[Migration. Opportunities for recruitment of skilled employees in the care sector].
A central objective of this study was to estimate the potential workforce for the elderly care sector in Germany and to compare it with the predicted demand for nurses in 2030. The authors describe the opportunities and obstacles in recruiting skilled professionals from EU member states and from countries outside the EU. Different scenarios of how to raise labor input are discussed so as to determine the domestic potential until 2030 in Germany. The results show that only by assuming unrealistic conditions, e. g., expectations of a high full-time working quota or far more working women, can the domestic potential meet the predicted future demands. Therefore, Germany's chances of attracting skilled foreign workers were assessed by analyzing wage differentials, unemployment probabilities, demographic developments, and professional and cultural aspects between the countries. A major finding study is that the German labor market cannot provide enough nursing care professionals for the elderly care sector by 2030. Secondly, most of the other EU member states are facing similar challenges, at least in the long run. Therefore, it is recommendable to intensify collaboration with populous Asian countries in the future.


Coronary artery endarterectomy: a method of myocardial preservation.
The lack of acceptable coronary arteries for grafting often causes the cardiac surgeon considerable problems in treating patients with severe coronary artery disease. By combining the standard approach of coronary bypass surgery with coronary endarterectomy and with retrograde coronary sinus cardioplegia perfusion, we can achieve a longer ischemic period and can flush the debris from the coronary arteries in a retrograde fashion. Using this approach, we managed 72 patients with near inoperable coronary artery disease. One third of these patients required endarterectomy of more than one vessel. A higher than expected number of patients had diabetes mellitus. The left coronary artery system required endarterectomy in almost 60% of patients, much higher than percentages reported in other series of patients. The mortality rate in our patients who underwent the left system endarterectomy was 5.7%. Endarterectomy must be considered an adjunct in the management of high-risk patients with severe coronary artery disease.


Intraoperative Kounis Syndrome and Fixation Errors: A Case Report.
Postinduction hypotension, though frequently due to anesthetic medications, has a variety of causes. We present a case of presumed intraoperative Kounis syndrome, or anaphylaxis-induced coronary vasospasm, in which the patient's perioperative course was initially attributed to anesthesia-induced hypotension and iatrogenic rebound hypertension leading to Takotsubo cardiomyopathy. A second anesthetic event with immediate recurrence of hypotension after the patient received levetiracetam appears to confirm the diagnosis of Kounis syndrome. In this report, we discuss the fixation error that led to this patient's original misdiagnosis.


Estimation of oncostatin M (OSM) secretion by peritoneal macrophages with regard to the progression of transplantable melanomas.
The authors have studied the influence of two kinds of transplantable melanomas on the secretion of oncostatin M (OSM) and total proteins by peritoneal macrophages. Culture supernatant samples were tested by ELISA. The macrophages of melanoma-bearing animals released a lower amount of OSM than those of the controls. At the same time the results showed statistically significant increase of protein content in the supernatants of cultured macrophages from melanoma-bearing hamsters in comparison with the controls. However, it has not been possible to demonstrate any relationship between melanoma progression and changes in the secretion of OSM by peritoneal macrophages.


Alteration of circulating innate lymphoid cells in patients with atherosclerotic cerebral infarction.
Innate lymphoid cells (ILCs) are associated with innate immunity and tissue remodeling. However, the changes in ILCs and their role in acute cerebral infarction (ACI) remain unexplored. This study aimed to examine the expression of ILCs in patients with ACI and explore the mechanism underlying changes in ILCs induced by the atherosclerotic factor oxidized low-density lipoprotein (ox-LDL). The levels of ILC1, ILC2, and ILC3 in the blood of patients with ACI and controls were examined at the time of admission. The correlation of serum levels of ox-LDL and inflammatory biomarkers with the level of ILCs and the effects of ox-LDL on ILCs in vitro were analyzed. Our results showed that the levels of ILC1 increased while the levels of ILC2 decreased in patients with ACI compared with controls. Serum levels of ox-LDL, LDL-C, and biochemical biomarkers correlated positively with the levels of ILC1 and ILC1/ILC2 ratio but negatively with the levels of ILC2. The in vitro incubation of peripheral blood mononuclear cells (PBMC) with ox-LDL resulted in an elevation of the levels of ILC1s and a marked reduction in the levels of ILC2s in a dose-dependent manner. ILC1s and ILC2s were more susceptible to ox-LDL-mediated alterations in patients with ACI than in controls. Furthermore, the expression of Interleukin 18 (IL-18), IL-33 and IL-23 in PBMCs was detected by real-time PCR, which showed the change trends of related key cytokines were highly consistent with the variation of ILC subsets. These results suggested that the levels of ILC1s and ILC2s appeared to be a novel, sensitive indicator for diagnosing ACI. Ox-LDL directly affected ILC1s and ILC2s, thus contributing to the alternations of ILC1 and ILC2 and occurrence of ACI.


Synthesis and characterization of iron silicon boron (Fe5Si2B) and iron boride (Fe3B) nanowires.
Single-crystal iron silicon boron (Fe(5)Si(2)B) and iron boride (Fe(3)B) nanowires were synthesized by a chemical vapor deposition (CVD) method on either silicon dioxide (SiO(2)) on silicon (Si) or Si substrates without introducing any catalysts. FeI(2) and BI(3) were used as precursors. The typical size of the nanowires is about 5-50 nm in width and 1-20 mum in length. Different kinds of Fe-Si-B and Fe-B structures were synthesized by adjusting the ratio of FeI(2) vapor to BI(3) vapor. Single-crystal Fe(5)Si(2)B nanowires formed when the FeI(2) sublimator temperature was kept in the range of 540-570 degrees C. If the FeI(2) sublimator temperature was adjusted in the range of 430-470 degrees C, single-crystal Fe(3)B nanowires were produced. Fe(3)B nanowires grow from polycrystalline Fe(5)SiB(2) particles, while Fe(5)Si(2)B nanowires grow out of the Fe(5)Si(2)B layers, which are attached to triangle shaped FeSi particles. Both the ratio of FeI(2) vapor to BI(3) vapor and the formation of the particles (Fe(5)SiB(2) particles for the growth of Fe(3)B nanowires, FeSi particles for the growth of Fe(5)Si(2)B nanowires) are critical for the growth of Fe(3)B and Fe(5)Si(2)B nanowires. The correct FeI(2) vapor to BI(3) vapor ratio assures the desired phase form, while the particles provide preferential sites for adsorption and nucleation of Fe(3)B or Fe(5)Si(2)B molecules. Fe(3)B or Fe(5)Si(2)B nanowires grow due to the preferred growth direction of <110>.


Repression of Abd-B by Polycomb is critical for cell identity maintenance in adult Drosophila testis.
Hox genes play a fundamental role in regulating animal development. However, less is known about their functions on homeostasis maintenance in adult stem cells. Here, we report that the repression of an important axial Hox gene, Abdominal-B (Abd-B), in cyst stem cells (CySCs) is essential for the homeostasis and cell identity maintenance in the adult Drosophila testis. Derepression of Abd-B in CySCs disrupts the proper self-renewal of both germline stem cells (GSCs) and CySCs, and leads to an excessive expansion of early stage somatic cells, which originate from both lineages. We further demonstrate that canonical Polycomb (Pc) and functional pathway of Polycomb group (PcG) proteins are responsible for maintaining the germline cell identity non-autonomously via repressing Abd-B in CySCs in the adult Drosophila testis.


HIV-1 env sequence variation in brain tissue of patients with AIDS-related neurologic disease.
We investigated sequence variation in the human immunodeficiency virus type 1 (HIV-1) env gene region that encodes the fourth disulfide-bonded domain of the external membrane glycoprotein, gp120, among three HIV-1 isolates from patients with AIDS-related neurologic disease. The sequences of HIV-1 isolated directly from brain tissue, blood cells, and in vitro cell cultures were compared. The results suggest that there may be many closely related HIV-1 genomes of several distinct subtypes in an HIV-1-infected individual. Differences were observed in the frequency distribution of sequence variants obtained from brain versus blood of the same individuals. Overall, the proportion of silent mutations is much lower than expected by random occurrence. Taken together, these results favor the possibility that selective forces may play a role in the tissue distribution of certain HIV-1 strains.


Cellular sequences related to three new onc genes of avian sarcoma virus (fps, yes, and ros) and their expression in normal and transformed cells.
Two onc genes of avian sarcoma viruses unrelated to the src gene have recently been identified: fps of Fujinami sarcoma virus/PRCII/UR1 and yes of Y73/Esh sarcoma virus. In the first part of this study we demonstrated that UR2, the most recently isolated avian sarcoma virus, contains in its genome a unique sequence, ros, nonhomologous to src, fps, and yes sequences or to transforming genes of avian acute leukemia viruses. Using cDNAs specific to the inserts of avian sarcoma virus genomes, we examined the existence and the transcription of cellular nucleotide sequences related to the three new onc genes of avian sarcoma virus (fps, yes and ros) in various cells. The progenitor cellular sequences for these onc genes (c-onc) were present in uninfected chicken DNA in one or few copies per haploid genome. These c-onc sequences were detectable in cellular DNA of a wide variety of vertebrates, and the homology between viral and cellular onc was inversely related to the phylogenetic distance of animal species. The pattern of expression of these c-onc genes in different tissues of chickens was found to be unique to each gene. The expression of c-fps and c-ros genes was generally repressed in many tissues, but c-fps was expressed at higher levels in bone marrow (2.5 copies per cell) and lung (1.1 copies per cell), whereas c-ros was mainly transcribed in kidney (2.5 copies per cell). On the other hand, c-yes transcripts were easily detectable in all tissues analyzed and were found at high levels in kidney (26 copies per cell). These c-onc expressions were unaffected by infection with avian sarcoma viruses that contained other onc genes. In a few cultures of chicken and quail transformed cells derived from tumors induced by chemical carcinogens, we found that the levels of transcription of the four c-onc genes remained unaltered, compared with that in normal tissues.


High-Voltage Aqueous Redox Flow Batteries Enabled by Catalyzed Water Dissociation and Acid-Base Neutralization in Bipolar Membranes.
Aqueous redox flow batteries that employ organic molecules as redox couples hold great promise for mitigating the intermittency of renewable electricity through efficient, low-cost diurnal storage. However, low cell potentials and sluggish ion transport often limit the achievable power density. Here, we explore bipolar membrane (BPM)-enabled acid-base redox flow batteries in which the positive and negative electrodes operate in the alkaline and acidic electrolytes, respectively. This new configuration adds the potential arising from the pH difference across the membrane and enables an open circuit voltage of ∼1.6 V. In contrast, the same redox molecules operating at a single pH generate ∼0.9 V. Ion transport in the BPM is coupled to the water dissociation and acid-base neutralization reactions. Interestingly, experiments and numerical modeling show that both of these processes must be catalyzed in order for the battery to function efficiently. The acid-base concept provides a potentially powerful approach to increase the energy storage capacity of aqueous redox flow batteries, and insights into the catalysis of the water dissociation and neutralization reactions in BPMs may be applicable to related electrochemical energy conversion devices.


The effect of α-tocopherol, sweet chestnut wood extract and their combination on oxidative stress in vivo and the oxidative stability of meat in broilers.
1. This study examined the effect of α-tocopherol (α-T), sweet chestnut wood extract (SCW) and their combination on oxidative stress in vivo and oxidative stability of meat in broilers given diets rich in PUFA. 2. A total of 60 male broilers were individually caged and divided into 6 groups of 10. The C-PALM group received a diet with 7·5% palm fat and the other 5 groups with 7·5% linseed oil. The linseed oil groups were either un-supplemented (C-LIN) or supplemented with α-T or/and SCW as follows: αT-85 (C-LIN diet + 68 IU vit E as all-rac-α-T/kg), αT-200 (C-LIN diet + 183 IU vit E as all-rac-α-T/kg), SCW (C-LIN diet + 3 g SCW/kg) and αT-SCW (C-LIN diet + 68 IU vit E as all-rac-α-T/kg + 3 g SCW/kg). Different parameters of oxidative stress were measured. 3. Linseed oil induced DNA fragmentation and malondialdehyde (MDA) formation, while α-T reduced both parameters, and SCW reduced the DNA damage. A combination (αT-SCW) also reduced plasma MDA. Larger antioxidant capacity of lipid soluble compounds were recorded in groups αT-85, αT-200 and αT-SCW than in the controls but there were no differences between these groups in antioxidant enzymes and total antioxidant status. A combination (αT-SCW) increased tocopherol concentrations in breast muscle and in comparison to the C-LIN group MDA concentrations were reduced in groups αT-85, αT-200 and αT-SCW. 4. It can be concluded that neither of the α-T concentrations were able to prevent all the negative effects of lipid oxidation in vivo and only high concentrations of α-T improved the stability of meat. With the exception of DNA damage, SCW had no impact on in vivo and in vitro measured markers of oxidative stress but may have a sparing or regenerating effect on α-T.


Tryptophan and Its Metabolites in Lung Cancer: Basic Functions and Clinical Significance.
Lung cancer is the most lethal malignancy worldwide. Recently, it has been recognized that metabolic reprogramming is a complex and multifaceted factor, contributing to the process of lung cancer. Tryptophan (Try) is an essential amino acid, and Try and its metabolites can regulate the progression of lung cancer. Here, we review the pleiotropic functions of the Try metabolic pathway, its metabolites, and key enzymes in the pathogenic process of lung cancer, including modulating the tumor environment, promoting immune suppression, and drug resistance. We summarize the recent advance in therapeutic drugs targeting the Try metabolism and kynurenine pathway and their clinical trials.


A pathological toe fracture as the first presentation of cervical cancer: A case report.
Cervical cancer is one of the most common gynecologic malignancies worldwide, and it spreads mainly through direct extension. Distinct metastases are less common and usually spread to distant lymph nodes, lungs, and bones. Bone metastases from cervical cancer are most commonly observed in the pelvis and spine. Thus, a pathological toe fracture as the initial presentation of cervical cancer is extremely rare. We report a patient with a toe metastasis that first presented with pain caused by a pathological fracture. The patient underwent surgery to remove the right great toe, and the histopathology revealed squamous carcinoma that originated from the cervix. The patient then underwent cervical cancer surgery, chemotherapy, and radiotherapy. A pathological toe fracture as the initial presentation of cervical cancer is extremely rare, but clinicians need to be aware that we should not exclude cancer when patients come to the hospital for pathological fractures.


Historical View on Lead: Guidelines and Regulations.
Lead has been used in many commodities for centuries. As a result, human exposure has occurred through the production and use of these lead-containing products. For example, leaded gasoline, lead-based paint, and lead solder/pipes in water distribution systems have been important in terms of exposure potential to the general population. Worker exposures occur in various industrial activities such as lead smelting and refining, battery manufacturing, steel welding or cutting operations, printing, and construction. Some industrial locations have also been a source of exposure to the surrounding communities. While the toxicity of relatively high lead exposures has been recognized for centuries, modern scientific studies have shown adverse health effects at very low doses, particularly in the developing nervous system of fetuses and children. This chapter reflects on historical and current views on lead toxicity. It also addresses the development and evolution of exposure prevention policies. As discussed here, these lead policies target a variety of potential exposure routes and sources. The changes reflect our better understanding of lead toxicity. The chapter provides lead-related guidelines and regulations currently valid in the U. S. and in many countries around the world. The reader will learn about the significant progress that has been made through regulations and guidelines to reduce exposure and prevent lead toxicity.


Electroencephalographic evidence for improved visual working memory performance during standing and exercise.
While a substantial body of research has investigated the effects of aerobic exercise on cognitive performance, few have monitored exercise-concurrent cognitive processes via electroencephalography and fewer still using an event-related potential (ERP) approach. As such, little is known regarding how the temporal dynamics of cognitive processing are influenced during aerobic activity. Here, we aimed to elucidate the influence of aerobic exercise on the temporal dynamics of concurrent visual working memory (VWM) performance. Participants performed a VWM retro-cue task at rest and during aerobic exercise across two postural modalities: seated (using a stationary bicycle) and standing upright (using a treadmill). Three consecutive phases of the VWM processing pipeline were assessed by means of lateralized ERPs: access of VWM representations, response selection, and response execution. Aerobic exercise and upright posture were found to have significant effects on VWM performance, facilitating processing speed in the retro-cue task. This facilitation arose primarily at an intermediary stage between the phases of accessing VWM representations and response selection. Our findings hold implications not only for understanding the influence of aerobic activity on VWM, but also for contemporary models of VWM that are built exclusively on data recorded during stationary, seated conditions.


The myelography needle: a new cannula for aspiration.
Painless recovery of radiopaque substances after positive contrast myelography is often difficult, especially if the initial spinal tap is not made precisely in the midline. The author has designed a cannula for aspiration which has performed favorably in clinical tests and which will soon be available commercially.


Genetic analysis of invasion and metastasis.
Metastasis formation is a multistep process that probably requires a complex interplay of a large and heterogeneous group of genes, including genes involved in cellular resistance to immunorejection and genes controlling the invasive potential of cells. Transfection experiments have shown that oncogenes of the ras gene family as well as oncogenes of the kinase group are able to induce invasive and metastatic properties in non-transformed cells as well as in tumorigenic, but non-metastatic, cells. However, these findings are not in agreement with observations on spontaneous human tumours in which no correlation was found between activation or increased expression of ras genes and the invasive and metastatic properties of these cells. Further studies have indicated that in particular cell types nuclear oncogenes like N-myc and adenovirus derived E1A may influence metastasis formation by trans-regulation of other genes, including class I genes of the major histocompatibility complex and genes coding for proteolytic enzymes. The many efforts to identify additional invasion and metastasis associated genes by transfection of high molecular weight metastatic tumour DNA met with little success. Somatic cell fusion studies, however, indicate that such genes exist and that one or more of them are located on human chromosome 7.


ASSOCIATIONS BETWEEN MITOCHONDRIAL AND NUCLEAR GENOTYPES IN CUTTHROAT TROUT HYBRID SWARMS.
We examined mtDNA and nuclear allozyme genotypes in hybrid populations formed from interbreeding of westslope cutthroat trout (Oncorhynchus clarki lewisi) and Yellowstone cutthroat trout (O. c. bouvieri). These subspecies show substantial genetic divergence (Nei's D = 0.30; mtDNA P = 0.02). Diagnostic alleles at multiple nuclear loci and two distinct mtDNA haplotypes segregate in the hybrids. Nuclear and mtDNA genotypes are largely randomly associated, although there is slight disequilibrium in both nuclear and cytonuclear measures in some samples. Consistent positive gametic disequilibria for three pairs of nuclear loci confirm one previously reported linkage, and indicate two more. Allele frequencies provide no evidence for selection on individual chromosome segments. However, westslope mtDNA haplotype frequencies exceed westslope nuclear allele frequencies in all samples. This may be explained by differences in the frequency of occurrence of reciprocal F1 matings, by viability, fertility, or sex ratio differences in the progeny of reciprocal matings, or by weak selection on mtDNA haplotypes.


Central nervous system involvement in multifocal demyelinating neuropathy with persistent conduction block.
We report the case of a 27-year-old man treated for bilateral optic neuritis 5 and 3 years before who within a few months developed sensorimotor disorders of the arms and legs characterized by asymmetric distribution and distal prominence. In addition to sensorimotor defects, which were particularly marked in the left arm and right leg, clinical examination showed nearly generalized areflexia. Electrophysiological studies revealed a multifocal neuropathy with persistent distal and proximal conduction blocks associated with a considerable slowing of motor nerve conduction, as well as central nervous system involvement indicated by motor-, somatosensory-, and visual-evoked potentials. CSF analysis showed a mildly elevated protein level; anti-GM1 activity was negative. Sural nerve biopsy revealed onion-bulb-like formations, and cerebral MRI showed a small, isolated, and aspecific high signal for white matter. First described by Lewis and Sumner in 1982, multifocal neuropathy with persistent conduction blocks may be associated with central demyelination. Our case is compared with 3 similar ones in the literature, and the favorable effects of steroid therapy are emphasized.


Caring for patients with lower limb amputation.
In 2014 a National Confidential Enquiry into Patient Outcome and Death report examined the care of people requiring lower limb amputation as a consequence of complications associated with vascular disease or diabetes. It suggests that less than half of patients who undergo surgery receive good care. This article summarises the key findings of the report and the implications for nursing practice.


[Regional myocardial blood flow measurement with radioactive microspheres in dogs with myocardial ischemia].
In order to evaluate the radioactive microsphere technique used in our laboratory for measuring regional myocardial blood flow (RMBF) in dogs with myocardial ischemia, simultaneous blood flow measurements with three different nuclide (141Ce, 51Cr or 113Sn)-labeled microspheres were performed after coronary artery occlusion. There were excellent correlations between all paired RMBF values in 80 samples. The linear regression lines were expressed as: 51Cr = 1.09x 141Ce-0.02 (r = 0.996, SEE = 0.06); 113Sn = 0.99x 141Ce + 0.01 (r = 0.997, SEE = 0.05); 113Sn = 0.90x 51Cr + 0.03 (r = 0.991, SEE = 0.08). The duplicate variability ranged from 5.5 +/- 0.7 to 9.9 +/- 1.1%. When RMBF was measured before and after intravenous administration of nipradilol (0.2 mg/kg), a new beta-blocker, in a dog with myocardial ischemia, RMBF fell in the normal zone (23.6 +/- 1.6%), and did not change in the severely ischemic zone. Thus, this study demonstrated that RMBF can be measured accurately and repeatedly with radioactive microspheres in dogs with regional myocardial ischemia.


The role of Gi-proteins and beta-adrenoceptors in the age-related decline of contraction in guinea-pig ventricular myocytes.
A decline in contractility in myocytes from ageing guinea-pig hearts was demonstrated, which is more pronounced for maximum beta-adrenoceptor-stimulated activity than contraction in high Ca2+. In this study the role of the inhibitory G-proteins (Gi) in this process was investigated. Comparisons were made between young (Y, < 400 g, < 4 weeks), adult (A. > 600 g, > 8 weeks) and senescent guinea pigs (S, 58-65 weeks, 1136 +/- 30 g). Gi alpha activity, detected by pertussis toxin-catalysed ADP ribosylation, was significantly increased in senescent compared to young animals, but immunodetectable levels of Gi alpha were unchanged, beta-adrenoceptor number was decreased by 27% in senescent compared with young animals (P < 0.002). Pertussis toxin treatment increased the maximum response to isoproterenol in contacting myocytes so that there was no longer any significant decline with age. Maximum contraction amplitudes (sarcomere length change, micron) with isoproterenol before pertussis toxin were 0.144 +/- 0.011 (Y, n = 22 animals), 0.104 +/- 0.009 (A. 18) and 0.098 +/- 0.009 (S. 14), P < 0.01 by analysis of variance (ANOVA). Following toxin treatment amplitudes were 0.140 +/- 0.012 (Y. 12), 0.117 +/- 0.010 (A. 10) and 0.117 +/- 0.018 (S. 8), P = N.S. Pertussis toxin treatment also reversed the effects of ageing on contraction and relaxation velocity in isoproterenol. In contrast, the effect of age on contraction amplitude or velocity in maximum Ca2+ was more pronounced after toxin treatment. The EC50 value for isoproterenol increased with age: pertussis treatment decreased the EC50 in each group, but the effect was especially pronounced for senescent animals. There was no significant difference in the concentration-response curves for the negative inotropic effect of adenosine (in the presence of isoprotenerol) between the three age groups before toxin treatment. All effects of adenosine were abolished after pertussis exposure. We conclude that increased Gi alpha activity is likely to contribute to the decreased response to isoproterenol, but not to high Ca2+, in myocytes from ageing guinea-pigs.


Excision of CN(-) and OCN(-) from acetamide and some amide derivatives triggered by low energy electrons.
Low energy electron attachment to acetamide and some of its derivatives shows unique features in that the unimolecular reactions of the transient anions are remarkably complex, involving multiple bond cleavages and the formation of new molecules. Each of the three compounds acetamide (CH(3)C(O)NH(2)), glycolamide (CH(2)OHC(O)NH(2)) and cyanoacetamide (CH(2)CNC(O)NH(2)) shows a pronounced resonance located near 2 eV and decomposing into CN(-) along a concerted reaction forming a neutral H(2)O molecule and the corresponding radical (methyl and methoxy). From glycolamide an additional reaction pathway resulting in the loss of water is operative, in this case generating two fragments and observable via the complementary anion (M-H(2)O)(-). The pseudohalogen OCN(-) is formed at comparatively lower intensity having a specific energy profile for each of the target molecules. In dibromocyanoacetamide (CBr(2)CNC(O)NH(2)) the situation changes completely as now comparatively intense CN(-) and OCN(-) signals appear already near zero eV. Electronic structure calculations predict that in dibromocyanoacetamide the extra electron resides in a molecular orbital (MO) which is strongly localized at the Br sites. For the other compounds, the relevant MOs are appreciably delocalized showing pi*(C=O) character.


[Surgical Case of Ulcerative Colitis Accompanied with Rectal Cancer Combined with Transanal Minimally Invasive Surgery].
A46 -year-old man developed ulcerative colitis at the age of 19 years. Although the colitis was medically treated, it relapsed and repeated over time. Periodic lower gastrointestinal endoscopy revealed lower rectal cancer, and he was referred to our department of surgery. Previous steroid therapy induced diabetes, and he was obese, with a height of 170.3 cm, weight of 89.6 kg, and BMI of 30.89 kg/m2, indicating that laparoscopic dissection near the anus would be difficult to perform. Therefore, the patient was scheduled for transanal minimally invasive surgery(TAMIS). The surgery involved as much laparoscopic rectal dissection as possible in the ventral to dorsal direction, followed by the TAMIS procedure. Dissection was started from the dentate line, and, after the closure of the anal stump, GelPOINT was placed, and made continuous with the previous dissection layer by applying the technique of down-to-up total mesorectal excision(TME)by TAMIS. The large intestine was excised through a small abdominal incision to create an ileal pouch, hand-sewn anastomosis was performed transanally to create a temporary colostomy, and the surgery was completed. Regarding TAMIS-TME several problems remain to be solved, including an understanding of its unique anatomy and the mastery of single-port surgical techniques. However, the herein reported patient with a high BMI had a definite indication for TAMIS-TME.


Prevalence of overweight in 2 to 17 year-old children and adolescents whose parents live separately: a Nordic cross-sectional study.
Comparative data of parental separation and childhood overweight has not been available before across the Nordic countries. The aim of this study was to examine the within-country prevalence and association between parental cohabitation and overweight in Nordic children. A cross-sectional survey of 2-17-year-old children was conducted in 2011, titled: "NordChild". A random sample of 3,200 parents in each of the Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden were invited to participate in the study with parents of 6,609 children accepting to give answers about their children's health and welfare including information on height and weight of each child and parental cohabitation (response rate 41.5%). The group differences in prevalence and adjusted odds ratio (OR) for overweight, with corresponding 95% confidence intervals (CI) were performed in children whose parents lived separately. Additionally, a missing data analysis was performed to determine whether the adjusted estimates might result from confounding or selection bias. A significant difference was observed in Iceland between children whose parents live separately compared to those who live with both parents (difference: 9.4%, 95% CI: 2.8; 15.9) but no such difference was observed in Denmark, Finland, Norway and Sweden. No significant odds of overweight were observed in children whose parents lived separately compared to children in normal weight at the time of study; Denmark: OR 1.03 (95% CI: 0.42; 2.53), Finland: OR 1.27 (95% CI: 0.74; 2.20), Iceland: OR 1.50 (95% CI: 0.79; 2.84), Norway: OR 1.46 (95% CI: 0.81; 2.62), and Sweden: 1.07 (95% CI: 0.61; 1.86). The missing data analysis indicated that the findings in Norway, Finland and Iceland were partly observed due to selection effects, whereas the adjustment in Denmark was due to confounding. The crude OR for overweight was higher in the 2-9-year-old group than in the 10-17-year-old group whose parents lived separately in Iceland, Norway and Sweden. No association between parental cohabitation and overweight in Nordic children was found. Our finding of greater prevalence of overweight in Icelandic children whose parents live separately may be an indication that the welfare system in Iceland is separating from the other Nordic countries.


High-load domestic wastewater treatment using a combined anaerobic-aerobic bio-filter with coal cinder as medium.
A combined anaerobic-aerobic bio-filter technology was used for field treatment of high-organic-load domestic wastewater with coal cinder as the bio-filter medium. The effects of parameters, including hydraulic retention time (HRT) and backflow ratio, on the decrease in the chemical oxygen demand (COD), NH3-N, total nitrogen (TN), total phosphorus (TP), and turbidity were investigated. The results showed the obvious influence of the HRT and ratio of backflow on wastewater treatment. Under the optimal HRT condition of 18 h, the removal efficiencies of COD, NH3-N, TN, TP, and turbidity were 67.9%, 95.6%, 30.4%, 65.6%, and 83.8%, respectively. When the backflow ratio (2:1) was added to the treatment system, the TN removal obviously increased, and the removal efficiencies of COD, NH3-N, TN, TP, and turbidity were 88.1%, 91.7%, 69.9%, 69.6%, and 97.5%, respectively. These results indicated that the combined technology has the potential as a treatment method for high-organic-load domestic wastewater.


Immobilization of simulated reducing agent at the surface of SiO2 fillers in dental composite resins.
To reduce the leachability of reducing agents from composite resins, immobilization of a simulated reducing agent at the surface of SiO2 fillers was examined. SiO2 plates were immersed in 2% 3-aminopropyltriethoxy silane/ethanol solution, and then immersed in dimethyl sulfoxide with 0.25 wt% 4-dimethyl amino benzoic acid (DMABA), 2.0 wt% 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride, and 0.5 wt% N-hydroxysuccinimide. Wide-scan spectrum of X-ray photoelectron spectroscopy did not detect carbon contamination. However, narrow scan detected an O=C-N peak at 399.8 eV, suggesting that DMABA could be immobilized on silane-coupled SiO2 plates. Further, surface plasmon resonance analysis indicated the adsorption of MMA at the surface of reducing agent-immobilized plate.


Increased risk of IgA nephropathy among individuals with celiac disease.
To determine the risk of future biopsy-verified IgA nephropathy (IgAN) among individuals with biopsy-verified celiac disease (CD). Individuals with CD suffer increased risk of end-stage renal disease. An association between CD and IgAN has been suggested; however, results have been inconclusive and no previous study has considered the risk of IgAN in biopsy-verified CD. We performed a population-based prospective cohort study. We identified 27,160 individuals with CD (Marsh stage III) and no previous renal disease through small-intestinal biopsy reports obtained between July 1969 and February 2008 in all (n=28) Swedish pathology departments. Individuals with IgAN were identified by biopsy reports acquired at the 4 Swedish pathology departments specialized in renal pathology. Cox regression analysis was used to determine the risk of future IgAN among individuals with CD compared with 133,949 age-matched and sex-matched reference individuals. Seven (0.026%) individuals with CD and 11 (0.008%) reference individuals developed IgAN. We found an increased risk of biopsy-verified IgAN among individuals with CD [hazard ratio, 3.03; 95% confidence interval, 1.22-7.56]. The risk increase remained statistically significant after adjustment for prior liver disease and country of birth. Individuals with CD suffer a 3-fold increased risk of future IgAN. Our findings warrant awareness of renal function in individuals with CD.


Cortical bone stem cells modify cardiac inflammation after myocardial infarction by inducing a novel macrophage phenotype.
Acute damage to the heart, as in the case of myocardial infarction (MI), triggers a robust inflammatory response to the sterile injury that is part of a complex and highly organized wound-healing process. Cortical bone stem cell (CBSC) therapy after MI has been shown to reduce adverse structural and functional remodeling of the heart after MI in both mouse and swine models. The basis for these CBSC treatment effects on wound healing are unknown. The present experiments show that CBSCs secrete paracrine factors known to have immunomodulatory properties, most notably macrophage colony-stimulating factor (M-CSF) and transforming growth factor-β, but not IL-4. CBSC therapy increased the number of galectin-3+ macrophages, CD4+ T cells, and fibroblasts in the heart while decreasing apoptosis in an in vivo swine model of MI. Macrophages treated with CBSC medium in vitro polarized to a proreparative phenotype are characterized by increased CD206 expression, increased efferocytic ability, increased IL-10, TGF-β, and IL-1RA secretion, and increased mitochondrial respiration. Next generation sequencing revealed a transcriptome significantly different from M2a or M2c macrophage phenotypes. Paracrine factors from CBSC-treated macrophages increased proliferation, decreased α-smooth muscle actin expression, and decreased contraction by fibroblasts in vitro. These data support the idea that CBSCs are modulating the immune response to MI to favor cardiac repair through a unique macrophage polarization that ultimately reduces cell death and alters fibroblast populations that may result in smaller scar size and preserved cardiac geometry and function.NEW & NOTEWORTHY Cortical bone stem cell (CBSC) therapy after myocardial infarction alters the inflammatory response to cardiac injury. We found that cortical bone stem cell therapy induces a unique macrophage phenotype in vitro and can modulate macrophage/fibroblast cross talk.


Transition age youth in publicly funded systems: identifying high-risk youth for policy planning and improved service delivery.
Youth with Serious Emotional Disturbances (SED) face many challenges as they approach the transition to adulthood and adult services. This study examines publicly funded transition-age youth in order to describe the numbers and type of youth in need of policy and service planning in one state. Using Medicaid enrollment and claims/encounter data, youth with high risk of transition difficulties were identified in the following groups: SED, state custody/foster care or risk of custody, users of intensive or frequent mental health services, or having diagnoses of major mental disorders, conduct disorders, or developmental disabilities. Almost one quarter of all enrolled 14 to 17-year olds met criteria for at least one of the high risk groups, and three-quarters of these were youth with SED. High risk youth are described, with greater detail on those with SED, and implications for policy, services, and research are discussed.


[Effects of Bioactive Substances from Citrus on the Central Nervous System and Utilization as Food Material].
We have recently shown that 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF) and auraptene (AUR) have neuroprotective effects on the central nervous system. HMF, a citrus flavonoid, altered NMDA-type glutamate receptor antagonist MK-801-induced memory dysfunction and schizophrenia-positive symptom-like behavior. HMF also showed a protective effect against ischemia-induced short-term memory dysfunction. In the ischemic brain, HMF induced the following protective effects against brain dysfunction: 1) rescue of neuronal cell death in the hippocampus; 2) increased production of brain-derived neurotrophic factor; 3) stimulation of neurogenesis in the dentate gyrus subgranular zone; 4) activation of the autophosphorylation of calcium-calmodulin-dependent protein kinase II; and 5) suppression of microglial activation. On the other hand, AUR, a citrus coumarin, ameliorated lipopolysaccharide-induced inflammation in the brain as shown by inhibition of microglial activation and inhibition of cyclooxygenase (COX)-2 expression in the hippocampus. AUR also showed antiinflammatory effects on the ischemic brain by inhibiting microglial activation, COX-2 expression, and neuronal cell death in the hippocampus. The peel of kawachibankan (Citrus kawachiensis), a noted citrus product of Ehime prefecture, Japan, contains AUR, HMF, naringin, and narirutin. The dried powder of both the peel and juice had antiinflammatory effects in the mouse hippocampus, suggesting that citrus compounds may be beneficial as neuroprotective agents in the treatment of neurological disorders.


[Study on the factors of Suanzaoren decoction action by correspondence analysis combined with uniform design].
To investigate the effect of administration dose, administration duration and the time from finishing the last administration to beginning the wild plain method on Suanzaorren decoction action. The number of spontaneous activities was determined to study the influence of the factors Suanzaoren decoction action by correspondence analysis combined with uniform design. According to the correlation degree of each factors, there was positive correlation between administration duration and the number of spontaneous activities, whereas there was negative correlation between the two other factors and the number of spontaneous activities. It is ecnoomical and efficient to use correspondence analysis combined with uniform design to study the influence of the three factors on Suanzaoren decoction action. The result may provide the basis for pharmacology and clinic.


Organ Donation, an Unexpected Benefit of Aggressive Resuscitation of Trauma Patients Presenting Dead on Arrival.
We sought to determine whether aggressive resuscitation in trauma patients presenting without vital signs, or "dead on arrival," was futile. We also sought to determine whether organ donation was an unexpected benefit of aggressive resuscitation. We conducted a review of adults presenting to our Level I trauma center with no signs of life (pulse = 0 beats/min; systolic blood pressure = 0 mmHg; and no evidence of neurologic activity, Glasgow Coma Scale score = 3). Primary end point was survival to hospital discharge or major organ donation (ie heart, lung, kidney, liver, or pancreas were harvested). We compared our survival rates with those of the National Trauma Data Bank in 2012. Patient demographics, emergency department vital signs, and outcomes were analyzed. Three hundred and forty patients presented with no signs of life to our emergency department after injury (median Injury Severity Score = 40). There were 7 survivors to discharge, but only 5 (1.5%) were functionally independent (4 were victims of penetrating trauma). Of the 333 nonsurvivors, 12 patients (3.6%) donated major organs (16 kidneys, 2 hearts, 4 livers, and 2 lungs). An analysis of the National Trauma Data Bank yielded a comparable survival rate for those presenting dead on arrival, with an overall survival rate of 1.8% (100 of 5,384); 2.3% for blunt trauma and 1.4% for penetrating trauma. Trauma patients presenting dead on arrival rarely (1.5%) achieve functional independence. However, organ donation appears to be an under-recognized outcomes benefit (3.6%) of the resuscitation of injury victims arriving without vital signs.


Arabidopsis BIG1 and BIG5 are crucial for male gametophyte transmission.
Arabidopsis contains five Brefeldin A-inhibited guanine nucleotide exchange factors (BIGs), which play a critical role in vesicle biogenesis for protein traffic from the Golgi to the plasma membrane. Biological processes regulated by BIG1-BIG4 are postulated to be distinct from those by BIG5. However, we show that the self-pollinated BIG1+/- big5 silique do not produce homozygous seeds, and some pollen tubes from BIG1+/- big5 anthers grew slowly in vitro and failed to target nearby ovules in vivo. We identified the big1 big5 homozygote from the progeny of BIG1+/- big5 plants transformed with BIG5, whose expression is driven by a pollen-specific promoter pLat52, indicating that male gametophyte transmission is blocked in the double mutant. Confocal microscopy indicated that BIG1 and BIG5 are co-localized in trans Golgi network. Thus, our data indicate that BIG1 and BIG5 are crucial for male gametophyte transmission.


[Is a duodenogastric reflux of pathogenic significance?].
Experimentally, the gastric and the duodenal mucosa can both be damaged by acute exposure to small intestinal juice. Though chronic exposure to bile causes mucosal erythema and hyperplasia, the gastric mucosal barrier is not damaged. Duodenogastric reflux is relevant in the pathogenesis of postoperative bilious vomiting and probably of "alkaline" reflux esophagitis. The exact mechanism of mucosal damage has not been established. Duodenogastric reflux is likely to be irrelevant in the pathogenesis of (microscopic) gastritis, of gastric ulcer, and of reflux esophagitis without previous gastric surgery.


Association of menstrual phase with smoking behavior, mood and menstrual phase-associated symptoms among young Japanese women smokers.
Previous studies of the relationship between the menstrual phases and smoking behavior have been problematic, so the association of menstrual phases with smoking behavior and correlations among smoking, psychological and physical conditions in each phase of the menstrual cycle are unclear. To accurately examine the association between menstrual phases and the amount of smoking (number of cigarettes smoked and breath CO concentration), craving of smoking on visual analogue scale (VAS), depression in the Center for Epidemiologic Studies Depression (CES-D) Scale, and menstrual phase-associated symptoms in the Menstrual Distress Questionnaire (MDQ), we improved various methodological issues, specifically, 1) Ovulation was confirmed by measuring the basal body temperature and identifying a urinary luteinizing hormone (LH) surge in two cycles; 2) The menstrual, follicular, and luteal phases were clearly defined for subjects with different menstrual cycles; 3) The breath CO concentration was measured every day. A notice was posted on public bulletin boards to recruit research subjects and twenty-nine young Japanese women smokers aged 19 to 25 years old were analyzed. The number of cigarettes smoked was greater and the CO concentration was higher in the luteal phase than in the follicular phase. The levels of craving for smoking (VAS), depressiveness (CES-D), and menstrual phase-associated symptoms (MDQ) in the menstrual and luteal phases were higher than those in the follicular phase. The mean score for CES-D was 16 points (the cut-off value in screening for depression) or higher in the menstrual (16.9 ± 8.2) and luteal phases (17.2 ± 8.4).The number of cigarettes smoked and CO concentration were significantly correlated with the levels of craving for smoking, depressiveness, and menstrual phase-associated symptoms in all phases except for MDQ scores in follicular phase. The amount of smoking in the luteal phase was most strongly correlated with these symptoms. In the menstrual and luteal phases, young Japanese women smokers increased their amount of smoking and suffered from greater craving for smoking, depressiveness and menstrual phase-associated symptoms. The amount of smoking was correlated with these symptoms, but their cause-effect relationship has not been determined yet.


Direct Phosphonation of Quinolinones and Coumarins Driven by the Photochemical Activity of Substrates and Products.
Light-promoted phosphonation of quinolinones and coumarins was developed without the need for an external photocatalyst. Investigations support a mechanism whereby both starting materials and products act as photosensitizers upon excitation using compact fluorescent light sources to photochemically promote the dissociation of the N-O bond in the pyridinium salt by a single electron transfer pathway. A wide range of quinolinone and coumarin substrates can be utilized in the phosphonation process under mild reaction conditions.


Brain metastasis from ovarian clear cell carcinoma: A case report.
Epithelial ovarian carcinoma (EOC) is the most common type of ovarian carcinoma, and the leading cause of female genital tract cancer-related deaths. However, brain metastasis (BM) of EOC is rare, with an incidence of only 1% to 2%. Ovarian clear cell carcinoma (OCCC), accounting for 5% to 25% of all EOC cases, has a poor prognosis compared with other epithelial cell type carcinomas. We retrospectively analyzed the clinical data of a 62-year-old female, who was hospitalized with the main complaint of BM detection for 1 month. She was first diagnosed with ovarian cancer in 2004, and underwent a left oophorectomy. Three years later, the cancer metastasized to the other side, and she underwent a right oophorectomy, followed by 7 courses of platinum-based chemotherapy. She received regular follow-up, and tumor markers and pelvic imaging did not show any signs of progression until July 2012. Combining the clinical manifestations with the results of radiological and pathological examinations, the findings were consistent with a diagnosis of BM from OCCC. She received more than 20 courses of chemotherapy since July 2012. The BM was detected in 2016, and she underwent an intracranial lesion resection. Unfortunately, the patient went into a coma after the surgery, and passed away 1 month later. For early detection of BM in long-term ovarian cancer, emphasis should be placed on the patient's neurological symptoms and signs as well as serum tumor marker changes. The combination of surgery, radiology, and chemotherapy may achieve long overall survival.


Properties and Roles of γδT Cells in Plasmodium yoelii nigeriensis NSM Infected C57BL/6 Mice.
Many kinds of immune cells are involved in malaria infection. γδT cells represent a special type of immune cell between natural and adaptive immune cells that play critical roles in anti-parasite infection. In this study, malaria infection model was constructed. Distribution of γδT cells in various immune organs and dynamic changes of γδT cells in the spleens of C57BL/6 mice after infection were detected by flow cytometry. And activation status of γδT cells was detected by flow cytometry. Then γδT cells in naive and infected mice were sorted and performed single-cell RNA sequencing (scRNA-seq). Finally, γδTCR KO mice model was constructed and the effect of γδT cell depletion on mouse T and B cell immunity against Plasmodium infection was explored. Here, splenic γδT cells were found to increase significantly on day 14 after Plasmodium yoelii nigeriensis NSM infection in C57BL/6 mice. Higher level of CD69, ICOS and PD-1, lower level of CD62L, and decreased IFN-γ producing after stimulation by PMA and ionomycin were found in γδT cells from infected mice, compared with naive mice. Moreover, 11 clusters were identified in γδT cells by scRNA-seq based t-SNE analysis. Cluster 4, 5, and 7 in γδT cells from infected mice were found the expression of numerous genes involved in immune response. In the same time, the GO enrichment analysis revealed that the marker genes in the infection group were involved in innate and adaptive immunity, pathway enrichment analysis identified the marker genes in the infected group shared many key signalling molecules with other cells or against pathogen infection. Furthermore, increased parasitaemia, decreased numbers of RBC and PLT, and increased numbers of WBC were found in the peripheral blood from γδTCR KO mice. Finally, lower IFN-γ and CD69 expressing CD4+ and CD8+ T cells, lower B cell percentage and numbers, and less CD69 expressing B cells were found in the spleen from γδTCR KO infected mice, and lower levels of IgG and IgM antibodies in the serum were also observed than WT mice. Overall, this study demonstrates the diversity of γδT cells in the spleen of Plasmodium yoelii nigeriensis NSM infected C57BL/6 mice at both the protein and RNA levels, and suggests that the expansion of γδT cells in cluster 4, 5 and 7 could promote both cellular and humoral immune responses.


IgG subclass profiles in infected HIV type 1 controllers and chronic progressors and in uninfected recipients of Env vaccines.
We have studied IgG subclass responses to the HIV-1 proteins gp120, gp41, p24, and Tat in individuals who control their infection without using antiretroviral drugs (HIV-1 controllers; HC) or who progress to disease (chronic progressors; CP). We also measured IgG subclass titers to gp120 in vaccinated individuals. In all cases, the IgG1 subclass dominated the overall response to each antigen. The only IgG titer that differed significantly between the HC and CP groups was to the p24 Gag protein, which was higher in the HC group. IgG1 titers to both p24 and gp120 were significantly higher in the HC group, and IgG3 anti-gp120 antibodies, although rare, were detected more frequently in that group than in CP. Overall, significantly more patients had IgG2 antibodies to gp120 than to gp41. Antibodies to other IgG subclasses were infrequent and their frequency or titers did not differ between the two patient groups. Anti-gp41 and anti-Tat responses also did not correlate with immune control, and anti-Tat antibodies were infrequently detected. Although we found isotypic differences in IgG responses to HIV-1 antigens among vaccinees and the HC and CP individuals, there were no indications of differential T(H)1:T(H)2 polarization between the different groups.


PLC/PRF/5 (Alexander) hepatoma cell line: further characterization and studies of infectivity.
The Alexander hepatoma cell line, PLC/PRF/5, was studied for evidence of hepatitis B virus markers and alpha-fetoprotein. Only hepatitis B surface antigen and alpha-fetoprotein were detected. Induction experiments with 5-iodo-2'-deoxyuridine and inoculation of chimpanzees with whole cells or tissue culture fluid did not reveal evidence of synthesis of additional hepatitis B virus markers or of production of infectious virus.


Role of fine-needle aspiration cytology in the preoperative evaluation of smooth muscle tumors.
A preliminary study was undertaken to assess the feasibility and the diagnostic role of fine-needle aspiration cytology (FNAC) in the preoperative evaluation of eight uterine smooth muscle tumors manifesting as single large masses with signs of growth. Percutaneous FNAC was performed under echographic control with a 22-gauge needle and the material was stained according to conventional techniques. Histology of surgically resected specimens was available for final diagnosis and comparative analysis in all the cases, including five leiomyomas (LM), one smooth muscle tumor of uncertain malignant potential (TUMP), and two low-grade leiomyosarcomas (LMS). Cellularity, as indicated by the density (crowding) of nuclei reflecting the amount of cytoplasmic volume, and the cohesiveness of the tissue fragments in the smears appeared to be the most important diagnostic parameters in the distinction between LM and LMS. LM usually showed few scattered poorly cellular fragments of highly cohesive tapering cells without nuclear crowding and with abundant cytoplasm. LMS usually showed a large number of single cells and fragments of loosely arranged tapering cells with nuclear enlargement and crowding and ill-defined scanty cytoplasm. Borderline forms such as TUMP were hardly distinguishable from LMS and LM. FNAC appears to be a feasible preoperative procedure in uterine smooth muscle tumors and may play a diagnostic role, especially in distinguishing frankly benign from overtly malignant forms.


Thromboembolism and bleeding risk scores and predictors of cardiac death in a population with atrial fibrillation.
Atrial fibrillation (AF) is a common arrhythmia, with risk of systemic embolism and death. It presents rheumatic etiology in up to 32% of developing countries, whose anticoagulation and evolution data are scarce. to determine the predictors of cardiac death considering the clinical profile, thromboembolism and bleeding scores of patients with AF of a single center, with high prevalence of rheumatic heart disease. 302 patients with AF were studied, mean age 58.1 years; 161 women; 96 pts with rheumatic etiology. Patients underwent clinical and laboratory evaluation, measurement of risk scores and the mean follow-up of 12.8 months. 174 were using warfarin. The averages of the HAS-BLED and ATRIA scores were 1.4 and 1.2, respectively. Percent time in therapeutic range of international normalized ratio was 45.8%. Thirty patients (9.9%) had cardiac death and 41 had some type of bleeding due to warfarin. By univariate analysis, there was statistical significance between cardiac death and permanent AF, blood pressure, systolic dysfunction, R2CHADS2, CCS, EHRA and HAS-BLED. There was no association with valvular AF. By multivariate analysis, systemic arterial and pulmonary artery pressures, classification CCS and systolic dysfunction showed statistical significance. There was no association between cardiac death and valvular AF. Independent predictors of cardiac death were low measures of blood pressure, higher score CCS classification and the presence of systolic ventricular dysfunction.


Influence of tetracycline on tetracycline-resistant heterotrophs and tet genes in activated sludge process.
The concentrations of tetracycline-intermediate resistant, tetracycline-resistant heterotrophic bacteria, and total heterotrophic bacteria were examined to assess the influence of tetracycline on tetracycline-resistant heterotrophs by the R2A agar cultivation method in the tetracycline fortified activated sludge process and in the natural background. Results showed that the percentages of both tetracycline-intermediate resistant and tetracycline-resistant heterotrophic bacteria in total heterotrophic bacteria were significantly increased, after tetracycline was fed to activated sludge for a 3 months period under four different operating conditions, as compared with the background. In order to investigate the mechanism of activated sludge resistance to tetracycline, polymerase chain reaction experiments were carried out to analyze the existence and evolution of tet genes in the presence of tetracycline. Results revealed that only tet A and tet B genes out of the 11 target tet genes were observed in tetracycline treated activated sludge while no tet gene was detected in background. This indicated that tet A gene could accumulate in activated sludge with slower and continuous influent, while the accumulation of tet B gene could be attributed to shorter hydraulic retention time. Therefore, it was proposed in this study that tetracycline-resistant genes created by efflux pumps spread earlier and quicker to encode resistance to tetracycline, which facilitated the increase in tetracycline-resistance.


Effectiveness of school-based mental well-being interventions among adolescents: A systematic review.
This systematic review aimed to identify school-based interventions for ensuring mental health and well-being of adolescents, synthesize existing interventions, and summarize the quality of identified studies. A systematic review, analysis, and synthesis were performed. Search was performed in Cochrane Library, PsychARTICLES, Web of Science, CINAHL, and Medline. Literature search was performed in March 2019 using inclusion and exclusion criteria. PRISMA guidelines were followed. Identified records were reviewed by title, abstract, and by the full text by two independent researchers. Three authors independently made a quality assessment of the included studies. Included studies were extracted and synthesized. A systematic review was registered in PROSPERO (CRD42019128919). The initial search yielded 1,199 articles. Of them, 57 articles were included in the final analysis and synthesis. Only four studies were assessed as high quality. Identified themes were mental health and well-being, positive psychology, problem-solving and stress reduction, mindfulness, and physical activity. More than half (N = 32, 56.14%) interventions showed a positive outcome after implementation. Most of those interventions focused on positive psychology and mindfulness. Mental well-being is important for the healthy development of adolescents. Countries are aware that healthy adolescents will become healthy adults who will contribute to his/her community and will lower costs of the absence of work and treatments. Thus, they support and invest in interventions that prevent mental disorders. There is a need for developing multidimensional mental well-being interventions that are effective in low- and secondary-income countries. This study ensured rigorous methodology, followed PRISMA recommendations and evaluated quality of identified literature using the GRADE guidelines. A critical synthesis was performed to produce an integrated conceptualization of the evidence. The synthesis represents a list of effective school interventions for the promotion of adolescents' mental well-being.


DIABRISK-SL trial: further consideration of age and impact of imputations.
Type 2 diabetes mellitus (T2DM) is a major cause of morbidity and mortality worldwide. Early interventions may help to delay or prevent onset of cardiometabolic endpoints of clinical importance to T2DM patients.Wijesuriya et al. (BMC Med 15:146, 2017) published results of a randomised controlled trial in Sri Lanka testing the effect of two lifestyle modification programmes of varying intensity in participants aged 5-40 years with risk factors for T2DM. The intervention measured the impact of the two programmes on the primary composite endpoint consisting of various predictors of cardiometabolic disease. The authors concluded that the more intensive programme significantly reduced the incidence of predictors of cardiometabolic disease. Further, they delivered a large-scale intervention with restricted resources with widespread acceptance as demonstrated by the high uptake rate. However, we believe that further analysis is required to fully understand the potential for benefit, particularly in relation to age, retention and missing data.


Epidemiology and genetic susceptibility to bladder cancer.
The incidence of bladder cancer varies considerably among countries; the highest incidence rates are in Western communities. The variation in occurrence can partly be explained by differences in registration and coding practices of pTa tumours. Factors that modify the occurrence of bladder cancer are smoking and exposure to many kinds of carcinogenic substances in the workplace. Evidence also exists for radiotherapy to the pelvis, infection with Schistosoma haematobium, and certain medications as risk factors for bladder cancer. Despite enormous efforts, other important environmental or lifestyle factors that clearly and consistently increase or decrease the risk of bladder cancer have not been identified. Bladder cancer in first-degree relatives doubles the risk of bladder cancer; this increased risk might be due to high-penetrance susceptibility genes in a small subset of families, but most of this risk is probably caused by common lower-penetrance DNA variants that influence risk through one or more different cancer pathways. In the next 2 years genome-wide association scans will probably yield important new information on such variants. This might also facilitate new studies on lifestyle factors restricted to groups of susceptible people. In the future it will also be necessary to pay more attention to potential risk factors for different types of bladder cancer, more specifically low- vs high-grade cancer. The ultimate goal is to build a risk-prediction model by integrating environmental and genetic factors that can project individualized probabilities of developing bladder cancer.


4D-Printed Temperature-Controlled Flow-Actuated Solid-Phase Extraction Devices.
Four-dimensional printing (4DP) technologies can extend the functionality and applicability of manufactured analytical devices through employing stimuli-responsive materials. In this study, we used a photocurable resin of stimuli-responsive shape-memory polymers and digital light processing three-dimensional printing (3DP) to fabricate a smart sample pretreatment device featuring a solid-phase extraction (SPE) column and a temperature-controlled flow-actuated valve. Through manipulation of the temperatures and flow rates of the sample, eluent, and rinsing streams, we used this 4D-printed SPE device to extract Mn, Co, Ni, Cu, Zn, Cd, and Pb ions from high-salt content samples and remove the sample matrix prior to their determination by inductively coupled plasma mass spectrometry. After optimizing the valve design and operation and the analytical scheme, this device displayed competitive analytical performance-the method detection limits (MDLs) ranged from 0.7 to 22.1 ng L-1 for these metal ions (the MDLs ranged from 0.5 to 18.8 ng L-1 when validating the same printed SPE column using an online automatic system equipped with electric switching valves). Furthermore, we performed analyses of these metal ions in three reference materials (CASS-4, 1643f, and 2670a) and spike analyses of collected samples (seawater, ground water, river water, and human urine) to confirm the reliability and applicability of this analytical method. For the first time, 4DP has been used to fabricate a multi-functional, stimuli-responsive sample pretreatment device displaying analytical performance equal to that of a commercial apparatus. This novel approach builds upon the functionality and diversity of 3DP-enabling devices with the goal of developing more efficient analytical schemes.


Levels of individual serum and cerebrospinal fluid proteins in purulent and tuberculous meningitis.
Serial determinations of nine proteins in sera and cerebrospinal fluid of 28 tuberculous and 27 purulent meningitis patients were carried out using the radial immunodiffusion technique. The results showed that mean fluid/serum ratios of most proteins before treatment were significantly higher in the purulent than in the tuberculous group. With treatment, all proteins improved in both groups at varying rates with IgM showing the fastest rate of improvement. These findings may prove to be of prognostic aid for the clinician in the follow-up of his patients.


CD8(+)CD28(-) T lymphocytes from HIV-1-infected patients secrete factors that induce endothelial cell proliferation and acquisition of Kaposi's sarcoma cell features.
Kaposi's sarcoma (KS) develops more frequently in human immunodeficiency virus type 1 (HIV-1)-infected patients. In this study, we report that molecules released by CD8(+)CD28(-) T lymphocytes from HIV-1-infected patients promote endothelial-cell (EC) growth and induce ECs to acquire spindle cell morphology and upregulation of intercellular adhesion molecule-1 (ICAM-1), E-selectin, and vascular endothelial cell growth factor receptor-3 (VEGFR-3) (a typical feature of the KS cell phenotype). The effects observed on ECs cocultured with in vivo activated CD28(-) cells were partly reproduced when ECs were grown in medium containing interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). At concentrations similar to those found in the supernatant of in vivo activated CD28(-) cells, the two proinflammatory cytokines sustained EC growth and survival only when combined. We, therefore, conclude that CD28(-) T lymphocytes from HIV-1-infected patients exert their effect on ECs through a mechanism involving both IFN-gamma and TNF-alpha. This finding may have wide implications for our basic understanding of the immunopathology of KS.


Lower tidal volume at initiation of mechanical ventilation may reduce progression to acute respiratory distress syndrome: a systematic review.
The most appropriate tidal volume in patients without acute respiratory distress syndrome (ARDS) is controversial and has not been rigorously examined. Our objective was to determine whether a mechanical ventilation strategy using lower tidal volume is associated with a decreased incidence of progression to ARDS when compared with a higher tidal volume strategy. A systematic search of MEDLINE, EMBASE, CINAHL, the Cochrane Library, conference proceedings, and clinical trial registration was performed with a comprehensive strategy. Studies providing information on mechanically ventilated patients without ARDS at the time of initiation of mechanical ventilation, and in which tidal volume was independently studied as a predictor variable for outcome, were included. The primary outcome was progression to ARDS. The search yielded 1,704 studies, of which 13 were included in the final analysis. One randomized controlled trial was found; the remaining 12 studies were observational. The patient cohorts were significantly heterogeneous in composition and baseline risk for developing ARDS; therefore, a meta-analysis of the data was not performed. The majority of the studies (n = 8) showed a decrease in progression to ARDS with a lower tidal volume strategy. ARDS developed early in the course of illness (5 hours to 3.7 days). The development of ARDS was associated with increased mortality, lengths of stay, mechanical ventilation duration, and nonpulmonary organ failure. In mechanically ventilated patients without ARDS at the time of endotracheal intubation, the majority of data favors lower tidal volume to reduce progression to ARDS. However, due to significant heterogeneity in the data, no definitive recommendations can be made. Further randomized controlled trials examining the role of lower tidal volumes in patients without ARDS, controlling for ARDS risk, are needed.


Identification of telomere-dependent "senescence-like" arrest in mouse embryonic fibroblasts.
In contrast to human primary cells, mouse embryonic fibroblasts (MEF) do not show telomere shortening-mediated replicative senescence due to the fact that they have telomerase activity and show sufficiently long telomeres. Instead, it is now generally accepted that the "senescence-like" arrest that occurs in MEF after 5-10 divisions in culture is mediated by telomere-length-independent mechanisms generally referred to as stress. Using telomerase-deficient MEF Terc(-/-), we show here that telomere shortening to a critical length leads to a premature senescence-like arrest in MEF, as well as has a negative effect on spontaneous immortalization. Similarly, elimination of the telomere end-capping protein Ku86 also leads to a premature senescence-like arrest and has a negative effect on spontaneous immortalization. Both Terc(-/-) MEF with short telomeres and Ku86(-/-) MEF show dysfunctional telomeres, as indicated by similarly increased frequencies of end-to-end fusions. These results suggest that loss of telomere function is a general mechanism leading to cell arrest. These observations also indicate that telomere dysfunction is interfering with successful cell division and thus interferes with tumor formation. In summary, we have identified here two different ways to induce a telomere-dependent senescence-like arrest in MEF.


Coupled As and Mn Redox Transformations in an Fe(0) Electrocoagulation System: Competition for Reactive Oxidants and Sorption Sites.
Iron electrocoagulation (EC) can be used for the decentralized treatment of arsenic(As)-contaminated groundwater. Iron EC involves the electrolytic dissolution of an Fe(0) electrode to Fe(II). This process produces reactive oxidants, which oxidize As(III) and Fe(II) to As(V) and a range of Fe(III) (oxyhydr)oxide phases. Here, we investigated the impact of manganese (Mn) on As removal, since the two often co-occur in groundwater. In the absence of Mn(II), we observed rapid As(III) oxidation and the formation of As(V)-Fe(III) polymers. Arsenic removal was achieved upon aggregation of the As(V)-Fe(III) polymers. In the presence of Mn, the mechanism of As removal varied with pH. At pH 4.5, As(III) was oxidized rapidly by OH• and the aggregation of the resulting As(V)-Fe(III) polymers was enhanced by the presence of Mn. At pH 8.5, As(III) and Mn(II) competed for Fe(IV), which led As(III) to persist in solution. The As(V) that did form was incorporated into a mixture of As(V)-Fe(III) polymers and a ferrihydrite-like phase that incorporated 8% Mn(III); some As(III) was also sorbed by these phases. At intermediate pH values, As(III) and Mn(II) also competed for the oxidants, but Mn(III) behaved as a reactive intermediate that reacted with Fe(II) or As(III). This result can explain the presence of As(V) in the solid phase. This detailed understanding of the As removal mechanisms in the presence of Mn can be used to tune the operating conditions of Fe EC for As removal under typical groundwater conditions.


Activity of Lymphostatin, A Lymphocyte Inhibitory Virulence Factor of Pathogenic Escherichia coli, is Dependent on a Cysteine Protease Motif.
Lymphostatin (LifA) is a 366 kDa protein expressed by attaching & effacing Escherichia coli. It plays an important role in intestinal colonisation and inhibits the mitogen- and antigen-stimulated proliferation of lymphocytes and the synthesis of proinflammatory cytokines. LifA exhibits N-terminal homology with the glycosyltransferase domain of large clostridial toxins (LCTs). A DTD motif within this region is required for lymphostatin activity and binding of the sugar donor uridine diphosphate N-acetylglucosamine. As with LCTs, LifA also contains a cysteine protease motif (C1480, H1581, D1596) that is widely conserved within the YopT-like superfamily of cysteine proteases. By analogy with LCTs, we hypothesised that the CHD motif may be required for intracellular processing of the protein to release the catalytic N-terminal domain after uptake and low pH-stimulated membrane insertion of LifA within endosomes. Here, we created and validated a C1480A substitution mutant in LifA from enteropathogenic E. coli strain E2348/69. The purified protein was structurally near-identical to the wild-type protein. In bovine T lymphocytes treated with wild-type LifA, a putative cleavage product of approximately 140 kDa was detected. Appearance of the putative cleavage product was inhibited in a concentration-dependent manner by bafilomycin A1 and chloroquine, which inhibit endosome acidification. The cleavage product was not observed in cells treated with the C1480A mutant of LifA. Lymphocyte inhibitory activity of the purified C1480A protein was significantly impaired. The data indicate that an intact cysteine protease motif is required for cleavage of lymphostatin and its activity against T cells.


HVCN1 Channels Are Relevant for the Maintenance of Sperm Motility During In Vitro Capacitation of Pig Spermatozoa.
The objective of the present study was to determine the physiological role of voltage-gated hydrogen channels 1 (HVCN1 channels) during in vitro capacitation of pig spermatozoa. Sperm samples from 20 boars were incubated in capacitating medium for 300 minutes (min) in the presence of 2-guanidino benzimidazole (2-GBI), a specific HVCN1-channel blocker, added either at 0 min or after 240 min of incubation. Control samples were incubated in capacitating medium without the inhibitor. In all samples, acrosomal exocytosis was triggered with progesterone after 240 min of incubation. Sperm viability, sperm motility and kinematics, acrosomal exocytosis, membrane lipid disorder, intracellular calcium levels and mitochondrial membrane potential were evaluated after 0, 60, 120, 180, 240, 250, 270 and 300 min of incubation. While HVCN1-blockage resulted in altered sperm viability, sperm motility and kinematics and reduced mitochondrial membrane potential as compared to control samples, at any blocker concentration and incubation time, it had a non-significant effect on intracellular Ca2+ levels determined through Fluo3-staining. The effects on acrosomal exocytosis were only significant in blocked samples at 0 min, and were associated with increased membrane lipid disorder and Ca2+ levels of the sperm head determined through Rhod5-staining. In conclusion, HVCN1 channels play a crucial role in the modulation of sperm motility and kinematics, and in Ca2+ entrance to the sperm head.


Immunoglobulin G4-related disease and its skin manifestations.
Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory condition characterized by tissue infiltration with IgG4+ plasma cells and an elevated serum IgG4 level. It usually occurs in middle-aged or older patients, with male predominance, and can involve multiple organs synchronously or metachronously. Patients with IgG4-RD generally respond to steroid therapy. IgG4-related skin lesions are typically erythematous and itchy plaques, subcutaneous nodules, or papules like prurigo nodularis located on the head and neck areas. Histologically, lymphoplasmacytic infiltrates with abundant IgG4+ plasma cells are seen in the dermis and/or subcutaneous tissue. The skin condition of IgG4-RD does not necessarily exhibit infiltration of IgG4+ plasma cells, which is a prerequisite for IgG4-related skin disease, but such skin lesions without infiltration by IgG4+ plasma cells can be included in the skin manifestations of IgG4-RD.


Ultrastructure of papillary serous carcinoma of the endometrium.
Three cases of papillary serous carcinoma of the endometrium ( PSCE ) have been studied by transmission electron microscopy, and the ultrastructural findings compared with those in classical "endometrioid" carcinoma of the endometrium ( CECE ) and papillary serous carcinoma of the ovary ( PSCO ). PSCE possesses many ultrastructural features in common with both CECE and PSCO , as well as with clear cell carcinoma of the endometrium, emphasizing the close relationship existing among these different tumors of Müllerian origin. The only useful ultrastructural distinguishing features between serous and endometrioid carcinomas of similar histologic grade are more numerous secretory granules in the former and prominent paranuclear microfilaments and tonofilaments in the latter. Despite its lack of ultrastructural distinctiveness, the clinical behavior of PSCE justifies its consideration as a unique clinicopathologic entity.


The angio-architecture of normal, hypertrophic and denervated muscle. A study in the rat, using micro-angiography and the scanning electron microscope.
The angio-architecture of normal, hypertrophic and denervated rat muscles was studied by micro-angiography and by scanning electron microscopy of vascular casts made of methylmethacrylate. In hypertrophy, there was a slightly coarse-meshed irregular capillary network with some loss of normal parallelism, an increased calibre and a slight spiralization of all vessels. Probably all these changes, except the slight spiralization, increase the circulation. In denervation atrophy, the vascular pattern was much more irregular, with much more marked spiralization and loss of parallelism and narrowed capillaries. The changes probably contribute to the impairment of the circulation.


Effects of ear plugging on single-unit azimuth sensitivity in cat primary auditory cortex. II. Azimuth tuning dependent upon binaural stimulation.
1. Single-unit recordings were carried out in primary auditory cortex (AI) of barbiturate-anesthetized cats. Observations were based on a sample of 131 high-best-frequency (> 5 kHz), azimuth-sensitive neurons. These were identified by their responses to a set of noise bursts, presented in the free field, that varied in azimuth and sound-pressure level (SPL). Each azimuth-sensitive neuron responded well to some levels at certain azimuths, but did not respond well to any level at other azimuths. 2. Unilateral ear plugging was used to infer each neuron's response to monaural stimulation. Ear plugs, produced by injecting a plastic ear mold compound into the external ear, attenuated sound reaching the tympanic membrane by 25-70 dB. The azimuth tuning of a large proportion of the sample (62/131), referred to as binaural directional (BD), was completely dependent upon binaural stimulation because with one ear plugged, these cells were insensitive to azimuth (either responded well at all azimuths or failed to respond at any azimuth) or in a few cases exhibited striking changes in location of azimuth function peaks. This report describes patterns of monaural responses and binaural interactions exhibited by BD neurons and relates them to each cell's azimuth and level tuning. The response of BD cells to ear plugging is consistent with the hypothesis that they derive azimuth tuning from interaural level differences present in noise bursts. Another component of the sample consisted of monaural directional (27/131) cells that derived azimuth tuning in part or entirely from monaural spectral cues. Cells in the remaining portion of the sample (42/131) responded too unreliably to permit specific conclusions. 3. Binaural interactions were inferred by statistical comparison of a cell's responses to monaural (unilateral plug) and binaural (no plug) stimulation. A larger binaural response than either monaural response was taken as evidence for binaural facilitation. A smaller binaural than monaural response was taken as evidence for binaural inhibition. Binaural facilitation was exhibited by 65% (40/62) of the BD sample (facilitatory cells). Many of these exhibited mixed interactions, i.e., binaural facilitation occurred in response to some azimuth-level combinations, and binaural inhibition to others. Binaural inhibition in the absence of binaural facilitation occurred in 35% (22/62) of the BD sample, a majority of which were EI cells, so called because they received excitatory (E) input from one ear (excitatory ear) and inhibitory (I) input from the other (inhibitory ear). One cell that exhibited binaural inhibition received excitatory input from each ear.(ABSTRACT TRUNCATED AT 400 WORDS)


A comparison in germ-free mice of the pathogenesis of Sendai virus and mouse pneumonia virus infections.
The poathogenesis of Sendai virus and pneumonia virus of mice (PVM) was studied using the immunoperoxidase technique on paraffin lung sections. The pathology of Sendai virus corresponds to that of a bronchopneumonia, with virus demonstrated by immunoperoxidase in the bronchial epithelium, and sometimes in macrophages, for a period of 2--9 days post-infection. Pneumonia virus of mice produces an interstitial pneumonia with virus demonstrated in the bronchial epithelium but also in the alveolar walls and alveolar macrophages. This virus can be demonstrated between 2 and 7 days post-infection. This technique was used to demonstrate PVM in the case of a natural outbreak of this disease and may eventually become a routine technique for the screening of lung tissue for respiratory viruses.


Fulminant hepatitis during self-medication with hydroalcoholic extract of green tea.
Despite an ancient reputation for potential phytotherapeutic effects and innocuity, traditional herbal medicine has previously been implicated in severe adverse events. Exolise is an 80% ethanolic dry extract of green tea (Camellia sinensis) standardized at 25% catechins expressed as epigallocatechin gallate, containing 5-10% caffeine. It has been available in France, Belgium, Spain and the United Kingdom since 1999, as an adjuvant therapy for use in weight loss programmes. In various studies, green tea has to date been considered useful for its potential hepatic protective properties. In this study, we report a case of fulminant hepatitis during self-medication with Exolise, requiring liver transplantation.


Contribution of dipolar bridging to phospholipid membrane interactions: A mean-field analysis.
We develop a model of interacting zwitterionic membranes with rotating surface dipoles immersed in a monovalent salt and implement it in a field theoretic formalism. In the mean-field regime of monovalent salt, the electrostatic forces between the membranes are characterized by a non-uniform trend: at large membrane separations, the interfacial dipoles on the opposing sides behave as like-charge cations and give rise to repulsive membrane interactions; at short membrane separations, the anionic field induced by the dipolar phosphate groups sets the behavior in the intermembrane region. The attraction of the cationic nitrogens in the dipolar lipid headgroups leads to the adhesion of the membrane surfaces via dipolar bridging. The underlying competition between the opposing field components of the individual dipolar charges leads to the non-uniform salt ion affinity of the zwitterionic membrane with respect to the separation distance; large inter-membrane separations imply anionic excess, while small nanometer-sized separations favor cationic excess. This complex ionic selectivity of zwitterionic membranes may have relevant repercussions on nanofiltration and nanofluidic transport techniques.


Studies on the fatty acid binding proteins in cytosol of rat liver.
Gel filtration on Sephadex G-75 of crude rat liver supernatant preincubated with [1-14C]oleic acid yields three peaks of radioactivity which are attributed to the presence in these fractions of fatty acid binding proteins. We have confirmed these observations with binding assays by phase partition, polyacrylamide gel electrophoresis, and thin layer electrofocusing. Peak I (mol. wt. 60,000 pI 5.01 was shown to be albumin, which mainly arises from a contamination of the liver preparation by blood. Peak II (mol. wt. 10,000, pI 5.9) is a fatty acid binding protein. Finally peak III (mol. wt. 1500, pI 5.7) is a fatty acid binding component, the chemical nature of which was not elucidated. These fatty acid binding fractions have no effect on the reaction of acyl-CoA synthetase whereas the crude liver supernatant does stimulate the activation of fatty acid as shown earlier. In consequence, the physiological role of these fatty acid binding fractions is not yet elucidated.


[Dynamics of the level of extracellular dopamine in the rat brain during formation of conditioned fear and acoustic startle habituation].
The content of extracellular dopamine (DA) was estimated in dorsal striatum (DS), nucleus accumbens (Nac), and prefrontal cortex (Pfc) of rat brain during two sessions of acoustic startle habituation consisting of 10 trials each with 24-hour intersession and 20-s intertrial intervals. Startle amplitude and freezing behavior were recorded. A decrease in the content of extracellular DA in the DS and an increase in the DA content in Nac were observed during both sessions of habituation with return to a baseline level immediately after termination of the sessions. During the second session, the startle amplitude and change in the DA content in both structures were much lower than during the first session. During the first session, the DA level in DS remained unchanged but dropped in Nac. In the Pfc the DA level increased during both habituation sessions and in the period between the session. Time of freezing prior to acoustic stimulation in the second sessions (that is known to be an indication of conditioned fear) correlated with the DA level in DS on the day of training and with the DA level in Nac just before the beginning of the second session. The role of the dopaminergic system in formation and retrieval of different components of defensive behavior is discussed.


The muscular dystrophies associated with central nervous system lesions: a brief review from a standpoint of the localization and function of causative genes.
The muscular dystrophies have been traditionally classified based mainly on clinical manifestation and mode of inheritance. Owing to the discoveries of causative genes, new terminologies derived from each gene, such as dystrophinopathy, α-dystroglycanopathy, sarcoglycanopathy and fukutinopathy, have also become common. Mutations of each gene may cause several clinical phenotypes. Some muscular dystrophies accompany central nervous system (CNS) lesions, especially in the congenital muscular dystrophies. Cobblestone lissencephaly (type II lissencephaly) is a well-known CNS malformation observed in severe forms of α-dystroglycanopathy. Moreover, CNS involvement has been reported in other muscular dystrophies, such as Duchenne muscular dystrophy. In this review, genes related to the muscular dystrophies associated with CNS lesions are briefly described along with the molecular characteristics of each gene and the pathomechanism of the CNS lesions. Understanding of both the clinicopathological characteristics of these CNS lesions and their molecular mechanisms is important for the diagnosis, care of patients, and development of new therapeutic strategies.


[Comparative study of sustained-release in theophylline (Slobid, Theolong, Theodur) by pharmacokinetics].
We made a comparative study of three kinds of sustained-release of theophylline compounds by means of analysis of plasma concentrations. The drugs were Slobid (SB) (Up-john) 11 patients (10 men, 1 woman), Theolong (TL) (Eisai) 22 (10 men, 12 women), Theodur (TD) (Nikken chemicals) 34 (18 men, 16 women), who were hospitalized from January 1989 to November 1994. These patients were given oral theophylline, bid at 9:00 and 21:00, plasma concentration of theophylline was determined at 9:00, 12:00, 15:00, 18:00 and 21:00, after plasma concentration reached a plateau. There were no significant differences as to the zero absorption rate, the moment absorption rate, clearance, but there were significant differences to the half life time (T1/2) of SB (18.9) > TL (13.5) > TD (10.1) (p = 0.0061), mean residence time (MRT) of SB (21.3 hr) > TL (16.7) > TD (15.2) (p = 0.0034), by measurements analysis of variance. These results suggest that these sustained-release drugs have different pharmacokinetics judging from the important indices including Cmax-Cmin, T1/2, V, MRT and Tml/2, and that the best one is the SB, the second is the TL, and the third is the TD for RTC therapy.


Vascular changes in the rat brain during chronic hypoxia in the presence and absence of hypercapnia.
Changes in brain vascularity in adult rats during adaptation to chronic normobaric hypoxia with or without elevated CO(2) were morphometrically investigated. Immunohistochemistry with anti-rat endothelial cell antigen (RECA-1) antibody was carried out for the vascular analysis. After the rats were subjected to hypoxia for 2 to 8 weeks (wks)(10 percent O(2) in N(2)), the total area of blood vessels was measured in 6 brain regions. After 2 wks of hypoxia, the blood vessel area was found to be significantly increased in the frontal cortex, striatum, hippocampus, thalamus, cerebellum, and medulla oblongata, by 44% , 96% , 65% , 50% , 102% and 97% , respectively. The ratio of large vessels with an area > 500 micro m(2) was also increased in all brain regions. Hypoxic adaptation in brain vascularity did not change during 8 wks of hypoxia, and the hypoxia-induced levels measured in the vasculature returned to control levels 2 wks after the termination of hypoxia in areas of the brain other than the cortex and thalamus. In addition, hypoxia-induced changes in terms of the total vascular area and vessel size distribution were significantly inhibited by the elevation in CO(2), whereas chronic hypercapnia without hypoxia had no effect on brain vascularity. These findings suggested that adaptations in brain vascularity in response to hypoxia are rapidly induced, and there are regional differences in the reversibility of such vascular changes. Carbon dioxide is a potent suppressor of hypoxia-induced vascular changes, and may play an important role in vascular remodeling during the process of adaptation to chronic hypoxia.


Structure and function of spliceosomal DEAH-box ATPases.
Splicing of precursor mRNAs is a hallmark of eukaryotic cells, performed by a huge macromolecular machine, the spliceosome. Four DEAH-box ATPases are essential components of the spliceosome, which play an important role in the spliceosome activation, the splicing reaction, the release of the spliced mRNA and intron lariat, and the disassembly of the spliceosome. An integrative approach comprising X-ray crystallography, single particle cryo electron microscopy, single molecule FRET, and molecular dynamics simulations provided deep insights into the structure, dynamics and function of the spliceosomal DEAH-box ATPases.


Molecular detection of per- and polyfluoroalkyl substances in water using time-of-flight secondary ion mass spectrometry.
Detection of per- and polyfluoroalkyl substances (PFASs) is crucial in environmental mitigation and remediation of these persistent pollutants. We demonstrate that time-of-flight secondary ion mass spectrometry (ToF-SIMS) is a viable technique to analyze and identify these substances at parts per trillion (ppt) level in real field samples without complicated sample preparation due to its superior surface sensitivity. Several representative PFAS compounds, such as perfluorooctanesulfonic acid (PFOS), perfluorobutanoic acid (PFBA), perfluoropentanoic acid (PFPeA), perfluoheptanoic acid (PFHpA), and perfluorononanoic acid (PFNA), and real-world groundwater samples collected from monitoring wells installed around at a municipal wastewater treatment plant located in Southern California were analyzed in this work. ToF-SIMS spectral comparison depicts sensitive identification of pseudo-molecular ions, characteristic of reference PFASs. Additionally, principal component analysis (PCA) shows clear discrimination among real samples and reference compounds. Our results show that characteristic molecular ion and fragments peaks can be used to identify PFASs. Furthermore, SIMS two-dimensional (2D) images directly exhibit the distribution of perfluorocarboxylic acid (PFCA) and PFOS in simulated mixtures and real wastewater samples. Such findings indicate that ToF-SIMS is useable to determine PFAS compounds in complex environmental water samples. In conclusion, ToF-SIMS provides simple sample preparation and high sensitivity in mass spectral imaging, offering an alternative solution for environmental forensic analysis of PFASs in wastewater in the future.


Clinical factors predict surgical outcomes in pediatric MRI-negative drug-resistant epilepsy.
Lack of a potentially epileptogenic lesion on brain magnetic resonance imaging (MRI) is a poor prognostic marker for epilepsy surgery. We present a single-center series of childhood-onset MRI-negative drug-resistant epilepsy (DRE) and analyze surgical outcomes and predictors. Children with MRI-negative DRE who had resective surgery from January 2007 to December 2013 were identified using an institutional database. Relevant clinical, neurophysiological, imaging, and surgical data was extracted. The primary outcome measure was seizure freedom. Predictors of seizure freedom were obtained using multivariate logistic regression. Out of 47 children with MRI-negative DRE, 12 (25.5%) were seizure free (International League Against Epilepsy [ILAE] outcome class I), after mean follow-up of 2.75 (±1.72) years. Seizure-free proportion was significantly higher in patients with single seizure semiology and concordant ictal EEG (50.0% vs. 15.2%, p=0.025). Multivariate analysis using only non-invasive pre-surgical data showed that children with daily seizures (OR 0.02, 95% CI<0.001-0.55), and earlier onset of seizures (OR 0.72, 95% CI 0.52-0.99) were less likely to be seizure-free. Also, each additional anti-epileptic drug (AED) tried before surgery decreased the probability of seizure-free outcome (OR 0.16, 95% CI 0.04-0.63). Repeat multivariate analysis after including surgical variables found no additional significant predictors of seizure-freedom. Cortical dysplasia (ILAE type IB) was the commonest histopathology. Surgical outcomes in children with MRI-negative DRE are determined by clinical factors including seizure frequency, age of onset of seizures, and number of failed AEDs.


The ecology and pathogenicity of urease-producing bacteria in the urinary tract.
Urease activity is a physiological function of many bacteria that enables these organisms to utilize urea as a source of nitrogen. The association of ureolytic bacteria with human or animal hosts varies widely from a commensal relationship as demonstrated with skin microflora, a symbiotic relationship in the gastrointestinal tract, to a pathogenic relationship in the urinary tract. Since similar or identical species of bacteria such as Staphylococcus aureus are found in all three environments, the effect of urease activity on the host must be solely a function of the environment of these organisms. In this review, the importance of urease to bacteria is discussed, identifying the gastrointestinal tract as a major reservoir of ureolytic bacteria and investigating the urinary tract environment and the infectious struvite stone production that often accompanies urease-producing bacteria there. Finally, an infection model is presented which explains the development and growth of these urinary calculi and their remarkable persistence in spite of modern urological treatments.


Contrast-enhanced ultrasound (CEUS) in an interdisciplinary intensive care unit (ICU): Diagnostic efficacy in the assessment of post-operative complications compared to contrast-enhanced computed tomography (CECT): First results.
To evaluate the effectiveness of high-resolution contrast-enhanced ultrasound (CEUS) to diagnose early post-operative complications in an interdisciplinary intensive care unit.In 50 patients (male 32; female 18) 64 CEUS examinations were performed in an intensive care unit (ICU) setting to detect post-operative complications. Multi-frequency transducer (1-5 and/or 6-9 MHz) were used. All 64 examinations were performed by one experienced examiner. CEUS findings were compared with contrast-enhanced computed tomography (CECT) findings. CECT images were acquired within 1-24 hours after CEUS examination in arterial and portal-venous phases of the abdomen using either a 16-slice computed tomography scanner or a 128-dual slice computed tomography scanner.In 56 out of 64 cases (88%) the CEUS-based diagnosis corresponded with the CECT diagnosis. Vascular stenosis in hepatic arteries and portal veins were recognised in both imaging modalities but were evaluated differently [5 cases]. In 3 cases (5%) small peripheral splenic infarction, retroperitoneal hematoma and fluid collection around the liver were not diagnosed by CEUS. CEUS in an ICU setting enables a reliable detection of postoperative abdominal complications as compared to CECT.