A Phase I study of an intravesically administered immunotoxin targeting EpCAM for the treatment of nonmuscle-invasive bladder cancer in BCGrefractory and BCG-intolerant patients.
A Phase I dose-escalation study was performed to determine the maximum tolerated dose (MTD) of the immunotoxin VB4-845 in patients with nonmuscle-invasive bladder cancer (NMIBC) refractory to or intolerant of bacillus Calmette-Guerin (BCG). Secondary objectives included evaluation of the safety, tolerability, pharmacokinetics, immunogenicity, and efficacy of VB4-845. Sixty-four patients with Grade 2 or 3, stage Ta or T1 transitional cell carcinoma or in situ carcinoma, either refractory to or intolerant of BCG therapy, were enrolled. Treatment was administered in ascending dose cohorts ranging from 0.1 to 30.16 mg. After receiving weekly instillations of VB4-845 to the bladder via catheter for 6 consecutive weeks, patients were followed for 4-6 weeks post-therapy and assessed at week 12. An MTD was not determined, as a dose-limiting toxicity was not identified over the dose range tested. VB4-845 therapy was safe and well tolerated with most adverse events reported as mild; as a result, no patients were removed from the study in response to toxicity. By the end of the study, the majority of patients had developed antibodies to the exotoxin portion of VB4-845. A complete response was achieved in 39% of patients at the 12-week time point. VB4-845 dosed on a weekly basis for 6 weeks was very well tolerated at all dose levels. Although an MTD was not determined at the doses administered, VB4-845 showed evidence of an antitumor effect that warrants further clinical investigation for the treatment of NMIBC in this patient population.


In Liquid Infrared Scattering Scanning Near-Field Optical Microscopy for Chemical and Biological Nanoimaging.
Imaging biological systems with simultaneous intrinsic chemical specificity and nanometer spatial resolution in their typical native liquid environment has remained a long-standing challenge. Here, we demonstrate a general approach of chemical nanoimaging in liquid based on infrared scattering scanning near-field optical microscopy (IR s-SNOM). It is enabled by combining AFM operation in a fluid cell with evanescent IR illumination via total internal reflection, which provides spatially confined excitation for minimized IR water absorption, reduced far-field background, and enhanced directional signal emission and sensitivity. We demonstrate in-liquid IR s-SNOM vibrational nanoimaging and conformational identification of catalase nanocrystals and spatio-spectral analysis of biomimetic peptoid sheets with monolayer sensitivity and chemical specificity at the few zeptomole level. This work establishes the principles of in-liquid and in situ IR s-SNOM spectroscopic chemical nanoimaging and its general applicability to biomolecular, cellular, catalytic, electrochemical, or other interfaces and nanosystems in liquids or solutions.


Genesis of Alzheimer's disease.
Our understanding of the pathogenesis of Alzheimer's disease (AD) had advanced rapidly, particularly in the area of genetics. Clinical trials of agents that offer the promise of going beyond symptomatic treatment to actually slowing the progression of disease, perhaps by enhancing the viability of neurons, are under way. Most of the ideas for therapeutic approaches that may slow progression of disease have come from a combination of epidemiologic and basic science observations. Anti-inflammatory agents, nicotine, estrogens, and free radical scavengers are major areas of inquiry. In addition to being a biological condition of considerable complexity, AD is also challenging from a social and cultural perspective. An appreciation of the changes occurring in our scientific and clinical environments may lead to building more effective bridges between science and society and to better diagnostic and therapeutic approaches to AD.


A Comparative Analysis of Liquid-Based Cytology and Conventional Smears in Fine-Needle Aspirates of Thyroid Lesions.
Background Palpable nodules in the thyroid are present in 4-7% of the general population. Fine-needle aspiration cytology is a safe and cost-effective method of choice for evaluating thyroid nodules. Aspirated samples can be manually spread directly onto the slide and stained in the conventional smear method. The liquid-cased cytology method has been recently introduced, which is an automated machine-based method, yielding a single slide with a clean background and greater preservation of cells and consuming less time for screening. This study aimed to compare the cytomorphological features and diagnostic accuracy of conventional smears and liquid-based cytology smears. Methodology This prospective study comprised 250 cases of thyroid lesions. Fine-needle aspiration cytology using conventional smears and liquid-based cytology smears was reported per the Bethesda system of reporting thyroid cytopathology. Detailed cytomorphological features were evaluated and compared in both techniques. Results The cellularity of conventional smears was significantly higher for scores 2+ and 3+ than paired liquid-based cytology smears (paired t-test, p < 0.001). The overall diagnostic efficacy of conventional smears and liquid-based cytology smears was equivalent in the majority of cases (n = 171, 68.4%). Conventional smears were better than liquid-cased cytology smears in 34 (13.6%) cases, and liquid-based cytology smears were better than conventional smears in eight (3.2%) cases. Liquid-based cytology smears showed a higher unsatisfactory rate compared to conventional Smears (15.6% vs. 5.2%). The sensitivity and specificity of conventional smears were 84.6% and 94.4%, respectively, compared to 68.7% and 92.4%, respectively, of liquid-based cytology smears. Conclusions Conventional smears are a cost-effective and easy method for diagnosing thyroid nodules. Liquid-based cytology smears can be used in association with conventional smears to enhance the accuracy of the evaluation of malignant thyroid nodules.


Performance of PROMIS Global-10 to Legacy Instruments in Patients With Lateral Epicondylitis.
To validate the Patient-Reported Outcomes Measurement Information System (PROMIS) Global-10 for patients who have lateral epicondylitis requiring surgical treatment in comparison with other gold standard patient-reported outcomes. Sixty-two patients with lateral epicondylitis of the elbow were prospectively enrolled before arthroscopic treatment. Inclusion criteria were patients 18 years of age or older with a diagnosis of lateral epicondylitis. Each patient completed the PROMIS Global-10, EuroQol 5 Dimension (EQ-5D), American Shoulder and Elbow Surgeons (ASES) assessment form, Mayo Elbow Performance Score (MEPS), and Quick Disabilities of the Arm, Shoulder and Hand Score (QuickDASH). Spearman correlations were calculated. Bland-Altman agreement tests were conducted between estimated EQ-5D scores from the PROMIS-10 and actual EQ-5D scores. Correlation between the PROMIS-10 and the EQ-5D was excellent (0.72, P < .0001). Bland-Altman 95% limits of agreement for estimated EQ-5D scores ranged from 0.33 below to 0.21 above actual EQ-5D scores. Correlation of the PROMIS-10 physical score was good to excellent with MEPS (0.61, P < .0001) and QuickDASH scores (0.64, P < .0001) and good with the ASES (0.58, P < .0001). Correlation of the PROMIS mental scores was good with QuickDASH (0.50, P < .0001) and poor with ASES (0.26, P = .0492) and MEPS (0.37, P = .0038). The PROMIS Global-10 physical scores showed good to excellent correlation with gold standard patient-reported outcome instruments, demonstrating it is a reliable tool for outcome assessment in populations with lateral epicondylitis. Despite the excellent correlation with the EQ-5D, the 95% limit of agreement and high variability among the estimated EQ-5D scores derived from the PROMIS-10 suggests that the PROMIS-10 cannot be used as a substitute for actual EQ-5D scores to derive quality-adjusted life years for economic evaluations and cost-effectiveness research. Level II, development of diagnostic criteria on the basis of consecutive patients.


Acylethanolamides and endocannabinoid signaling system in dorsal striatum of rats exposed to perinatal asphyxia.
Endocannabinoids (eCBs) and acylethanolamides (AEs) have lately received more attention due to their neuroprotective functions in neurological disorders. Here we analyze the alterations induced by perinatal asphyxia (PA) in the main metabolic enzymes and receptors of the eCBs/AEs in the dorsal striatum of rats. To induce PA, we used a model developed by Bjelke et al. (1991). Immunohistochemical techniques were carried out to determine the expression of neuronal and glial markers (NeuN and GFAP), eCBs/AEs synthesis and degradation enzymes (DAGLα, NAPE-PLD and FAAH) and their receptors (CB1 and PPARα). We found a decrease in NAPE-PLD and PPARα expression. Since NAPE-PLD and PPARα take part in the production and reception of biochemical actions of AEs, such as oleoylethanolamide, these results may suggest that PA plays a key role in the regulation of this system. These data agree with previous results obtained in the hippocampus and encourage us to develop further studies using AEs as potential neuroprotective compounds.


Toxic stress and burnout: John Henryism and social dominance in the laboratory and STEM workforce.
Persons Excluded from science because of Ethnicity and Race (PEERs) face chronic exposure to interpersonal stressors, such as social discrimination, throughout their scientific careers, leading to a long-term decline in physical and mental health. Many PEERs exhibit John Henryism, a coping mechanism to prolonged stress where an individual expends higher levels of effort and energy at the cost of their physical and mental health. In this article, we discuss how social dominance may increase John Henryism within the STEM community; the causes, effects and costs of John Henryism; and highlight solutions to combat these social adversity stressors within the academic institution.


Histone Methylation in Nickel-Smelting Industrial Workers.
Nickel is an essential trace metal naturally found in the environment. It is also common in occupational settings, where it associates with various levels of both occupational and nonoccupational exposure In vitro studies have shown that nickel exposure can lead to intracellular accumulation of Ni2+, which has been associated with global decreases in DNA methylation, increases in chromatin condensation, reductions in H3K9me2, and elevated levels of H3K4me3. Histone modifications play an important role in modulating chromatin structure and gene expression. For example, tri-methylation of histone H3k4 has been found to be associated with transcriptional activation, and tri-methylation of H3k27 has been found to be associated with transcriptional repression. Aberrant histone modifications have been found to be associated with various human diseases, including cancer. The purpose of this work was to identify biomarkers for populations with occupational nickel exposure and to examine the relationship between histone methylation and nickel exposure. This may provide a scientific indicator of early health impairment and facilitate exploration of the molecular mechanism underlying cancer pathogenesis. One hundred and forty subjects with occupational exposure to Ni and 140 referents were recruited. H3K4 and H3K27 trimethylation levels were measured in subjects' blood cells. H3K4me3 levels were found to be higher in nickel smelting workers (47.24±20.85) than in office workers (22.65±8.81; P = 0.000), while the opposite was found for levels of H3K27me3(nickel smelting workers, 13.88± 4.23; office workers, 20.67± 5.96; P = 0.000). H3K4me3 was positively (r = 0.267, P = 0.001) and H3K27 was negatively (r = -0.684, P = 0.000) associated with age and length of service in smelting workers. This study indicated that occupational exposure to Ni is associated with alterations in levels of histone modification.


De Novo SOX4 Variants Cause a Neurodevelopmental Disease Associated with Mild Dysmorphism.
SOX4, together with SOX11 and SOX12, forms group C of SRY-related (SOX) transcription factors. They play key roles, often in redundancy, in multiple developmental pathways, including neurogenesis and skeletogenesis. De novo SOX11 heterozygous mutations have been shown to cause intellectual disability, growth deficiency, and dysmorphic features compatible with mild Coffin-Siris syndrome. Using trio-based exome sequencing, we here identify de novo SOX4 heterozygous missense variants in four children who share developmental delay, intellectual disability, and mild facial and digital morphological abnormalities. SOX4 is highly expressed in areas of active neurogenesis in human fetuses, and sox4 knockdown in Xenopus embryos diminishes brain and whole-body size. The SOX4 variants cluster in the highly conserved, SOX family-specific HMG domain, but each alters a different residue. In silico tools predict that each variant affects a distinct structural feature of this DNA-binding domain, and functional assays demonstrate that these SOX4 proteins carrying these variants are unable to bind DNA in vitro and transactivate SOX reporter genes in cultured cells. These variants are not found in the gnomAD database of individuals with presumably normal development, but 12 other SOX4 HMG-domain missense variants are recorded and all demonstrate partial to full activity in the reporter assay. Taken together, these findings point to specific SOX4 HMG-domain missense variants as the cause of a characteristic human neurodevelopmental disorder associated with mild facial and digital dysmorphism.


Consonant voicing in the Buckeye corpus.
Many claims about the prevalence of phonetic voicing in English obstruents have been made in the literature over the decades, particularly concerning the stops and affricate [b, d, ɡ, ʤ]. An examination of this literature reveals that many of these claims are based on a paucity of speech data and measurements. For the present study, voiced consonants in the Buckeye corpus of American English (39 speakers) have been measured to determine the percentage of their duration that shows vocal cord vibrations. The prevalence of voicing in the 53 690 voiced stop and affricate tokens has been examined in all contexts, including the initial, intervocalic, and final positions. The results generally contradict the common notion that the nominally "voiced" stops of English are phonetically unvoiced in all positions but intervocalic. Here, they are found to be mostly voiced in final position as well as intervocalically, but usually less than 50% voiced in initial position. A significant proportion of these stops, however, were found to be nearly 100% voiced in the initial position, and this could not be explained by interspeaker variation.


PB2 protein of a highly pathogenic avian influenza virus strain A/chicken/Yamaguchi/7/2004 (H5N1) determines its replication potential in pigs.
It has been shown that not all but most of the avian influenza viruses replicate in the upper respiratory tract of pigs (H. Kida et al., J. Gen. Virol. 75:2183-2188, 1994). It was shown that A/chicken/Yamaguchi/7/2004 (H5N1) [Ck/Yamaguchi/04 (H5N1)] did not replicate in pigs (N. Isoda et al., Arch. Virol. 151:1267-1279, 2006). In the present study, the genetic basis for this host range restriction was determined using reassortant viruses generated between Ck/Yamaguchi/04 (H5N1) and A/swine/Hokkaido/2/1981 (H1N1) [Sw/Hokkaido/81 (H1N1)]. Two in vivo-generated single-gene reassortant virus clones of the H5N1 subtype (virus clones 1 and 2), whose PB2 gene was of Sw/Hokkaido/81 (H1N1) origin and whose remaining seven genes were of Ck/Yamaguchi/04 (H5N1) origin, were recovered from the experimentally infected pigs. The replicative potential of virus clones 1 and 2 was further confirmed by using reassortant virus (rg-Ck-Sw/PB2) generated by reverse genetics. Interestingly, the PB2 gene of Ck/Yamaguchi/04 (H5N1) did not restrict the replication of Sw/Hokkaido/81 (H1N1), as determined by using reassortant virus rg-Sw-Ck/PB2. The rg-Sw-Ck/PB2 virus replicated to moderate levels and for a shorter duration than parental Sw/Hokkaido/81 (H1N1). Sequencing of two isolates recovered from the pigs inoculated with rg-Sw-Ck/PB2 revealed either the D256G or the E627K amino acid substitution in the PB2 proteins of the isolates. The D256G and E627K mutations enhanced viral polymerase activity in the mammalian cells, correlating with replication of virus in pigs. These results indicate that the PB2 protein restricts the growth of Ck/Yamaguchi/04 (H5N1) in pigs.


Differential expression of bone marrow stromal cell-surface antigens on myeloid and lymphoid cells.
Two monoclonal antibodies (MAb) that recognize cell-surface determinants present on bone marrow stromal cells have been generated. The 5B3 antibody recognizes a major histocompatibility class I-like molecule. This antigen is coexpressed on all bone marrow B-lineage cells and myeloid progenitors responsive to recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF). The 9D3 antibody recognizes a protein similar in size to those encoded by the Ly-6 locus. A comparable bone marrow staining pattern and inhibition of 9D3 binding to bone marrow cells by anti-Ly-6C antibodies strongly suggests that the 9D3 antigen is Ly-6C. These data provide a further phenotypic characterization of bone marrow stroma and indicate that these cells express cell-surface determinants also present on myeloid and lymphoid cells.


Quantitative proteomic profiling of muscle type-dependent and age-dependent protein carbonylation in rat skeletal muscle mitochondria.
Carbonylation is a highly prevalent protein modification in skeletal muscle mitochondria, possibly contributing to its functional decline with age. Using quantitative proteomics, we identified mitochondrial proteins susceptible to carbonylation in a muscle type (slow- vs fast-twitch)-dependent and age-dependent manner from Fischer 344 rat skeletal muscle. Fast-twitch muscle contained twice as many carbonylated mitochondrial proteins than did slow-twitch muscle, with 22 proteins showing significant changes in carbonylation state with age, the majority of these increasing in their amount of carbonylation. Ingenuity pathway analysis revealed that these proteins belong to functional classes and pathways known to be impaired in muscle aging, including cellular function and maintenance, fatty acid metabolism, and citrate cycle. Although our studies do not conclusively link protein carbonylation to these functional changes in aging muscle, they provide a unique catalogue of promising protein targets deserving further investigation because of their potential role in aging muscle decline.


Misfolding pathways of the prion protein probed by molecular dynamics simulations.
Although the cellular monomeric form of the benign prion protein is now well characterized, a model for the monomer of the misfolded conformation (PrP(Sc)) remains elusive. PrP(Sc) quickly aggregates into highly insoluble fibrils making experimental structural characterization very difficult. The tendency to aggregation of PrP(Sc) in aqueous solution implies that the monomer fold must be hydrophobic. Here, by using molecular dynamics simulations, we have studied the cellular mouse prion protein and its D178N pathogenic mutant immersed in a hydrophobic environment (solution of CCl4), to reveal conformational changes and/or local structural weaknesses of the prion protein fold in unfavorable structural and thermodynamic conditions. Simulations in water have been also performed. Although observing in general a rather limited conformation activity in the nanosecond timescale, we have detected a significant weakening of the antiparallel beta-sheet of the D178N mutant in CCl4 and to a less extent in water. No weakening is observed for the native prion protein. The increase of beta-structure in the monomer, recently claimed as evidence for misfolding to PrP(Sc), has been also observed in this study irrespective of the thermodynamic or structural conditions, showing that this behavior is very likely an intrinsic characteristic of the prion protein fold.


Valvular surgery in the elderly.
In previous studies from this university, advanced age was identified as an independent predictor of operative mortality for valvular surgery. Therefore, between January 1982 and December 1986, early results were compared in 469 patients greater than 70 years old (Old; 74.0 +/- 3.4 years, mean +/- SD) and in 2,040 patients less than 70 years old (Young; 53.7 +/- 12.1 years). Patients underwent single- or multiple-valve repair or replacement with or without concomitant coronary artery bypass surgery. Data consisting of 31 clinical and angiographic variables were collected prospectively and were analyzed by univariate and multivariate statistics. Old patients were characterized by having more frequent left ventricular dysfunction (left ventricular ejection fraction less than 40%: Old, 33.5%; Young, 22.4%; p less than 0.001), coronary artery disease (Old, 54.5%; Young, 24.2%; p less than 0.001), and urgent surgery (Old, 15.6%; Young, 11.8%; p = 0.02). Aortic valve procedures (Old, 59.7%; Young, 40.1%; p less than 0.001) and concomitant coronary artery bypass surgery (Old, 46.4%; Young, 20.3%; p less than 0.001) were performed more commonly in the Old patient. Operative mortality occurred in 10.0% of Old patients compared with 5.6% of Young patients (p less than 0.001), and major morbidity (low-output syndrome, perioperative myocardial infarction, intra-aortic balloon pump counterpulsation, and stroke) occurred significantly more frequently (p less than 0.001) in the Old. Stepwise logistic regression identified that urgent operation (p = 0.002), mitral or double-valve surgery (p = 0.004), coronary artery disease especially when not treated by bypass surgery (p = 0.02), female gender (p = 0.02), and left ventricular dysfunction (p = 0.05) independently predicted operative death in the Old population. The significant predictors of mortality in the Young patient were urgent operation (p less than 0.001), New York Heart Association class IV (p less than 0.001), associated tricuspid valve disease (p = 0.002), decreased left ventricular function (p = 0.01), valvular re-replacement (p = 0.02), and increasing age (p = 0.03). The predicted probability of operative mortality in Old patients ranged between 0.9 +/- 0.5% and 76 +/- 16%. Elderly patients in good risk categories should be offered surgical intervention for correction of valvular lesions. Alternative therapy may be indicated in patients with multiple risk factors.


Impact of GAN artifacts for simulating mammograms on identifying mammographically occult cancer.
Generative adversarial networks (GANs) can synthesize various feasible-looking images. We showed that a GAN, specifically a conditional GAN (CGAN), can simulate breast mammograms with normal, healthy appearances and can help detect mammographically-occult (MO) cancer. However, similar to other GANs, CGANs can suffer from various artifacts, e.g., checkerboard artifacts, that may impact the quality of the final synthesized image, as well as the performance of detecting MO cancer. We explored the types of GAN artifacts that exist in mammogram simulations and their effect on MO cancer detection. We first trained a CGAN using digital mammograms (FFDMs) of 1366 women with normal/healthy breasts. Then, we tested the trained CGAN on an independent MO cancer dataset with 333 women with dense breasts (97 MO cancers). We trained a convolutional neural network (CNN) on the MO cancer dataset, in which real and simulated mammograms were fused, to identify women with MO cancer. Then, a radiologist who was independent of the development of the CGAN algorithms evaluated the entire MO cancer dataset to identify and annotate artifacts in the simulated mammograms. We found four artifact types, including checkerboard, breast boundary, nipple-areola complex, and black spots around calcification artifacts, with an overall incidence rate over 69% (the individual incident rate ranged from 9% to 53%) from both normal and MO cancer samples. We then evaluated their potential impact on MO cancer detection. Even though various artifacts existed in the simulated mammogram, we found that it still provided complementary information for MO cancer detection when it was combined with the real mammograms. We found that artifacts were pervasive in the CGAN-simulated mammograms. However, they did not negatively affect our MO cancer detection algorithm; the simulated mammograms still provided complementary information for MO cancer detection when combined with real mammograms.


New outlook on the biology of cowpox virus.
Analysis of cowpox outbreaks revealed an extremely wide range of virus pathogenicity including 9 orders of mammals. Recent serological and virological data support the hypothesis that wild rodents may be a natural reservoir of cowpox virus. Cowpox infection of humans occurring without any contact with infected cattle (registered in the U. K. and Poland) is especially interesting for medical and veterinary virology. Surveillance seems justified of the possible virus dissemination beyond its natural reservoir resulting in further infection of man and animals.


AIDS-associated lymphomas.
Patients with HIV infection, like immunosuppressed transplant recipients, are at high risk for the development of non-Hodgkin's lymphoma. These are high-grade lymphomas of B cell origin. Most patients present with advanced extralymphatic disease, and primary lymphoma of the central nervous system has frequently been reported. The cause of the non-Hodgkin's lymphomas in the setting of HIV infection remains unclear. In contrast to those lymphomas observed in transplant recipients, Epstein-Barr virus DNA sequences have been identified in a minority of AIDS-associated lymphomas. Response to therapy in these patients has been disappointing. Response rates to chemotherapy have been lower than those observed in other lymphoma patients, and treatment has been complicated by lack of adequate bone marrow reserve and the occurrence of frequent opportunistic infections. Survivals have been short. Good performance status and absence of a prior AIDS diagnosis are important predictors of response and survival. Although Hodgkin's disease has been observed in HIV-infected patients, epidemiologic data are not suggestive of a direct causal relationship. Hodgkin's disease in this setting is characterized by poor prognosis histologic pattern, advanced disease, and median survivals of less than 1 year.


Robotic DIEP Flap Harvest through a Totally Extraperitoneal Approach Using a Single-Port Surgical Robotic System.
Deep inferior epigastric artery perforator (DIEP) flap surgery is one of the most common techniques for breast reconstruction using abdominal tissue. Although the DIEP flap reduces donor-site morbidity when compared with the conventional free transverse rectus abdominis musculocutaneous flap, violation of the anterior rectus sheath, rectus muscle, and motor nerves cannot be avoided. To further minimize tissue damage in the donor site, the use of a surgical robotic system for DIEP flap harvest with a totally extraperitoneal approach has been suggested. This totally extraperitoneal approach has a long learning curve because of the narrow preperitoneal space and the difficulty of converting a potential space to an actual space. Thus, the authors suggest a single-port robotic system optimized for narrow surgical spaces as a feasible option for DIEP flap harvest by a totally extraperitoneal approach, which has a shorter learning curve.


Serum cholesterol and long-term prognosis in middle-aged men with myocardial infarction and angina pectoris. A 16-year follow-up of the Primary Prevention Study in Göteborg, Sweden.
To compare the role of serum cholesterol in the long-term prognosis of men with a history of myocardial infarction, in men with clinical angina without myocardial infarction, and men without clinical coronary disease. In the second screening of the Primary Prevention Study in Göteborg which comprised 7100 men aged 51 to 59 years at baseline in 1974-1977, 314 men with clinical angina but no myocardial infarction at baseline were identified and 195 men who had survived a myocardial infarction for 0 to 19 years (median 3 years). Of the men without clinical coronary disease at baseline and cholesterol at or below 5.2 mmol.l-1, 2.7 per 1000 observation years died from coronary disease compared to 8.5 per 1000 of the men with serum cholesterol of 7.2 mmol.l-1 or more. Corresponding figures for men with angina was 5.5 and 31.0 per 1000 observation years, and for men with prior myocardial infarction 19.8 and 58.3, respectively, per 1000. After adjustment for age, smoking, systolic blood pressure, body mass index and diabetes the risk of coronary death in men with serum cholesterol above 7.2 mmol.l-1 compared to below 5.2 mmol.l-1 was 2.42 (1.66-3.51) in healthy men, 4.82 (1.44-16.09) in men with angina, 2.70 (0.95-7.67) in survivors of myocardial infarction, and 4.07 (1.86-8.91) in the combined group of men with either angina or prior infarction. The strongest effect was seen during the first half of the follow-up, with an adjusted relative risk for high in relation to low serum cholesterol of 8.08 (1.95-33.55) in men with preexisting coronary disease. Non-coronary deaths varied little by serum cholesterol or coronary disease status at baseline. After 16 years, 76% of the healthy men with low cholesterol and 65% of healthy men with cholesterol above 7.2 mmol.l-1 were still alive. Of the men with prior myocardial infarction, 50% in the group with low cholesterol were alive after 16 years, as compared to 21% of those with high cholesterol. The long-term absolute risk of death in men with coronary disease and elevated serum cholesterol is very high. Implementation of lipid-lowering strategies shown to be efficacious is important in this high-risk group.


Analysis of tandem repeats found in 44 prokaryotic genomes.
Genomes contain various types of repetitive sequences. They may be used as probes for seeking genome rearrangements because they are rather free from the natural selection if they are located in the intergenic regions. In this study, we searched for tandem repeats (TRs) in 44 prokaryotic genomes by the color-coding method and sought the signs of genome rearrangements by detailed analysis of the detected TRs. We found 13,542 tandem repeats from 44 prokaryotic genomes in total ranging from several tens to one thousand per genome. The results of statistical analysis show that TRs tend to exist on high base composition bias regions in some genomes. Moreover, we recognized the characteristic distribution patterns of equivalent TR-pairs in 12 genomes, which are expected to indicate the occurrence of whole-genome duplication (WGD) on the genomes. It is demonstrated that TRs could indeed be used for seeking genome rearrangements. Although it has not been made clear at this time whether or not WGD had occurred in prokaryotic genomes, the results of the analyses of equivalent TR-pairs in this study are thought to be evidences of WGD in these genomes.


Nevus lipomatosus superficialis: A series of six cases.
Nevus lipomatosus still imposes diagnostic, categorization, and etiologic challenges. Even though an intradermal adipose tissue is a histopathologic prerequisite, the lesions are clinically divided into classic multiple forms and a solitary variant, which some consider a separate so-called lipofibroma clinicopathologic entity. This further complicates the true prevalence, classification and etiopathogenesis of nevus lipomatosus. Case reports and series studies have reflected either consistent or variable and sometimes conflicting clinicopathologic findings. A few have reported electron microscopic findings. Immunohistochemistry is lacking. We report two multiple and four solitary forms of nevus lipomatosus in six patients, highlighting their salient histopathologic features and immunohistochemical profile. Both forms showed intradermal groups of perivascular S100+ lipogenic and CD34+ mesenchymal cells intermixed with scattered CD1a+ and FXIIIa+ dendrocytes, CD3 lymphocytic and CD117 mast cells in a fibromyxoid milieu. Epidermal nevoid and comedonal follicular alterations, attenuated dermal connective tissue and adnexal structures were variably present in both forms. We compared our findings with seven series of studies reporting classic and solitary forms. Both forms showed similar histopathologic findings, comparable clinicopathologic features, predominantly pelvic, and shoulder girdle distribution patterns in bimodal age onsets. Even though some lipomatous skin lesions clinically and histopathologically overlap with nevus lipomatosus, certain findings are helpful distinguishing features. Small intradermal islands of lipocytic fibroplasia have characteristic perivascular milieu that may function as a niche of preadipose CD34 mesenchymal stem cells. They are most likely represented in the dermis of the pelvic and shoulder areas in certain individuals prone to maintain these embryonic reservoirs, which are clinically manifested at different ages. Some may have unifocal or multifocal residues reflecting multiple and solitary forms.


[Anorexia nervosa and involuntary treatment].
Anorexia nervosa is a mental health disorder typical for adolescent girls and young adults. The clinical picture is often characterized by distorted body image and intense fear of gaining weight or becoming fat in spite of actual underweight. It is associated with severe disturbance of psychological, physical and social functioning. When the patient strongly resist all weight gaining measures clinicians may have to consider the possibility of involuntary treatment. In the Finnish Mental Health Act there are different definitions for involuntary treatment in adults as compared with under-aged patients. In adults the core question is whether anorexia nervosa can be defined as a psychotic disorder or not. The present review also summarizes literature concerning benefits and disadvantages of involuntary treatment in these patients.


Combined Haemophilus Influenzae type B-Neisseria meningitidis serogroup C vaccine is immunogenic and well tolerated in preterm infants when coadministered with other routinely recommended vaccines.
Preterm infants are at greater risk of morbidity from vaccine-preventable diseases. Therefore, their responses to vaccination are of particular interest. In this open, controlled, Spanish multicenter study, we assessed immunogenicity and safety following primary vaccination of 163 preterm infants (n = 56, <31 weeks' gestation; n = 107, 31-36 weeks' gestation) and 150 full-term infants (>36 weeks' gestation), with Haemophilus Influenzae type B (Hib)-MenC-TT, DTaP(diphtheria-tetanus-acellular pertussis vaccine)-HepB-IPV, and PCV7 at 2 to 4-6 months of age followed by booster vaccination at 16 to 18 months of age. Serum bactericidal activity (rabbit complement) against MenC, and antibodies to Hib and hepatitis b (anti-HBs) were determined. Local/general symptoms were assessed after each vaccination via diary cards. Serious adverse events were recorded throughout the study. There were no statistically significant differences between preterm and full-term infants in either Hib or MenC seroprotection rates or geometric mean concentrations at 1 month postdose 3, before or 1 month postbooster. Postdose 3, >99% of participants had seroprotective anti-HBs antibody concentrations. Anti-HBs geometric mean concentrations was significantly lower in the <31-week group compared with other groups and this difference persisted until 16 to 18 months of age. Hib-MenC-TT vaccine was well tolerated at all ages. There was one death caused by meningococcal serogroup-B sepsis (full term). No serious adverse events were assessed by the investigator as being vaccine related. Hib-MenC-TT vaccine had a similar immunogenicity and safety profile in preterm and full-term infants. These results demonstrate that preterm infants can be safely vaccinated with Hib-MenC-TT at the recommended chronologic age without impacting the responses to the Hib and MenC antigens.


Slow conduction through an arc of block: A basis for arrhythmia formation postmyocardial infarction.
The electrophysiologic basis for characteristic rate-dependent, constant-late-coupled (390 + 54 milliseconds) premature ventricular beats (PVBs) present 4-5 days following coronary artery occlusion were examined in 108 anesthetized dogs. Fractionated/double potentials were observed in injured zone bipolar and composite electrograms at prolonged sinus cycle lengths (1,296 ± 396 milliseconds). At shorter cycle lengths, conduction of the delayed potential decremented, separating from the initial electrogram by a progressively prolonged isoelectric interval. With sufficient delay of the second potential following an isoelectric interval, a PVB was initiated. Both metastable and stable constant-coupled PVBs were associated with Wenckebach-like patterns of delayed activation following an isoelectric interval. Signal-averaging from the infarct border confirmed the presence of an isoelectric interval preceding the PVBs (N = 15). Pacing from the site of double potential formation accurately reproduced the surface ECG morphology (N = 15) of spontaneous PVBs. Closely-spaced epicardial mapping demonstrated delayed activation across an isoelectric interval representing "an arc of conduction block." Rate-dependent very slow antegrade conduction through a zone of apparent conduction block (N = 8) produced decremental activation delays until the delay was sufficient to excite epicardium distal to the original "arc of conduction block," resulting in PVB formation. The present experiments demonstrate double potential formation and rate-dependent constant-coupled late PVB formation in infarcted dog hearts. Electrode recordings demonstrate a prolonged isoelectric period preceding PVB formation consistent with very slow conduction (<70 mm/s) across a line of apparent conduction block and may represent a new mechanism of PVB formation following myocardial infarction.


[Quality assessment of long-term prescription records: QMP study].
The growing concern surrounding health safety issues makes it essential that everyone, in particular the elderly due to their commonly prescribed multiple drugs, has a complete and up to date list of prescriptions. We planned to assess the quality of the electronic records of prolonged medication. This is an observational, transversal and descriptive study, with an analytical component, in which we assessed the technical quality of prolonged medication records of elderly patients of four primary health care, before and after a guided intervention. The doctors received training in good practice recording methods and both professionals and patients were stimulated to use the prolonged medication guide. We evaluated 388 medical records of 33 physicians. The ideal category 'Appropriated medication with posology' improved from 23.5% to 48% (p < 0,001). The remaining categories 'Inappropriated Medication' and 'Appropriated medication but absent posology' decreased from 16.7% to 7% (p = 0,006) and from 59.8% to 46.0% (p = 0,02), respectively. The variables mentor's training skills, workplace, length of family practice and the percentage of elderly in the physician's list showed statistical significance differences at the beginning of the study which disappeared after the intervention, except for the latter. In this study, physicians accepted the proposed changes, regardless of age, gender, mentor's training skills, workplace or length of family practice. Longer duration appointments in the eldery group may be an obstacle in achieving the best results. This original study reveals the necessity to implement periodic postgraduate training to encourage physicians to keep medical records up to date.


Biological activity of Pityrosporum. I. Enhancement of resistance in mice stimulated by Pityrosporum against Salmonella typhimurium.
The effect of administration with Pityrosporum (P. orbiculare, P. ovale, P. pachydermatis and Pityrosporum sp.) on susceptibility of mice to Salmonella typhimurium infection was studied. Pretreatment of mice with 50 mg (wet weight) of killed Pityrosporum 4 days prior to the intraperitoneal (i.p.) challenge of 4 X 10(5) (10 LD50) S. typhimurium elicited resistance comparable to that induced by 500 micrograms (dry weight) of killed Propionibacterium acnes and over 30% of the infected mice survived. Among the species tested, P. pachydermatis was slightly less effective. The challenged organisms were not detected from the blood of mice treated with Pityrosporum but were present in the liver and spleen in approximately level amounts (10(4)-10(5)/organ) during the course of testing. These results suggest that the increased resistance in mice is the result of stimulation of the reticuloendothelial system by Pityrosporum.


Influence of ramipril on right ventricular hypertrophy induced by pulmonary artery stenosis in rats.
The influence of the angiotensin-converting enzyme (ACE) inhibitor ramipril (1 mg/kg orally in a single daily dose) on right ventricular (RV) hypertrophy was studied in Sprague Dawley rats. The pulmonary artery was banded to an outer diameter of 1.7 mm. After 14 days, left (LV) and RV hemodynamic parameters were measured in anesthetized animals. Furthermore, regional heart weights were determined, and myocytes of three different heart regions were isolated and subjected to morphometric analysis. Pulmonary artery stenosis caused a marked increase in RV systolic blood pressure (SBP) without alteration of LV functional parameters as compared with sham-operated animals. Correspondingly, the weight of the RV free wall as well as the RV cell volume were increased to about the same extent, while the LV weight was unchanged. Administration of ramipril to pulmonary artery-constricted animals slightly reduced LV SBP and LVdP/dtmax as compared with banded animals without treatment. The increase in RV SBP and the weight gain of the RV free wall were not affected, however. In contrast, the increase in cell volume of isolated myocytes was less pronounced in this group (+27% as compared with +58% in untreated animals). Because there were no differences in water content of the tissue, interstitial or cellular edema cannot be responsible for this discrepancy. Thus, ACE inhibition with ramipril appears to blunt the cellular hypertrophy in this model without affecting the weight gain of the RV.


What is 'heavy'?
One of the work practices frequently taught to employees is to estimate the heaviness of load before it is actually handled. If it is 'heavy', then one should ask for help. However, limited information can be found in the ergonomics literature about what a person perceives as a 'heavy load'. This study was conducted on 20 male and 20 female workers in the package delivery industry to estimate the amounts of load that correspond to various levels of load heaviness (e.g. 'somewhat heavy'). Experienced employees were used for this purpose. The distribution of loads within each heaviness level was developed using fuzzy sets theory. The maximum load (i.e. 23 kg) defined by the US National Institute for Occupational Safety and Health represents a 'somewhat heavy' load based on the analysis of load distribution (corresponding to a 1.0 certainty factor). Also, the 40 kg considered in the 1981 NIOSH guidelines may be classified as a 'very heavy' load. A comparative analysis of the results of this study with norms established in prior research indicates that one should be more careful in the interpretation of statistical norms for human perception of load handling. A 'moderate' level of load heaviness (i.e. 14 kg) can be handled by 85% of the worker population.


Effects of antibacterial peptide on cellular immunity in weaned piglets.
The aim of this study was to evaluate the effects of antibacterial peptide (ABP) sufficiency on cellular immune functions by determining the spleen cell cycle and apoptosis, peripheral blood T cell subsets, and T cell proliferation function in weaned piglets. A total of 90 piglets (Duroc × Landrace × Yorkshire) of both sexes were randomly allotted to 5 dietary treatments. Each treatment consisted of 3 replicates with 6 piglets per replicate. The dietary treatments consisted of the negative control (NC; basal diet), positive control (PC; basal diet supplemented with 400 mg/kg Astragalus polysaccharide), and ABP (basal diet mixed with 250, 500, and 1,000 mg/kg ABP). The experimental lasted for 28 d. Two piglets from each replicate were selected randomly for blood samples extraction from the jugular vein to obtain peripheral blood T cell subsets, and T cell proliferation function analysis was performed on d 32, 39, 46, and 53. Two piglets from each replicate were selected and euthanized to observe the spleen cell cycle and apoptosis on d 39 and 53. In ABP-sufficient piglets, the G0/G1 phase of the spleen cell cycle was much lower (P < 0.05) and the S and G2 + M phases and proliferation index (PI) were greater (P < 0.05) than in NC piglets. The percentage of apoptotic cells in the spleen significantly decreased under ABP sufficiency (P < 0.05). The proliferation function of peripheral blood T cells increased (P < 0.05) in ABP-sufficient piglets. Percentages of CD3 (+) and CD3 (+)CD4 (+) ratios (d 39, 46, and 53) and CD4 (+)CD8 (+) ratios (d 32, 39, 46, and 53) increased remarkably (P < 0.05) under ABP sufficiency compared with NC. These results suggest that ABP sufficiency could increase the T cell population and proliferation function of T cells and could induce decreased percentages of apoptotic cells. Overall, the cellular immune function was evidently improved in weaned piglets. We suggest optimal dosages of 500 mg/kg ABP for 4-wk addition and 1,000 mg/kg ABP for 2-wk addition.


Early diagnosis of subungual squamous cell carcinoma of the hallux.
Primary subungual squamous cell carcinoma (SCC) of the toe is rare in the literature and frequently late or misdiagnosed. Lack of awareness among physicians of the specific clinical findings, the indolent course of the disease, and the high prevalence of benign conditions of the nail unit may account for delays in diagnosis. In addition to difficulties in identifying the true incidence of this tumor, a standardized therapeutic approach does not currently exist. We present a case of subungual SCC of the first toe without bone invasion. The tumor was diagnosed early, treated with conservative surgical excision, and showed no recurrence or metastasis after 2 years of follow-up.


Histopathologic background for resistance to conventional catheter ablation of common atrial flutter.
Histopathologic examination of the cavotricuspid isthmus in which a large-tip catheter was necessary to achieve conduction block is presented. No thickened myocardium or prominent trabeculation was observed on the ablation line. A small cardiac vein extending through the isthmus across the ablation scar was detected. The remaining myocardial cells were distributed along the small cardiac vein. It is possible that the luminal blood flow of the small cardiac vein protects the surrounding atrial muscle from effective delivery of radiofrequency energy.


Nanoparticles with tunable shape and composition fabricated by nanoimprint lithography.
Cone-like and empty cup-shaped nanoparticles of noble metals have been demonstrated to provide extraordinary optical properties for use as optical nanoanntenas or nanoresonators. However, their large-scale production is difficult via standard nanofabrication methods. We present a fabrication approach to achieve arrays of nanoparticles with tunable shape and composition by a combination of nanoimprint lithography, hard-mask definition and various forms of metal deposition. In particular, we have obtained arrays of empty cup-shaped Au nanoparticles showing an optical response with distinguishable features associated with the excitations of localized surface plasmons. Finally, this route avoids the most common drawbacks found in the fabrication of nanoparticles by conventional top-down methods, such as aspect ratio limitation, blurring, and low throughput, and it can be used to fabricate nanoparticles with heterogeneous composition.


l-DOPA as a small molecule surrogate to promote angiogenesis and prevent dexamethasone-induced ischemia.
The foreign body response to implantable biosensors has been successfully countered through the use of corticosteroids, such as dexamethasone. However, while controlling inflammation, dexamethasone also decreases angiogenesis, which may lead to delayed analyte readings. The concurrent application of VEGF with dexamethasone increases angiogenesis, but VEGF has physical stability issues and is not cost-effective. The use of l-DOPA, a small molecule drug shown to up-regulate VEGF in the Parkinsonian brain, can potentially resolve these issues by substituting for VEGF. In this work, l-DOPA was used for the first time as a pro-angiogenic agent to counteract dexamethasone-induced ischemia. Angiogenesis was modeled using the CAM assay and changes in blood vessel formation were recorded with both manual and digital techniques. As expected, dexamethasone reduced blood vessel formation in the CAM. Application of l-DOPA, on the other hand, increased blood vessel formation when dexamethasone and l-DOPA were administered simultaneously. This novel finding suggests the utility of l-DOPA in the field of implantable medical devices, such as biosensors, as well as tissue engineering applications where both a vascularized tissue environment and control of tissue response is desired.


Robot-Assisted Infratrigonal Vesicovaginal Fistula Repair.
Although relatively rare, vesicovaginal fistula is the most common genitourinary fistula, causing a significant decrease in patients' quality of life. Location of fistula is major supratrigonal, with some cases located in the trigone and rarely below it. Disease treatment is surgical, and repair can be performed by several techniques, including robot-assisted. We present a case of a patient who developed an infratrigonal vesicovaginal fistula after treatment of a cervical cancer. The patient was submitted to robotic repair of the vesicovaginal fistula. The use of robot-assisted laparoscopy is expanding over all areas of urology and its applicability to repair vesicovaginal fistulas brings good results.


Lateral Habenula Responses During Eye Contact in a Reward Conditioning Task.
For many animals, social interaction may have intrinsic reward value over and above its utility as a means to the desired end. Eye contact is the starting point of interactions in many social animals, including primates, and abnormal patterns of eye contact are present in many mental disorders. Whereas abundant previous studies have shown that negative emotions such as fear strongly affect eye contact behavior, modulation of eye contact by reward has received scant attention. Here we recorded eye movement patterns and neural activity in lateral habenula while monkeys viewed faces in the context of Pavlovian and instrumental conditioning tasks. Faces associated with larger rewards spontaneously elicited longer periods of eye contact from the monkeys, even though this behavior was not required or advantaged in the task. Concurrently, lateral habenula neurons were suppressed by faces signaling high value and excited by faces signaling low value. These results suggest that the reward signaling of lateral habenula may contribute to social behavior and disorders, presumably through its connections with the basal ganglia.


Screening of the respiratory functions of workers engaged in bearing manufacture.
The lung functions of 285 workers were investigated. It was found that the ventilatory functions of 20.5% of the female and 23.5% of the male testes were impaired. Prevalence of mild obstructions was established which can be attributed to both cigarette smoking and the length of service. Maximal expiratory flows are worth a special attention in mild airflow obstructions as they could be decreased when forced expiratory volume in the first second (FEV1) remains unchanged.


Marital conflict, respiratory sinus arrhythmia, and allostatic load: interrelations and associations with the development of children's externalizing behavior.
Allostatic load theory hypothesizes that stress and the body's responses to stressors contribute to longer term physiological changes in multiple systems over time (allostasis), and that shifts in how these systems function have implications for adjustment and health. We investigated these hypotheses with longitudinal data from two independent samples (n = 413; 219 girls, 194 boys) with repeated measures at ages 8, 9, 10, and 11. Initial parental marital conflict and its change over time indexed children's exposure to an important familial stressor, which was examined in interaction with children's respiratory sinus arrhythmia (RSA) reactivity to laboratory tasks (stress response) to predict children's basal levels of RSA over time. We also investigated children's sex as an additional possible moderator. Our second research question focused on examining whether initial levels and changes in resting RSA over time predicted children's externalizing behavior. Boys with a strong RSA suppression response to a frustrating laboratory task who experienced higher initial marital conflict or increasing marital conflict over time showed decreases in their resting RSA over time. In addition, boys' initial resting RSA (but not changes in resting RSA over time) was negatively related to change over time in externalizing symptoms. Findings for girls were more mixed. Results are discussed in the context of developmental psychobiology, allostatic load, and implications for the development of psychopathology.


Developmentally-regulated expression of tissue-specific splice variant of rat vesicular glutamate transporter 1 in retina and pineal gland.
Three distinct subtypes of vesicular glutamate transporters (VGLUTs) have been identified to date that are expressed basically in a cell type-specific manner. We have found a splice variant of VGLUT1 mRNA that is expressed almost exclusively in photosensitive tissues, i.e. the retina and the pineal gland. The variant mRNA, termed VGLUT1v, contains an additional 75 base pair sequence derived from part of a second intron (designated as exon IIa) between exons 2 and 3. The variant accounted for approximately 70% and 25%of VGLUT1 mRNA in the adult retina and pineal gland, respectively. The expression of VGLUT1v was developmentally regulated in both tissues. Organ culture showed that expression of the variant in the retina increased in association with the development of rod cells, suggesting that VGLUT1v is expressed in rod cells. In situ hybridization with variant-specific probes showed expression of VGLUT1v in the inner segment layer of photoreceptor cells. On the other hand, variant expression did not parallel the development of rhodopsin-positive cells in the pineal gland. As rod cells and pinealocytes are known to release glutamate continuously at ribbon synapses, it is possible that the variant has some functional advantage over the wild-type transporter in such a specialized manner of glutamate release.


Endometriomas and assisted reproductive technology.
Endometriomas in the assisted reproductive technology patient present a challenging clinical scenario for the infertility specialist. Although surgical management is often pursued in cases of pain or large cyst diameter, patients without such factors must be counseled regarding surgical versus expectant management. Decisions to pursue surgery must be viewed in the context of potentially decreased ovarian reserve and more difficult stimulation for in vitro fertilization. In this article, three distinct cases are presented along with a summary of the most current literature available to guide clinicians in the optimal management of in vitro fertilization patients with endometriomas.


Few-layered graphene-supported palladium as a highly efficient catalyst in oxygen reduction reaction.
New, active and stable catalysts competitive to Pt catalysts are necessary for fuel cell development. Here, we present few-layered graphene-supported Pd, revealing a performance superior to Pt/C and Pd/C ORR (positive half-wave potential shift E(1/2) by 50 mV, approximately one order of magnitude higher area- and mass-normalized current densities, I(area), I(mass), after 2500 cycles). The catalyst preparation is easily scalable, simple, inexpensive and eco-friendly.


Demonstration of a 65 kDa tumor-specific phosphoprotein in urine and serum of rats with N-methyl-N-nitrosourea-induced mammary adenocarcinomas.
Polyclonal antibodies against a 65 kDa tumor-associated phosphoprotein (p65) were used to develop an ELISA to analyze the presence of p65 in urine and serum of rats bearing N-methyl-N-nitrosourea-induced mammary gland adenocarcinomas. Highly purified rat p65 was added to normal urine and serum to establish a quantitative standard curve with the average correlation coefficient being 0.98 and 0.99 respectively. All samples of urine and serum obtained from different carcinoma-bearing rats showed p65 concentrations above the normal levels found in the control urine and sera. The correlation coefficient between tumor burden and p65 concentration in urine and serum was 0.65 and 0.77 respectively. The average levels of p65 in normal urine and normal serum were 37.0 +/- 32.0 and 48.0 +/- 38.0 ng/ml respectively. In the case of urine obtained from rats bearing mammary adenocarcinomas, the mean p65 level was 119.0 +/- 35.9 ng/ml and their serum level was 225.4 +/- 67.5 ng/ml. Sensitivity, specificity and predictive value for serum and urine marker elevation were 78.5, 70.0 and 78.5% respectively. Following in vitro phosphorylation of concentrated urinary proteins, isoelectrofocusing, SDS-PAGE and autoradiography, a phosphorylated form of the 65 kDa protein with a pI of 5.8 was identified in the urine of tumor-bearing rats. This phosphoprotein bound to an antiphosphotyrosine monoclonal antibody and an anti-p65 polyclonal as determined by Western blot analysis. Using the anti-p65 antibodies in an immunoprecipitation procedure, the main radio- and immunoactive band of 65 kDa and two lower mol. wt bands of 50 and 41 kDa, apparently representing degradation products of p65, were identified after in vitro and in vivo phosphorylation of urinary proteins obtained from mammary carcinoma-bearing rats.


Synovial Fluid α-MSH Levels are Inversely Correlated with Articular Cartilage Degeneration in Anterior Cruciate Ligament Deficient Knees.
Secondary osteoarthritis after ligament or meniscus injury generally causes great burdens to patients. Alpha-melanocyte-stimulating hormone (α-MSH ), a 13 amino acid neuropeptide produced by intracellular cleavage of the proopiomelanocortin (POMC) hormone, has been proven to suppress inflammation and protect cartilage from damage. The present study was carried out to explore the relationship between synovial fluid α-MSH levels and articular cartilage degeneration in patients with anterior cruciate ligament (ACL) deficiency. 51 patients with ACL deficiency admitted to our hospital were enrolled. The Noyes score method was used to assess articular cartilage damage arthroscopically. Synovial fluid α-MSH levels were examined using a double antibody radioimmunoassay method. Inflammation markers such as IL-6, MMP-3, and degradation biomarker of collagen type II (CTX-II) were also explored by enzyme-linked immunosorbent assay (ELISA). The articular cartilage in ACL deficiency patients deteriorated significantly with time after injury (r = 0.673, p < 0.001). Synovial fluid α-MSH levels are inversely associated with Noyes scores (r = -0.682, p < 0.001), levels of inflammation markers IL-6 (r = -0.302, p = 0.035), MMP-3 (r = -0.652, p < 0.001) and degradation biomarker CTX-II (r = -0.584, p < 0.001). Synovial fluid α-MSH levels showed an independent and negative correlation with articular cartilage degeneration in patients with knee ACL deficiency. Supplementing with a-MSH may serve as a possible adjuvant therapy for delaying cartilage degeneration after ACL injury.


Acceptance of Cervical Cancer Screening and its Correlates Among Women of a Peri-Urban High-Density Residential Area in Ndola, Zambia.
Zambia has one of the highest cervical cancer incidence and mortality rates in the world. Cervical cancer screening leads to reduction in the incidence of invasive disease. The objectives of the study were to determine the level of acceptance of cervical cancer screening and its correlates among women of a peri-urban high-density residential area in Ndola, Zambia. A cross sectional study was conducted. With a population size of 12,000 women in reproductive age and using an expected frequency of 50 + 5% and at 95% confidence interval, the required sample size was 372. A stratified sampling method was used to select participants. Independent factors that were associated with the outcome were established using multi-variate logistic regression. Adjusted odds ratios and their 95% confidence intervals are reported. In total, 355 out of 372 questionnaires were administered, achieving a response rate of 95.4%. Out of 355 participants, 9 (2.5%) had ever been screened for cervical cancer. In bivariate analyses, factors associated with screened were knowledge of body part affected, screening as a prevention tool, whether cervical cancer was curable in its early stages or not, awareness of cervical cancer screening, knowledge on frequency of screening and cervical cancer screening causing harm. However, in multivariate analysis, participants who knew that cervical cancer screening prevented cervical cancer were 3.58 (95% CI [1.49, 8.64]) times more likely to have been screened than those who did not have the knowledge. Participants who knew that cervical cancer is curable were 2.76 (95% CI [1.92, 8.31]) times more likely to have been screened than those who did not have the knowledge. The uptake of screening was low. Interventions should be designed to increase uptake of screening for cervical cancer by considering factors that have been identified in the current study that are independently associated with cervical cancer screening among this population.


Dentascan an excellent tool for assessment of variations in the management of periodontal defects.
The purpose of the present study was to envisage the effectiveness of demineralized freeze-dried bone allograft (DFDBA) and bovine bone graft (BBG) for promoting defect fill in periodontal intrabony defects using dentascan. A total of 13 subjects (15 intrabony defects) aged between 24 and 56 years affected by moderate to severe periodontitis were randomly divided into Control (CG) and Test groups (TG1 and TG2). In CG only debridement, TG1 debridement plus DFDBA, and TG2 debridement plus BBG were performed. The clinical parameters probing pocket depth (PPD), clinical attachment level (CAL) was used. The radiological analysis was done by dentascan, which is a single-slice spiral computed tomographic scanner. Six months after, regenerative treatment clinical measurements were recorded. The bone fill was assessed using Dentascan as previously mentioned. PPD reduction and CAL gain were significant in all the groups after 6 months whereas, on intergroup comparisons, insignificant finding was observed both at baseline and after 6 months. Coronoapical bone status decreased significantly in all groups, buccolingual measurements decreased significantly in TG1 and TG2, but no such trend was seen in CG. Significant reduction in mesiodistal bone status was noticed only in TG1 whereas insignificant on intergroup comparisons. Dentascan-based analysis attested that DFDBA was superior to BBG.


B lymphocytes and systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by B cell hyperactivity in association with autoantibodies, most prominently those directed to components of the cell nucleus. The source of the antigens that drive B cell responses in SLE is unknown, although recent studies suggest mechanisms by which the self-antigens become immunogenic and stimulate responses. Among these mechanisms, abnormalities in the generation of apoptotic cells or their clearance may increase the availability of nuclear antigens to drive responses. In addition, autoantibody crossreactivity may promote induction of responses to disparate antigens, foreign and self, and enable a single autoantibody to cause disease by crossreactive binding. In addition to reflecting increased exposure to self-antigen, autoantibody responses in SLE may result from abnormalities in B cell signaling and regulation by cytokines. New approaches to therapy aim to abrogate autoantibody production by targeting specific steps in B cell activation, including blockade of T cell costimulation.


A B23-interacting sequence as a tool to visualize protein interactions in a cellular context.
We report the characterization of a nucleolar localization sequence (NoLS) that targets the green fluorescent protein (GFP) into the granular component (GC) of nucleoli. This NoLS interacts in vitro specifically and directly with the major nucleolar protein B23 and more precisely with the region of B23 including the two acidic stretches. The affinity of NoLS for B23 is stronger than that of the HIV-1 Rev protein in vitro. Moreover, B23-NoLS interaction also occurs in vivo. Indeed, (1) NoLS confers on the GFP the behavior of B23 throughout the cell cycle, (2) the GFP-NoLS fusion and B23 remain colocalized after drug treatments, (3) a selective delocalization of B23 from nucleoli to nucleoplasm induces a concomitent delocalization of the GFP-NoLS fusion, and (4) the fusion of NoLS to fibrillarin makes it possible to colocalize fibrillarin and B23. Interestingly, by fusing NoLS to fibrillarin, both fibrillarin and the fibrillarin partner Nop56 are mislocalized in the GC of nucleoli. Similarly, by fusing the NoLS to MafG, part of the nuclear transcription factor NF-E2 composed of both MafG and p45 NF-E2, NF-E2 is redirected from the nucleoplasm to the nucleoli. Thus, we propose that the NoLS may be used as a tool to visualize and prove protein interactions in a cellular context.


The decidua-the maternal bed embracing the embryo-maintains the pregnancy.
The decidua has been known as maternal uterine tissue, which plays essential roles in protecting the embryo from being attacked by maternal immune cells and provides nutritional support for the developing embryo prior to placenta formation. However, there are questions that still remain to be answered: (1) How does the decidua supply nutrition and provide a physical scaffold for the growing embryo, before placental vascular connection is established? (2) How is the balance between preventing an anti-embryo immune response and protecting both embryo and mother from infections established? To understand basic personas in decidual tissues, we review the structure of the decidua composed of terminally differentiated uterine stromal cells, blood vessels, and a number of repertoire of uterine local immune cells, including the well-known uterine natural killer (uNK) cells and recently discovered innate lymphoid cells (ILCs). Decidual macrophages and uterine dendritic cells (DCs) are supposed to modulate adaptive immunity via balancing cytokines and promoting generation of regulatory T (Treg) cells. During decidualization, vascular and tissue remodeling in the uterus provide nutritional and physical support for the developing embryo. Secretion of various cytokines and chemokines from both the embryo and the decidual cells activates multiple signaling network between the mother and the embryo upon implantation. Defects in the decidual development during early pregnancy result in loss of pregnancy or complications in later gestational stage.


[Introduction of new GCP (good clinical practice)].
In 1997, a new GCP has taken effect by the Ministry of Health and Welfare, Japan, and will be enforced as of April, 1998. The GCP regulates the method of clinical trials in the light of ethics and science. The New GCP requires written informed consent, enforcement of the responsibility of the client and so on.


"It Is Definitely a Game Changer": A Qualitative Study of Experiences with In-home Overnight Closed-Loop Technology Among Adults with Type 1 Diabetes.
This qualitative study explored trial participants' experiences of four nights of in-home closed loop. Sixteen adults with type 1 diabetes, who completed a randomized crossover trial, were interviewed after four consecutive nights of closed-loop. Interviews were audio recorded, transcribed, and analyzed with a coding framework developed to identify the main themes. Participants had a mean age of 42 ± 10 years, nine were women; mean diabetes duration was 27 ± 7 years, and all were using insulin pumps. Overall, first impressions were positive. Participants found closed-loop easy to use and understand. Most experienced more stable overnight glucose levels, although for some these were similar to usual care or higher than they expected. Compared with their usual treatment, they noticed the proactive nature of the closed-loop, being able to predict trends and deliver micro amounts of insulin. Most reported technical glitches or inconveniences during one or more nights, such as transmission problems, problematic connectivity between devices, ongoing alarms despite addressing low glucose levels, and sensor inaccuracy. Remote monitoring by the trial team and their own hypoglycemic awareness contributed to feelings of trust and safety. Although rare, safety concerns were raised, related to feeling unsure whether the system would respond in time to falling glucose levels. This study provides relevant insights for implementation of closed-loop in the real world. For people with diabetes who are less familiar with technology, remote monitoring for the first few days may provide reassurance, strengthen their trust/skills, and make closed-loop an acceptable option for more people with type 1 diabetes.


Fabrication of self-setting β-tricalcium phosphate granular cement.
Bone defect reconstruction would be greatly improved if β-tricalcium phosphate (β-TCP) granules had the ability to self-set without sacrificing their osteoconductivity potential. This study aimed to identify a method to permit β-TCP self-setting whilst maintaining good osteoconductivity. When mixed with acidic calcium phosphate solution, β-TCP granules were found to readily set, forming a fully interconnected porous structure. On mixing, dicalcium phosphate dihydrate crystals formed on the surface of β-TCP granules, bridging the granules and resulting in the setting reaction. The setting time of the β-TCP granular cement (β-TCP GC) was approximately 1 min and its mechanical strength, in terms of diametral tensile strength, was approximately 0.8 MPa. The β-TCP GC and β-TCP granules both showed the same level of osteoconductivity within rat calvaria bone defects. At 2 and 4 weeks post-implantation, new bone formation was comparable between the two β-TCP based bone substitutes. We conclude that β-TCP GC has excellent potential for use as a cement in bone defect reconstruction. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 800-807, 2018.


Bone characteristics and body weight of broilers in different husbandry systems.
1. An experiment was conducted to determine the effect of husbandry systems on bone characteristics and body weight. Broilers were reared in 5 different husbandry systems: wire mesh (WM) floored cages from 0 to 7 weeks; WM floored cages from 0 to 3 weeks and then transferred to floor pens; plastic mesh (PM) floored cages from 0 to 7 weeks; PM floored cages from 0 to 3 weeks and then transferred to floor pens; floor pens from 0 to 7 weeks. 2. Body weight at 3 weeks of age was affected by the husbandry systems, being greatest for the birds reared in floor pens. At 7 weeks of age, male broilers reared in PM floored cages had the lowest body weight and body weight gain from 4 to 7 weeks. 3. Humerus weight and ash content were affected by cage rearing whereas tibia weight and ash were not. Birds reared in PM cages had shorter tibia and humeri than birds reared in floor pens.


Evaluation of Acoustic Reflex Thresholds in COVID-19 Patients With Taste Disorders.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, can result in persistent loss of taste and smell. This study was performed to assess acoustic reflex threshold (ART) in patients with taste disorders caused by SARS-CoV-2. This retrospective study enrolled 11 patients (9 men, 2 women; average age = 22.3 years) with a history of COVID-19 and had complaints of taste disorder and sensitivity to loud sounds. The control group consisted of 13 healthy participants (10 men, 3 women; average age = 23.4 years). Anamnesis, neuro-otological, ear, nose and throat, and eye examinations, as well as a taste test, pure tone audiometry, speech discrimination test, and impedance audiometry were performed in all participants. All participants in the study group had a negative taste test result. In addition, ART values were significantly higher in the study group than the control group at all frequencies. SARS-CoV-2 could be a neurotropic virus that can cause facial nerve neuropathy.


The Impact of Skin Color on the Recognition of Blunt Force Injuries.
Dark skin may obscure injuries. This is reflected in the illustrations in textbooks, which generally depict blunt force injuries in victims with light skin tones. We explored whether forensic pathologists can reliably recognize blunt force injuries in dark-toned skin by comparing the average number of contusions and abrasions of motor vehicle accident victims with dark- and light-toned skin. We also investigated whether the race of the forensic pathologist observer mattered. We found a significant difference in the number of injuries recorded in autopsies of motor vehicle accident victims based upon skin tone; there was also a difference in the race of the observer.


Post-translational arginylation of calreticulin: a new isospecies of calreticulin component of stress granules.
Post-translational arginylation consists of the covalent union of an arginine residue to a Glu, Asp, or Cys amino acid at the N-terminal position of proteins. This reaction is catalyzed by the enzyme arginyl-tRNA protein transferase. Using mass spectrometry, we have recently demonstrated in vitro the post-translational incorporation of arginine into the calcium-binding protein calreticulin (CRT). To further study arginylated CRT we raised an antibody against the peptide (RDPAIYFK) that contains an arginine followed by the first 7 N-terminal amino acids of mature rat CRT. This antibody specifically recognizes CRT obtained from rat soluble fraction that was arginylated in vitro and also recognizes endogenous arginylated CRT from NIH 3T3 cells in culture, indicating that CRT arginylation takes place in living cells. Using this antibody we found that arginylation of CRT is Ca2+-regulated. In vitro and in NIH 3T3 cells in culture, the level of arginylated CRT increased with the addition of a Ca2+ chelator to the medium, whereas a decreased arginine incorporation into CRT was found in the presence of Ca2+. The arginylated CRT was observed in the cytosol, in contrast to the non-arginylated CRT that is in the endoplasmic reticulum. Under stress conditions, arginylated CRT was found associated to stress granules. These results suggest that CRT arginylation occurs in the cytosolic pool of mature CRT (defined by an Asp acid N-terminal) that is probably retrotranslocated from the endoplasmic reticulum.


Paleotemperature record of the Middle Devonian Kačák Episode.
The Middle Devonian Epoch, ~ 393-383 million years ago, is known for a peak in diversity and highest latitudinal distribution of coral and stromatoporoid reefs. About 388 million years ago, during the late Eifelian and earliest Givetian, climax conditions were interrupted by the polyphased Kačák Episode, a short-lived period of marine dys-/anoxia associated with climate warming that lasted less than 500 kyr. Reconstruction of the seawater temperature contributes to a better understanding of the climate conditions marine biota were exposed to during the event interval. To date, conodont apatite-based paleotemperatures across the Eifelian-Givetian boundary interval have been published from Belarus, France, Germany and North America (10-36° S paleolatitude). Here we provide new δ18Oapatite data from the Carnic Alps (Austria, Italy) and the Prague Synform (Czech Republic). For better approximation of the paleotemperature record across the Kačák Episode, a latitude-dependent correction for Middle Devonian seawater δ18O is applied. Because δ18Oapatite data from shallow marine sections are influenced by regional salinity variations, calculated mean sea surface temperatures (SST) are restricted to more open marine settings (22-34° S paleolatitude). Water temperatures reach ~ 34 °C in the Prague Synform and ~ 33 °C in the Carnic Alps and suggest that SSTs of the southern hemisphere low latitudes were ~ 6 °C higher than previously assumed for this time interval.


The Modification Mechanism, Evaluation Method, and Construction Technology of Direct-to-Plant SBS Modifiers in Asphalt Mixture: A Review.
To further promote the development of research on direct-to-plant SBS-modified asphalt, this article analyzes the development of direct-to-plant SBS modifiers. Starting from the material composition and mechanism of action, common direct-to-plant SBS modifiers were analyzed and classified into four categories based on their mechanism of action, including the instant dissolution principle, intramolecular lubrication principle, non-granulation principle, and vulcanization principle. From the evaluation of the modification effect, the method of studying the performance of direct-to-plant SBS-modified asphalt is summarized, including fluorescence microscopy, AFM technology, and molecular dynamics simulation technology. From the perspective of practical application, the construction process of direct-to-plant SBS-modified asphalt was discussed, including the design stage, raw material preparation stage, mix design stage, and on-site construction stage. The results show that common direct-to-plant SBS modifiers are primarily SBS with a small particle size (less than 200 mesh) or specific model, supplemented by additives (EVA, naphthenic oil, sulfur, petroleum resin, etc.), which improve melting efficiency and lubricity or make it undergo vulcanization reaction, change the proportion of asphalt components, and improve stability. In the evaluation of the modification effect of direct-to-plant SBS-modified asphalt, the disparity of the direct-to-plant SBS modifier is determined by observing the particle residue after dry mixing. Macroscopic indexes of modified asphalt and modified asphalt mixture are used to determine the cross-linking effect of direct-to-plant SBS modifier and asphalt, and the modification mechanism and modification effect of wet SBS modifier are evaluated at the microscopic level. The development of direct-to-plant SBS-modified asphalt should combine the characteristics of direct-to-plant SBS modifiers and the attributes of field application, targeted research, and the development of high-performance direct-to-plant SBS modifiers and complete production technologies applicable to different regions, strengthen the improvement of modification effect evaluation, and form a complete theoretical system.


Age-Dependent Seroprevalence of JCV Antibody in Children.
Progressive multifocal leukoencephalopathy (PML) is an opportunistic central nervous system infection, caused by the John Cunningham virus (JCV). PML may occur during treatment with immunosuppressive agents or monoclonal antibodies such as natalizumab. The JCV seroprevalence increases with age with a seropositivity of 60% in the adult human population. In this study, we analyzed sera from 109 pediatric multiple sclerosis (MS) patients (mean age 14 years) as well as sera from 162 patients with a wide range of suspected neurologic disorders (mean age 6.3 years). Our results showed a considerably lower seroprevalence for JCV in our pediatric cohort with 33.3% and equal distribution in both subgroups, compared with reported seropositivity in adult population. This could result in a lower risk for drug-induced PML in pediatric patients compared with adult patients and can influence the indication for natalizumab therapy in pediatric MS patients.


A novel mouse model of central cord syndrome.
Patients with potential spinal stenosis are susceptible to central cord syndrome induced by blunt trauma. Suitable animal models are helpful for studying the pathogenesis and treatment of such injuries. In this study, we established a mouse model of acute blunt traumatic spinal cord injury by compressing the C6 spinal cord with 5 and 10 g/mm2 compression weights to simulate cervical central cord syndrome. Behavioral testing confirmed that this model exhibited the characteristics of central cord syndrome because motor function in the front paws was impaired, whereas basic motor and sensory functions of the lower extremities were retained. Hematoxylin-eosin staining showed that the diseased region of the spinal cord in this mouse model was restricted to the gray matter of the central cord, whereas the white matter was rarely affected. Magnetic resonance imaging showed a hypointense signal in the lesion after mild and severe injury. In addition, immunofluorescence staining showed that the degree of nerve tract injury in the spinal cord white matter was mild, and that there was a chronic inflammation reaction. These findings suggest that this mouse model of central cord syndrome can be used as a model for preclinical research, and that gray matter is most vulnerable to injury in central cord syndrome, leading to impaired motor function.


Competence of dogs as reservoirs for Lyme disease spirochetes (Borrelia burgdorferi).
Dogs become infected with Borrelia burgdorferi after being bitten by infected adult ticks. However, it is not known whether dogs are competent reservoirs of the organism, that is, it is not known whether infected dogs can subsequently transmit the bacterium to feeding immature ticks. To determine reservoir competence of dogs, 11 Beagles were experimentally infected by means of challenge exposure to infected adult deer ticks (Ixodes scapularis). Three weeks later, larval ticks were allowed to feed on the dogs. Engorged larvae were collected, allowed to molt to the nymph stage, and tested, by means of a direct fluorescent antibody assay, to detect the presence of B burgdorferi organisms. Overall, 78% of immature ticks tested were found to have become infected. We concluded that dogs might serve to increase human risk of exposure to B burgdorferi-infected ticks and, therefore, should be protected from exposure to infected ticks as well as immature ticks seeking a blood meal.


Reproducibility of transthoracic 3D echocardiography in the assessment of mitral valve area in patients with rheumatic mitral stenosis: real time versus ECG-gated 3D echocardiography.
To assess reproducibility of Real time 3D echocardiography (RT3D) and ECG-gated 3D echocardiography (EG3D) when measuring the mitral valve area (MVA) in rheumatic mitral stenosis (MS). MVA was assessed by three operators in 68 MS patients using RT3D and EG3D. Reproducibility of each technique was determined by calculating the standard error of measurements (SEM). SEM was similar between RT3D and EG3D. MVA variability was of 0.4 cm² or 30% of any RT3D or EG3D measured MVA. The minimal change in MVA above which two measurements should be considered to differ significantly for the same operator was of 0.4 cm² for RT3D and 0.5 cm² for EG3D. For two different operators making successive measurements, the minimum significant change was of 0.5 cm² for RT3D and 0.6 cm² for EG3D. The minimum significant difference when switching from RT3D to EG3D or vice versa is of 0.6 cm². Low temporal resolution of 6 Hz has the least variability when using RT3D (0.19 cm² vs. 0.26 cm², p = 0.009) but significantly underestimated MVA (1.3 ± 0.4 cm² vs. 1.4 ± 0.4 cm², p < 10- 3) when compared to EG3D. MVA variability was significantly higher in mild MS when compared to severe MS whether it is RT3D (0.23 cm² vs. 0.18 cm², p = 0.02) or EG3D (0.27 cm² vs. 0.16 cm², p < 0.001). RT3D and EG3D are equally reproducible in the assessment of MVA in patients with MS. Further measurements standardization is required to have a clinically acceptable estimations of the true 3D MVA and minimal detectable differences.


Improved confidence interval for average annual percent change in trend analysis.
This paper considers an improved confidence interval for the average annual percent change in trend analysis, which is based on a weighted average of the regression slopes in the segmented line regression model with unknown change points. The performance of the improved confidence interval proposed by Muggeo is examined for various distribution settings, and two new methods are proposed for further improvement. The first method is practically equivalent to the one proposed by Muggeo, but its construction is simpler, and it is modified to use the t-distribution instead of the standard normal distribution. The second method is based on the empirical distribution of the residuals and the resampling using a uniform random sample, and its satisfactory performance is indicated by a simulation study. Copyright © 2017 John Wiley & Sons, Ltd.


[ Onchocerciasis control program in West Africa: socioeconomic development and risk of recrudescence of transmission. 1. Experimental study of the transmission of Onchocerca volvulus strains from Southwestern Sierra Leone by Simulium sirbanum].
As part of the return of savanna migrants installed since a long time in forest regions, in the south of Sierra Leone, we carried out an experimental study about a cross-transmission between Simulium sirbanum from Missira (West-Mali) and the forest strain of Onchocerca volvulus in the south-west of Sierra Leone. This study will allow to know if there is a risk of onchocerciasis transmission recrudescence in relation to the reinstallation of these migrants in their native region. Because of the very high limitation to the forest strain of O. volvulus microfilariae output of the peritrophic membrane reduction with savanna black-flies and according to the very low mature parasite out put of S. sirbanum with this strain observed along this experimentation, the forest strain of O. volvulus from the south Sierra Leone appears maladjusted to S. sirbanum, the main vector of onchocerciasis in savanna regions. This observation implicates a very low intensity of transmission for this forest strain by savanna onchocerciasis vectors. The return of savanna migrants in their native region, installed in the south Sierra Leone since several decades, could not be, in a short time, an origin of onchocerciasis recrudescence in savanna regions of the Onchocerciasis Control Programme area cleaned by an effective vector control carried out since 1975 sustained now by a chemotherapeutic treatment reducing the human parasite reservoir. However, the preservation of this acquired necessitates an epidemiological supervision increased, because the interactions between the vector and the parasite for a long time could carry away a mutual adaptation and a sickness recrudescence.


Effect of national recommendation on sweet selling as an intervention for a healthier school environment.
In 2007, the Finnish National Board of Education (FNBE) and the National Institute for Health and Welfare (THL) gave a national recommendation that Finnish upper comprehensive schools should not sell sweet products. The aim was to find out how the national recommendation changed the schools' selling of sweet products. This longitudinal survey was conducted in Finnish upper comprehensive school classes 7-9 (13-15-year-old pupils) in 2007 and 2010. All the schools (N=970) were invited to answer the questionnaire and 237 schools answered in both years (response rate 24%). The questionnaires contained questions concerning the selling of sweet and healthy products and school policy on sweet selling guidelines. Of the nine items in the questionnaire, three weighted sum scores were formed for oral health promotion: Exposure, enabling and policy (higher score indicating better actions). These sum scores were also trichotomized. Statistical significances of the changes were analyzed using nonparametric Wilcoxon's test, McNemar's test, and McNemar-Bowker's test. Schools had decreased exposure of pupils to sweet products (p<0.001), more often provided oral health protecting items (p=0.047) and had improved their oral health-promoting policy (p<0.001). The selling of some sweet products, candies and soft drinks had decreased (p<0.001) whereas the selling of other sweet products had not changed (p=0.665). Schools tended to improve their exposure and policy status (p<0.001). It is possible to improve school environments by means of a national recommendation. Other actions are needed both inside and outside schools in order to decrease the total consumption of sweet products among adolescents.


[Evaluation the application of intra-operative cell salvage in cesarean section based on multicenter data].
Objective: To investigate the safety, efficacy and application indication of intra-operative cell salvage (IOCS) in cesarean section. Methods: A total of 1 265 pregnant women who received IOCS blood transfusion during cesarean section in 11 tertiary A hospitals from August 2016 to January 2019 were collected and divided into <1 500 ml group (796 cases) and ≥1 500 ml group (469 cases) according to the amount of blood loss during cesarean section. The general clinical data, ultrasonic imaging data, perinatal and puerperium indicators were analyzed retrospectively. The risk factors of intraoperative blood loss ≥1 500 mL using IOCS transfusion were analyzed by logistic multivariate regression. Results: (1) A total of 848 001 ml of blood was recovered and a total of 418 649 ml of blood was transfused in 1 265 pregnant women who received IOCS transfusions, which was equivalent to 23 258 U red blood cell suspension, greatly saving medical resources. The intraoperative blood loss in <1 500 ml group and ≥1 500 ml group was 800 ml (300-1 453 ml) and 2 335 ml (1 500-20 000 ml), respectively. No amniotic fluid embolism, severe adverse reactions, shock and death occurred in the two groups. (3) Multivariate regression analysis showed that age ≥35 years (OR=1.5, 95%CI: 1.1-1.9), prenatal hemoglobin level <110 g/L (OR=1.7, 95%CI: 1.3-2.2), history of uterine surgery (OR=1.8, 95%CI: 1.3-2.6), placenta previa (OR=1.9, 95%CI: 1.1-3.1), placenta accreta (OR=2.6, 95%CI: 1.8-3.9), blood pool in the placenta (OR=1.6, 95%CI: 1.1-2.3), abnormal posterior placenta muscle wall (OR=1.8, 95%CI: 1.2-2.6), placenta projecting to the anterior uterine wall (OR=3.0, 95%CI: 1.3-7.0) were risk factors for blood loss ≥1 500 ml in obstetric transfusion using IOCS technique, with statistical significance (all P<0.05). Conclusion: IOCS is safe and effective in cesarean section, which could save the medical resources and reduces medical expenses, however, it is necessary to strictly master the application indication.


[Cellular electrophysiological basis of proarrhythmic and antiarrhythmic effects of ischemia-related lipid metabolites].
Lysophosphatidylcholine, an amphiphilic lipid metabolite, accumulates in the ischemic myocardium and plays a pivotal role in the production of arrhythmias. To clarify its cellular ionic mechanism(s), we investigated the effect of 1-palmitoyl-lysophosphatidylcholine (LPC) on the guinea pig ventricular myocytes, using whole cell- and patch-voltage clamp methods. In whole cell recordings, extracellular application of LPC (20-100 microM) depolarized the resting potential within several minutes and produced automatic action potential discharges from the resting and plateau potentials. Such effects were attributed mostly to the decrease in inward going rectifier K current (Ik1). Single channel recordings in the cell attached mode revealed that this decrease in Ik1 is secondary to the reduction of the single channel conductance and not due to decreased open probability. LPC (5-50 microM) also decreased the excitatory Na+ current (INa) in an all-or-nothing manner, depending upon the concentration used. Such decreases in the resting potential and peak INa could be responsible for the marked retardation of conduction velocity and therefore production of reentry. Another amphiphilic lipid metabolite, a long-chain acylcarnitine or 1-palmitoylcarnitine (PALC), had LPC-like depressant effects on INa, albeit the effect was reversible in the majority of cells tested. On the other hand, a short-chain acylcarnitine, 1-propionylcarnitine (PROC) did not affect the INa by itself even at a high concentration (50-500 microM), whereas it prevented the LPC's depressant effect on INa. Like PROC, the middle-chain acylcarnitine, e.g., 1-hexanoylcarnitine (HEXC) did not decrease the INa, but prevented the LPC's deleterious effects on INa, albeit the latter effect was much weaker than that of PROC.(ABSTRACT TRUNCATED AT 250 WORDS)


Modulation of human tumor colony growth in soft agar by serum.
The factors controlling the growth of human tumor cells in soft agar are poorly understood. However, it has been demonstrated that serum provides factors which promote anchorage-independent growth. We tested 58 tumor specimens, which were obtained from patients with adenocarcinoma of the lung, colon, ovary or squamous cell carcinoma, for their ability to form colonies in soft agar in serum-free or serum-supplemented media. The cells were unable to replicate, and none of the hormones or growth factors tested: insulin (I), transferrin (T), selenium (S), estradiol (E), hydrocortisone (H) or epidermal growth factor (EGF) could substitute for serum. Examination of the serum dose-response curves indicated that growth factors reduced the serum concentrations needed to support anchorage-independent growth. The addition of the supplements and the lowering of serum concentrations increased cloning efficiencies (C.E.) in 38/51 trials, when cells were able to grow initially. The addition of ITS increased C.E. in 18/21 cases, HITES in 15/17 cases and EGF in 12/18 cases as compared to controls. ITS and HITES increased the number of colonies only when serum was the limiting factor. EGF, however, increased the number of colonies even when serum was not the limiting factor. The ability of the supplements to enhance growth could not be correlated to tumor type or initial cloning efficiencies. However, in only 1/25 cases were cells that were unable to form colonies under standard conditions induced to form colonies in the presence of the growth factors. Normal and tumor-derived human fibroblasts did not form colonies in soft agar in the presence of these growth factors. The results suggest that human tumor cells may require the presence of serum-derived factors for growth in soft agar.


Clinical aspects of monosodium urate monohydrate crystal deposition disease (gout).
Gout is a clinical syndrome with a limited range of manifestations arising as a result of the deposition of crystals of monosodium urate, the final product of purine metabolism in humans. Hyperuricemia is a common chemical aberration that is most often mild and remains asymptomatic. Thus, hyperuricemia should be distinguished from gout, even though urate supersaturation is necessary for the expression of gout. Uric acid overproduction and diminished renal uric acid excretion are the major mechanisms resulting in hyperuricemia, and an understanding of the basis of hyperuricemia in individual gout patients is an important step in determining appropriate treatment and in identifying underlying disorders, offending drugs and toxins, and inherited enzyme defects, all of which can result in hyperuricemia and gout. A scheme is presented for the evaluation of patients with new-onset gout, along with a discussion of the relationships between gout/hyperuricemia and a variety of metabolic disorders that are unusually prevalent in gouty populations.


Ultrahigh Sensitivity Multifunctional Nanoprobe for the Detection of Hydroxyl Radical and Evaluation of Heavy Metal Induced Oxidative Stress in Live Hepatocyte.
Hydroxyl radical (•OH) is an important marker of the progress of heavy metal induced oxidative stress. However, most reported probes and detection methods cannot meet the need of monitoring the •OH concentration within the whole progress because of the limited linear range. Besides, a low detection limit, high sensitivity, and good selectivity were also required. In this study, an ultrahigh sensitivity multifunctional nanoprobe (ICG-modified NaLuF4:Yb,Er) was developed to evaluate heavy metal induced oxidative stress by detecting •OH concentration, with a colorimetric, upconversion luminescence, and photothermal stepped method. This method has a broad linear detection range, from 16 pM to 2 μM, and a low detection limit of 4 pM. Besides, the nanoprobe showed less response to ions, amino acids, biomolecules, and other radical oxygen species (H2O2 and O2-) than •OH. This highly selective, highly sensitive probe with a broad linear detection range has great potential utility for monitoring •OH concentration in live hypatocyte within the progress of heavy metal induced oxidative stress, with probable in vivo applications in the future.