SVF, with a mean cell number of (4.8±3.79)×10⁷ cells/mL and a mean cell viability of 71.8%, and autologous PRF, with sustained release of multiple angiogenic growth factors, were created before surgical use. The following adipose tissue implants were injected subcutaneously into a rabbit ear's auricula according to the following study design: 2 mL adipose granules and 0.2 mL normal saline solution (AG+NS group), 2 mL adipose granules and 0.2 mL SVF (AG+SVF group), 2 mL adipose granules and 0.2 mL PRF (AG+PRF group), or 2 mL adipose granules combined with 0.1 mL SVF and 0.1 mL PRF (AG+SVF+PRF group). Histological examinations showed that the implanted adipose granules were well engrafted in the AG+SVF+PRF group, with a higher microvessel density 4 weeks postimplantation compared with the other three groups (p<0.01). Twenty-four weeks postimplantation, the resorption rates of implanted tissue in each group were 49.39%±9.47%, 27.25%±4.37%, 36.41%±8.47%, and 17.37%±6.22%, respectively, and were significantly different (p<0.01). The results demonstrated that the efficacy of adipose tissue implantation can be enhanced by using autologous PRF and SVF as therapeutic adjuvants, offering a clinically translatable strategy for soft tissue augmentation and reconstruction.


Gain optimization of an erbium-ytterbium co-doped amplifier via a Si3N4 photonic platform.
Erbium-doped waveguide amplifiers enable the integration of various active functions on a silicon platform. Er3+ can provide the basis for efficient optical amplification of photonic integrated circuits, but the gain is limited by cooperative upconversion leading to doping concentration limitations and insufficient optimization of the waveguide structure. In this paper, an erbium-ytterbium co-doped Al2O3 amplifier has been innovatively implemented on a low loss Si3N4 waveguide by careful design and optimization with the finite difference method. A more accurate and comprehensive theoretical model of erbium-ytterbium co-doping is established, with consideration of upconversions, energy transfer, amplified spontaneous radiation and propagation loss to perform optimization of the high-gain erbium-ytterbium co-doped waveguide amplifier. The optimized waveguide amplifier achieves a small-signal gain of more than 36 dB at 1550 nm under Er3+ concentration of 3 × 1020 cm-3 and Yb3+ concentration of 3 × 1021 cm-3. Endowing Si3N4 photonic integrated circuits with gain can enable the miniaturization of various on-chip based active devices.


Potentiation of Muscarinic M3 Receptor Activation through a New Allosteric Site with a Novel Positive Allosteric Modulator ASP8302.
Muscarinic M3 (M3) receptors mediate a wide range of acetylcholine (ACh)-induced functions, including visceral smooth-muscle contraction and glandular secretion. Positive allosteric modulators (PAMs) can avoid various side effects of muscarinic agonists with their spatiotemporal receptor activation control and potentially better subtype selectivity. However, the mechanism of allosteric modulation of M3 receptors is not fully understood, presumably because of the lack of a potent and selective PAM. In this study, we investigated the pharmacological profile of ASP8302, a novel PAM of M3 receptors, and explored the principal site of amino-acid sequences in the human M3 receptor required for the potentiation of receptor activation. In cells expressing human M3 and M5 receptors, ASP8302 shifted the concentration-response curve (CRC) for carbachol to the lower concentrations with no significant effects on other subtypes. In a binding study with M3 receptor-expressing membrane, ASP8302 also shifted the CRC for ACh without affecting the binding of orthosteric agonists. Similar shifts in the CRC of contractions by multiple stimulants were also confirmed in isolated human bladder strips. Mutagenesis analysis indicated no interaction between ASP8302 and previously reported allosteric sites; however, it identified threonine 230 as the amino acid essential for the PAM effect of ASP8302. These results demonstrate that ASP8302 enhances the activation of human M3 receptors by interacting with a single amino acid distinct from the reported allosteric sites. Our findings suggest not only a novel allosteric site of M3 receptors but also the potential application of ASP8302 to diseases caused by insufficient M3 receptor activation. SIGNIFICANCE STATEMENT: The significance of this study is that the novel M3 receptor positive allosteric modulator ASP8302 enhances the activation of human M3 receptor by interacting with a residue distinct from the reported allosteric sites. The finding of Thr230 as a novel amino acid involved in the allosteric modulation of M3 receptors provides significant insight into further research of the mechanism of allosteric modulation of M3 and other muscarinic receptors.


[Psychological abnormalities in patients with complex regional pain syndrome (CRPS)].
Do comorbid psychological disorders, dysfunctional pain processing, and psychosocial pain coping occur with complex regional pain syndrome (CRPS) and is a connection between clinical and psychological manifestations apparent? In addition to securing information on case histories and performing clinical neurological examinations of chronic CRPS patients, the structured clinical interview (SCID), pain perception scale, and the Kiel Pain Inventory were employed. The structured clinical interview revealed evidence of a depressive episode in 65% of CRPS patients. Pain perception is similar to neuropathic pain syndromes and patient history revealed a slightly increased frequency of anxiety and affective disorders. Depressive syndrome occurred significantly more often in right-sided CRPS; otherwise, there were no significant correlations between medical history, clinical examination, and frequency of psychological disorders. However, CRPS patients with allodynia manifest clinical signs of special psychological distress. In chronic CRPS depressive syndrome frequently develops and psychological treatment can be recommended.


Medical decision-making in the nursing home: a comparison of physician and nurse perspectives.
The purpose of this study is to clarify the perspectives of physicians and nurses in the medical decision-making process at the time of status change events in nursing home residents. The decision-making processes studied involved 28 cognitively impaired nursing home residents in a large suburban nursing home. In interviews, the authors ascertained the personal opinions of physicians and the nurses related to the status change event and the decision-making process using the Medical Decision-Making During a Status Change Event Questionnaire. Nurses reported a greater degree of familiarity with the family's and resident's wishes than did physicians. Physicians reported considering more treatment options and choosing more treatments for residents than nurses. Both physicians and nurses reported that the physicians had a major role in decision-making and that nurses did not, yet the gap in reported roles was greater based on physicians' reports in comparison to nurse reports. In a third of the reported cases, physicians and nurses disagreed about whether advance directives had been followed. These findings reflect a division of roles and perspectives of nurses versus physicians in the medical decision-making process. This study demonstrates the ability of the questionnaire to reveal several key differences in perceptions of care. This information could be useful in developing forums for communication among the professionals to enhance mutual understanding.


Exploring the relation between clinician ratings and patient-reported experience and outcomes.
Patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) are increasingly recognized as important ways for patients to be more actively involved in their treatment and enhance shared decision-making. The current study investigated the associations between PROMs, PREMs and various symptoms measures reported by clinicians and psychiatric patients. One hundred and twenty people admitted to a psychiatric hospital completed two PREMs, one PROM (the shortened version of the Manchester Short Assessment of Quality of Life scale) and Effects of Symptoms on Daily Functioning (the Sheehan Disability Scale), the Patient Clinical Global Impression and the Modified Colorado Symptom Index. Their psychiatrists rated them using the Global Assessment of Functioning scale, the Health of the Nation Outcome Scales and the Therapist Clinical Global Impression. There was a strong correlation between patient's evaluation of their quality of life (PROM), experience of their care (PREM) and the overall severity of their condition and their progress. The pattern of correlation between patients' and clinicians' measures revealed a three-layer structure representing a continuum from inner experience to external presentation of experiences. Together these findings help identify and emphasize various domains of subjective experiences and their relation to external ratings.


Solitary fibrous tumor of the liver. Case report and review of the literature.
Solitary fibrous tumor (SFT) is a rare mesenchymal tumor. Given its origin, it can appear in almost any location. In the literature, only 50 cases of SFT in the liver parenchyma have been reported. Despite its rarity, this entity should be included in the differential diagnosis of liver masses. We report the first case with imaging data from five years prior to diagnosis, which was treated by right portal embolization and arterial tumor embolization, and subsequent liver resection. We also present an exhaustive review of the cases described to date.


Pain Severity and Psychosocial Quality of Life in Adolescents with Migraine and Tension-Type Headache: Mediation by Perceived Expressed Emotion and Self-Esteem.
To investigate perceived expressed emotion (EE) and self-esteem in adolescents with primary headaches and to assess the psychologic factors, especially perceived EE, that may play a mediating role in the relationship between pain severity and psychosocial quality of life (QoL). The sample of this single-center cross-sectional case-control study consisted of 102 adolescents with migraine without aura, 36 adolescents with tension-type headache (TTH), 62 age- and sex-matched healthy adolescents, and their parents. Perceived EE was evaluated with the Shortened Level of Expressed Emotion Scale (SLEES). The Rosenberg Self-Esteem Scale (RSS) was used to assess the self-esteem of the participants. There were significant differences in both SLEES (F [2.199] = 7.913, P < .001) and RSS (F [2.199] = 8.138, P < .001) scores between the groups. When the two groups were compared in terms of SLEES score, adolescents with migraine and TTH had significantly higher levels of perceived EE and lower levels of self-esteem than their healthy peers. In mediation analyses, RSS and SLEES scores were found to be partial mediating factors in the relationship between pain severity and psychosocial QoL. Adolescents with migraine and TTH had higher perceived EE and lower self-esteem than their healthy peers. The most important result of this study was the demonstration that self-esteem and perceived EE can be two factors that play a mediating role in the relationship between headache and psychosocial QoL.