Methimazole protection of rats against chemically induced kidney damage in vivo.
Because methimazole has antioxidant properties, the effects of methimazole treatment on cephaloridine, S-(1,2-dichlorovinyl)-L-cysteine (DCVC), 2-bromohydroquinone (2-BHQ) and cis-diaminedichloroplatinum (II) (cisplatin)-induced nephrotoxicity were investigated. Rats given cephaloridine (1 g/kg), cisplatin (5 mg/kg), DCVC (100 mg/kg) or 2-BHQ (157 mg/kg) i.p. exhibited significant elevations in blood urea nitrogen concentrations, which correlated with appearance of distinct renal histopathological changes. Cephaloridine, DCVC or 2-BHQ-induced nephrotoxicity was reduced only when methimazole (20-40 mg/kg) was given 30 min before the nephrotoxicant, whereas cisplatin-induced nephrotoxicity was reduced when methimazole was given 30 min before and up to 4 hr after cisplatin. Because the renal organic acid transport system plays an important role in the nephrotoxicity of cephaloridine, cisplatin and DCVC, the role of the organic acid transport system in the renal uptake of methimazole was investigated. With rat kidney cortical slices, methimazole uptake was time- and concentration-dependent; however, the organic acid transport substrates, probenecid (1 mM) and p-aminohippuric acid (7.5 mM), were ineffective in blocking methimazole uptake. Furthermore, cephaloridine (1 mM) uptake by kidney cortical slices was not affected by methimazole (5 mM). Rats given methimazole (40 mg/kg) 30 min before cephaloridine (2 g/kg) had serum and kidney cephaloridine concentrations similar to rats given cephaloridine only, but the methimazole-pretreated rats were significantly protected against cephaloridine-induced oxidation of renal nonprotein thiols. These results show that methimazole does not inhibit the transport of cephaloridine into the kidneys, but may protect against cephaloridine-induced renal damage by acting as an antioxidant within the kidneys.


Alpha-Tocopherol Alters Transcription Activities that Modulates Tumor Necrosis Factor Alpha (TNF-α) Induced Inflammatory Response in Bovine Cells.
To further investigate the potential role of α-tocopherol in maintaining immuno-homeostasis in bovine cells (Madin-Darby bovine kidney epithelial cell line), we undertook in vitro experiments using recombinant TNF-α as an immuno-stimulant to simulate inflammation response in cells with or without α-tocopherol pre-treatment. Using microarray global-profiling and IPA (Ingenuity Pathways Analysis, Ingenuity(®) Systems, http://www.ingenuity.com) data analysis on TNF-α-induced gene perturbation in those cells, we focused on determining whether α-tocopherol treatment of normal bovine cells in a standard cell culture condition can modify cell's immune response induced by TNF-α challenge. When three datasets were filtered and compared using IPA, there were a total of 1750 genes in all three datasets for comparison, 97 genes were common in all three sets; 615 genes were common in at least two datasets; there were 261 genes unique in TNF-α challenge, 399 genes were unique in α-tocopherol treatment, and 378 genes were unique in the α-tocopherol plus TNF-α treatment. TNF-α challenge induced significant change in gene expression. Many of those genes induced by TNF-α are related to the cells immune and inflammatory responses. The results of IPA data analysis showed that α-tocopherol-pretreatment of cells modulated cell's response to TNF-α challenge. In most of the canonical pathways, α-tocopherol pretreatment showed the antagonistic effect against the TNF-α-induced pro-inflammatory responses. We concluded that α-tocopherol pre-treatment has a significant antagonistic effect that modulates the cell's response to the TNF-α challenge by altering the gene expression activities of some important signaling molecules.


[The study of clinical pathology on bronchial hyperresponsiveness].
To study mechanism of bronchial hyperresponsiveness (BHR) and the relationship between asymptomatic BHR and asthma. Bronchial biopsies were taken through fiberoptic bronchoscope from 17 cases of asymptomatic BHR, 12 cases of chronic asthma with remission and 10 normal control subjects. Bronchial mucosas were investigated by light microscopy and transmission electron microscope. Analysed by morphometric technique for the granules in both eosinophils (EOS) and mast cells (MC). Airway allergic inflammation (AAI) existed in 9 cases (53%) with asymptomatic BHR. It was similar in bronchial mucosal pathologic changes to chronic asthma with remission. Inflammation existed in the other 8 cases (47%), but unlike AAI, there were no infiltration of EOS and MC in bronchial mucosa. The pathological changes of asthma in bronchial mucosa were existed in a part of patients with asymptomatic BHR.


Preventive medicines: vaccination, prophylaxis of infectious diseases, disinfectants.
Immunizations belong to the most successful interventions in medicine. Like other drugs, vaccines undergo long periods of pre-clinical development, followed by careful clinical testing through study Phases I, II, and III before they receive licensure. A successful candidate vaccine will move on to be an investigational vaccine to undergo three phases of pre-licensure clinical trials in a stepwise fashion before it can be considered for approval, followed by an optional fourth phase of post-marketing assessment. The overall risk-benefit assessment of a candidate vaccine is very critical in making the licensure decision for regulatory authorities, supported by their scientific committees. It includes analyses of immunogenicity, efficacy, reactogenicity or tolerability, and safety of the vaccine. Public trust in vaccines is a key to the success of immunization programs worldwide. Maintaining this trust requires knowledge of the benefits and scientific understanding of real or perceived risks of immunizations. Under certain circumstances, pre- or post-exposure passive immunization can be achieved by administration of immunoglobulines. In terms of prevention of infectious diseases, disinfection can be applied to reduce the risk of transmission of pathogens from patient to patient, health-care workers to patients, patients to health-care workers, and objects or medical devices to patients.


Controlling the use of stat testing.
Overused stat testing consumes an excessive share of the laboratory budget in many health care settings. The clinical practitioners and laboratory personnel in the setting described in this article negotiated a multifaceted program that resulted in a 95 percent reduction in the use of stat testing and improved the turnaround time of stat results for patients with potentially emergent problems. Financial savings from the program allowed a no-growth laboratory budget for the following fiscal year.


Drug metabolic activity is a critical cell-intrinsic determinant for selection of hepatocytes during long-term culture.
The liver plays an important role in various metabolic processes, including protein synthesis, lipid and drug metabolisms and detoxifications. Primary culture of hepatocytes is used for the understanding of liver physiology as well as for the drug development. Hepatocytes are, however, hardly expandable in vitro making it difficult to secure large numbers of cells from one donor. Alternatively, systems using animal models and hepatocellular carcinoma cells have been established, but interspecies differences, variation between human cell sources and limited hepatic functions are among the challenges faced when using these models. Therefore, there is still a need for a highly stable method to purify human hepatocytes with functional sufficiency. In this study, we aimed to establish an in vitro long-term culture system that enables stable proliferation and maintenance of human hepatocytes to ensure a constant supply. We first established a growth culture system for hepatocytes derived from patients with drug-induced liver injury using fetal mouse fibroblasts and EMUKK-05 medium. We then evaluated the morphology, proliferative capacity, chromosome stability, gene and protein expression profiles, and drug metabolic capacity of hepatocytes in early, middle and late passages with and without puromycin. In addition, hepatic maturation in 3D culture was evaluated from morphological and functional aspects. In our culture system, the stable proliferation of human hepatocytes was achieved by co-culturing with mouse fetal fibroblasts, resulting in dedifferentiation into hepatic progenitor-like cells. We purified human hepatocytes by selection with cytocidal puromycin and cultured them for more than 60 population doublings over a span of more than 350 days. Hepatocytes with high expression of cytochrome P450 genes survived after exposure to cytocidal antibiotics because of enhanced drug-metabolizing activity. These results show that this simple culture system with usage of the cytocidal antibiotics enables efficient hepatocyte proliferation and is an effective method for generating a stable supply of hepatocytes for drug discovery research at a significant cost reduction.


[Clinical techniques for use in neurological physical examinations. I. General organisation, cranial and peripheral spinal nerves].
The purpose of this work is to focus on the main practical aspects of the techniques used for the physical examination of the nervous system and to present an approach for the practice of this study in adult patients. We recommend clinicians to carry out a brief but consistent and effective exploration in a systematic, flexible and orderly manner to check for alterations in the functioning of the nervous system. Should any anomalies be detected, then a more detailed and thorough neurological exploration must be performed selectively. The techniques and data from this examination are organised into five broad categories: mental status, cranial nerves, motor function, reflex function and sensory function. The practical aspects of the main techniques used in the physical exploration are reviewed and we also describe the technique to be employed for palpating the main peripheral nerves. The study offers a detailed description of the chief clinical techniques used in the physical exploration of the cranial nerves and for the palpation of the peripheral nerves; we also present an approach to performing the neurological examination. Furthermore, we highlight the importance of physically examining the nervous system in contemporary medicine and the need to continually perfect the way these techniques are performed in order to achieve an efficient clinical practice.


Results of tension-free vaginal tape in patients with or without vaginal hysterectomy.
To assess complications and cure rates of tension-free vaginal tape (TVT) procedure performed with or without vaginal hysterectomy. Retrospective comparison of 41 women with urinary incontinence treated by a TVT procedure alone and 40 combined with vaginal hysterectomy. Objective cure was evaluated by clinical and urodynamic examination and by the contilife questionnaire. All patients were operated under regional anesthesia. The two groups were similar in age, parity, menopausal status and type and severity of incontinence. There was no difference in overall complication rates. In the TVT-hysterectomy group, there was a trend towards more bladder perforation (P=0.09). Post-operative urinary flow was lower in the TVT-hysterectomy group: 14 versus 24 ml/pc (P=0.02). The mean follow-up was similar: 23 and 25 months, respectively. No difference in objective and subjective cure rates was found between TVT group and TVT-hysterectomy group: 97.6% versus 92.5% and 68.3% versus 75%, respectively. TVT is a safe and effective surgical treatment of urinary incontinence. The association of the procedure with vaginal hysterectomy gave similar short-term objective and subjective cure rates than TVT technique alone.


Fabrication of Durably Superhydrophobic Cotton Fabrics by Atmospheric Pressure Plasma Treatment with a Siloxane Precursor.
The surface treatment of fabrics in an atmospheric environment may pave the way for commercially viable plasma modifications of fibrous matters. In this paper, we demonstrate a durably superhydrophobic cotton cellulose fabric prepared in a single-step graft polymerization of hexamethyldisiloxane (HMDSO) by N₂ and O₂ atmospheric pressure plasma. We systematically investigated effects on contact angle (CA) and surface morphology of the cotton fabric under three operational parameters: precursor value; ionization gas flow rate; and plasma cycle time. Surface morphology, element composition, chemical structure and hydrophobic properties of the treated fabric were characterized by scanning electron microscope (SEM), EDS, FTIR and CA on the fabrics. The results indicated that a layer of thin film and nano-particles were evenly deposited on the cotton fibers, and graft polymerization occurred between cellulose and HMDSO. The fabric treated by O₂ plasma exhibited a higher CA of 162° than that treated by N₂ plasma which was about 149°. Furthermore, the CA of treated fabrics decreased only 0°~10° after storing at the ambient conditions for four months, and treated fabrics could also endure the standard textile laundering procedure in AATCC 61-2006 with minimum change. Therefore, this single-step plasma treatment method is shown to be a novel and environment-friendly way to make durable and superhydrophobic cotton fabrics.


IKKalpha controls p52/RelB at the skp2 gene promoter to regulate G1- to S-phase progression.
The IkappaB-inducing kinase (IKK) is composed of two catalytic subunits, IKKalpha and IKKbeta, and a regulatory subunit, IKKgamma. IKK-regulated signaling pathways are believed to promote the proliferation of normal cells as well as the aberrant proliferation of cancer cells. The molecular mechanisms linking the IKK signaling pathway components to the cell cycle machinery are not entirely understood. To study the function(s) of the catalytic subunits of the IKK complex, we used pancreatic cancer cells, with constitutive IKK activity. We show that the G1 phase of the cell cycle is specifically regulated by the IKKalpha subunit, which regulates the stability of the cyclin-dependent kinase inhibitor p27(Kip1). Increased p27(Kip1) protein levels following the transfection of IKKalpha-specific siRNAs are a result of the downregulation of the F-box protein S-phase kinase-associated protein 2 (skp2). Additionally, we demonstrate that IKKalpha signaling regulates the transcription of the skp2 gene by controlling the composition of a RelB-containing NF-kappaB complex. Together, this work defines a novel IKKalpha-regulated growth pathway involving the p52/RelB-dependent transcriptional regulation of the skp2 gene.


Experiences of Interpersonal Trauma Among Parents With Intellectual Disabilities: A Systematic Review.
Research has suggested highly elevated levels of interpersonal trauma (IPT) among parents with intellectual disabilities (ID), and that such experiences may contribute to the caregiving and child developmental problems often seen in this population. Conflicting results have however been reported, and there is no systematic review on this matter. This study therefore systematically reviewed the empirical evidence concerning (a) prevalence of IPT among parents with ID, and links with (b) caregiving-relevant and (c) child developmental outcomes, in accordance with the PRISMA 2020 guidelines. Searches were conducted in MEDLINE, CINAHL, PsycINFO, and PTSDpubs. Peer-reviewed empirical articles reporting exposure to any form of systematically assessed IPT (unspecified IPT, physical, sexual, and emotional abuse, neglect, prolonged childhood separations from caregivers, witnessing abuse in the family) among parents with ID were included, yielding a final selection of 20 studies. Findings consistently indicated markedly elevated levels of IPT among parents with ID, with a majority (>50%) having experienced some form of IPT. Estimates for both unspecified and specific forms were typically higher than corresponding estimates in other groups at elevated risk, and than meta-analytical general population estimates in comparable countries. Findings regarding caregiving-relevant outcomes were mixed but indicated links with adverse outcomes, particularly regarding parental mental health. Reports pertaining to child developmental outcomes were scant and inconsistent. We highlight important limitations in the extant literature and provide directions for future research and clinical practice.


Montelukast added to fluticasone propionate does not alter inflammation or outcomes.
Airway inflammation is a key pathological feature of asthma which underlies its clinical presentation. To examine whether adding a leukotriene modifier to an inhaled corticosteroid produces further clinical and/or anti-inflammatory benefits in patients symptomatic on short-acting beta(2)-agonists. Patients uncontrolled on short-acting beta(2)-agonists were treated for 12 weeks with either fluticasone propionate (100mcg BD) or fluticasone propionate (100mcg BD) and montelukast (10mg QD) in a randomized, double-blind, parallel group study. Bronchoscopy with endobronchial biopsy and bronchoalveolar lavage (BAL) was performed before and after treatment to compare effects on airway inflammation. Of 103 subjects enrolled, 89 subjects completed treatment and 82 subjects had matched pair biopsy samples. Submucosal eosinophil counts, the primary endpoint, and asthma control improved to similar extents after both treatments (p<or=0.008). Both treatments significantly reduced submucosal mast cell, CD3+, CD4+, CD8+ and CD25+ cell counts. Submucosal mast cell reduction was greater in the fluticasone propionate plus montelukast group. There were no differences between treatments in BAL markers of inflammation or thickness of sub-epithelial collagen. Low-dose fluticasone propionate significantly improves clinical disease control and reduces airway inflammation in asthma patients uncontrolled with short-acting beta(2)-agonists without further improvement when montelukast is added to low-dose fluticasone propionate.


Curriculum content in geriatric dentistry in USA dental schools.
The aim of this study was to re-examine the teaching of geriatric dentistry in the USA dental schools, to identify curriculum content and compare the findings to previous reports. All dental schools in the United States were contacted via email with a questionnaire to assess the teaching of geriatric dentistry. Non-responding schools were sent a minimum of three reminder emails to complete the survey. A statistical analysis was performed. Descriptive statistics were conducted to profile the variables of interest. Bivariate analysis was performed to explore if any of the variables were related using Fisher's exact test, non-parametric Wilcoxon rank-sum test and the Kruskal-Wallis test. Fifty-six of the 67 dental schools completed the questionnaire. Geriatric dentistry was taught in all dental schools; for 92.8%, the course was compulsory. We found that 62.5% were teaching it as an independent course, 25% as an organised series of lectures and 8.9% as occasional lectures in parts of other courses. Clinically, 84.2% have some form of compulsory education in geriatric dentistry. Public schools were marginally associated with an increased interest in expanding the geriatric dentistry curriculum (P = .078). No differences were found between these variables and school location. Geriatric dentistry is now required in 92.8% of dental schools. The teaching of traditional topics has not changed much; however, the number of gerontological topics has increased. Clinical teaching needs to be expanded, as in only 57.1% of schools was it a requirement. The ageing imperative will require research to determine the impact of teaching on services to the geriatric community.


The ADAMTS(L) family and human genetic disorders.
ADAMTS designates a family of 19 secreted enzymes, whose the first member ADAMTS1 was described in 1997. The ADAMTS family has a role in extracellular matrix degradation and turn over and has previously been involved in various human biological processes, including connective tissue structure, cancer, coagulation, arthritis, angiogenesis and cell migration. More recently, the ADAMTS(L) family has been described, sharing the same ancillary domain but distinct by the absence of any enzyme activity. Mutations in ADAMTS13, ADAMTS2, ADAMTS10, ADAMTS17, ADAMTSL2 and ADAMTSL4 have been identified in distinct human genetic disorders ranging from thrombotic thrombocytopenic purpura to acromelic dysplasia. The aim of our review was to emphasize the role of this family in the extracellular matrix based on human phenotypes so far identified in relation with ADAMTS(L) mutations.


Electron spin polarization of functionalized fullerenes. Reversed quartet mechanism.
Time-resolved electron paramagnetic resonance (TREPR) spectroscopy was used to study two functionalized fullerenes consisting of a C60 moiety covalently linked to TEMPO radical via spacers of different length. Photoinduced electron spin polarization (ESP) reflecting a non-Boltzmann population within the energy levels of the spin system was observed in the electronic ground and excited states. Both fullerenes are characterized by a sign inversion of their TREPR spectra. A new mechanism of ESP generation was suggested to explain the experimental results. This mechanism, termed as the reversed quartet mechanism (RQM), includes the intersystem crossing process, which generates ESP in the excited trip-doublet and trip-quartet (2T1 and 4T1) states. This ISC is accompanied by ESP transfer to the ground state (2S0) by either electron-transfer reaction (in our case via charge transfer state, 2CT, i.e., 2T1--> 2CT --> 2S0 or internal conversion, 2T1--> 2S0.


Transmutation of long-lived fission products in an advanced nuclear energy system.
Disposal of long-lived fission products (LLFPs) produced in reactors has been paid a lot attention for sustainable and clean nuclear energy. Although a few transmutation means have been proposed to address this issue, there are still scientific and/or engineering challenges to achieve efficient transmutation of LLFPs. In this study, we propose a novel concept of advanced nuclear energy system (ANES) for transmuting LLFPs efficiently without isotopic separation. The ANES comprises intense photoneutron source (PNS) and subcritical reactor, which consist of lead-bismuth (Pb-Bi) layer, beryllium (Be) layer, and fuel, LLFPs and shield assemblies. The PNS is produced by bombarding radioactive cesium and iodine target with a laser-Compton scattering (LCS) γ-ray beam. We investigate the effect of the ANES system layout on transmutation efficiency by Monte Carlo simulations. It is found that a proper combination of the Pb-Bi layer and the Be layer can increase the utilization efficiency of the PNS by a factor of ~ 10, which helps to decrease by almost the same factor the LCS γ-beam intensity required for driving the ANES. Supposing that the ANES operates over 20 years at a normal thermal power of 500 MWt, five LLFPs including 99Tc, 129I, 107Pd, 137Cs and 79Se could be transmuted by more than 30%. Their effective half-lives thus decrease drastically from ~ 106 to less than 102 years. It is suggested that this successful implementation of the ANES paves the avenue towards practical transmutation of LLFPs without isotopic separation.


The Crystal Structure of Ba3Nb2O8 Revisited: A Neutron Diffraction and Solid-State NMR Study.
The structure of Ba3Nb2O8 has been investigated using high resolution neutron powder diffraction. Our results show that, while the structure has some features in common with the 9R perovskite and palmierite structures, it is a new and distinct structure. It is shown to follow a (chh)(hhc)(chh) sequence with BaO3-δ packing layers and is a cation- and anion-deficient 9H perovskite polytype. Nb atoms occupy octahedral sites with vacancies between hexagonal close-packed layers. Isolated, corner-sharing and face-sharing Nb-O octahedra all occur within the unit cell. The identification of purely octahedral Nb is supported by solid-state 93Nb wideline NMR measurements. A two-component line shape was detected: a narrow featureless resonance with an isotropic chemical shift of δiso -928 ± 5 ppm consistent with regular Nb octahedra, and a much broader featureless resonance with an approximate isotropic chemical shift in the range δiso ∼ -944 to -937 ± 10 ppm consistent with Nb octahedra influenced by O vacancies. These are both characteristic of 6-fold oxo-coordinated Nb environments. The highly distorted octahedral environments in Ba3Nb2O8 make it a potential candidate for dielectric and photocatalytic applications.


Steroid 21 hydroxylase deficiency congenital adrenal hyperplasia.
Steroid 21 hydroxylase deficiency is the most common form of congenital adrenal hyperplasia (CAH). The severity of this disorder depends on the extent of impaired enzymatic activity, which is caused by various mutations of the 21 hydroxylase gene. This article reviews adrenal steroidogenesis and the pathophysiology of 21 hydroxylase deficiency. The three forms of CAH are then discussed in terms of clinical presentation, diagnosis and treatment, and genetic basis. Prenatal diagnosis and treatment are also reviewed. The goal of therapy is to correct the deficiency in cortisol secretion and suppress androgen overproduction. Glucocorticoid replacement has been the mainstay of treatment for CAH, but new treatment strategies continue to be developed and studied.


Enhanced Recovery after Surgery for Knee Arthroplasty in the Era of COVID-19.
Enhanced recovery after surgery (ERAS) represents a paradigm shift in perioperative care, aimed at achieving early recovery for surgical patients, reducing length of hospital stay, and complications. The purpose of this study was to provide an insight of the impact of the COVID-19 on ERAS protocols for knee arthroplasty patients in a tertiary hospital and potential strategy changes for postpandemic practice. We retrospectively reviewed all cases that underwent surgery utilizing ERAS protocols in the quarter prior to the pandemic (fourth quarter of 2019) and during the first quarter of 2020 when the pandemic started. A review of the literature on ERAS protocols for knee arthroplasty during the COVID-19 pandemic was also performed and discussed. A total of 199 knee arthroplasties were performed in fourth quarter of 2019 as compared with 76 in the first quarter of 2020 during the COVID-19 outbreak. Patients who underwent surgery in the first quarter of 2020 had shorter inpatient stays (3.8 vs. 4.5 days), larger percentage of discharges by postoperative day 5 (86.8 vs. 74.9%), and a larger proportion of patients discharged to their own homes (68 vs. 54%). The overall complication rate (1.3 vs. 3%) and readmission within 30 days (2.6 vs. 2%) was similar between both groups. ERAS protocols appear to reduce hospital lengths of stay for patients undergoing knee arthroplasty without increasing the risk of short-term complications and readmissions. The beneficial effects of ERAS appear to be amplified by and are synchronous with the requirements of operating in the era of a pandemic.


Fanconi syndrome induced by adefovir dipivoxil: a case report and clinical review.
More than 150 cases of Fanconi syndrome (FS) or hypophosphatemia osteomalacia induced by low-dose adefovir dipivoxil (ADV) have been reported since 2002, when ADV was introduced for the long-term treatment of hepatitis B virus (HBV) infection. Because the life expectancy of HBV-infected individuals has increased, the adverse effects of long-term treatment with antiviral therapies are increasingly observed, and nephrotoxicity is one of the most severe adverse effects of ADV. Therefore, the number of cases may be far higher than reported. Moreover, ADV-induced FS is often misdiagnosed or diagnosed long after it first develops. ADV-induced FS may seriously decrease patient quality of life and lead to bone fractures and even disability. Although progress has been made in the identification of biomarkers and treatments, few systematic clinical guidelines or clinical reviews for FS induced by ADV have been reported. In this study, we highlighted the recent progress toward understanding of FS induced by ADV, described a clinical case, and summarized the primary characteristics and laboratory findings of this disease.


Attitudes and experiences of women admitted to hospital with abortion complications in Ghana.
Unsafe abortion is one of the major contributors to high levels of maternal mortality in Ghana, despite a relatively liberal legal environment. This paper presents findings from a semi-structured hospital-based survey of 131 Ghanaian women who had experienced unsafe abortion. The majority of respondents were young and single, with no children or just one child. Most had middle-school education or higher and were employed, as were their partners. While knowledge of family planning was high, knowledge of specific methods was barely moderate and only 17% respondents had ever used it - much lower than the national ever-use of 39%. There were widespread misunderstandings about who could use family planning and 41% said they were afraid of side-effects. Eleven percent said their pregnancy was planned and 31% that they wanted their pregnancy but were pressured by partners or families to abort. Overall, about one-third of respondents said they aborted because they were not married and two-thirds said they aborted because of socio-cultural pressures. This study highlights clear ongoing failings of the family planning programme which needs to be revamped, as well as an urgent need for improving public knowledge about access to safe, legal abortion services.


Predicting and mapping soil available water capacity in Korea.
The knowledge on the spatial distribution of soil available water capacity at a regional or national extent is essential, as soil water capacity is a component of the water and energy balances in the terrestrial ecosystem. It controls the evapotranspiration rate, and has a major impact on climate. This paper demonstrates a protocol for mapping soil available water capacity in South Korea at a fine scale using data available from surveys. The procedures combined digital soil mapping technology with the available soil map of 1:25,000. We used the modal profile data from the Taxonomical Classification of Korean Soils. The data consist of profile description along with physical and chemical analysis for the modal profiles of the 380 soil series. However not all soil samples have measured bulk density and water content at -10 and -1500 kPa. Thus they need to be predicted using pedotransfer functions. Furthermore, water content at -10 kPa was measured using ground samples. Thus a correction factor is derived to take into account the effect of bulk density. Results showed that Andisols has the highest mean water storage capacity, followed by Entisols and Inceptisols which have loamy texture. The lowest water retention is Entisols which are dominated by sandy materials. Profile available water capacity to a depth of 1 m was calculated and mapped for Korea. The western part of the country shows higher available water capacity than the eastern part which is mountainous and has shallower soils. The highest water storage capacity soils are the Ultisols and Alfisols (mean of 206 and 205 mm, respectively). Validation of the maps showed promising results. The map produced can be used as an indication of soil physical quality of Korean soils.


Immunocytochemical double labeling of glial fibrillary acidic protein and transferrin permits the identification of astrocytes and oligodendrocytes in the rat brain.
Sequential immunocytochemical double labeling of glial fibrillary acidic protein (GFAP) and transferrin (Tf) was used for the simultaneous identification of astrocytes and oligodendrocytes in paraffin-embedded sections of the rat brain. Paraformaldehyde or formalin-alcohol-acetic acid fixation followed by protease treatment of paraffin-embedded sections provided the most satisfactory double-labeling. The results demonstrated GFAP-positive astrocytes and Tf-positive oligodendrocytes as two subpopulations of glia with no overlap. Our results suggest that, with some exceptions, immunocytochemical double labeling of GFAP and Tf has a potential application for the simultaneous identification of astrocytes and oligodendrocytes in the rat brain.


Structures of two dideoxynucleosides: 2',3'-dideoxyadenosine and 2',3'-dideoxycytidine.
2',3'-Dideoxyadenosine, C10H13N5O2, Mr = 235.24, orthorhombic, P2(1)2(1)2(1), a = 7.7404(4), b = 9.9843(9), c = 14.0842(10) A, V = 1088.46 A3, Z = 4, Dx = 1.435 Mg m-3, lambda(CuK alpha) = 1.5418 A, mu = 0.8326 mm-1, F(000) = 496, T = 296 K, final R = 0.032 for 1088 observed reflections. 2',3'-Dideoxycytidine, C9H13N3O3, Mr = 211.21, tetragonal, P4(1)2(1)2, a = 8.6802(4), c = 26.1386(14) A, V = 1969.44 A3, Z = 8, Dx = 1.424 Mg m-3, lambda(CuKa) = 1.5418 A, mu = 0.8701 mm-1, F(000) = 896, T = 296 K, final R = 0.050 for 1116 observed reflections. In both compounds the sugar rings have conformations intermediate between envelope and half chair but somewhat different pseudorotations. The relative orientations of the sugar and base are different in the two molecules with dideoxyadenosine being at the boundary of syn and anti and deoxycytidine being anti.


[Genes and cardiovascular diseases].
In recent years there has been observed a relatively fast progress of explaining genetic mechanisms of development of many cardiovascular system diseases, mainly diseases conditioned by the mutation of single genes. The situation is different when analyzing the dependencies of complex cardiovascular system diseases whose development has many stages depending on exogenous or hereditary factors. The development of those diseases is due to interactions between particular environmental factors, individual differences in response to environmental factors and often complex genetic relations. The complexity of etiopathogenesis and clinical differentiation are the result of superposition of the effects of the action of single genes responsible for the development, predisposing and/or modulating the course. The analysis of genetic causes of cardiovascular system diseases is made on the basis of models and multigene polymorphisms.


Co-operative effect between gamma-aminobutyric acid A receptors and central-type benzodiazepine receptors on amylase release in rat parotid acinar cells.
We investigated the inhibitory role of gamma-aminobutyric acid A (GABA(A)) receptors on amylase release and the evidence for functional coupling with central-type benzodiazepine receptors in rat parotid acinar cells. Muscimol and GABA decreased isoprenaline-induced amylase release. This effect was blocked by bicuculline, a GABA(A)-receptor antagonist, and enhanced by clonazepam, a central-type benzodiazepine-receptor agonist, and diazepam, a central- and peripheral-type benzodiazepine-receptor agonist. Although bicuculline completely blocked the combination effect of GABA(A)-receptor agonist and clonazepam, it did not completely block the combination effect with diazepam. These results suggest that protein secretion is suppressively regulated by GABA(A) receptors coupled with central-type benzodiazepine receptors.


Pd(II)-Catalyzed Cross-Coupling of C(sp2 )-H Bonds and Alkyl-, Aryl- and Vinyl-Boron Reagents via Pd(II)/Pd(0) Catalysis.
Pd(II)-catalyzed cross-coupling of ortho-C-H bonds in benzoic acid and phenylacetic acid amides with alkyl-, aryl- and vinyl-boron reagents have been achieved via Pd(II)/Pd(0) catalysis, demonstrating the unprecedented versatility of C-H activation reactions.


Sensory and receptor responses to umami: an overview of pioneering work.
This article provides a selective overview of the early studies of umami taste and outlines significant questions for further research. Umami compounds such as the amino acid glutamate [often in the form of the sodium salt monosodium glutamate (MSG)] and the nucleotide monophosphates 5'-inosinate and 5'-guanylate occur naturally in, and provide flavor for, many foods and cuisines around the world. Early researchers in the United States found that the flavor of pure MSG was difficult to describe. But they all agreed that, although humans found umami compounds, when tasted alone, to be unpalatable, subjects reported that these compounds improved the taste of foods. This taste "dichotomy" may be partly unlearned because it is also observed in very young infants. The uniqueness of umami perception is based on several lines of evidence. First, numerous perceptual studies have shown that the sensation aroused by MSG is distinct from that of the other 4 taste qualities. Second, biochemical studies that show the synergy of the binding of MSG and 5'-guanylate to tongue taste tissue mirror this hallmark perceptual effect. Third, several specific receptors that may mediate umami taste have recently been identified. There remain, however, a number of puzzles surrounding the umami concept, including the molecular basis for an apparent tactile component to umami perception, the reason for the unpalatability of pure umami, and the functional significance for human health and nutrition of umami detection. Future work aimed at understanding these and other open issues will profitably engage scientists in umami research well into the next century.


Distribution and Properties of a Potassium-dependent Asparaginase Isolated from Developing Seeds of Pisum sativum and Other Plants.
Asparaginase (EC 220.127.116.11) was isolated from the developing seed of Pisum sativum. The enzyme is dependent upon the presence of K(+) for activity, although Na(+) and Rb(+) may substitute to a lesser extent. Maximum activity was obtained at K(+) concentrations above 20 millimolar. Potassium ions protected the enzyme against heat denaturation. The enzyme has a molecular weight of 68,300.Asparaginase activity developed initially in the testa, with maximum activity (3.6 micromoles per hour per seed) being present 13 days after flowering. Maximum activity (1.2 micromoles per hour per seed) did not develop in the cotyledon until 21 days after flowering. Glutamine synthetase and glutamate dehydrogenase were also present in the testae and cotyledons but maximum activity developed later than that of asparaginase.Potassium-dependent asparaginase activity was also detected in the developing seeds of Vicia faba, Phaseolus multiflorus, Zea mays, Hordeum vulgare, and two Lupinus varieties. No stimulation of activity was detected with the enzyme isolated from Lupinus polyphyllus, which has previously been shown to contain a K(+)-independent enzyme.


Quantitative assessment of WT1 expression by real time quantitative PCR may be a useful tool for monitoring minimal residual disease in acute leukemia patients.
In order to verify if quantitative assessment of the WT1 transcript amount by the real time quantitative PCR (RQ-PCR) can be used as a marker for minimal residual disease detection, the WT1 transcript amount was determined in BM and PB samples of patients with myeloid and lymphoid acute leukemia, in normal controls, in regenerating bone marrow samples and in purified CD34-positive cells from normal subjects. In 10 patients bearing a fusion gene transcript suitable for minimal residual disease quantitative assessment, we performed a simultaneous analysis of the WT1 and of the fusion-gene transcript at sequential time intervals during follow-up. Sequential WT1 analysis was also performed in five AML patients lacking additional molecular markers. The data obtained show that normal and regenerating BM samples and purified CD34-positive cells consistently express minimal amounts of WT1 transcript and that this is extremely low and frequently undetectable in normal PB. By contrast, high levels of WT1 expression are present in the BM and PB samples of all acute leukemia (AL) cases at diagnosis. The WT1 levels during follow-up were found to follow the pattern of the other molecular markers (fusion gene transcripts) used for MRD monitoring and increased WT1expression in the BM and/or PB during follow-up of AL patients was always found to be predictive of an impending hematological relapse.


The earliest Baltic amber in Western Europe.
The occurrence of Baltic amber through Europe has traditionally been associated to the spread of the Bell Beaker culture during the 3rd millennium BC. In Iberia, this phenomenon is particularly noticeable in the southern half. Here we present an amber bead recovered in a Late Neolithic funerary cave (3634-3363 cal BC) from northeastern Iberia where more than 12 individuals had been buried. Fourier transform infrared spectroscopy results of four samples revealed their complete resemblance with Baltic succinite reference spectra. Despite being a single bead, this finding provides the earliest evidence for the arrival of Baltic amber to the Mediterranean and Western Europe, before the Bell Beaker phenomenon and more than a millennium earlier than traditionally thought. This finding has implications for our understanding of early exchange networks of exotic materials, and their associated social structures.


Selective Photocatalytic Disinfection by Coupling StrepMiniSog to the Antibody Catalyzed Water Oxidation Pathway.
For several decades reactive oxygen species have been applied to water quality engineering and efficient disinfection strategies; however, these methods are limited by disinfection byproduct and catalyst-derived toxicity concerns which could be improved by selectively targeting contaminants of interest. Here we present a targeted photocatalytic system based on the fusion protein StrepMiniSOG that uses light within the visible spectrum to produce reactive oxygen species at a greater efficiency than current photosensitizers, allowing for shorter irradiation times from a fully biodegradable photocatalyst. The StrepMiniSOG photodisinfection system is unable to cross cell membranes and like other consumed proteins, can be degraded by endogenous digestive enzymes in the human gut, thereby reducing the consumption risks typically associated with other disinfection agents. We demonstrate specific, multi-log removal of Listeria monocytogenes from a mixed population of bacteria, establishing the StrepMiniSOG disinfection system as a valuable tool for targeted pathogen removal, while maintaining existing microbial biodiversity.


The effect of Pendelluft and dead space on nitrogen clearance: mathematical and experimental models and their application to the study of the distribution of ventilation.
Reinspired mixed dead space gas and Pendelluft may be considered to be part of a single process of interalveolar gas transfer. The effect of interalveolar gas transfer on nitrogen clearance from a two chamber lung model can be described by a single set of equations which hold for synchronous, and series ventilation. Interalveolar gas transfer may theoretically be either bidirectional or unidirectional. Bidirectional transfer results in an underestimation of the effective ventilation and volume of the well-ventilated compartment when nitrogen washout is analyzed by available methods. The volume of the poorly ventilated compartment is overestimated and its effective ventilation is usually overestimated but may be correctly or underestimated as distribution becomes more uneven. Unidirectional transfer has the same qualitative effect except that the ventilation of the poorly ventilated space is always overestimated. The distortions produced by both types of gas transfer become less marked as ventilation becomes more uneven.Nitrogen washout data from a model consisting of two rubber balloons connected with a Y tube agree well with the mathematical predictions. Application of the theory to data obtained from patients with advanced chronic obstructive lung disease suggests that estimates of the functional residual capacity and of the volume and ventilation of the poorly ventilated spaces are not greatly affected by interalveolar gas transfer when nitrogen washout is analyzed by usual methods.


Age-related changes in the Brazilian woman's smile.
The aim of this research was to evaluate age-related changes in the smile of Brazilian women. The sample consisted of 249 Brazilian women who had not undergone previous orthodontic treatment or facial surgery. They were divided into four groups, according to age: G1 (20-29), G2 (30-39), G3 (40-49) and G4 (50 or older). Standardized front view photographs were taken while smiling and at rest. Measurements were evaluated by ANOVA and post-hoc Tukey. The Chi-square test was applied for qualitative variables. Upper lip thickness at rest and exposure of upper incisors on smiling decreased with age. Most individuals (60.9%) exhibited a medium smile. High smiles were more often seen in G1 (45%) and less frequently in G4 (18.8%), whereas the opposite occurred with the low smile, i.e., G4 (21.9%) and G1 (6.7%). Variations among the groups were observed in the transverse exposure of the teeth on smiling. In G1 and G3, there was a balance between tooth exposures, so that the teeth were exposed as far as the premolars and/or molars. Most of the women (56.3%) in G2 exposed their teeth as far as the first molars on smiling, whereas most of those (40.6%) in G4 exposed their teeth only as far as the first premolars on smiling. As age increased, there was decreased exposure of the upper incisors, decreased upper lip thickness and lower exposure of teeth vertically and transversely.


Effect of occluding one umbilical artery on placental oxygen transport.
Placental O2 transport was studied in seven fetal lambs before and after occluding one of the two umbilical arteries. Ethanol was used to measure uterine and umbilical blood flows using the steady-state transplacental diffusion method. Blood samples were drawn from umbilical artery, umbilical vein, both uterine veins, and maternal artery and analyzed for blood flow indicator, O2 content, PO2, PCO2, and pH. Occlusion reduced the placental mass and the uterine blood flow, which was available for transplacental exchange, to 49.5 and 46.5% of control, respectively. After occlusion, fetal blood pressure increased 38%, total umbilical blood flow decreased 25%, total fetal O2 uptake decreased 26%, fetal blood flow to the unoccluded placenta increased 52%, and the O2 flux from unoccluded placenta to fetus increased 49%. This increased flux was accompanied by a decrease in the PO2 of maternal venous blood from the unoccluded placenta and an enlargement of the transplacental PO2 gradient, resulting in a marked drop in umbilical venous PO2 (28.3 to 17.7 Torr). This evidence supports the hypothesis that placental O2 diffusing capacity is a limiting factor in placental O2 transport and agrees with other studies indicating the absence of homeostatic mechanisms for preventing acute changes of PO2 in the placental circulation.


Decoupling the function of Hox and Shh in developing limb reveals multiple inputs of Hox genes on limb growth.
Limb development relies on an exquisite coordination between growth and patterning, but the underlying mechanisms remain elusive. Anterior-posterior and proximal-distal specification initiates in early limb bud concomitantly with the proliferative expansion of limb cells. Previous studies have shown that limb bud growth initially relies on fibroblast growth factors (FGFs) produced in the apical ectodermal ridge (AER-FGFs), the maintenance of which relies on a positive-feedback loop involving sonic hedgehog (Shh) and the BMP antagonist gremlin 1 (Grem1). The positive cross-regulation between Shh and the HoxA and HoxD clustered genes identified an indirect effect of Hox genes on the maintenance of AER-FGFs but the respective function of Shh and Hox genes in this process remains unknown. Here, by uncoupling Hox and Shh function, we show that HoxA and HoxD genes are required for proper AER-FGFs expression, independently of their function in controlling Shh expression. In addition, we provide evidence that the Hox-dependent control of AER-FGF expression is achieved through the regulation of key mesenchymal signals, namely Grem1 and Fgf10, ensuring proper epithelial-mesenchymal interactions. Notably, HoxA and HoxD genes contribute to both the initial activation of Grem1 and the subsequent anterior expansion of its expression domain. We propose that the intricate interactions between Hox genes and the FGF and Shh signaling pathways act as a molecular network that ensures proper limb bud growth and patterning, probably contributing to the coordination of these two processes.


A macro-scale perspective on within-farm management: how climate and topography alter the effect of farming practices.
Organic farming has the potential to reverse biodiversity loss in farmland and benefit agriculture by enhancing ecosystem services. Although the mixed success of organic farming in enhancing biodiversity has been attributed to differences in taxa and landscape context, no studies have focused on the effect of macro-scale factors such as climate and topography. This study provides the first assessment of the impact of macro-scale factors on the effectiveness of within-farm management on biodiversity, using spiders in Japan as an example. A multilevel modelling approach revealed that reducing pesticide applications increases spider abundance, particularly in areas with high precipitation, which were also associated with high potential spider abundance. Using the model we identified areas throughout Japan that can potentially benefit from organic farming. The alteration of local habitat-abundance relations by macro-scale factors could explain the reported low spatial generality in the effects of organic farming and patterns of habitat association.


Contribution of recurrent venous thrombosis and inherited thrombophilia to the pathogenesis of postthrombotic syndrome.
Postthrombotic syndrome (PTS) is a common complication of deep vein thrombosis. This study aims to assess the role of recurrent venous thrombosis and inherited thrombophilia in the pathogenesis of PTS. A series of 206 patients diagnosed with lower extremity venous thrombosis were retrospectively reviewed. The PTS was observed in 30.58% of the patients. Recurrent venous thrombosis was identified in 3.4% of the patients without PTS and in 33.3% of patients with PTS (P < .001). Inherited thrombophilia alone or in association with recurrent venous thrombosis was more commonly detected when PTS was moderate to severe (P = .04 and <.001) or severe (P < .001). Recurrent venous thrombosis increases the incidence of PTS significantly. The severity of PTS raises when an underlying thrombophilia is present either alone or in association with recurrent venous thrombosis.


Efficacy and safety assessment of severe COVID-19 patients with Chinese medicine: A retrospective case series study at early stage of the COVID-19 epidemic in Wuhan, China.
The coronavirus disease 2019 (COVID-19) has formed a global pandemic since late 2019. Benefitting from the application experience of Chinese Medicine (CM) for influenza and SARS, CM has been used to save patients at the early stage of COVID-19 outbreak in China. In order to evaluate the efficacy and safety of CM, and compare with Western Medicine (WM) for COVID-19, we conducted a retrospective case series study based on the patients in Wuhan Jinyintan Hospital, Wuhan, China. The inclusion and exclusion criteria of data extraction were set for this retrospective study. All patients who were admitted by the Wuhan Jinyintan Hospital between January 17th and February 25th 2020 were considered. In addition, patients enrolled met the severe defined by the guidelines released by the National Health Commission of the People's Republic of China. In these cases included in the study, CM or WM treatment was selected according to the wishes of the patients at the beginning of hospitalization. The patients in CM group were treated with Huashi Baidu granule (137 g po, bid) combined with the injections of Xiyanping (100 mg iv, bid), Xuebijing (100 ml iv, bid) and Shenmai (60 ml iv, qd) according to the syndrome of epidemic toxin blocking the lung in the theory of Traditional Chinese Medicine. The WM group received antiviral therapy (including abidor capsule 0.2 g po, tid; Lopinavir-Ritonavir tablets, 500 mg po, bid), antibiotics (such as cefoperazone 2 g iv, bid; moxifloxacin hydrochloride tablets, 0.4 g po, qd) or corticosteroid therapy (such as methylprednisolone succinate sodium 40 mg iv, qd; prednisone, 30 mg po, qd). In addition, patients in both groups received routine supportive treatment, including oxygen inhalation, symptomatic therapy, and/or human intravenous immunoglobulin, and/or serum albumin, and treatment for underlying diseases. The clinical outcomes were evaluated based on changes related with clinical manifestations, computer tomography (CT) scan images, and laboratory examinations before and after the treatment. 55 severe COVID-19 patients, with 23 in CM group and 32 in WM group, were included for analyzed. There was no case of death, being transferred to ICU, or receiving invasive mechanical ventilation in two groups during hospitalization. The median time of SARS-CoV-2 RNA clearance in CM and WM group were 12 days and 15.5 days respectively, the ratio of nucleic acid negative conversion of CM group at different follow-up time points was significantly higher than that of WM group (HR: 2.281, P = 0.018). Further, the chest CT imaging showed more widely lung lesion opacity absorbed in the CM group. The high sensitivity C-reactive protein and serum ferritin decreased significantly in the CM group (P<0.05). There was no significant difference in adverse events in terms of liver function and renal function between the two groups. Based on this retrospective analysis from Wuhan Jinyintan Hospital, CM has better effects in SARS-CoV-2 RNA clearance, promoting lung lesion opacity absorbed and reducing inflammation in severe COVID-19 patients, which is effective and safe therapy for treating severe COVID-19 and reducing mortality.


Pivotal antitumor role of the immune checkpoint molecule B7-H1 in pancreatic cancer.
Immune checkpoint molecule B7-H1 plays a decisive immune regulatory role in different pathologies including cancer, and manipulation of B7-H1 expression became an attractive approach in cancer immunotherapy. Pancreatic cancer (PDAC) is characterized by pronounced immunosuppressive environment and B7-H1 expression correlates with PDAC prognosis. However, the first attempts to diminish B7-H1 expression in patients were not so successful. This points the complicity of PDAC immunosuppressive network and requires further examinations. We investigated the effect of B7-H1 deficiency in PDAC. Our results clearly show that partial or complete B7-H1 inhibition in vivo let to reduced tumor volume and improved survival of PDAC-bearing mice. This oncological benefit is due to the abrogation of immunosuppression provided by MDSC, macrophages, DC and Treg, which resulted in simultaneous restoration of anti-tumor immune response, namely improved accumulation and functionality of effector-memory CD4 and CD8 T cells. Our results underline the potential of B7-H1 molecule to control immunosuppressive network in PDAC and provide new issues for further clinical investigations.


In vivo and in vitro analysis of Bordetella pertussis catalase and Fe-superoxide dismutase mutants.
Bordetella pertussis produces a catalase and a Fe-superoxide dismutase. The importance of these enzymes in virulence was investigated, in vitro as well as in vivo, by using mutants deficient in their production. The catalase-deficient mutant survived within polymorphonuclear leukocytes, killed J774A.1 macrophages through apoptosis, and behaved as the parental strain in a murine respiratory infection model. These results suggest no direct role for catalase in B. pertussis virulence. The absence of expression of Fe-superoxide dismutase had profound effects on the bacterium including a reduced ability to express adenylate cyclase-hemolysin and pertactin, two factors important for B. pertussis pathogenesis. The Fe-superoxide dismutase-deficient mutant also had decreased abilities to colonize and persist in the murine respiratory infection model.


[Methylation of Runx3 promoter in different breast lesions].
To investigate the methylation status of Runx3 promoter and Runx3 expression in breast lesion tissues. One hundred and fourteen breast lesions, including 35 cases of fibroadenoma, 39 cases of intraductal carcinoma, 40 cases of invasive ductal carcinoma, and 33 cases of normal breast tissue from Fabruary 2010 to August 2012 were included in this study. Runx3 protein expression was assessed by immunohistochemical SP method; whereas methylation of Runx3 promoter was assessed by high resolution melting (HRM) analysis. Runx3 protein was mainly expressed in the cytoplasm of ductal epithelial cells. The expression rates of Runx3 in normal breast tissue, fibroadenoma, ductal carcinoma in situ, invasive ductal carcinoma were 87.9% (29/33), 85.7% (30/35), 53.8% (21/39), and 40.0% (16/40) respectively. The methylation rates of Runx3 promoter were 12.1% (4/33), 20.0% (7/35), 46.2% (18/39), and 57.5% (23/40), respectively. Correlation analysis between promoter methylation and protein expression of Runx3 in different breast tissue showed the r value in normal breast tissue, fibroadenoma, ductal carcinoma in situ and invasive ductal carcinoma was -0.431 (P = 0.012), -0.408 (P = 0.015), -0.589 (P = 0.000) and -0.743 (P = 0.000) respectively. Runx3 protein expression shows a downward trend in ductal carcinoma in situ and invasive ductal carcinoma, meanwhile its promoter methylation increases significantly. The methylation of Runx3 promoter may be one of the important factors in the occurrence and development of breast cancer.


Primary pulmonary leiomyosarcoma with coexistent pulmonary aspergillosis: a case report.
Coexisting primary pulmonary leiomyosarcoma (PPL) with pulmonary Aspergillosis in immunocompetent patients is a rare occurrence. Here, we presented a 54-year-old woman presented with a dry cough for two months. Bronchoscopy revealed pulmonary aspergillosis. The patient was treated with antifungal therapy for one month without improvement. To evaluate further, a chest computed tomography (CT) scan showed a large heterogeneous enhancing mass in the lower lobe of the left lung with left atrium thrombosis. Computed tomography-guided biopsy was performed, and histopathology demonstrated the diagnosis of PPL. The metastasis workup staging showed multiple metastases in vertebrae, scapula, rib, and liver. The patient was treated with chemotherapy followed by tumor bed radiotherapy. Unfortunately, her general condition worsened, and she passed away with overall survival of fourteen months. In conclusion, clinicians should be alert to underlying malignant disease if airway Aspergillus infection is suspicious in patients without strong risk factors for invasive fungal infection.


Conversion to below-elbow cast after 3 weeks is safe for diaphyseal both-bone forearm fractures in children.
It is unclear whether it is safe to convert above-elbow cast (AEC) to below-elbow cast (BEC) in a child who has sustained a displaced diaphyseal both-bone forearm fracture that is stable after reduction. In this multicenter study, we wanted to answer the question: does early conversion to BEC cause similar forearm rotation to that after treatment with AEC alone? Children were randomly allocated to 6 weeks of AEC, or 3 weeks of AEC followed by 3 weeks of BEC. The primary outcome was limitation of pronation/supination after 6 months. The secondary outcomes were re-displacement of the fracture, limitation of flexion/extension of the wrist and elbow, complication rate, cast comfort, complaints in daily life, and cosmetics of the fractured arm. 62 children were treated with 6 weeks of AEC, and 65 children were treated with 3 weeks of AEC plus 3 weeks of BEC. The follow-up rate was 60/62 and 64/65, respectively with a mean time of 6.9 (4.7-13) months. The limitation of pronation/supination was similar in both groups (18 degrees for the AEC group and 11 degrees for the AEC/BEC group). The secondary outcomes were similar in both groups, with the exception of cast comfort, which was in favor of the AEC/BEC group. Early conversion to BEC cast is safe and results in greater cast comfort.


Diet quality indices and their associations with health-related outcomes in children and adolescents: an updated systematic review.
To describe a-priori diet quality indices used in children and adolescents, appraise the validity and reliability of these indices, and synthesise evidence on the relationship between diet quality and physical and mental health, and growth-related outcomes. Five electronic databases were searched until January 2019. An a-priori diet quality index was included if it applied a scoring structure to rate child or adolescent (aged 0-18-years) dietary intakes relative to dietary or nutrient guidelines. Diagnostic accuracy studies and prospective cohort studies reporting health outcomes were appraised using the Academy of Nutrition and Dietetics Quality Criteria Checklist. From 15,577 records screened, 128 unique paediatric diet quality indices were identified from 33 countries. Half of the indices' scores rated both food and nutrient intakes (n = 65 indices). Some indices were age specific: infant (< 24-months; n = 8 indices), child (2-12-years; n = 16), adolescent (13-18 years; n = 8), and child/adolescent (n = 14). Thirty-seven indices evaluated for validity and/or reliability. Eleven of the 15 indices which investigated associations with prospective health outcomes reported significant results, such as improved IQ, quality of life, blood pressure, body composition, and prevalence of metabolic syndrome. Research utilising diet quality indices in paediatric populations is rapidly expanding internationally. However, few indices have been evaluated for validity, reliability, or association with health outcomes. Further research is needed to determine the validity, reliability, and association with health of frequently utilised diet quality indices to ensure data generated by an index is useful, applicable, and relevant. PROSPERO number: CRD42018107630 .


Uric acid as a predictor of endothelial dysfunction in patients with metabolic syndrome.
We conducted a study to examine the association of endothelial dysfunction and oxidative stress with uric acid levels in patients of metabolic syndrome. One hundred and two patients of Metabolic Syndrome (International Diabetes Federation definition) were included in the study. Anthropometric measurements, serum uric acid levels, fasting blood sugar levels and lipid levels, as well as malondialdehyde and reactive nitrogen intermediates were measured after an 8-hour fasting period. Flow mediated vasodilation (FMD) of the brachial artery was measured and endothelial dysfunction was defined as an increase in diameter < 10% post compression. A total of 102 patients were included in the study. Mean uric acid level was 5.49 ± 1.61 mg%. A total of 59 patients in the study had endothelial dysfunction, defined by an abnormal FMD. Patients with an abnormal FMD had higher levels of serum uric acid which was statistically significant (p value = 0.010). Serum RNI and MDA levels were negatively correlated with uric acid, but did not reach statistical significance. Patients with an abnormal FMD had a lower RNI level, but this did not reach statistical significance. Serum MDA levels were significantly higher in patients with an abnormal FMD (p value = 0.038). Uric acid was significantly associated with endothelial dysfunction in patients with metabolic syndrome in our study. It was inversely correlated with serum RNI and MDA levels, but this did not reach statistical significance.


Hemifacial spasm as a manifestation of pilocytic astrocytoma in a pediatric patient.
Hemifacial spasm is a disorder of the seventh cranial nerve, which is characterized by irregular, involuntary and recurrent tonic and clonic contractions of the ipsilateral facial expression muscles. This disorder affects mainly adults, and there are few cases reported in childhood. The main etiologies are vascular problems, although tumors are an important cause of hemifacial spasm via a direct or an indirect mass effect. We report a 6-year-old girl who presented with right hemifacial spasm. Magnetic resonance imaging showed a lesion in the cerebellopontine angle, extending from the midbrain to the pons with a slight mass effect on the fourth ventricle. The histological examination revealed a pilocytic astrocytoma.


Identifying structural and energetic trends in isovalent core-shell nanoalloys as a function of composition and size mismatch.
We locate the putative global minimum structures of Na(x)Cs(55-x) and Li(x)Cs(55-x) nanoalloys through combined empirical potential and density functional theory calculations, and compare them to the structures of 55-atom Li-Na and Na-K nanoalloys obtained in a recent paper [A. Aguado and J. M. López, J. Chem. Phys. 133, 094302 (2010)]. Alkali nanoalloys are representative of isovalent metallic mixtures with a strong tendency towards core-shell segregation, and span a wide range of size mismatches. By comparing the four systems, we analyse how the size mismatch and composition affect the structures and relative stabilities of these mixtures, and identify useful generic trends. The Na-K system is found to possess a nearly optimal size mismatch for the formation of poly-icosahedral (pIh) structures with little strain. In systems with a larger size mismatch (Na-Cs and Li-Cs), frustration of the pIh packing induces for some compositions a reconstruction of the core, which adopts instead a decahedral packing. When the size mismatch is smaller than optimal (Li-Na), frustration leads to a partial amorphization of the structures. The excess energies are negative for all systems except for a few compositions, demonstrating that the four mixtures are reactive. Moreover, we find that Li-Cs and Li-Na mixtures are more reactive (i.e., they have more negative excess energies) than Na-K and Na-Cs mixtures, so the stability trends when comparing the different materials are exactly opposite to the trends observed in the bulk limit: the strongly non-reactive Li-alkali bulk mixtures become the most reactive ones at the nanoscale. For each material, we identify the magic composition x(m) which minimizes the excess energy. x(m) is found to increase with the size mismatch due to steric crowding effects, and for Li(x)Cs(55-x) the most stable cluster has almost equiatomic composition. We advance a simple geometric packing rule that suffices to systematize all the observed trends in systems with large size mismatch (Na-K, Na-Cs, and Li-Cs). As the size mismatch is reduced, however, electron shell effects become more and more important and contribute significantly to the stability of the Li-Na system.


Prebirth Household Challenges To Predict Adverse Childhood Experiences Score by Age 3.
With this study, we seek to understand the relationship between prebirth household challenges and the child's adverse childhood experiences (ACEs) score by age 3 in a statewide-representative birth cohort to inform primary prevention strategies. We used a longitudinally linked data set from the Alaska 2009-2011 Pregnancy Risk Assessment Monitoring System, its 3-year follow-up survey, and multiple administrative data sources. Using this linked data set, we predicted an expanded ACEs score by age 3 using maternal reported prebirth household challenges. The number of household challenges reported during the 12 months before or during pregnancy predicted ACEs score in a graded, dose-response manner. On average, reporting 4+ prebirth household challenges was associated with an ACEs score 4.1 times that of those reporting 0 challenges. Homelessness was associated with the greatest increase in ACEs score (relative rate ratio = 3.0). Prebirth household challenges that were independently associated with an elevated ACEs score in our final model included problems paying bills, someone close to the mother having a drinking and/or drug problem, homelessness, mother or husband or partner being in jail, husband or partner losing job, separation or divorce, and being checked or treated for anxiety or depression. The accumulation and certain prebirth household challenges are strongly associated with the accumulation of childhood ACEs. Addressing and reducing household challenges during the prebirth period may serve as a primary point of ACEs prevention. Many evidence-based, multidisciplinary intervention strategies can and should be implemented in the prebirth period to strengthen the household unit before the introduction of a new child.


Therapeutic Effects in a Transient Middle Cerebral Artery Occlusion Rat Model by Nose-To-Brain Delivery of Anti-TNF-Alpha siRNA with Cell-Penetrating Peptide-Modified Polymer Micelles.
We previously reported that siRNA delivery to the brain is improved by the nose-to-brain delivery route and by conjugation with polyethylene glycol-polycaprolactone (PEG-PCL) polymer micelles and the cell-penetrating peptide, Tat (PEG-PCL-Tat). In this study, we evaluated the nose-to-brain delivery of siRNA targeting TNF-α (siTNF-α) conjugated with PEG-PCL-Tat to investigate its therapeutic effects on a transient middle cerebral artery occlusion (t-MCAO) rat model of cerebral ischemia-reperfusion injury. Intranasal treatment was provided 30 min after infarction induced via suturing. Two hours after infarction induction, the suture was removed, and blood flow was released. At 22 h post-reperfusion, we assessed the infarcted area, TNF-α production, and neurological score to determine the therapeutic effects. The infarcted area was observed over a wide range in the untreated group, whereas shrinkage of the infarcted area was observed in rats subjected to intranasal administration of siTNF-α with PEG-PCL-Tat micelles. Moreover, TNF-α production and neurological score in rats treated by intranasal administration of siTNF-α with PEG-PCL-Tat micelles were significantly lower than those in untreated and naked siTNF-α-treated rats. These results indicate that nose-to-brain delivery of siTNF-α conjugated with PEG-PCL-Tat micelles alleviated the symptoms of cerebral ischemia-reperfusion injury.


Vectors control importance on leishmaniasis transmission.
We reviewed the control of transmission of leishmaniasis regarding chemotherapy, reservoirs elimination, vaccination and insect control through the use of chemical insecticides. We also discussed complementary measures like monitoring traps, impregnated bednets and curtains, repelents, pheromones, biological control, etc. A cost comparison of insecticide interventions through the use of products belonging to the four main chemical groups was also done, comparing together conventional formulations versus a slow-release insecticide developed by the Núcleo de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro. We finally did recommendations on the situation that would justify an insecticide intervention to control sandflies.


Recent Advances in the Production of Genome-Edited Rats.
The rat is an important animal model for understanding gene function and developing human disease models. Knocking out a gene function in rats was difficult until recently, when a series of genome editing (GE) technologies, including zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the type II bacterial clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated Cas9 (CRISPR/Cas9) systems were successfully applied for gene modification (as exemplified by gene-specific knockout and knock-in) in the endogenous target genes of various organisms including rats. Owing to its simple application for gene modification and its ease of use, the CRISPR/Cas9 system is now commonly used worldwide. The most important aspect of this process is the selection of the method used to deliver GE components to rat embryos. In earlier stages, the microinjection (MI) of GE components into the cytoplasm and/or nuclei of a zygote was frequently employed. However, this method is associated with the use of an expensive manipulator system, the skills required to operate it, and the egg transfer (ET) of MI-treated embryos to recipient females for further development. In vitro electroporation (EP) of zygotes is next recognized as a simple and rapid method to introduce GE components to produce GE animals. Furthermore, in vitro transduction of rat embryos with adeno-associated viruses is potentially effective for obtaining GE rats. However, these two approaches also require ET. The use of gene-engineered embryonic stem cells or spermatogonial stem cells appears to be of interest to obtain GE rats; however, the procedure itself is difficult and laborious. Genome-editing via oviductal nucleic acids delivery (GONAD) (or improved GONAD (i-GONAD)) is a novel method allowing for the in situ production of GE zygotes existing within the oviductal lumen. This can be performed by the simple intraoviductal injection of GE components and subsequent in vivo EP toward the injected oviducts and does not require ET. In this review, we describe the development of various approaches for producing GE rats together with an assessment of their technical advantages and limitations, and present new GE-related technologies and current achievements using those rats in relation to human diseases.


Simplified analysis of 11-hydroxy-delta-9-tetrahydrocannabinol and 11-carboxy-delta-9-tetrahydrocannabinol in human meconium: method development and validation.
We describe the development of a sensitive analytical method for the analysis of 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-THC) and 11-carboxy-delta-9-tetrahydrocannabinol (THCC) in meconium using a gas chromatography-mass spectrometry (GC/MS) platform. The method was validated according to protocols, which included assessment of accuracy, precision, robustness, stability in meconium and in-process stability, interference and sensitivity and specificity. The method consists of a solid phase extraction with alkaline hydrolysis and derivatization of the analytes with N, O-Bis(trimethylsilyl)trifluoroacteamide, followed by GC/MS analysis using selected ion monitoring. The method uses deuterated internal standards for both analytes. Calibration curves had r(2) values >0.998, and extraction efficiency was determined to be 84.7% for THCC and 78.6% for 11-OH-THC. The detection limit for both analytes was 5 ng/g. This confirmatory method was successfully applied to 183 meconium samples that had screened positive by enzyme-linked immunosorbent assay, and 67.2% were confirmed for THCC, and 2.2% were confirmed positive for 11-OH-THC. The mean (SD) and median (range) THCC (n = 123) concentrations detected were 55.0 ng/g (±59.0) and 33.75 ng/g (5-265 ng/g), while the mean and median (range) for 11-OH-THC (n = 4) concentrations were 8.25 ng/g (±4.71) and 6.5 ng/g (5-15 ng/g).


An affordable multideterminant plasma-derived hepatitis B virus vaccine.
A new vaccine is reported which contains hepatitis B virus (HBV) e antigen (HBeAg) and pre-S determinants, in addition to highly purified HBV surface antigen (HBsAg). The rationale for this approach depends on the following data indicating that anti-HBe and antibody to the core antigen (anti-HBc), and antibody to pre-S determinants may play an active role in preventing HBV infection: (1) active immunization of chimpanzees with HBeAg(s) devoid of detectable HBsAg protected against subsequent challenge with HBV; (2) passive immunization of chimpanzees with an anti-HBe/anti-HBc intravenous immunoglobulin devoid of anti-HBs significantly delayed and appeared to attenuate HBV infection following subsequent challenge with HBV; (3) antibody to pre-S determinants appears to be able to neutralize infective HBV. The purification procedure used for the production of the New York Blood Center vaccine was designed to accomplish a high degree of purification with minimal use of complex equipment. This may facilitate eventual utilization of the vaccine on a mass scale for prevention of the HBV carrier state in high-prevalence regions of the world. The procedure uses polyethylene glycol (PEG) precipitations and hydroxylapatite adsorption steps, followed by only a single isopycnic separation in a zonal rotor, to achieve a vaccine which is substantially free of serum proteins and detectable HBV DNA yet contains HBsAg, HBeAg and pre-S determinants. The original vaccine was inactivated by Tween 80 and formalin. Four lots passed chimpanzee safety tests; two of these have been tested in clinical trials. Recently an improved vaccine has been developed in which two heat inactivation steps are used instead of formalin inactivation. This has resulted in further improvement in yields of antigenicity and immunogenicity, and provides an additional margin of safety.


Mössbauer study of temperature-dependent cycloidal ordering in BiFeO3 nanoparticles.
To study the effects of different temperatures and particle sizes on the anharmonic cycloidal spin structure in BiFeO3 nanoparticles, Mössbauer spectroscopy was applied to three sets of particles with different mean diameters in the range of 54 nm to 1.6 μm at temperatures between 4.2 and 800 K. The paramagnetic transition showed a distinct broadening upon decreasing particle size with Néel temperatures decreasing from 652 to 631 K. The anharmonicity of the long-range cycloidal structure, calculated from experimental Mössbauer spectra, is revealed to decrease upon rising temperature, starting at 150-200 K and reaching the harmonic state at about 400 K.


Chromatographic isolation and identification of methylated derivatives obtained from modified fibrinogen.
Polymerization was accomplished in the fibrinogen system by methylation with diazomethane, thionyl chloride and dimethyl sulphate. The duration and extent of polymerization were dependent on the modifying agent which was applied to the fibrinogen system. When fibrinogen was methylated with a very narrow range group-specific methylating agent, like dimethyl sulphate, the polymerization process was accelerated and proceeded with a reduction in the extent of modification of that obtained with the other methylating reagents utilized in these experiments. Chromatographic analysis revealed that diazomethane and thionyl chloride induced both O-methylation and N-methylation, as well as esterification of the carboxylate groups of aspartic and glutamic acid in fibrinogen. However, dimethyl sulphate resulted primarily in esterification accompanied by a small amount of histidine methylation. The proposed mechanism for the polymerization is through the esterification of the aspartic and glutamic acid residues which produces an increased protein-protein interaction resulting in polymer formation.


Utilization review, DRGs, and physician autonomy.
Utilization review and the current Medicare prospective payment system are part of a continuum of Federal legislation aimed at controlling scarce health care resources. Physicians have met these attempts to establish standards of utilization and fiscal control with varying levels of cooperation and resistance. This paper examines the physician's perceived threat to professional practice that these allocation strategies represent. The paper addresses four major areas of concern: bureaucratic tensions; income; clinical decision-making; and self-regulation. The paper ends by discussing the benefits for physicians in taking a proactive stance toward these measures.


Regression of chronic L -NAME-treatment-induced left ventricular hypertrophy: effect of captopril.
Long-term administration of N(G)-nitro- L -arginine methyl ester (L -NAME) induces development of NO-deficient hypertension and left ventricular (LV) hypertrophy. In this work, we examined the effect of spontaneous and captopril-induced recovery on LV hypertrophy and protein composition in rats with developed L -NAME-induced hypertension. Four groups of rats were investigated: control L -NAME 40 mg/kg/day for 4 weeks (L -NAME) L -NAME 40 mg/kg/day for 4 weeks followed by 3-week spontaneous recovery (L -NAME+R) L -NAME 40 mg/kg/day for 4 weeks followed by 3 weeks of captopril treatment at a dose of 100 mg/kg/day (L -NAME+C). LV hypertrophy in the L -NAME group was associated with an increase in content and concentration of left ventricular DNA and RNA, concentration of metabolic proteins (MP) and soluble collagenous proteins (SCP). Spontaneous recovery period reduced the hypertension, without regression of LV hypertrophy. Left ventricular DNA and RNA content were increased in the L -NAME+R group. In this group, concentrations of MP, contractile proteins (CP), and collagenous proteins did not differ from those in the L -NAME group. Captopril treatment caused total regression of hypertension and LV hypertrophy and decreased both content and concentration of DNA and RNA, as well as the contents of MP, CP and SCP v the L -NAME group. However, after captopril treatment, concentration of collagenous and non-collagenous protein fractions remained increased v control. We conclude that spontaneous regression of L -NAME-induced hypertension is not associated with regression of LV hypertrophy. LV hypertrophy was regressed only in captopril-treated animals.


Proximity Effects in Bilayer Graphene on Monolayer WSe_{2}: Field-Effect Spin Valley Locking, Spin-Orbit Valve, and Spin Transistor.
Proximity orbital and spin-orbit effects of bilayer graphene on monolayer WSe_{2} are investigated from first principles. We find that the built-in electric field induces an orbital band gap of about 10 meV in bilayer graphene. Remarkably, the proximity spin-orbit splitting for holes is 2 orders of magnitude-the spin-orbit splitting of the valence band at K is about 2 meV-more than for electrons. Effectively, holes experience spin valley locking due to the strong proximity of the lower graphene layer to WSe_{2}. However, applying an external transverse electric field of some 1 V/nm, countering the built-in field of the heterostructure, completely reverses this effect and allows, instead of holes, electrons to be spin valley locked with 2 meV spin-orbit splitting. Such a behavior constitutes a highly efficient field-effect spin-orbit valve, making bilayer graphene on WSe_{2} a potential platform for a field-effect spin transistor.


Magnetic and Mössbauer Studies of Magnetite-Loaded Polyvinyl Alcohol Hydrogels.
Materials producing strain in a magnetic field are known as magnetoelastic or magnetostrictive materials. A new type of material that is able to produce giant strain in a nonhomogeneous magnetic field has been developed. In these magnetic-field-sensitive gels (ferrogels) fine colloidal particles having superparamagnetic behavior are incorporated into a highly swollen elastic polymer network. Magnetic properties of ferrogels have been investigated using electron microscopy, static magnetization measurements, and Mössbauer spectroscopy. Analysis of the data yielded information on the superparamagnetic behavior of ferrogels and made it possible to estimate the size distribution of the magnetic cores of magnetite particles made by chemical precipitation and built into a chemically cross-linked polyvinyl alcohol matrix. The results are interpreted on the basis of a core-shell model. Copyright 2000 Academic Press.


Impact of ligands on CO(2) adsorption in metal-organic frameworks: First principles study of the interaction of CO(2) with functionalized benzenes. II. Effect of polar and acidic substituents.
Intermolecular interactions between the CO(2) molecule and a range of functionalized aromatic molecules have been investigated using density functional theory. The work is directed toward the design of linker molecules which could form part of new metal-organic framework materials with enhanced affinity for CO(2) adsorption at low pressure. Here, the focus was on the effect of introducing polar side groups, and therefore functionalized benzenes containing -NO(2), -NH(2), -OH, -SO(3)H, and -COOH substituents were considered. The strongest types of intermolecular interactions were found to be: (i) between lone pair donating atoms (N,O) of the side groups and the C of CO(2) (enhancement in binding energy of up to 8 kJ mol(-1) compared to benzene); and (ii) hydrogen bond interactions between acidic protons (of COOH and SO(3)H groups) and CO(2) oxygen (enhancement of 3-4 kJ mol(-1)). Both of these types of interaction have the effect of polarizing the CO(2) molecule. Weaker types of binding include hydrogen-bond-like interactions with aromatic H and pi-quadrupole interactions. The strongest binding is found when more than one interaction occurs simultaneously, as in C(6)H(5)SO(3)H and C(6)H(5)COOH, where simultaneous lone pair donation and H-bonding result in binding energy enhancements of 10 and 11 kJ mol(-1), respectively.


Real-world treatment patterns and outcomes in small-cell lung cancer: a systematic literature review.
Small-cell lung cancer (SCLC) accounts for 12-15% of lung cancers and is associated with poor survival outcomes and high symptom burden. This study employed a broad, systematic search strategy and timeframe to identify evidence on real-world treatment patterns and outcomes for SCLC outside the USA, including understanding sub-populations such as extensive-stage (ES) or limited-stage (LS) disease. Databases (MEDLINE, Embase, and EBM reviews) were searched for journal articles published in the English language between 1 January 2000-1 March 2020 and supplemented by hand searching of conference abstracts and posters presented at conferences between 1 January 2016-1 March 2020 reporting real-world treatment outcomes in patients with SCLC. A targeted clinical guideline review was also completed. One-hundred studies provided quantitative data; 57 were available as full-text articles, whilst the remaining 43 were presented as abstracts or posters. The majority (80 studies, 80%) of included studies reported treatment in the first-line setting, where platinum-based chemotherapy and chemoradiotherapy was the most commonly used treatment strategy, in line with current treatment guidelines in SCLC. First-line treatments were found to have a high response rate; however, most patients relapsed early. No studies reported treatment or outcomes with immune-oncology therapies. Second-line treatment options were very limited, and primarily consisted of either re-treatment with first-line regimen or topotecan, but the prognosis for these patients remained poor. Outcomes were particularly poor amongst those with ES or relapsed disease vs. LS disease. SCLC treatment patterns and short survival outcomes have remained constant over the previous 20 years. Due to the search timeframe, none of the studies identified reported on the impact of recently approved immune-oncology therapies in SCLC. Further data is needed on the impact of immunotherapies on treatment patterns and real-world outcomes in SCLC.


The Yersinia enterocolitica Ysa type III secretion system is expressed during infections both in vitro and in vivo.
Yersinia enterocolitica biovar 1B maintains two type III secretion systems (T3SS) that are involved in pathogenesis, the plasmid encoded Ysc T3SS and the chromosomally encoded Ysa T3SS. In vitro, the Ysa T3SS has been shown to be expressed only at 26°C in a high-nutrient medium containing an exceptionally high concentration of salt - an artificial condition that provides no clear insight on the nature of signal that Y. enterocolitica responds to in a host. However, previous research has indicated that the Ysa system plays a role in the colonization of gastrointestinal tissues of mice. In this study, a series of Ysa promoter fusions to green fluorescent protein gene (gfp) were created to analyze the expression of this T3SS during infection. Using reporter strains, infections were carried out in vitro using HeLa cells and in vivo using the mouse model of yersiniosis. Expression of green fluorescent protein (GFP) was measured from the promoters of yspP (encoding a secreted effector protein) and orf6 (encoding a structural component of the T3SS apparatus) in vitro and in vivo. During the infection of HeLa cells GFP intensity was measured by fluorescence microscopy, while during murine infections GFP expression in tissues was measured by flow cytometry. These approaches, combined with quantification of yspP mRNA transcripts by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), demonstrate that the Ysa system is expressed in vitro in a contact-dependent manner, and is expressed in vivo during infection of mice.


[A case report of Ebstein's anomaly treated with Carpentier's procedure].
A 42-year-old male patient was admitted with congestive heart failure. Echocardiogram and cardiac angiogram revealed Ebstein's anomaly and severe tricuspid valve incompetence. He underwent Carpentier's procedure for the treatment of Ebstein's anomaly. Carpentier's procedure consists of the following two new points; (1) the right atrium and atrialized ventricle is plicated longitudinally; (2) the anterior leaflet and the posterior leaflet of tricuspid valve are transposed with a clockwise rotation to the level of the normal tricuspid anulus. Compared with Hardy's procedure (transverse plication), longitudinal plication preserves the cavity and the function of the right ventricle and excludes atrialized chamber. In our case, there is a trivial residual regurgitation of tricuspid valve postoperatively, but the patient's clinical status has improved remarkably. We conclude that Carpentier's procedure is an effective operation for Ebstein's anomaly.


Emotions in context: pictorial influences on affective attributions.
The visual illusion Terror Subterra, by Roger Shepard (1990), depicts a seemingly large creature chasing another in a tunnel, yet both creatures are physically identical. In addition to this visual illusion, the two creatures also appear to exhibit different emotions, as the background creature (the pursuer) appears angry whereas the foreground creature (the pursued) appears fearful. We explored this context effect by first establishing the magnitude of the emotional bias effect. We then modified the original drawing in various ways, such as equating for perceived size, removing one creature from the scene, and removing the pictorial context altogether. Findings suggest that the emotional bias is due to the pictorial setting and to the perceived social-emotional relationship between the two creatures. These results highlight the importance of both perceptual and social-emotional influences in driving affective attributions.


[Questionnaire on crossover renal transplantations in Germany].
Due to increasingly better long-term survival rates with dialysis the number of patients with renal failure constantly increases by 4% annually worldwide. Despite great progress in operative and perioperative management as well as improved immunosuppressive drugs, kidney transplantation still faces two major problems. First of all there is a huge deficit of donor organs and secondly the long-term results of the kidney grafts must be improved. One way to relieve this tense situation may be live kidney donation. In many countries not participating in Eurotransplant, especially the United States and Scandinavia, live kidney donation is performed more often than kidney transplantation from deceased donors. Germany implemented a transplantation law in December 1997. This law also regulates living donation, with exclusion of crossover transplantations. Cross-over transplantation is a special variation of live donation for couples who cannot donate/receive in their respective couple constellation. Therefore, the donor of the one couple donates his/her kidney to the recipient of the other couple and vice versa. According to German legislation this is illegal. We performed a study in order to evaluate the opinions of the German kidney transplant centers on crossover kidney transplantations. The majority of the German transplantation centers believe that crossover transplantation is acceptable with regard to ethical and medical concerns. To enable this kind of kidney transplantation the transplantation law would have to be changed. Nevertheless, nationwide polls show that live kidney donation represents only a very small portion of all transplantations taking place. Live kidney donation should be granted higher priority as dialysis triggers psychological and physical damage, especially in children. For many patients live kidney donation is the only chance for early transplantation with an excellent long-lasting kidney graft function.


Evaluation of preincubation time interval in testicular biopsy to obtain optimum sperm parameters.
In sever oligospermia; one of the paths used for surgical sperm retrieval (SSR) is to extract sperm via a testicular biopsy. The aim of our study is to determine the reliable time interval between testicular biopsy and intracytoplasmic sperm injection (ICSI) procedure in order to obtain optimumsperm parameters (count, motility and normal morphology). This cohort study was carried out on 30 patients which were candidates for ICSI. After collection and keeping the samples obtained from the testicular biopsy in Ham's F10 environment, the concentration, motility and morphology of the sperm in each sample was evaluated immediately as well as 2 and 4 hours after processing. The Data were then compared with each other. For the statistical analysis, Friedman, Willcoxon and Cochran tests were used. The mean of sperm concentration was 5.69 ± 6.14 million and the motility was10.83 ± 12.63% at 2 hours following biopsy which was significantly higher than those obtained after 0 and 4 hours of the biopsy (p <0.05). The reliable preincubation time which resulted in the highest rate of spermatozoa parameters after testicular biopsy and before incubation was 2 hours.


Evolution of a fourth generation catalyst for the amination and thioetherification of aryl halides.
Many active pharmaceuticals, herbicides, conducting polymers, and components of organic light-emitting diodes contain arylamines. For many years, this class of compound was prepared via classical methods, such as nitration, reduction and reductive alkylation, copper-mediated chemistry at high temperatures, addition to benzyne intermediates, or direct nucleophilic substitution on particularly electron-poor aromatic or heteroaromatic halides. However, during the past decade, palladium-catalyzed coupling reactions of amines with aryl halides have largely supplanted these earlier methods. Successive generations of catalysts have gradually improved the scope and efficiency of the palladium-catalyzed reaction. This Account describes the conceptual basis and utility of our latest, "fourth-generation" palladium catalyst for the coupling of amines and related reagents with aryl halides. In the past five years, we have developed these catalysts using the lessons learned from previous generations of catalysts developed in our group and in other laboratories. The ligands on the fourth-generation catalyst combine the chelating properties of the aromatic bisphosphines of the second-generation systems with the steric properties and strong electron donation of the hindered alkylphosphines of the third-generation systems. The currently most reactive catalyst in this class is generated from palladium and a sterically hindered version of the Josiphos family of ligands that possesses a ferrocenyl-1-ethyl backbone, a hindered di-tert-butylphosphino group, and a hindered dicyclohexylphosphino group. This system catalyzes the coupling of aryl chlorides, bromides, and iodides with primary amines, N-H imines, and hydrazones in high yield. The reaction has broad scope, high functional group tolerance, and nearly perfect selectivity for monoarylation. It also requires the lowest levels of palladium that have been used for C-N coupling. In addition, this latest catalyst has dramatically improved the coupling of thiols with haloarenes to form C-S bonds. Using ligands that lacked one or more of the structural elements of the most active catalyst, we examined the effects of individual structural elements of the Josiphos ligand on catalyst activity. This set of studies showed that each one of these elements contributes to the high reactivity and selectivity of the catalyst containing the hindered, bidentate Josiphos ligand. Finally, we examined the effect of electronic properties on the rates of reductive elimination to distinguish between the effect of the properties of the M-N sigma-bond and the nitrogen electron pair. We have found that the effects of electronic properties on C-C and C-N bond-forming reductive elimination are similar. Because the amido ligands contain an electron pair, while the alkyl ligands do not, we have concluded that the major electronic effect is transmitted through the sigma-bond.